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The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.
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The purpose of this analysis was to compare health care costs and utilization among COPD patients who had long-acting beta-2 agonist (LABA) OR long-acting muscarinic antagonist (LAMA); LABA AND LAMA; or LABA, LAMA, AND inhaled corticosteroid (ICS) prescription claims.,This was a 12 month pre-post, retrospective analysis using COPD patients in a national administrative insurance database.,Propensity score and exact matching were used to match patients 1:1:1 between the LABA or LAMA (formoterol, salmeterol, or tiotropium), LABA and LAMA (tiotropium/formoterol or tiotropium/salmeterol), and LABA, LAMA and ICS (bronchodilators plus steroid) groups.,Post-period comparisons were evaluated with analysis of covariance.,Costs were evaluated from a commercial payer perspective.,A total of 523 patients were matched using 29 pre-period variables (e.g., demographics, medication exposure).,Post-match assessments indicated balance among the cohorts.,COPD-related costs differed among groups (LABA or LAMA $2,051 SE = 91; LABA and LAMA $2,823 SE = 62; LABA, LAMA and ICS $3,546 SE = 89; all p < .0001) with the differences driven by study medication costs.,However, non-study COPD medication costs were higher for the LABA or LAMA therapy group ($911 SE = 91) compared to the LABA and LAMA therapy group ($668 SE = 58; p = 0.0238) and non-study respiratory medications were approximately $100 greater for the LABA or LAMA therapy group relative to both LABA and LAMA (p = .0018) and LABA, LAMA, and ICS (p = .0071) therapy groups.,While there was no observed difference in outpatient costs, there was a slightly higher number of outpatient visits per patient in the LABA and LAMA (25.5 SE = 0.9, p = 0.0070) relative to the LABA or LAMA therapy group (22.3 SE = 0.8) and higher utilization (89.7% of patients) with COPD visits in the LABA and LAMA therapy group relative to both the LABA or LAMA (73.8%; p < .0001) and LABA, LAMA and ICS therapy groups (85.3; p = 0.0305).,Significant cost differences driven mainly by pharmaceuticals were observed among LABA or LAMA, LABA and LAMA and LABA, LAMA and ICS therapies.,A COPD-related cost offset was observed from single bronchodilator to two bronchodilators.,Addition of an ICS with two bronchodilators resulted in higher treatment costs without reduction in other COPD-related costs compared with two bronchodilators.
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Pulmonary emphysema is characterized histologically by destruction of alveolar walls and enlargement of air spaces due to lung epithelial cell apoptosis.,Cell adhesion molecule 1 (CADM1) is an immunoglobulin superfamily member expressed in lung epithelial cells.,CADM1 generates a membrane-associated C-terminal fragment, αCTF, through A disintegrin- and metalloprotease-10-mediated ectodomain shedding, subsequently releasing the intracellular domain (ICD) through γ-secretase-mediated intramembrane shedding of αCTF. αCTF localizes to mitochondria and induces apoptosis in lung epithelial cells. αCTF contributes to the development and progression of emphysema as a consequence of increased CADM1 ectodomain shedding.,The purpose of this study was to examine whether the ICD makes a similar contribution.,The ICD was synthesized as a 51-amino acid peptide, and its mutant was synthesized by substituting seven amino acids and deleting two amino acids.,These peptides were labeled with fluorescein isothiocyanate and were introduced into various cell lines.,ICD peptide-derived fluorescence was well visualized in lung epithelial cells at the site of Mitotracker mitochondrial labeling, but was detected in locations other than mitochondria in other cell types.,Mutant peptide-derived fluorescence was detected in locations other than mitochondria, even in lung epithelial cells.,Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays revealed that transduction of the ICD peptide increased the proportion of apoptotic cells 2- to 5-fold in the lung epithelial cell lines, whereas the mutant peptide did not.,Abundance of the ICD was below the Western blot detection limit in emphysematous (n = 4) and control (n = 4) human lungs.,However, the ICD was detected only in emphysematous lungs when it was immunoprecipitated with anti-CADM1 antibody (4/4 vs.,0/4, P = 0.029).,As the abundance of ICD molecules was sparse but present, increased CADM1 shedding appeared to contribute to the development of emphysema by generating αCTF and the ICD in lung epithelial cells.,The online version of this article (doi:10.1186/s12929-015-0173-8) contains supplementary material, which is available to authorized users.
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Chronic pulmonary obstructive disease (COPD) has become the fourth leading cause of death worldwide.,Cigarette smoking induces neutrophil elastase (NE) and contributes to COPD, but the detailed mechanisms involved are not fully established.,In an animal model of pulmonary emphysema, there are increased expressions of placenta growth factor (PlGF) and lung epithelial (LE) cell apoptosis.,This study hypothesized that excessive NE may up-regulate PlGF and that PlGF-induced LE apoptosis mediates the pathogenesis of pulmonary emphysema.,Human bronchial epithelial cells, BEAS-2B, and primary mouse type II alveolar epithelial cells were treated with NE.,The PlGF promoter activity was examined by luciferase activity assay, while PlGF expression and secretion were evaluated by RT-PCR, Western blotting, and ELISA.,Both cell lines were treated with PlGF to evaluate its effects and the downstream signaling pathways leading to LE cell apoptosis.,PlGF knockout and wild-type mice were instilled with NE to determine the roles of PlGF and its downstream molecules in NE-promoted mice pulmonary apoptosis and emphysema phenotype.,The transcriptional factor, early growth response gene-1, was involved in the NE-promoted PlGF promoter activity, and the expression and secretion of PlGF mRNA and protein in LE cells.,PlGF-induced LE cell apoptosis and NE-induced mice pulmonary apoptosis and emphysema were mediated by the downstream c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)δ signaling pathways.,The NE-PlGF-JNK/PKCδ pathway contributes to the pathogenesis of LE cell apoptosis and emphysema.,PlGF and its downstream signaling molecules may be potential therapeutic targets for COPD.,The online version of this article (doi:10.1186/s12931-014-0106-1) contains supplementary material, which is available to authorized users.
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Despite the availability of treatment guidelines and inhaled medications for asthma and chronic obstructive pulmonary disease (COPD), much remains to be done to lessen the burden of these respiratory diseases for patients.,The challenge of selecting effective and efficacious drugs for patients is a key focus area for healthcare professionals.,Here we discuss the concept of “drivers of effectiveness”- features of a medicine which may increase or decrease its effectiveness in the presence of real-world factors - and highlight the importance of considering these drivers in the early stages of drug development, and exploring their impact in carefully designed pragmatic trials.,Using the Salford Lung Studies (SLS) in asthma and COPD as an illustrative example, we discuss various features of the inhaled corticosteroid/long-acting β2-agonist combination, fluticasone furoate/vilanterol (FF/VI), as potential drivers of effectiveness that may have contributed to the improved patient outcomes observed with initiation of FF/VI versus continuation of usual care in the UK primary care setting.
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In patients with chronic obstructive pulmonary disease, all efforts should be made to prevent exacerbations because each event modifies the trajectory of the disease.,Treatment recommendations are mostly built on results from randomized controlled trials (RCTs) whose methodology ensure internal validity.,However, their relevance may be compromised by the lack of generalizability, due to poor representability of study populations compared to real-life patients.,In order to delimit to whom the results of studies on current and future treatments apply, we sought to identify and characterize the fraction of COPD population that would be eligible for inclusion into RCTs aiming at decreasing exacerbation risk.,We used the Initiatives-BPCO database, a French cohort of 1309 real-life COPD patients monitored in academic centers.,We identified industry-sponsored phase III and IV trials that enrolled more than 500 patients, lasted at least one year and used exacerbations related endpoints.,Eligibility criteria were extracted from each trial and applied to the patients.,The eligibility criteria of 16 RCTs were applied to the 1309 patients.,The most discriminating eligibility criteria were FEV1, minimum exacerbation rate in the previous year and smoking history, responsible for the exclusion of 39.9, 36.7 and 16.8% of patients, respectively.,Altogether, 2.3 to 46.7% of our patients would have satisfied all eligibility criteria.,These analyses confirm that an important gap exists between real-life patients and clinical trials populations in COPD, which limits the relevance of results and therefore should be considered when grading levels of evidence and designing future studies.
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We previously reported satisfactory results with the Karakoca resector balloon in 10 patients with stage IV chronic obstructive pulmonary disease (COPD) who did not respond to medical treatment.,In this article, we present the outcomes of the Karakoca resector balloon dilatation and curettage technique in a larger case series (n = 188).,A total of 188 COPD patients [mean age (SD): 69.2 (8.0) years; 46 females] classified as stage III to IV by the Global Initiative for Obstructive Lung Disease criteria underwent balloon desobstruction for segmental and subsegmental bronchi by therapeutic bronchoscopy.,None of the patients could have achieved symptom relief even under high-dose inhaled bronchodilators and corticosteroids, oral corticosteroids, or oxygen and noninvasive mechanical ventilation therapy before the intervention.,Forced expiratory volume in 1 s (FEV1) and oxygen saturation (SpO2) were measured, and modified Borg dyspnea scale (MBS) scores were determined before and 1 week and 1 month after the intervention.,All patients were active smokers and 80% had concomitant chronic diseases.,After the intervention, there was a notable reduction in the oxygen need of the patients.,Comparison of lung function tests 1 week after the procedure with results before the procedure showed significant improvements in FEV1, MBS, and SpO2 levels (P < 0.001 for each), and the improvements were maintained for the entire postprocedural month (P < 0.001 for each).,Except for 4 males, all patients were free of symptoms.,These results confirmed our early observations that balloon dilatation and curettage is a safe and successful technique for medical treatment-resistant COPD.
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Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction.,Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms.,To evaluate ‘targeted lung denervation’ (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD.,This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted).,Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators.,Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD.,The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year.,Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life.,Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W).,The procedures were technically feasible 93% of the time.,Primary safety endpoint was achieved in 95%.,Asymptomatic bronchial wall effects were observed in 3 patients at 20 W.,The clinical safety profiles were similar between the two energy doses.,At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (−11.1 points ±9.1 vs −0.9 points ±8.6, p=0.044).,Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated.,Further investigation of this novel therapy is warranted.,NCT01483534.
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Pulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum.,The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.,In a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis.,Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.,In COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001).,The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01).,SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers.,In addition, smoking lead to disruption of the quaternary structure.,Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state.,Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.,no interventional trial
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The potential role of growth factors in chronic obstructive pulmonary disease (COPD) has begun to be addressed only recently and is still poorly understood.,For this study, we investigated potential abnormalities of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in patients with COPD.,To this end, we compared the levels of HGF and KGF, measured by enzyme-linked immunosorbent assay (ELISA), in bronchoalveolar lavage (BAL) fluid and in serum in 18 patients with COPD (62 ± 9 yrs, forced expiratory volume in one second [FEV1] 57 ± 12% ref, X ± standard deviation of mean), 18 smokers with normal lung function (58 ± 8 yrs, FEV1 90 ± 6% ref) and 8 never smokers (67 ± 9 yrs, 94 ± 14% ref).,We found that in BAL, HGF levels were higher in patients with COPD than in the other two groups whereas, in serum, HGF concentration was highest in smokers with normal lung function (p < 0.01).,KGF levels were not significantly different between groups, neither in blood nor in BAL (most values were below the detection limit).,These results highlight a different response of HGF in BAL and serum in smokers with and without COPD that may be relevant for tissue repair in COPD.
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Chronic obstructive pulmonary disease (COPD) is an incurable and prevalent respiratory disorder that is characterized by chronic inflammation and emphysema.,COPD is primarily caused by cigarette smoke (CS).,CS alters numerous cellular processes, including the post-transcriptional regulation of mRNAs.,The identification of RNA-binding proteins (RBPs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as main factors engaged in the regulation of RNA biology opens the door to understanding their role in coordinating physiological cellular processes.,Dysregulation of post-transcriptional regulation by foreign particles in CS may lead to the development of diseases such as COPD.,Here we review current knowledge about post-transcriptional events that may be involved in the pathogenesis of COPD.
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In chronic obstructive pulmonary disease (COPD), endothelial dysfunction and stiffness of systemic arteries may contribute to increased cardiovascular risk.,Pulmonary vascular disease (PVD) is frequent in COPD.,The association between PVD and systemic vascular dysfunction has not been thoroughly evaluated in COPD.,A total of 108 subjects were allocated into four groups (non-smoking controls, smoking controls, COPD without PVD and COPD with PVD).,In systemic arteries, endothelial dysfunction was assessed by flow-mediated dilation (FMD) and arterial stiffness by pulse wave analysis (PWA) and pulse wave velocity (PWV).,PVD was defined by a mean pulmonary artery pressure (PAP) ≥25 mmHg at right heart catheterization or by a tricuspid regurgitation velocity >2.8 m/s at doppler echocardiography.,Biomarkers of inflammation and endothelial damage were assessed in peripheral blood.,FMD was lower in COPD patients, with or without PVD, compared to non-smoking controls; and in patients with COPD and PVD compared to smoking controls.,PWV was higher in COPD with PVD patients compared to both non-smoking and smoking controls in a model adjusted by age and the Framingham score; PWV was also higher in patients with COPD and PVD compared to COPD without PVD patients in the non-adjusted analysis.,FMD and PWV correlated significantly with forced expiratory volume in the first second (FEV1), diffusing capacity for carbon monoxide (DLCO) and systolic PAP.,FMD and PWV were correlated in all subjects.,We conclude that endothelial dysfunction of systemic arteries is common in COPD, irrespective if they have PVD or not.,COPD patients with PVD show increased stiffness and greater impairment of endothelial function in systemic arteries.,These findings suggest the association of vascular impairment in both pulmonary and systemic territories in a subset of COPD patients.
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Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065.
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Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD).,We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD.,In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations.,There were 492 exacerbations in 224 patients.,The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week.,Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks.,The course of symptoms was similar around a first and second exacerbation.,Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70.,Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation.,COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.
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COPD is a highly heterogeneous disease composed of different phenotypes with different aetiological and prognostic profiles and current classification systems do not fully capture this heterogeneity.,In this study we sought to discover, describe and validate COPD subtypes using cluster analysis on data derived from electronic health records.,We applied two unsupervised learning algorithms (k-means and hierarchical clustering) in 30,961 current and former smokers diagnosed with COPD, using linked national structured electronic health records in England available through the CALIBER resource.,We used 15 clinical features, including risk factors and comorbidities and performed dimensionality reduction using multiple correspondence analysis.,We compared the association between cluster membership and COPD exacerbations and respiratory and cardiovascular death with 10,736 deaths recorded over 146,466 person-years of follow-up.,We also implemented and tested a process to assign unseen patients into clusters using a decision tree classifier.,We identified and characterized five COPD patient clusters with distinct patient characteristics with respect to demographics, comorbidities, risk of death and exacerbations.,The four subgroups were associated with 1) anxiety/depression; 2) severe airflow obstruction and frailty; 3) cardiovascular disease and diabetes and 4) obesity/atopy.,A fifth cluster was associated with low prevalence of most comorbid conditions.,COPD patients can be sub-classified into groups with differing risk factors, comorbidities, and prognosis, based on data included in their primary care records.,The identified clusters confirm findings of previous clustering studies and draw attention to anxiety and depression as important drivers of the disease in young, female patients.,The online version of this article (10.1186/s12911-019-0805-0) contains supplementary material, which is available to authorized users.
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Asthma and chronic obstructive pulmonary disease (COPD) are two common different clinical diagnoses with overlapping clinical features.,Both conditions have been increasingly studied using electronic health records (EHR).,Asthma-COPD overlap syndrome (ACOS) is an emerging concept where clinical features from both conditions co-exist, and for which, however, there is no consensus definition.,Nonetheless, we expect EHR data of people with ACOS to be systematically different from those with “asthma only” or “COPD only”.,We aim to develop a latent class model to understand the overlap between asthma and COPD in EHR data.,From the Secure Anonymised Information Linkage (SAIL) databank, we will use routinely collected primary care data recorded in or before 2014 in Wales for people who aged 40 years or more on 1st Jan 2014.,Based on this latent class model, we will train a classification algorithm and compare its performance with commonly used objective and self-reported case definitions for asthma and COPD.,The resulting classification algorithm is intended to be used to identify people with ACOS, ‘asthma only’, and ‘COPD only’ in primary care datasets.
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A variety of maintenance inhaler therapies are available to treat asthma and COPD.,Patient-centric treatment choices require understanding patient preferences for the alternative therapies.,A self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes.,Selection of attributes was informed by patient focus groups and literature review.,The discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD.,Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1.,Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1.,Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids.,Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations.,The most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations.,Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important.
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Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult.,Incorporation of patient preferences is widely encouraged.,To summarize original research articles determining patient preference in moderate-to-severe disease.,Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma.,The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease.,We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences.,Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion.,Data were tabulated and analyzed descriptively.,About 478 articles identified, 448 were rejected and 30 analyzed.,There were 25 on COPD and five on asthma.,Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient-physician relationship, quality-of-life impairments, and information availability.,Patients strongly preferred sponsors’ inhalers.,At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention.,While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience.,Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler.,Few studies have examined patient preference in these diseases.,More research is needed to fill in knowledge gaps.
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In respiratory disorders, patient- and physician-perceived satisfaction with the maintenance inhaler device is an important factor driving treatment compliance and outcomes.,We examine inhaler preferences in asthma and COPD from patient and physician perspectives, particularly focusing on the relative importance of individual device attributes and patient characteristics guiding inhaler choice.,Real-world data from >7,300 patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS) consulting for routine care were derived from respiratory Disease Specific Programs conducted in Europe, USA, Japan, and China.,Outcome variables included current pattern of inhaled maintenance therapy and device type, physician preference, patient-reported device attribute importance, and satisfaction.,The most commonly prescribed inhalers for maintenance therapy of asthma, COPD, and ACOS were dry powder inhalers (62.8%-88.5% of patients) and pressurized metered dose inhalers (18.9%-35.3% of patients).,One-third of physicians stated no preference for maintenance device when prescribing treatment, and less than one-third of patients reported being “extremely satisfied” with any attribute of their device.,Instructions being “simple and easy to follow” was the inhaler attribute most commonly selected as important.,For approximately one-third of patients across all groups, “ease of use/suitability of inhaler device” was a reason for the prescribing decision, as stated by the physician.,Device characteristics were more likely to impact the prescribing decision in older patients (in asthma and COPD; P<0.01) and those with worse disease severity (in COPD; P<0.001).,A relatively high proportion of physicians had no preference for inhaler type across asthma, COPD, and ACOS.,Simplicity of use was the most important inhaler attribute from a patient’s perspective.,Physicians appeared to place most importance on ease of use and device suitability when selecting inhalers for older patients and those with more severe disease, particularly in COPD.
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The ability of a long-acting muscarinic antagonist (LAMA) and long-acting beta 2 agonists (LABAs; long-acting bronchodilators, LABDs) with or without inhaled corticosteroids (ICSs) to reduce early readmission in hospitalized patients with COPD is unknown.,We studied a 5% sample of Medicare beneficiaries enrolled in Medicare parts A, B and D and hospitalized for COPD in 2011.,We examined prescriptions filled for LABDs with or without ICSs (LABDs±ICSs) within 90 days prior to and 30 days after hospitalization.,Primary outcome was the 30-day readmission rate between “users” and “nonusers” of LABDs±ICSs.,Propensity score matching and sensitivity analysis were performed by limiting analysis to patients hospitalized for acute exacerbation of COPD (AECOPD).,Among 6,066 patients hospitalized for COPD, 3,747 (61.8%) used LABDs±ICSs during the specified period.,The “user” and “nonuser” groups had similar rates of all-cause emergency room (ER) visits and readmissions within 30 days of discharge date (22.4% vs 20.7%, P-value 0.11; 18.0% vs 17.8%, P-value 0.85, respectively).,However, the “users” had higher rates of COPD-related ER visits (5.3% vs 3.4%, P-value 0.0006), higher adjusted odds ratio (aOR) 1.47 (95% CI, 1.11-1.93) and readmission (7.8% vs 5.0%, P-value <0.0001 and aOR 1.48 [95% CI, 1.18-1.86]) than “nonusers”.,After propensity score matching, the aOR of COPD-related ER visits was 1.45 (95% CI, 1.07-1.96) and that of readmission was 1.34 (95% CI, 1.04-1.73).,The results were similar when restricted to patients hospitalized for AECOPD.,Use of LABDs±ICSs did not reduce 30-day readmissions in patients hospitalized for COPD.
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Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services.
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Objective To assess the effect of second generation, home based telehealth on health related quality of life, anxiety, and depressive symptoms over 12 months in patients with long term conditions.,Design A study of patient reported outcomes (the Whole Systems Demonstrator telehealth questionnaire study; baseline n=1573) was nested in a pragmatic, cluster randomised trial of telehealth (the Whole Systems Demonstrator telehealth trial, n=3230).,General practice was the unit of randomisation, and telehealth was compared with usual care.,Data were collected at baseline, four months (short term), and 12 months (long term).,Primary intention to treat analyses tested treatment effectiveness; multilevel models controlled for clustering by general practice and a range of covariates.,Analyses were conducted for 759 participants who completed questionnaire measures at all three time points (complete case cohort) and 1201 who completed the baseline assessment plus at least one other assessment (available case cohort).,Secondary per protocol analyses tested treatment efficacy and included 633 and 1108 participants in the complete case and available case cohorts, respectively.,Setting Provision of primary and secondary care via general practices, specialist nurses, and hospital clinics in three diverse regions of England (Cornwall, Kent, and Newham), with established integrated health and social care systems.,Participants Patients with chronic obstructive pulmonary disease (COPD), diabetes, or heart failure recruited between May 2008 and December 2009.,Main outcome measures Generic, health related quality of life (assessed by physical and mental health component scores of the SF-12, and the EQ-5D), anxiety (assessed by the six item Brief State-Trait Anxiety Inventory), and depressive symptoms (assessed by the 10 item Centre for Epidemiological Studies Depression Scale).,Results In the intention to treat analyses, differences between treatment groups were small and non-significant for all outcomes in the complete case (0.480≤P≤0.904) or available case (0.181≤P≤0.905) cohorts.,The magnitude of differences between trial arms did not reach the trial defined, minimal clinically important difference (0.3 standardised mean difference) for any outcome in either cohort at four or 12 months.,Per protocol analyses replicated the primary analyses; the main effect of trial arm (telehealth v usual care) was non-significant for any outcome (complete case cohort 0.273≤P≤0.761; available case cohort 0.145≤P≤0.696).,Conclusions Second generation, home based telehealth as implemented in the Whole Systems Demonstrator Evaluation was not effective or efficacious compared with usual care only.,Telehealth did not improve quality of life or psychological outcomes for patients with chronic obstructive pulmonary disease, diabetes, or heart failure over 12 months.,The findings suggest that concerns about potentially deleterious effect of telehealth are unfounded for most patients.,Trial Registration ISRCTN43002091.
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Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject.
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Inflammation is considered to be of primary pathogenic importance in COPD but the evidence on which current understanding is based does not distinguish between cause and effect, and no single mechanism can account for the complex pathology.,We performed a prospective longitudinal study of subjects with COPD that related markers of sputum inflammation at baseline to subsequent disease progression.,A cohort of 56 patients with chronic bronchitis was characterized in the stable state at baseline and after an interval of four years, using physiological measures and CT densitometry.,Sputum markers of airway inflammation were quantified at baseline from spontaneously produced sputum in a sub-group (n = 38), and inflammation severity was related to subsequent disease progression.,Physiological and CT measures indicated disease progression in the whole group.,In the sub-group, sputum myeloperoxidase correlated with decline in FEV1 (rs = -0.344, p = 0.019, n = 37).,LTB4 and albumin leakage correlated with TLCO decline (rs = -0.310, p = 0.033, rs = -0.401, p = 0.008, respectively, n = 35) and IL-8 correlated with progression of lung densitometric indices (rs = -0.464, p = 0.005, n = 38).,The data support a principal causative role for neutrophilic inflammation in the pathogenesis of COPD and suggest that the measurement of sputum inflammatory markers may have a predictive role in clinical practice.
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Neuromuscular electrical stimulation (NMES) has been shown to produce benefits in the muscle function of chronic obstructive pulmonary disease (COPD) patients.,The definite effectiveness of NMES, applied in isolation or concurrently with conventional pulmonary rehabilitation (PR) or exercise training, remains unclear.,This review was to determine the effects of NMES on exercise capacity, functional performance, symptoms, and health-related quality of life (HRQoL) in COPD patients.,Electronic databases (PubMed, Embase, Web of Science, the Cochrane Library) were searched for relevant randomized controlled trials (RCTs).,Two investigators independently screened the eligible studies up to February 2020 that used NMES as the intervention group.,The outcome measures were 6-min walking distance (6MWD), peak rate of oxygen uptake (VO2 peak), St George’s Respiratory Questionnaire (SGRQ), and symptoms of dyspnoea and fatigue.,Data were extracted using a predefined table and papers were appraised using Downs and Black tool.,We analyzed 13 RCTs with 447 COPD patients.,In the analysis of 6MWD, pooled estimates showed a significant increase in the NMES group, compared with the control group (mean difference (MD) = 27.05, 95% confidence interval (CI): 8.46-45.63, P<0.001).,There were also improvements in symptoms of dyspnea or leg fatigue, and reduction in London Chest Activity of Daily Living (LCADL) scores.,No statistically significant difference was observed in VO2 peak, peak power, and SGRQ.,NMES could improve exercise capacity and reduce perceived sensation of dyspnea during exercise in patients with COPD, but not to be recommended as an effective alternative training modality in the rehabilitation of stable COPD patients.
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Anabolic steroids are known to improve body composition and muscle strength in healthy people.,However, whether anabolic steroids improve the physical condition and function in patients with chronic obstructive pulmonary disease (COPD) remains undetermined.,A meta-analysis was conducted to review the current evidence regarding the effects of anabolic steroids on COPD patients.,A comprehensive literature search of PubMed and EMBASE was performed to identify randomised controlled trials that examine the effects of anabolic steroids on COPD patients.,Weighted mean differences (WMDs) with 95% confidence intervals were calculated to determine differences between anabolic steroid administration and control conditions.,Eight eligible studies involving 273 COPD patients were identified in this meta-analysis.,Significant improvements were found in body weight (0.956 kg), fat-free mass (1.606 kg), St.,George's Respiratory Questionnaire total score (−6.336) and symptom score (−12.148).,The apparent improvements in maximal inspiratory pressure (2.740 cmH2O) and maximal expiratory pressure (12.679 cmH2O) were not significant.,The effects on handgrip strength, forced expiratory volume in one second (FEV1), predicted FEV1 percent, PaO2, PaCO2 and six-min walk distance were negative, with WMDs of −0.245 kg, −0.096 L/sec, −1.996% of predicted, −1.648 cmHg, −0.039 cmHg and −16.102 meters, respectively.,Limited evidence available from the published literature suggests that the benefit of anabolic steroids on COPD patients cannot be denied.,However, further studies are needed to identify the specific benefits and adverse effects of anabolic steroids on COPD patients and to determine the optimal populations and regimes of anabolic steroids in COPD patients.
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Our aim was to evaluate the use and impact of the practice walk test on enrolment, completion, and clinical functional response to pulmonary rehabilitation (PR) using the 2015 UK National Chronic Obstructive Pulmonary Disease (COPD) Pulmonary Rehabilitation audit data.,Patients were assessed according to whether a baseline practice walk test was performed or not.,Study outcomes included use of the practice walk test, baseline and change in incremental shuttle walk test distance (ISWD) or 6-minute walk test distance (6MWD), and enrolment to and completion of PR program.,Of 7,355 patients, only 1,666 (22.6%) had a baseline practice test.,At baseline, the practice walk test group walked further as compared to the no practice walk test group: ISWD, 17.9 m [95% confidence interval (CI) 8.2-27.5 m] and 6MWD, 34.8 m (95% CI 24.7-44.9 m).,The practice walk test group were 2.2 times (95% CI 1.8-2.6) more likely to enroll and 17% (95% CI 1.03-1.34) more likely to complete PR.,Although the change in ISWD and 6MWD with PR was lower in the practice walk test group, they walked further at discharge assessment.,Only 22.6% of the patients in the 2015 National PR audit had a practice walk test at assessment.,Those who did had better enrolment, completion, and better baseline walking distance, from which the prescription is set.
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Outcomes in early trials of bronchoscopic lung volume reduction using endobronchial valves for the treatment of patients with advanced emphysema were inconsistent.,However improvements in patient selection with focus on excluding those with interlobar collateral ventilation and homogeneous emphysema resulted in significant benefits in the BeLieVeR-HIFi study compared with sham treated controls.,In this manuscript we present data from the control patients in the BeLieVeR-HIFi study who went on to have open label endobronchial valve treatment after completion of the clinical trial (n=12), combined with data from those in the treatment arm who did not have collateral ventilation (n=19).,Three months after treatment FEV1 increased by 27.3 (36.4)%, residual volume reduced by 0.49 (0.76) L, the 6 min walk distance increased by 32.6 (68.7) m and the St George Respiratory Questionnaire for COPD score improved by 8.2 (20.2) points.,These data extend the evidence for endobronchial valve placement in appropriately selected patients with COPD.,ISRCTN04761234; Results.
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Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings.,Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests.,The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV.,To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease.,The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality.,Both tests were also significantly associated with health-related quality of life but not with exacerbations.,The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62).,The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings.,The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settingshttp://ow.ly/mxrPx
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Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires.,The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality.,Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology.,Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD.
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Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients.
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While chronic morbidity and mortality from COPD is well documented, little is known about the treatment burden faced by patients with COPD.,Patients with severe airflow obstruction (forced expiratory volume in 1 second [FEV1] <50% predicted) representing different age-groups, sex, and number of comorbidities participated in a semistructured interview.,Interviews were conducted until thematic saturation was reached.,Interviews were recorded, transcribed, and analyzed thematically using an established treatment-burden framework.,A total of 26 patients (42% male, mean age 66.7±9.8 years) with severe (n=15) or very severe (n=11) airflow limitation (mean FEV1 32.1%±9.65% predicted) were interviewed.,Participants struggled with various treatment-burden domains, predominantly with changing health behaviors, such as smoking cessation and exercise.,Interviewees often only ceased smoking after a major health event, despite being advised to do so earlier by a doctor.,Recommended exercise regimens, such as pulmonary rehabilitation classes, were curtailed, although some patients replaced them with light home-based exercise.,Interviewees had difficulty attending medical appointments, often relying on others to transport them.,Overall, COPD patients indicated they were not willing to accept the burden of treatments where they perceived minimal benefit.,This study describes the substantial treatment burden experienced by patients with COPD.,Medical advice may be rejected by patients if the benefit of following the advice is perceived as insufficient.,Health professionals need to recognize treatment burden as a source of nonadherence, and should tailor treatment discussions to fit patients’ values and capacity to achieve optimal patient outcomes.
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The burden of chronic obstructive pulmonary disease (COPD) to patients and health services is steadily increasing.,Self-management supported by mobile device applications could improve outcomes for people with COPD.,Our aim was to synthesize evidence on the effectiveness of mobile health applications compared with usual care.,A systematic review was conducted to identify randomized controlled trials.,Outcomes of interest included exacerbations, physical function, and Quality of Life (QoL).,Where possible, outcome data were pooled for meta-analyses.,Of 1709 citations returned, 13 were eligible trials.,Number of exacerbations, quality of life, physical function, dyspnea, physical activity, and self-efficacy were reported.,Evidence for effectiveness was inconsistent between studies, and the pooled effect size for physical function and QoL was not significant.,There was notable variation in outcome measures used across trials.,Developing a standardized outcome-reporting framework for digital health interventions in COPD self-management may help standardize future research.
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Within telehealth there are a number of domains relevant to pulmonary care: telemonitoring, teleassistance, telerehabilitation, teleconsultation and second opinion calls.,In the last decade, several studies focusing on the effects of various telemanagement programs for patients with chronic obstructive pulmonary disease (COPD) have been published but with contradictory findings.,From the literature, the best telemonitoring outcomes come from programs dedicated to aged and very sick patients, frequent exacerbators with multimorbidity and limited community support; programs using third-generation telemonitoring systems providing constant analytical and decisionmaking support (24 h/day, 7 days/week); countries where strong community links are not available; and zones where telemonitoring and rehabilitation can be delivered directly to the patient’s location.,In the near future, it is expected that telemedicine will produce changes in work practices, cultural attitudes and organization, which will affect all professional figures involved in the provision of care.,The key to optimizing the use of telemonitoring is to correctly identify who the ideal candidates are, at what time they need it, and for how long.,The time course of disease progression varies from patient to patient; hence identifying for each patient a ‘correct window’ for initiating telemonitoring could be the correct solution.,In conclusion, as clinicians, we need to identify the specific challenges we face in delivering care, and implement flexible systems that can be customized to individual patients’ requirements and adapted to our diverse healthcare contexts.
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COPD is a leading cause of morbidity and mortality worldwide.,Patients suffer from refractory breathlessness, unrecognized anxiety and depression, and decreased quality of life.,Palliative care improves symptom management, patient reported health-related quality of life, cost savings, and mortality though the majority of patients with COPD die without access to palliative care.,There are many barriers to providing palliative care to patients with COPD including the difficulty in prognosticating a patient’s course causing referrals to occur late in a patient’s disease.,Additionally, physicians avoid conversations about advance care planning due to unique communication barriers present with patients with COPD.,Lastly, many health systems are not set up to provide trained palliative care physicians to patients with chronic disease including COPD.,This review analyzes the above challenges, the available data regarding palliative care applied to the COPD population, and proposes an alternative approach to address the unmet needs of patients with COPD with proactive primary palliative care.
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According to the Word Health Organization, patients who can benefit from palliative care should be identified earlier to enable proactive palliative care.,Up to now, this is not common practice and has hardly been addressed in scientific literature.,Still, palliative care is limited to the terminal phase and restricted to patients with cancer.,Therefore, we trained general practitioners (GPs) in identifying palliative patients in an earlier phase of their disease trajectory and in delivering structured proactive palliative care.,The aim of our study is to determine if this training, in combination with consulting an expert in palliative care regarding each palliative patient's tailored care plan, can improve different aspects of the quality of the remaining life of patients with severe chronic diseases such as chronic obstructive pulmonary disease, congestive heart failure and cancer.,A two-armed randomized controlled trial was performed.,As outcome variables we studied: place of death, number of hospital admissions and number of GP out of hours contacts.,We expect that this study will increase the number of identified palliative care patients and improve different aspects of quality of palliative care.,This is of importance to improve palliative care for patients with COPD, CHF and cancer and their informal caregivers, and to empower the GP.,The study protocol is described and possible strengths and weaknesses and possible consequences have been outlined.,The Netherlands National Trial Register: NTR2815
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In patients with chronic obstructive pulmonary disease (COPD), the extent of physical activity (PA) is correlated with disease severity and prognosis.,However, factors associated with low-level PA in elderly COPD patients are not known.,We assessed the levels of PA and clinical factors associated with low-level of PA in elderly COPD patients.,This was a secondary analysis of a multicenter, prospective study of 245 patients with COPD.,Among them, 160 patients with 65 years or more were included.,Three PA groups were defined with respect to daily activity time (low, moderate, and high).,Health related quality of life (HRQL) was measured using St.,George’s respiratory questionnaire (SGRQ) and 36-item short-form health survey.,Anxiety and depression status were assessed employing the hospital anxiety and depression scale (HADS).,Multivariate logistic regression was performed to identify independent predictors of low-level PA in elderly COPD patients.,Of all the 160 patients, 103 (64.4%) engaged in low-level PA.,Upon univariate analysis, a decreased exercise capacity (6-minute walk test < 250 m), an increased dyspnea (the modified medical research council [MMRC] dyspnea scale ≥ 2), a decreased HRQL (total SGRQ score), and a presence of depression (HADS-D ≥ 8) were significantly associated with low-level PA.,Upon multivariate analysis, an MMRC grade ≥ 2 (hazard ratio [HR], 2.550; p = 0.034), and HADS-D ≥ 8 (HR, 2.076; p = 0.045) were independently associated with low-level PA in elderly COPD patients.,Two-thirds of elderly patients with COPD reported low-level of PA.,More severe dyspnea and a presence of depression were independently associated with low-level PA in elderly COPD patients.
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Beta-blockers are frequently withheld in patients with cardiovascular disease who also have chronic obstructive pulmonary disease (COPD) because of concerns that they might provoke bronchospasm and cause deterioration in health status.,Although beta1-selective beta-blockers are associated with reduced mortality in COPD patients, their effects on health status are unknown.,The aim of this study was to investigate the relationship between beta-blockers and health-related quality of life (HRQOL) in patients with peripheral arterial disease and COPD.,Of the original cohort of 3371 vascular surgery patients, 1310 had COPD of whom 469 survived during long-term follow-up.,These COPD patients were sent the Short Form-36 (SF-36) health-related quality of life questionnaire, which was completed and returned by 326 (70%) patients.,No significant differences in any of the SF-36 domains were observed between COPD patients who did and did not use beta-blockers (p > 0.05 for all).,Furthermore, beta-blockers were not associated with any impairment in HRQOL among patients with COPD.,Beta-blockers had no material impact on the HRQOL of patients with peripheral arterial disease who also had COPD.,This suggests that beta-blockers can, in most circumstances, be administered to patients with COPD without impairment in HRQOL.
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The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users.
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The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function.,The aims of this study were to investigate total mortality risks in GOLD stages 0-4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1-4.,Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits.,Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses.,Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0-4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group.,HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1-4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.,The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively.,The proportion of smokers among men was 50% and among women 40%.,Self reported comorbidity was present in 4.6% of the men and 6.6% of the women.,Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32-2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31-1.70).,The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98-1.29).,Among male smokers with stage 1; HR: 2.04 (1.34-3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38-7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.,Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2).
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The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y
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The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages.
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Although patients with COPD often have various comorbidities and symptoms, limited data are available on the contribution of these aspects to health care costs.,This study analyzes the association of frequent comorbidities and common symptoms with the annual direct and indirect costs of patients with COPD.,Self-reported information on 33 potential comorbidities and symptoms (dyspnea, cough, and sputum) of 2,139 participants from the baseline examination of the German COPD cohort COSYCONET was used.,Direct and indirect costs were calculated based on self-reported health care utilization, work absence, and retirement.,The association of comorbidities, symptoms, and COPD stage with annual direct/indirect costs was assessed by generalized linear regression models.,Additional models analyzed possible interactions between COPD stage, the number of comorbidities, and dyspnea.,Unadjusted mean annual direct costs were €7,263 per patient.,Other than COPD stage, a high level of dyspnea showed the strongest driving effect on direct costs (+33%).,Among the comorbidities, osteoporosis (+38%), psychiatric disorders (+36%), heart disease (+25%), cancer (+24%), and sleep apnea (+21%) were associated with the largest increase in direct costs (p<0.01).,A sub-additive interaction between advanced COPD stage and a high number of comorbidities reduced the independent cost-driving effects of these factors.,For indirect costs, besides dyspnea (+34%), only psychiatric disorders (+32%) and age (+62% per 10 years) were identified as significant drivers of costs (p<0.04).,In the subsequent interaction analysis, a high number of comorbidities was found to be a more crucial factor for increased indirect costs than single comorbidities.,Detailed knowledge about comorbidities in COPD is useful not only for clinical purposes but also to identify relevant cost factors and their interactions and to establish a ranking of major cost drivers.,This could help in focusing therapeutic efforts on both clinically and economically important comorbidities in COPD.
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In 2011, the traditional Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD spirometry-based severity classification system was revised to also include exacerbation history and COPD Assessment Test (CAT) and modified Medical Research Council Dyspnea Scale (mMRC) scores.,This study examined how COPD patients treated in primary care are reclassified by the new GOLD system compared to the traditional system, and each system’s level of agreement with patient’s or physician’s severity assessments.,In this US multicenter cross-sectional study, COPD patients were recruited by 83 primary care practitioners (PCPs) to complete spirometry testing and a survey.,Patients were classified by the traditional spirometry-based system (stages 1-4) and under the new system (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results.,Concordance between physician and patient-reported severity, spirometry stage, and ABCD grade based on either mMRC or CAT scores was examined.,Data from 445 patients with spirometry-confirmed COPD were used.,As compared to the traditional system, the GOLD mMRC system reclassifies 47% of patients, and GOLD CAT system reclassifies 41%, but the distributions are very different.,The GOLD mMRC system resulted in relatively equal distributions by ABCD grade (33%, 22%, 19%, 26%, respectively), but the GOLD CAT system put most into either B or D groups (9%, 45%, 4%, and 42%).,The addition of exacerbation history reclassified only 19 additional patients.,Agreement between PCPs’ severity rating or their patients’ self-assessment and the new ABCD grade was very poor (κ=0.17 or less).,As compared to the traditional system, the GOLD 2011 multidimensional system reclassified nearly half of patients, but how they were reclassified varied greatly by whether the mMRC or CAT questionnaire was chosen.,Either way, the new system had little correlation with the PCPs or their patients’ impressions about the COPD severity.
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Self-management is becoming increasingly important in COPD health care although it remains difficult to embed self-management into routine clinical care.,The implementation of self-management is understood as a complex interaction at the level of patient, health care provider (HCP), and health system.,Nonetheless there is still a poor understanding of the barriers and effective facilitators.,Comprehension of these determinants can have significant implications in optimizing self-management implementation and give further directions for the development of self-management interventions.,Data were collected among COPD patients (N=46) and their HCPs (N=11) in three general practices and their collaborating affiliated hospitals.,Mixed methods exploration of the data was conducted and collected by interviews, video-recorded consultations (N=50), and questionnaires on consultation skills.,Influencing determinants were monitored by 1) interaction and communication between the patient and HCP, 2) visible and invisible competencies of both the patient and the HCP, and 3) degree of embedding self-management into the health care system.,Video observations showed little emphasis on effective behavioral change and follow-up of given lifestyle advice during consultation.,A strong presence of COPD assessment and monitoring negatively affects the patient-centered communication.,Both patients and HCPs experience difficulties in defining personalized goals.,The satisfaction of both patients and HCPs concerning patient centeredness during consultation was measured by the patient feedback questionnaire on consultation skills.,The patients scored high (84.3% maximum score) and differed from the HCPs (26.5% maximum score).,Although the patient-centered approach accentuating self-management is one of the dominant paradigms in modern medicine, our observations show several influencing determinants causing difficulties in daily practice implementation.,This research is a first step unravelling the determinants of self-management leading to a better understanding.
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COPD self-management is a complex behavior influenced by many factors.,Despite scientific evidence that better disease outcomes can be achieved by enhancing self-management, many COPD patients do not respond to self-management interventions.,To move toward more effective self-management interventions, knowledge of characteristics associated with activation for self-management is needed.,The purpose of this study was to identify key patient and disease characteristics of activation for self-management.,An explorative cross-sectional study was conducted in primary and secondary care in patients with COPD.,Data were collected through questionnaires and chart reviews.,The main outcome was activation for self-management, measured with the 13-item Patient Activation Measure (PAM).,Independent variables were sociodemographic variables, self-reported health status, depression, anxiety, illness perception, social support, disease severity, and comorbidities.,A total of 290 participants (age: 67.2±10.3; forced expiratory volume in 1 second predicted: 63.6±19.2) were eligible for analysis.,While poor activation for self-management (PAM-1) was observed in 23% of the participants, only 15% was activated for self-management (PAM-4).,Multiple linear regression analysis revealed six explanatory determinants of activation for self-management (P<0.2): anxiety (β: −0.35; −0.6 to −0.1), illness perception (β: −0.2; −0.3 to −0.1), body mass index (BMI) (β: −0.4; −0.7 to −0.2), age (β: −0.1; −0.3 to −0.01), Global Initiative for Chronic Obstructive Lung Disease stage (2 vs 1 β: −3.2; −5.8 to −0.5; 3 vs 1 β: −3.4; −7.1 to 0.3), and comorbidities (β: 0.8; −0.2 to 1.8), explaining 17% of the variance.,This study showed that only a minority of COPD patients is activated for self-management.,Although only a limited part of the variance could be explained, anxiety, illness perception, BMI, age, disease severity, and comorbidities were identified as key determinants of activation for self-management.,This knowledge enables health care professionals to identify patients at risk of inadequate self-management, which is essential to move toward targeting and tailoring of self-management interventions.,Future studies are needed to understand the complex causal mechanisms toward change in self-management.
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Chronic obstructive pulmonary disease (COPD) is a major cause of mortality worldwide.,Patients with COPD frequently have systemic comorbidities that often require unscheduled hospitalization for exacerbation and deterioration of physical conditions, and can have a poor prognosis.,We verified factors affecting patients’ short-term mortality, using a national inpatient database in Japan.,We retrospectively collected data for COPD patients (age: >40 years) with emergency admission between July 2010 and March 2013, using the Diagnosis Procedure Combination database.,We performed multivariate logistic analyses fitted with a generalized estimating equation to assess factors associated with all-cause in-hospital mortality.,A total of 177,207 patients (mean age: 77.5 years; males: 72.9%) were identified.,All-cause in-hospital death occurred in 23,614 patients (13.7%).,Higher mortality was associated with older age, male sex, lower body mass index, more severe dyspnea, lower level of consciousness, and worse activities of daily life.,Higher mortality was also associated with comorbid conditions, including bacterial pneumonia, aspiration pneumonia, interstitial pneumonitis, pulmonary embolism, respiratory failure, lung cancer, heart failure, cerebral infarction, liver cirrhosis, and chronic renal failure.,Our study demonstrated that all-cause in-hospital mortality in patients with COPD who required emergency hospitalization was associated with deteriorated general conditions and comorbidities at admission.,Physicians should take into account these prognostic factors to choose better treatment options for COPD patients.
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COPD is a major cause of mortality and morbidity worldwide with an estimated 2.75 million deaths in 2000 (fourth leading cause of death).,In addition to the considerable morbidity and mortality associated with COPD, this disease incurs significant healthcare and societal costs.,Current COPD guidelines acknowledge that the following can improve COPD mortality: smoking cessation; long-term oxygen therapy; and lung volume reduction surgery in small subsets of COPD patients.,To date, no randomized controlled trials have demonstrated an effect of pharmacological treatment on mortality, although several observational studies suggest that both long-acting bronchodilators and inhaled corticosteroids may provide a survival benefit.,The possibility that these treatments reduce mortality is being investigated in ongoing large-scale clinical trials.
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COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment.,Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation.,We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens.,COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015.,Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured.,Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality.,Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed.,Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined.,A total of 62 COPD patients were enrolled.,These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively.,Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria.,Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively.,Influenza was the most commonly detected viral pathogen.,Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar.,Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation.,Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P=0.035).,Increased serum PCT is associated with longer LOS in COPD exacerbation.,However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.
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COPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality.,Only 10%-25% of COPD exacerbations are eosinophilic.,To assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU.,This retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014.,Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included.,Data were collected electronically from the hospital database.,Subjects’ characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded.,COPD subjects were grouped according to eosinophil levels (>2% or ≤2%) (group 1, eosinophilic; group 2, non-eosinophilic).,These groups were compared with the recorded data.,Over the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2).,Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU.,Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (2-7 days) vs 6 days (3-9 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively.,COPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%.,NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management.
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Decreasing exercise tolerance is one of the key features related to a poor prognosis in patients with chronic obstructive pulmonary disease (COPD).,Cardiopulmonary exercise testing (CPET) is useful for evaluating exercise tolerance.,The present study was performed to clarify the correlation between exercise tolerance and clinical parameters, focusing especially on the cross-sectional area (CSA) of skeletal muscle.,The present study investigated 69 patients with COPD who underwent CPET.,The correlations between oxygen uptake (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\dot{\text{V}} \text{O}}}_{2}$$\end{document}V˙O2) at peak exercise and clinical parameters of COPD, including skeletal muscle area measured using single-section axial computed tomography (CT), were evaluated.,The COPD assessment test score (ρ = − 0.35, p = 0.02) was weakly correlated with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\dot{\text{V}} \text{O}}}_{2}$$\end{document}V˙O2 at peak exercise.,In addition, forced expiratory volume in one second (FEV1) (ρ = 0.39, p = 0.0009), FEV1/forced vital capacity (ρ = 0.33, p = 0.006), and the CSA of the pectoralis muscles (PMs) (ρ = 0.36, p = 0.007) and erector spinae muscles (ECMs) (ρ = 0.39, p = 0.003) were correlated with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\dot{\text{V}} \text{O}}}_{2}$$\end{document}V˙O2 at peak exercise.,Multivariate analysis adjusted by age and FEV1 indicated that PMCSA was weakly correlated after adjustment (β value [95% confidence interval] 0.175 [0.03-0.319], p = 0.02).,In addition, ECMCSA tended to be correlated, but not significantly after adjustment (0.192 [− 0.001-0.385] p = 0.052).,The COPD assessment test, FEV1, FEV1/FVC, PMCSA, and ECMCSA were significantly correlated with \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\dot{\text{V}} \text{O}}}_{2}$$\end{document}V˙O2 at peak exercise.
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The Test of Incremental Respiratory Endurance (TIRE) provides a comprehensive assessment of inspiratory muscle performance by measuring maximal inspiratory pressure (MIP) over time.,The integration of MIP over inspiratory duration (ID) provides the sustained maximal inspiratory pressure (SMIP).,Evidence on the reliability and validity of these measurements in COPD is not currently available.,Therefore, we assessed the reliability, responsiveness and construct validity of the TIRE measures of inspiratory muscle performance in subjects with COPD.,Test-retest reliability, known-groups and convergent validity assessments were implemented simultaneously in 81 male subjects with mild to very severe COPD.,TIRE measures were obtained using the portable PrO2 device, following standard guidelines.,All TIRE measures were found to be highly reliable, with SMIP demonstrating the strongest test-retest reliability with a nearly perfect intraclass correlation coefficient (ICC) of 0.99, while MIP and ID clustered closely together behind SMIP with ICC values of about 0.97.,Our findings also demonstrated known-groups validity of all TIRE measures, with SMIP and ID yielding larger effect sizes when compared to MIP in distinguishing between subjects of different COPD status.,Finally, our analyses confirmed convergent validity for both SMIP and ID, but not MIP.,The TIRE measures of MIP, SMIP and ID have excellent test-retest reliability and demonstrated known-groups validity in subjects with COPD.,SMIP and ID also demonstrated evidence of moderate convergent validity and appear to be more stable measures in this patient population than the traditional MIP.
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Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids.,Azithromycin can contribute to exacerbation prevention.,Roflumilast, a phosphodiesterase (PDE) 4 inhibitor administered orally, also prevents exacerbations in selected patients with chronic bronchitis, recurrent exacerbations, severe airflow limitation and concomitant therapy with long-acting inhaled bronchodilators.,This outcome likely results from anti-inflammatory effects since PDE4 is expressed by all inflammatory cell types involved in COPD.,The use of this agent is, however, limited by side-effects, particularly nausea and diarrhea.,To address remaining unmet needs and enrich therapeutic options for patients with COPD, inhaled dual PDE3/4 inhibitors have been developed, with the aim of enhancing bronchodilation through PDE3 inhibition and modulating inflammation and mucus production though PDE4 inhibition, thus producing a potentially synergistic effect on airway calibre.,Experimental preclinical data confirmed these effects in vitro and in animal models.,At present, RPL554/ensifentrine is the only agent of this family in clinical development.,It decreases sputum markers of both neutrophilic and eosinophilic inflammation in patients with COPD.,Clinical Phase II trials confirmed its bronchodilator effect and demonstrated clinically meaningful symptom relief and quality of life improvements in these patients.,The safety profile appears satisfactory, with less effects on heart rate and blood pressure than salbutamol and no other side effect.,Altogether, these data suggest that ensifentrine could have a role in COPD management, especially in addition to inhaled long-acting bronchodilators with or without corticosteroids since experimental studies suggest potentiation of ensifentrine effects by these agents.,However, results from ongoing and future Phase III studies are needed to confirm both beneficial effects and favourable safety profile on a larger scale and assess other outcomes including exacerbations, lung function decline, comorbidities and mortality.
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Management of acute exacerbations of chronic obstructive pulmonary disease (COPD) is sometimes inadequate leading to either prolonged duration and/or an increased risk of recurrent exacerbations in the period following the initial event.,To evaluate the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ inhibitor, in patients experiencing an acute exacerbation of COPD.,In this double-blind, placebo-controlled study, COPD patients (40-80 years, ≥10 pack-year smoking history, current moderate/severe acute exacerbation of COPD requiring standard-of-care treatment) were randomized to placebo or nemiralisib 12.5 µg, 50 µg, 100 µg, 250 µg, 500 µg, or 750 µg (ratio of 3:1:1:1:1:1:3; N=938) for 12 weeks with an exploratory 12-week follow-up period.,The primary endpoint was change from baseline in post-bronchodilator FEV1 at week 12.,Key secondary endpoints were rate of re-exacerbations, patient-reported outcomes (Exacerbations of Chronic Pulmonary Disease Tool, COPD Assessment Test, St George's Respiratory Questionnaire-COPD), plasma pharmacokinetics (PK) and safety/tolerability.,There was no difference in change from baseline FEV1 at week 12 between the nemiralisib and placebo treatment groups (posterior adjusted median difference, nemiralisib 750 µg and placebo: −0.004L (95% CrI: −0.051L to 0.042L)).,Overall, there were also no differences between nemiralisib and placebo in secondary endpoints, including re-exacerbations.,Plasma PK increased in a dose proportional manner.,The most common adverse event for nemiralisib was post-inhalation cough which appeared to be dose-related.,The addition of nemiralisib to standard-of-care treatment for 12 weeks did not improve lung function or re-exacerbations in patients with, and following an acute exacerbation of COPD.,However, this study demonstrated that large clinical trials recruiting acutely exacerbating patients can successfully be conducted.
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Changes in physical activity (PA) are difficult to interpret because no framework of minimal important difference (MID) exists.,We aimed to determine the minimal important difference (MID) in physical activity (PA) in patients with Chronic Obstructive Pulmonary Disease and to clinically validate this MID by evaluating its impact on time to first COPD-related hospitalization.,PA was objectively measured for one week in 74 patients before and after three months of rehabilitation (rehabilitation sample).,In addition the intraclass correlation coefficient was measured in 30 patients (test-retest sample), by measuring PA for two consecutive weeks.,Daily number of steps was chosen as outcome measurement.,Different distribution and anchor based methods were chosen to calculate the MID.,Time to first hospitalization due to an exacerbation was compared between patients exceeding the MID and those who did not.,Calculation of the MID resulted in 599 (Standard Error of Measurement), 1029 (empirical rule effect size), 1072 (Cohen's effect size) and 1131 (0.5SD) steps.day-1.,An anchor based estimation could not be obtained because of the lack of a sufficiently related anchor.,The time to the first hospital admission was significantly different between patients exceeding the MID and patients who did not, using the Standard Error of Measurement as cutoff.,The MID after pulmonary rehabilitation lies between 600 and 1100 steps.day-1.,The clinical importance of this change is supported by a reduced risk for hospital admission in those patients with more than 600 steps improvement.
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People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity.,The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up.,In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR), health education with upper body resistance training (ED-UBR), or health education with gentle chair exercises (ED-Chair).,Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory.,Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up.,The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity.,Differences were observed in light physical activity (LPA) after 4 months of training, time by group interaction effect (P=0.045).,The SE-UBR group increased time spent in LPA by +20.68±29.30 minutes/day and the other groups decreased time spent in LPA by −22.43±47.88 minutes/day and -25.73±51.76 minutes/day.,Changes in LPA were not sustained at 12-month follow-up.,There were no significant changes in moderate-to-vigorous physical activity, sedentary time, or functional performance.,Subjects spent most of their waking hours sedentary: 72%±9% for SE-UBR, 68%±10% for ED-UBR, and 74%±9% for ED-Chair.,The self-efficacy enhancing intervention produced a modest short-term increase in LPA.,Further work is needed to increase the magnitude and duration of effect, possibly by targeting LPA.
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The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398.
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Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system.,Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity.,They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases.,However, the pathological mechanism of neutrophils remains complex and obscure.,The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD), pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed.,With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis) in diseases.,We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.
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Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation.
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Bodyweight and fat distribution may be related to COPD risk.,Limited prospective evidence linked COPD to abdominal adiposity.,We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.,The China Kadoorie Biobank recruited participants aged 30-79 years from 10 areas across China.,Anthropometric indexes were objectively measured at the baseline survey during 2004-2008.,After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016.,We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.,Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported.,Compared with subjects with normal BMI (18.5-<24.0 kg·m−2), underweight (BMI <18.5 kg·m−2) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66-1.89).,Overweight (BMI 24.0-<28.0 kg·m−2) and obesity (BMI ≥28.0 kg·m−2) were not associated with an increased risk after adjustment for waist circumference.,A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI.,Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.,Abdominal adiposity and underweight were risk factors for COPD in Chinese adults.,Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.http://bit.ly/36To4fk
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Impaired immune function contributes to the development of chronic obstructive pulmonary disease (COPD).,Disease progression is further exacerbated by pathogen infections due to impaired immune responses.,Elimination of infected cells is achieved by cytotoxic CD8+ T cells that are activated by MHC I-mediated presentation of pathogen-derived antigenic peptides.,The immunoproteasome, a specialized form of the proteasome, improves generation of antigenic peptides for MHC I presentation thereby facilitating anti-viral immune responses.,However, immunoproteasome function in the lung has not been investigated in detail yet.,In this study, we comprehensively characterized the function of immunoproteasomes in the human and murine lung.,Parenchymal cells of the lung express low constitutive levels of immunoproteasomes, while they are highly and specifically expressed in alveolar macrophages.,Immunoproteasome expression is not altered in whole lung tissue of COPD patients.,Novel activity-based probes and native gel analysis revealed that immunoproteasome activities are specifically and rapidly induced by IFNγ treatment in respiratory cells in vitro and by virus infection of the lung in mice.,Our results suggest that the lung is potentially capable of mounting an immunoproteasome-mediated efficient adaptive immune response to intracellular infections.
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New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between these deadly diseases, despite their obvious clinical, radiological and pathologic differences.,There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema).,The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD).
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The aim of this study was to explore to what extent a combined counselling and pulmonary rehabilitation program (PR) influences the perception of physical activity (PA) and motivation for behavioral change in PA in individuals with COPD.,The results of previous quantitative trial that investigated the effect of this combined treatment on daily PA were inconclusive.,It is conjectured that a more targeted tailoring of the counselling and PR intervention could improve its effectiveness.,Eighteen individuals with COPD (median age 69, 8 females) who had participated in the PneumoReha program were interviewed twice (following PR and at three-month follow-up).,These interviews were transcribed and analyzed thematically.,Based on the codes thus identified, three categories ‘perception of PA intensity’, ‘quality of motivation to perform PA’, and ‘strategies to cope with barriers’ were used to differentiate ‘types’ of participants.,Four different types of COPD individuals were distinguished.,Study findings indicate that those individuals who participated in the PR program combined with embedded counselling tended to be more active and intrinsically motivated.,A typology of four types of people with COPD was developed, characterized by their perception of activity, individual motivation and strategies for managing barriers.,The patients’ physical activity level might be influenced by their concept of physical activity and the quality of motivation.,Recognizing patients’ different activity behaviors is important for improving the quality of outpatient PR programs and developing tailored (according to each type) counselling interventions embedded in outpatient PR programs.,The study was registered on the website of https://www.clinicaltrials.gov/ with the identifier NCT02455206 (27/05/2015), as well as on the Swiss National Trails Portal SNCTP000001426 (05/21/2015).
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To compare the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index scores and its individual components between COPD patients with and without severe physical inactivity, as well as to correlate the number of steps/day with scores of physical activity questionnaires, age, and the BODE index (including its components).,We included 30 patients, who were evaluated for body composition, pulmonary function (FEV1), perception of dyspnea (modified Medical Research Council scale), and exercise capacity (six-minute walk distance [6MWD]).,The patients also completed the International Physical Activity Questionnaire (IPAQ), short version, and the modified Baecke questionnaire (mBQ).,The level of physical activity was assessed by the number of steps/day (as determined by pedometer), using the cut-off of 4,580 steps/day to form two groups: no severe physical inactivity (SPI−) and severe physical inactivity (SPI+).,We used the Mann-Whitney test or t-test, as well as Pearson's or Spearman's correlation tests, in the statistical analysis.,In comparison with the SPI− group, the SPI+ group showed more advanced age, higher mBQ scores (leisure domain), lower 6MWD (in m and % of predicted), and lower IPAQ scores (metabolic equivalent-walk/week domain and total).,The IPAQ scores showed weak correlations with steps/day (r = 0.399), age (r = −0.459), and 6MWD-in m (r = 0.446) and in % of predicted (r = 0.422).,In our sample, the cut-off of 4,580 steps/day was not sensitive enough to identify differences between the groups when compared with the predictors of mortality.,The IPAQ, short version score correlated with steps/day.,Comparar a pontuação do índice Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) e seus componentes individuais em pacientes com DPOC com grave inatividade física ou não, assim como correlacionar o número de passos diários com pontuações de questionários de atividade física, idade, índice BODE e seus componentes.,Foram incluídos 30 pacientes, os quais foram avaliados quanto a sua composição corporal, função pulmonar (VEF1), percepção de dispneia (escala modified Medical Research Council) e capacidade de exercício distância percorrida no teste de caminhada de seis minutos (DTC6).,Além disso, os participantes responderam ao International Physical Activity Questionnaire (IPAQ) versão curta e questionário de Baecke modificado (QBm).,O nível de atividade desses pacientes foi avaliado pelo número de passos diários por pedômetro, utilizando-se o ponto de corte de 4.580 passos para a formação de dois grupos: grupo sem grave inatividade física (GIF−) e grupo com grave inatividade física (GIF+).,Foram utilizados os testes de Mann-Whitney ou t não pareado, assim como os testes de correlação de Spearman ou de Pearson, na análise estatística.,Idade mais avançada, maiores escores no QBm (domínio lazer), menor DTC6 (em m e em % do previsto) e menores escores no IPAQ (domínios equivalentes metabólicos em caminhada e total por semana) foram encontrados no grupo GIF+ do que no grupo GIF−.,Houve correlações fracas dos escores do IPAQ com o número de passos diários (r =0,399), idade (r = -0,459), DTC6 em m (r = 0,446) e em % do previsto (r = 0,422).,Na amostra estudada, o ponto de corte de 4.580 passos diários não foi sensível para identificar diferenças entre os grupos estudados quando comparado com os preditores de mortalidade.,O questionário IPAQ versão curta correlacionou-se com o número de passos diários.
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In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity.,Intercostal muscle ultrasound offers a repeatable and radiation-free alternative, however requires validation.,We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters.,Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2nd and 3rd parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT.,Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91.,Inter-rater ICC was fair to excellent.,Ultrasound intercostal thickness moderately correlated with FEV1% predicted (r = 0.33) and quadriceps thickness (r = 0.31).,Echogenicity correlated negatively with FEV1% predicted (r = −0.32).,CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness.,These data confirm ultrasound of parasternal intercostal musculature is reproducible.,Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity.,This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics.,The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall.
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Inspiratory muscle weakness in patients with COPD is of major clinical relevance.,For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD.,Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening.,However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature.,Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness.,The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers.,Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury.,This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD.,Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities.,Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD.
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Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD).,The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes.,Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.,Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time.,Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time.,Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile.,Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.,Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL).,Delivered dose was 88% of the nominal dose for both formulation strengths.,The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL.,Nebulization times were 1-2.5 minutes with no apparent increasing trend with use over a 60-day period.,The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1-0.2 μm) after 60-day simulated use.,Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.,Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition.,The unit dose vial mitigates medication misuse and ensures dose uniformity.,Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD.
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Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users.
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Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov.
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Guidelines on COPD diagnosis and management encourage primary care physicians to detect the disease at an early stage and to treat patients according to their condition and needs.,Problems in guideline implementation include difficulties in diagnosis, using spirometry and the disputed role of reversibility testing.,These lead to inaccurate diagnostic registers and inadequacy of administered treatments.,This study represents an audit of COPD diagnosis and management in primary care practices in Devon.,Six hundred and thirty two patients on COPD registers in primary care practices were seen by a visiting Respiratory Specialist Nurse.,Diagnoses were made according to the NICE guidelines.,Reversibility testing was carried out either routinely or based on clinical indication in two sub-samples.,Dyspnoea was assessed.,Data were entered into a novel IT-based software which computed guideline-based treatment recommendations.,Current and recommended treatments were compared.,Five hundred and eighty patients had spirometry.,Diagnoses of COPD were confirmed in 422 patients (73%).,Thirty nine patients were identified as asthma only, 94 had normal spirometry, 23 were restrictive and 2 had a cardiac disorder.,Reversibility testing changed diagnosis of 11% of patients with airflow obstruction, and severity grading in 18%.,Three quarters of patients with COPD had been offered practical help with smoking cessation.,Short and long-acting anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15-18% of patients they were indicated but not received.,Inhaled steroids had been over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients with a chronic productive cough were receiving mucolytics.,Pulmonary rehabilitation was not available in some areas and was under-used in other areas.,Diagnostic registers of COPD in primary care contain mistakes leading to inaccurate prevalence estimates and inappropriate treatment decisions.,Use of pre-bronchodilator readings for diagnosis overestimates the prevalence and severity in a significant minority, thus post bronchodilator readings should be used.,Management of stable COPD does often not correspond to guidelines.,The IT system used in this study has the potential to improve diagnosis and management of COPD in primary care.
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Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition associated with a high health care resource consumption and health care expenditures, driven mainly by exacerbations-related hospitalizations.,Telemedicine has been proposed as a mean for timely detection of exacerbation, but the available evidence is inadequate to provide conclusive information on its efficacy.,The aim of this study is to evaluate the efficacy of a telemonitoring system in reducing COPD-related hospitalizations in an elderly population with COPD.,This is a parallel arms, randomized trial including patients aged 65 or older with COPD in GOLD stages II and III enrolled in a Pulmonary Medicine outpatient facility.,Patients were randomly assigned to receive a non-invasive system able to telemonitor vital signs (oxygen saturation, heart rate, near-body temperature, overall physical activity) or standard care, and were followed up for 9 months.,The outcome measures were the number of exacerbations and exacerbation-related hospitalization.,Fifty patients were included in the telemonitoring group and 49 in the control group.,The incidence rate of respiratory events was 28/100 person/years in the telemonitoring group vs. 42/100 person/years in the control group (incidence rate ratio: 0.67, 95% CI: 0.32 - 1.36).,The corresponding figures for hospital admissions where 13/100 person/years and 20/100 person/years, respectively (IRR: 0.66, 95% CI: 0.21 - 1.86).,In our study, COPD patients followed up with the aid of a multiparametric remote monitoring system experienced a lower rate of exacerbations and COPD-related hospitalizations compared to patients followed up using the standard model of care.,These results need to be replicated in larger studies before they can be applied to the general COPD population.,Trial registration number: NCT01481506 (clinicaltrials.gov).,Funding: co-financed by Lazio Region and Intersistemi Inc.
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There is growing evidence that home telemonitoring can be advantageous in societies with increasing prevalence of chronic diseases.,The main objective of this study is to evaluate the effect of a primary care-based telemonitoring intervention on the number and length of hospital admissions.,A randomised controlled trial was carried out across 20 health centres in Bilbao (Basque Country, Spain) to assess the impact of home telemonitoring on in-home chronic patients compared with standard care.,The study lasted for one year.,Fifty-eight in-home patients, diagnosed with heart failure (HF) and/or chronic lung disease (CLD), aged 14 or above and with two or more hospital admissions in the previous year were recruited.,The intervention consisted of daily patient self-measurements of respiratory-rate, heart-rate, blood pressure, oxygen saturation, weight, body temperature and the completion of a health status questionnaire using PDAs.,Alerts were generated when pre-established thresholds were crossed.,The control group (CG) received usual care.,The primary outcome measure was the number of hospital admissions that occurred at 12 months post-randomisation.,The impact of telemonitoring on the length of hospital stay, use of other healthcare resources and mortality was also explored.,The intervention group (IG) included 28 patients and the CG 30.,Patient baseline characteristics were similar in both groups.,Of the 21 intervention patients followed-up for a year, 12 had some admissions (57.1%), compared to 19 of 22 controls (86.4%), being the difference statistically significant (p = 0.033, RR 0.66; 95%CI 0.44 to 0.99).,The mean hospital stay was overall 9 days (SD 4.3) in the IG versus 10.7 (SD 11.2) among controls, and for cause-specific admissions 9 (SD 4.5) vs.,11.2 (SD 11.8) days, both without statistical significance (p = 0.891 and 0.927, respectively).,Four patients need to be telemonitored for a year to prevent one admission (NNT).,There were more telephone contacts in the IG than in the CG (22.6 -SD 16.1- vs.,8.6 -SD 7.2-, p = 0.001), but fewer home nursing visits (15.3 -SD 11.6- vs.,25.4 -SD 26.3-, respectively), though the difference was not statistically significant (p = 0.3603).,This study shows that telemonitoring of in-home patients with HF and/or CLD notably increases the percentage of patients with no hospital admissions and indicates a trend to reduce total and cause-specific hospitalisations and hospital stay.,Home telemonitoring can constitute a beneficial alternative mode of healthcare provision for medically unstable elderly patients.,Current Controlled Trials ISRCTN89041993
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Despite the frequency and negative impact of low physical activity among patients with chronic obstructive pulmonary disease (COPD), little is known about how it persists and remits over time or the factors predicting new states of low physical activity.,The aim of the study was to determine the probability of a transition between states of low and nonlow physical activity in a cohort of patients with stable COPD followed for 2 years.,We also investigated different potentially modifiable factors to determine whether they can predict new states of low physical activity.,We prospectively included 137 patients with stable COPD (mean age 66.9 ± 8.3 years).,Physical activity was measured at baseline and at 1 and 2 years of follow up.,Low physical activity was defined according to energy expenditure by cut-off points from the Fried frailty model.,The likelihood of annual transition towards new states and recovery was calculated.,We evaluated demographic, frailty, nonrespiratory, and respiratory variables as potential predictors, using generalized estimating equations.,At baseline, 37 patients (27%) presented with low physical activity.,During the study period, a total of 179 annual transitions were identified with nonlow physical activity at the beginning of the year; 17.5% transitioned to low physical activity.,In contrast, 34.3% of the 67 transitions that started with low physical activity recovered.,Predictors of transition to new states of low physical activity were dyspnea ⩾2 (odds ratio = 3.21; 95% confidence interval: 1.20-8.61) and poor performance on the five sit-to-stand test (odds ratio = 4.75; 95% confidence interval: 1.30-17.47).,The change between levels of low and nonlow physical activity is dynamic, especially for recovery.,Annual transitions toward new states of low physical activity are likely among patients with dyspnea or poor performance on the five sit-to-stand test.,The reviews of this paper are available via the supplemental material section.
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Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.
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Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae.,Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations.,S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients.,The immune response and the cytokine production were evaluated.,Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells.,This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells.,Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration.,In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion.,This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation.,Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.
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The aim of the present study was to characterize and quantify the numbers and expression levels of cells markers associated with dendritic cell (DC) maturation in small airways in current smokers and non-smokers with or without chronic obstructive pulmonary disease (COPD).,Lung tissues from the following 32 patients were obtained during resection for lung cancer: Eight smokers with COPD, eight non-smokers with COPD, eight current smokers without COPD and eight non-smokers without COPD, serving as a control.,The tissue sections were immunostained for cluster of differentiation (CD)83+ and CD1a+ to delineate mature and immature DCs, and chemokine receptor type 7 (CCR7+) to detect DC migratory ability.,Myeloid DCs were collected from the lung tissues, and subsequently the CD83+ and CCR7+ expression levels in the lung myeloid DCs were detected using flow cytometry.,The expression levels of CD83+, CD1a+ and CCR7+ mRNA in total lung RNA were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR).,Evident chronic bronchitis and emphysema pathological changes were observed in the lung tissues of patients with COPD.,The results revealed that the numbers of CD83+ and CCR7+ DCs were reduced but the numbers of CD1a+ DCs were significantly increased in the COPD group as compared with the control group (P<0.05, respectively).,Using RT-qPCR, the expression levels of CCR7+ and CD83+ mRNA were found to be reduced in the smokers with COPD as compared with the non-smokers without COPD group (P<0.05, respectively).,Excessive local adaptive immune responses are key elements in the pathogenesis of COPD.,Cigarette smoke may stimulate immune responses by impairing the homing of airway DCs to the lymph nodes and reduce the migratory potential of DCs.,The present study revealed that COPD is associated with reduced numbers of mature CD83+ DCs and lower CCR7+ expression levels in small airways.
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Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung and systemic inflammation as well as airway goblet cell hyperplasia (GCH).,Mucin production is activated in part by stimulation of the epidermal growth factor (EGF) receptor pathway through neutrophils and macrophages.,How circulating cytokine levels relate to GCH is not clear.,We performed phlebotomy and bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, and eight COPD subjects FEV1 30-60 %).,Six endobronchial biopsies per subject were performed.,GCH was measured by measuring mucin volume density (MVD) using stereological techniques on periodic acid fast-Schiff stained samples.,We measured the levels of chemokines CXCL8/IL-8, CCL2/MCP-1, CCL7/MCP-3, CCL22/MCD, CCL3/MIP-1α, and CCL4/MIP-1β, and the cytokines IL-1, IL-4, IL-6, IL-9, IL-17, EGF, and vascular endothelial growth factor (VEGF).,Differences between groups were assessed using one-way ANOVA, t test, or Chi squared test.,Post hoc tests after ANOVA were performed using Bonferroni correction.,MVD was highest in healthy smokers (27.78 ± 10.24 μL/mm2) compared to COPD subjects (16.82 ± 16.29 μL/mm2, p = 0.216) and nonsmokers (3.42 ± 3.07 μL/mm2, p <0.0001).,Plasma CXCL8 was highest in healthy smokers (11.05 ± 8.92 pg/mL) compared to nonsmokers (1.20 ± 21.92 pg/mL, p = 0.047) and COPD subjects (6.01 ± 5.90 pg/mL, p = 0.366).,CCL22 and CCL4 followed the same trends.,There were no significant differences in the other cytokines measured.,When the subjects were divided into current smokers (healthy smokers and COPD current smokers) and non/ex-smokers (nonsmokers and COPD ex-smokers), plasma CXCL8, CCL22, CCL4, and MVD were greater in current smokers.,No differences in other cytokines were seen.,Plasma CXCL8 moderately correlated with MVD (r = 0.552, p = 0.003).,In this small cohort, circulating levels of the chemokines CXCL8, CCL4, and CCL22, as well as MVD, attain the highest levels in healthy smokers compared to nonsmokers and COPD subjects.,These findings seem to be driven by current smoking and are independent of airflow obstruction.,These data suggest that smoking upregulates a systemic pattern of neutrophil and macrophage chemoattractant expression, and this correlates significantly with the development of goblet cell hyperplasia.
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Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers.,Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor-alpha, infliximab did not show clinical efficacy in a double-blind, placebo-controlled, phase II clinical trial.,This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation.,Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab.,Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109).,Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay.,Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins.,This profile was largely independent of smoking status, age, and clinical phenotype.,The majority of these associations of serum analytes with COPD are novel findings.,Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement.,Infliximab did not affect this systemic inflammatory profile.,A robust systemic inflammatory profile was associated with COPD.,This profile was generally independent of disease severity.,Because anti-tumor necrosis factor-alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear.,ClinicalTrials.gov, No.: NCT00056264.
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Interactions between spirometry and patient-reported outcomes in COPD are not well understood.,This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy.,Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations.,Mean and standard deviations of treatment effects were extracted for each arm of each study.,Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling.,The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score.,Thirty-six studies (≥3 months) were included.,Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data.,Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ.,The correlation strengthened with increasing study duration from 3 to 12 months.,Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1.,The association between change in FEV1 and other patient-reported outcomes was generally weak.,Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status.
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Dyspnoea is a debilitating and distressing symptom that is reflected in different verbal descriptors.,Evidence suggests that dyspnoea, like pain perception, consists of sensory quality and affective components.,The objective of this study was to develop an instrument that measures overall dyspnoea severity using descriptors that reflect its different aspects.,81 dyspnoea descriptors were administered to 123 patients with chronic obstructive pulmonary disease (COPD), 129 with interstitial lung disease and 106 with chronic heart failure.,These were reduced to 34 items using hierarchical methods.,Rasch analysis informed decisions regarding further item removal and fit to the unidimensional model.,Principal component analysis (PCA) explored the underlying structure of the final item set.,Validity and reliability of the new instrument were further assessed in a separate group of 53 patients with COPD.,After removal of items with hierarchical methods (n = 47) and items that failed to fit the Rasch model (n = 22), 12 were retained.,The “Dyspnoea-12” had good internal reliability (Cronbach’s alpha = 0.9) and fit to the Rasch model (χ2 p = 0.08).,Items patterned into two groups called “physical”(n = 7) and “affective”(n = 5).,In the separate validation study, Dyspnoea-12 correlated with the Hospital Anxiety and Depression Scale (anxiety r = 0.51; depression r = 0.44, p<0.001, respectively), 6-minute walk distance (r = −0.38, p<0.01) and MRC (Medical Research Council) grade (r = 0.48, p<0.01), and had good stability over time (intraclass correlation coefficient = 0.9, p<0.001).,Dyspnoea-12 fulfills modern psychometric requirements for measurement.,It provides a global score of breathlessness severity that incorporates both “physical” and “affective” aspects, and can measure dyspnoea in a variety of diseases.
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COPD is a major cause of death and morbidity worldwide, and is characterized by persistent airflow obstruction.,The evaluation of obstruction is critically dependent on sensitive methods for lung-function testing.,A wide body of knowledge has been accumulated in recent years showing that these methods have been significantly refined and seems promising for detection of early disease.,This review focuses on research on pulmonary function analysis in COPD performed in Brazil during this century.,The literature was searched using a systematic search strategy limited to English language studies that were carried out in Brazil from the year 2000 onward, with study objectives that included a focus on lung function.,After we applied our inclusion and exclusion criteria, 94 articles addressed our stated objectives.,Among the new methods reviewed are the forced-oscillation technique and the nitrogen-washout test, which may provide information on small-airway abnormalities.,Studies investigating the respiratory muscles and thoracoabdominal motion are also discussed, as well as studies on automatic clinical decision-support systems and complexity measurements.,We also examined important gaps in the present knowledge and suggested future directions for the cited research fields.,There is clear evidence that improvements in lung-function methods allowed us to obtain new pathophysiological information, contributing to improvement in our understanding of COPD.,In addition, they may also assist in the diagnosis and prevention of COPD.,Further investigations using prospective and longitudinal design may be of interest to elucidate the use of these new methods in the diagnosis and prevention of COPD.
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Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD).,The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system.,The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases.,Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects.,Results from a group of 28 smokers with a tobacco consumption of 11.2 ± 7.3 pack-years were compared with a control group formed by 28 healthy subjects using receiver operating characteristic (ROC) curves and a questionnaire as a gold standard.,The early adverse effects of smoking were adequately detected by the absolute value of the respiratory impedance (Z4Hz), the intercept resistance (R0), and the respiratory system dynamic compliance (Crs, dyn).,Z4Hz was the most accurate parameter (Se = 75%, Sp = 75%), followed by R0 and Crs, dyn.,The performances of the FOT parameters in the detection of the early effects of smoking were higher than that of spirometry (p < 0.05).,This study shows that FOT can be used to detect early smoking-induced respiratory changes while these pathologic changes are still potentially reversible.,These findings support the use of FOT as a versatile clinical diagnostic tool in aiding COPD prevention and treatment.
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Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.
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Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD.,Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents.,Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent.,The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations.,Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes.,In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs.,Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results.,In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily).,Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments.,Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed.,Overall, the safety profiles of the FDCs were similar to placebo.,Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations.
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Although step counters are popularly employed for physical rehabilitation in chronic obstructive pulmonary disease (COPD) patients, their effectiveness is inconsistent and even questioned.,This meta-analysis aimed to investigate whether step counter use increases physical activity or improves exercise capacity in COPD patients.,Electronic databases were searched for randomized controlled trials that assessed the efficacy of step counter use in increasing physical activity or in improving exercise capacity.,Data were aggregated using a random-effects model to get the overall effect sizes [standard mean difference (SMD) with 95% confidence interval (CI)], and subgroup analyses were performed.,A total of 15 trials enrolling 1316 patients with moderate to severe COPD were included.,Step counter use increased physical activity compared with controls (SMD = 0.57, 95% CI 0.31-0.84), which is equal to a magnitude of 1026 steps/day in daily steps.,It also enhanced exercise capacity with an effect size of 0.30 (95% CI 0.16-0.45), approximating to a magnitude of 11.6 m in the 6-min walking distance.,Step counter use could augment physical activity (SMD = 0.64, 95% CI 0.19-1.08) and exercise capacity (SMD = 0.32, 95% CI 0.01-0.62) for patients receiving pulmonary rehabilitation.,Yet it cannot enhance physical activity or exercise capacity in patients with severe COPD or among studies with intervention durations ⩾6 months (both p > 0.50).,Step counter use increases physical activity and improves exercise capacity in COPD patients, at least in the short term, which supports the notion of recommending step counter use in COPD management.
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High-level activities are typically not performed by patients with chronic obstructive pulmonary disease (COPD), which results in reduced functional performance; however, the physiological parameters that contribute to this reduced performance are unknown.,The aim of this study was to determine the relationships between high-level functional performance, leg muscle strength/power, aerobic power, and anaerobic power.,Thirteen patients with COPD underwent an incremental maximal cardiopulmonary exercise test, quadriceps isokinetic dynamometry (isometric peak torque and rate of torque development; concentric isokinetic peak torque at 90°/sec, 180°/sec, and 270°/sec; and eccentric peak torque at 90°/sec), a steep ramp anaerobic test (SRAT) (increments of 25 watts every 10 seconds), and three functional measures (timed up and go [TUG], timed stair climb power [SCPT], and 30-second sit-to-stand test [STS]).,TUG time correlated strongly (P < 0.05) with all muscle strength variables and with the SRAT.,Isometric peak torque was the strongest determinant of TUG time (r = −0.92).,SCPT and STS each correlated with all muscle strength variables except concentric at 270°/sec and with the SRAT.,The SRAT was the strongest determinant of SCPT (r = 0.91), and eccentric peak torque at 90°/sec was most significantly associated with STS (r = 0.81).,Performance on the SRAT (anaerobic power); slower-velocity concentric, eccentric, and isometric contractions; and rate of torque development are reflected in all functional tests, whereas cardiopulmonary exercise test performance (aerobic power) was not associated with any of the functional or muscle tests.,High-level functional performance in patients with COPD is associated with physiological parameters that require high levels of muscle force and anaerobic work rates.
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COPD is characterized by persistent respiratory symptoms and airflow limitation, caused by a mixture of small airway disease and pulmonary emphysema.,Programmed cell death has drawn the attention of COPD researchers because emphysema is thought to result from epithelial cell death caused by smoking.,Although apoptosis has long been thought to be the sole form of programmed cell death, recent studies have reported the existence of a genetically programmed and regulated form of necrosis called necroptosis.,Autophagy was also previously considered a form of programmed cell death, but this has been reconsidered.,However, recent studies have revealed that autophagy can regulate programmed cell death, including apoptosis and necroptosis.,It is also becoming clear that autophagy can selectively degrade specific proteins, organelles, and invading bacteria by a process termed “selective autophagy” and that this process is related to the pathogenesis of human diseases.,In this review, we outline the most recent studies implicating autophagy, selective autophagy, and necroptosis in COPD.,Strategies targeting these pathways may yield novel therapies for COPD.
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Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation.,Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.,Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7).,Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro.,In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy.,CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression.,Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression.,Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion.,Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis.,Egr-1 −/− mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.,We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo.,The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.
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A previous Phase IIIb study (NCT01462929) in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo.,This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study.,Symptomatic patients (defined as those with Evaluating Respiratory Symptoms [E-RS™] in COPD baseline score ≥10 units) received aclidinium bromide 400 μg twice daily (BID), tiotropium 18 μg once daily (QD), or placebo, for 6 weeks.,Lung function, COPD respiratory symptoms, and incidence of adverse events (AEs) were assessed.,In all, 277 symptomatic patients were included in this post hoc analysis.,Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second (FEV1) from baseline to week 6 at all time points over 24 hours versus placebo.,In addition, improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 (aclidinium 157 mL, tiotropium 67 mL; P<0.001) and week 6 (aclidinium 153 mL, tiotropium 90 mL; P<0.05).,Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 (aclidinium 136 mL, tiotropium 68 mL; P<0.05) and week 6 (aclidinium 137 mL, tiotropium 71 mL; P<0.05).,Aclidinium also improved early-morning and nighttime symptom severity, limitation of early-morning activities, and E-RS Total and domain scores versus tiotropium (except E-RS Chest Symptoms) and placebo over 6 weeks.,Tolerability showed similar incidence of AEs in each arm.,In this post hoc analysis of symptomatic patients with moderate to severe COPD, aclidinium 400 μg BID provided additional improvements compared with tiotropium 18 μg QD in: 1) bronchodilation, particularly during the nighttime, 2) daily COPD symptoms (E-RS), 3) early-morning and nighttime symptoms, and 4) early-morning limitation of activity.
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This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated.
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To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results.
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The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.
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Purpose: Women with chronic obstructive pulmonary disease (COPD) have more symptoms, more exacerbations, lower health status scores, and more comorbidity.,However, it is unclear whether management of COPD differs by sex.,The aim of the study was to investigate differences by sex in the care of patients with COPD.,Patients and methods: The population included 1329 primary and secondary care patients with a doctor´s diagnosis of COPD in central Sweden.,Data were obtained from patient questionnaires and included patient characteristics and data on achieved COPD care.,Analyses included cross-tabulations, chi-squared test and multiple logistic regression using several measures in COPD management as dependent variables, female sex as independent variable, and with adjustment for age groups, previous exacerbations, COPD Assessment Test, level of dyspnea assessed by the modified Medical Research Council scale, comorbid conditions, self-rated moderate/severe disease, level of education and body mass index.,Results: Women were more likely to receive triple therapy (OR 1.86 (95% CI 1.38-2.51)), to have any maintenance treatment (OR 1.82 (95% CI 1.31-2.55)), to be on sick leave (OR 2.16 (95% CI 1.19-3.93)), to have received smoking cessation support (OR 1.80 (95% CI 1.18-2.75)) and to have had pneumococcal vaccination (OR 1.82 (95% CI 1.37-2.43)), all independently of age, severity of disease or other potential confounders.,Conclusion: Management of COPD differs by sex, with women being more actively managed than men.,It is unclear whether this is due to patient- or care-related factors.
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Previous studies suggest that gender differences exist in COPD diagnosis and symptoms; these differences may be more pronounced in younger adults.,Our objective was to explore age-associated gender differences across a range of COPD severities.,A total of 4,484 current and former smokers with COPD from the Genetic Epidemiology of COPD cohort were investigated using regression modeling to explore the association between gender, age, disease severity, and the contributing elements of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification system (symptoms, exacerbation risk, airflow limitation).,The age-gender interaction was observed across multiple age categories.,Compared to men with COPD, younger women with COPD had a greater likelihood of more severe dyspnea, airflow limitation, greater risk for exacerbations, and categorization in GOLD groups B and D.,These differences were less pronounced in older women with COPD.,However, older women remained more likely to experience severe dyspnea and to manifest more severe COPD (B vs A) than older men, despite lower pack-years of smoking.,These data demonstrate the significant symptom burden of COPD in women, especially younger women.,More research is needed to understand the pathogenesis of increased severity of COPD in women and to develop gender-targeted clinical assessment and management approaches to improve outcomes for women and men with COPD at all ages.
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Identifying the predictors of noninvasive ventilation (NIV) failure has attracted significant interest because of the strong link between failure and poor outcomes.,However, very little attention has been paid to the timing of the failure.,This narrative review focuses on the causes of NIV failure and risk factors and potential remedies for NIV failure, based on the timing factor.,The possible causes of immediate failure (within minutes to <1 h) are a weak cough reflex, excessive secretions, hypercapnic encephalopathy, intolerance, agitation, and patient-ventilator asynchrony.,The major potential interventions include chest physiotherapeutic techniques, early fiberoptic bronchoscopy, changing ventilator settings, and judicious sedation.,The risk factors for early failure (within 1 to 48 h) may differ for hypercapnic and hypoxemic respiratory failure.,However, most cases of early failure are due to poor arterial blood gas (ABGs) and an inability to promptly correct them, increased severity of illness, and the persistence of a high respiratory rate.,Despite a satisfactory initial response, late failure (48 h after NIV) can occur and may be related to sleep disturbance.,Every clinician dealing with NIV should be aware of these risk factors and the predicted parameters of NIV failure that may change during the application of NIV.,Close monitoring is required to detect early and late signs of deterioration, thereby preventing unavoidable delays in intubation.
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Dyspnea is a complex, prevalent, and distressing symptom of chronic obstructive pulmonary disease (COPD) associated with decreased quality of life, significant disability, and increased mortality.,It is a major reason for referral to pulmonary rehabilitation.,We reviewed 23 COPD studies to examine the evidence for the effectiveness of cognitive-behavioral strategies for relieving dyspnea in COPD.,Preliminary evidence from randomized controlled trials exists to support cognitive- behavioral strategies, used with or without exercise, for relieving sensory and affective components of dyspnea in COPD.,Small to moderate treatment effects for relieving dyspnea were noted for psychotherapy (effect size [ES] = 0.08-0.25 for intensity; 0.26-0.65 for mastery) and distractive auditory stimuli (ES = 0.08-0.33 for intensity; 0.09 to −0.61 for functional burden).,Small to large dyspnea improvements resulted from yoga (ES = 0.2-1.21 for intensity; 0.67 for distress; 0.07 for mastery; and −8.37 for functional burden); dyspnea self-management education with exercise (ES = −0.14 to −1.15 for intensity; −0.62 to −0.69 for distress; 1.04 for mastery; 0.14-0.35 for self-efficacy); and slow-breathing exercises (ES = −0.34 to −0.83 for intensity; −0.61 to −0.80 for distress; and 0.62 for self-efficacy).,Cognitive-behavioral interventions may relieve dyspnea in COPD by (1) decreasing sympathetic nerve activity, dynamic hyperinflation, and comorbid anxiety, and (2) promoting arterial oxygen saturation, myelinated vagus nerve activity, a greater exercise training effect, and neuroplasticity.,While evidence is increasing, additional randomized controlled trials are needed to evaluate the effectiveness of psychosocial and self-management interventions in relieving dyspnea, in order to make them more available to patients and to endorse them in official COPD, dyspnea, and pulmonary rehabilitation practice guidelines.,By relieving dyspnea and related anxiety, such interventions may promote adherence to exercise programs and adaptive lifestyle change.
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The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a short questionnaire that has facilitated health status measurements in subjects with COPD.,However, it remains controversial as to whether the CAT can be used as a suitable substitute for the St George’s Respiratory Questionnaire (SGRQ).,This study investigated the reliability and score distributions of the CAT and SGRQ and evaluated which factors contributed to health status for each questionnaire.,A total of 109 consecutive subjects with stable COPD from a single center were enrolled in this study.,Each subject completed pulmonary function tests, exercise tests, and the following self-administered questionnaires: the Baseline Dyspnea Index, the Hospital Anxiety and Depression Scale, the CAT, and SGRQ.,Internal consistencies of CAT and SGRQ total scores were both excellent (Cronbach’s α coefficients =0.890 and 0.933).,Statistically significant correlations were observed between CAT and SGRQ total scores (R=0.668, P<0.001).,Correlations of CAT scores with parameters related to pulmonary function, dyspnea, exercise performance, and psychological factors were inferior to correlations with those parameters with SGRQ total scores.,Both multiple regression analyses and principal component analyses revealed that there were slight differences between SGRQ total scores and CAT scores.,The CAT is similar to SGRQ in terms of discriminating health status.,However, we demonstrated that what is assessed by the CAT may differ slightly from what is measured by SGRQ.
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Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide.,Few studies have focused on the quality of life (QoL) associated medical costs for COPD in China.,A cross-sectional survey of 678 COPD patients was conducted in four major cities (Beijing, Shanghai, Guangzhou and Chengdu), China, in 2011.,Data on socio-demographic information, health conditions and medical costs were collected through a face-to-face interview combined with medical record searching.,The EuroQol (EQ-5D) health questionnaire was applied to assess the QoL of COPD patients.,Among 678 patients with COPD, nearly 40% had difficulties in mobility, usual activities and pain/discomfort, one third had various degrees of anxiety/depression, and one fifth had difficulties in self-care.,The COPD patients had a median utility score of 0.768 and a median visual analog scale score of 70.,The degree of difficulties in any dimensions significantly increased, and utility and health scores decreased with severity of the disease.,Age, gender and disease severity were significantly associated with the quality of life after taking other covariates into consideration.,Poorer QoL was a significant indicator of higher direct medical costs for COPD patients.,Impaired quality of life was significantly linked to increased medical costs for COPD patients and could be an important measure for policy- and decision-making in COPD care.
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Little is known about the effect of ambient fine particulate matter (PM2.5) on chronic obstructive pulmonary disease (COPD) in China.,The objective of this study was to explore the short-term effects of PM2.5 on outpatient and inpatient visits for COPD in Beijing, China.,A total of 3,503,313 outpatient visits and 126,982 inpatient visits for COPD between January 1, 2010, and June 30, 2012, were identified from the Beijing Medical Claim Data for Employees.,A generalized additive Poisson model was applied to estimate the percentage change with 95% confidence interval (CI) in hospital visits for COPD in relation to an interquartile range (IQR) (90.8 μg/m3) increase in PM2.5 concentrations.,Short-term exposure to PM2.5 was significantly associated with increased use of COPD-related health services.,There were clear exposure-response associations of PM2.5 with COPD outpatient and inpatient visits.,An IQR increase in the concurrent day PM2.5 concentrations was significantly associated with a 2.38% (95% CI, 2.22%-2.53%) and 6.03% (95% CI, 5.19%-6.87%) increase in daily outpatient visits and inpatient visits, respectively.,Elderly people were more sensitive to the adverse effects.,The estimated risk was higher during the warm season compared to the cool season.,Short-term exposure to PM2.5 was associated with increased risk of hospital visits for COPD.,Our findings contributed to the limited evidence concerning the effects of ambient PM2.5 on COPD morbidity in developing countries.,The online version of this article (10.1186/s12940-018-0369-y) contains supplementary material, which is available to authorized users.
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Evidence between air pollution and COPD admissions is inconsistent and limited in China.,In this study, we aimed to explore the effects of air pollutants on COPD admissions in Beijing, China.,Daily COPD hospital admission visits derived from tertiary and secondary hospitals in Beijing were retrieved from January 2013 to February 2017.,Air pollutant levels and meteorological data over the same periods were also achieved.,Generalized additive model was applied to estimate the percentage changes with 95% CIs in daily admissions corresponding to 10 µg/m3 increases in pollutants levels [1 mg/m3 in carbon monoxide (CO)], stratified by age, gender, and season.,Seventy-three thousand seventy-six COPD hospital admission visits were included with mean daily visits of 48 (21).,Cumulative lag effect with per 10 µg/m3 increase in air pollutant levels was largest for nitrogen dioxide (NO2) with 3.03% (95% CI: 1.82%-4.26%) at lag 06, for sulfur dioxide (SO2) with 2.07% (95% CI: 1.00%-3.15%) at lag 01, for particulate matter ≤10 µm in aerodynamic diameter (PM10) with 0.92% (95% CI: 0.55%-1.30%) at lag 07, and for particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5) with 0.82% (95% CI: 0.38%-1.26%) at lag 06, respectively.,Percentage increase for each 1 mg/m3 increase in CO was 5.99% (95% CI: 2.74%-9.34%) at lag 06.,Further, stronger effects on COPD admissions were found in warm seasons than in cold seasons.,Short-term exposures to PM2.5, PM10, NO2, SO2, and CO had adverse effects on COPD hospitalizations in Beijing with different magnitudes and lag days.
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Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility.,Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD.,Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future.,We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests.,The COPD patients were divided in two groups: emphysematous and bronchitic.,Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test.,We analyzed the differences in the balance tests between the studied groups.,Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001) and activities balance confidence (53.2 vs 74.2; P=0.001).,Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001).,Patients with COPD have a higher balance impairment than their healthy peers.,Moreover, we observed that the bronchitic COPD phenotype is more likely to experience falls compared to the emphysematous phenotype.
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Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease.,Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life.,The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.,Five databases were searched with no dates or language limits.,The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords.,The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014.,The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale.,Studies supplied by the database search strategy were assessed independently by two blinded researchers.,A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords.,Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome.,Thus, only 14 studies had postural control as their primary outcome.,Our study examiners found only seven studies that had a PEDro score higher than five points.,The examiners’ interrater agreement was 76.4%.,Six of those studies were accomplished with a control group and one study used their patients as their own controls.,The studies were published between 2004 and 2013.,Patients with COPD present postural control impairment when compared with age-matched healthy controls.,Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility.
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Chronic obstructive pulmonary disease (COPD) was the fourth leading cause of death worldwide in 2015.,Current treatments for patients ease discomfort and help decrease disease progression; however, none improve lung function or change mortality.,COPD is heterogeneous in its molecular and clinical presentation, making it difficult to understand disease aetiology and define robust therapeutic strategies.,Given the complexity of the disease we propose a precision medicine approach to understanding and better treating COPD.,It is possible that multiOMICs can be used as a tool to integrate data from multiple fields.,Moreover, analysis of electronic medical records could aid in the treatment of patients and in the predictions of outcomes.,The Precision Medicine Initiative created in 2015 has made precision medicine approaches to treat disease a reality; one of these diseases being COPD.
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Health care utilization and costs among US veterans with chronic obstructive pulmonary disease (COPD) were compared with those in veterans without COPD.,A cohort of veterans with COPD was matched for age, sex, race, and index fiscal year to a cohort of veterans without COPD (controls) using data from the Veterans Integrated Service Network (VISN) 16 from 10/1/1997 to 9/30/2004.,Annual total and respiratory-related health care service utilization, costs of care, comorbidities, and respiratory medication use at the time of diagnosis were assessed.,A total of 59,906 patients with COPD were identified for a 7-year period prevalence of 8.2%, or 82 per 1000 population.,Patients with COPD compared with controls had significantly higher all-cause and respiratory-related inpatient and outpatient health care utilization for every parameter examined including mean numbers of physician encounters, other outpatient encounters, emergency room visits, acute inpatient discharges, total bed days of care, and percentage of patients with any emergency room visits or any acute inpatient discharge.,Patients with COPD had statistically significantly higher mean outpatient, inpatient, pharmacy, and total costs than the control group.,The mean Charlson comorbidity index in patients with COPD was 1 point higher than in controls (2.85 versus 1.84, P < 0.001). 60% of COPD patients were prescribed medications recommended in treatment guidelines at diagnosis.,Veterans with COPD compared with those without COPD suffer a tremendous disease burden manifested by higher rates of all-cause and respiratory-related health care utilization and costs and a high prevalence of comorbidities.,Furthermore, COPD patients do not receive appropriate treatment for their disease on diagnosis.
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This systematic review aimed to identify the most effective components of interventions to facilitate self-management of health care behaviors for patients with COPD.,PROSPERO registration number CRD42011001588.,We used standard review methods with a systematic search to May 2012 for randomized controlled trials of self-management interventions reporting hospital admissions or health-related quality of life (HRQoL).,Mean differences (MD), hazard ratios, and 95% confidence intervals (CIs) were calculated and pooled using random-effects meta-analyses.,Effects among different subgroups of interventions were explored including single/multiple components and multicomponent interventions with/without exercise.,One hundred and seventy-three randomized controlled trials were identified.,Self-management interventions had a minimal effect on hospital admission rates.,Multicomponent interventions improved HRQoL (studies with follow-up >6 months St George’s Respiratory Questionnaire (MD 2.40, 95% CI 0.75-4.04, I2 57.9).,Exercise was an effective individual component (St George’s Respiratory Questionnaire at 3 months MD 4.87, 95% CI 3.96-5.79, I2 0%).,While many self-management interventions increased HRQoL, little effect was seen on hospital admissions.,More trials should report admissions and follow-up participants beyond the end of the intervention.
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Objective To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients’ management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice.,Design 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial.,Setting 15 general practices in the eastern part of the Netherlands.,Participants Patients with COPD confirmed by spirometry and treated in general practice.,Patients with very severe COPD or treated by a respiratory physician were excluded.,Interventions A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients’ own initiative).,Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score.,Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale.,Results 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55).,At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant.,Secondary outcomes did not differ, except for exacerbation management.,Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58).,Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice.,Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group.,Trial registration Clinical trials NCT00128765.
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Chronic obstructive pulmonary disease (COPD) is a major public health problem and cause of mortality worldwide.,However, COPD in the early stage is usually not recognized and diagnosed.,It is necessary to establish a risk model to predict COPD development.,A total of 441 COPD patients and 192 control subjects were recruited, and 101 single-nucleotide polymorphisms (SNPs) were determined using the MassArray assay.,With 5 clinical features as well as SNPs, 6 predictive models were established and evaluated in the training set and test set by the confusion matrix AU-ROC, AU-PRC, sensitivity (recall), specificity, accuracy, F1 score, MCC, PPV (precision) and NPV.,The selected features were ranked.,Nine SNPs were significantly associated with COPD.,Among them, 6 SNPs (rs1007052, OR = 1.671, P = 0.010; rs2910164, OR = 1.416, P < 0.037; rs473892, OR = 1.473, P < 0.044; rs161976, OR = 1.594, P < 0.044; rs159497, OR = 1.445, P < 0.045; and rs9296092, OR = 1.832, P < 0.045) were risk factors for COPD, while 3 SNPs (rs8192288, OR = 0.593, P < 0.015; rs20541, OR = 0.669, P < 0.018; and rs12922394, OR = 0.651, P < 0.022) were protective factors for COPD development.,In the training set, KNN, LR, SVM, DT and XGboost obtained AU-ROC values above 0.82 and AU-PRC values above 0.92.,Among these models, XGboost obtained the highest AU-ROC (0.94), AU-PRC (0.97), accuracy (0.91), precision (0.95), F1 score (0.94), MCC (0.77) and specificity (0.85), while MLP obtained the highest sensitivity (recall) (0.99) and NPV (0.87).,In the validation set, KNN, LR and XGboost obtained AU-ROC and AU-PRC values above 0.80 and 0.85, respectively.,KNN had the highest precision (0.82), both KNN and LR obtained the same highest accuracy (0.81), and KNN and LR had the same highest F1 score (0.86).,Both DT and MLP obtained sensitivity (recall) and NPV values above 0.94 and 0.84, respectively.,In the feature importance analyses, we identified that AQCI, age, and BMI had the greatest impact on the predictive abilities of the models, while SNPs, sex and smoking were less important.,The KNN, LR and XGboost models showed excellent overall predictive power, and the use of machine learning tools combining both clinical and SNP features was suitable for predicting the risk of COPD development.
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COPD patients are burdened with a daily risk of acute exacerbation and loss of control, which could be mitigated by effective, on-demand decision support tools.,In this study, we present a machine learning-based strategy for early detection of exacerbations and subsequent triage.,Our application uses physician opinion in a statistically and clinically comprehensive set of patient cases to train a supervised prediction algorithm.,The accuracy of the model is assessed against a panel of physicians each triaging identical cases in a representative patient validation set.,Our results show that algorithm accuracy and safety indicators surpass all individual pulmonologists in both identifying exacerbations and predicting the consensus triage in a 101 case validation set.,The algorithm is also the top performer in sensitivity, specificity, and ppv when predicting a patient’s need for emergency care.
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Acute Exacerbations of COPD (AECOPD) identified from electronic healthcare records (EHR) are important for research, public health and to inform healthcare utilisation and service provision.,However, there is no standardised method of identifying AECOPD in UK EHR.,We aimed to validate the recording of AECOPD in UK EHR.,We randomly selected 1385 patients with COPD from the Clinical Practice Research Datalink.,We selected dates of possible AECOPD based on 15 different algorithms between January 2004 and August 2013.,Questionnaires were sent to GPs asking for confirmation of their patients’ AECOPD on the dates identified and for any additional relevant information.,Responses were reviewed independently by two respiratory physicians.,Positive predictive value (PPV) and sensitivity were calculated.,The response rate was 71.3%.,AECOPD diagnostic codes, lower respiratory tract infection (LRTI) codes, and prescriptions of antibiotics and oral corticosteroids (OCS) together for 5-14 days had a high PPV (>75%) for identifying AECOPD.,Symptom-based algorithms and prescription of antibiotics or OCS alone had lower PPVs (60-75%).,A combined strategy of antibiotic and OCS prescriptions for 5-14 days, or LRTI or AECOPD code resulted in a PPV of 85.5% (95% CI, 82.7-88.3%) and a sensitivity of 62.9% (55.4-70.4%).,Using a combination of diagnostic and therapy codes, the validity of AECOPD identified from EHR can be high.,These strategies are useful for understanding health-care utilisation for AECOPD, informing service provision and for researchers.,These results highlight the need for common coding strategies to be adopted in primary care to allow easy and accurate identification of events.
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The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004.
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The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD.,During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients.,Both a definition based on health care utilization and a symptom-based definition of AECOPD were applied.,For multivariate analyses, we chose a negative binomial regression model.,COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively.,The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22-4.95), 3.43 (95% CI 1.59-7.38), and 5.67 (95% CI 2.58-12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively.,The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96-4.84), 3.45 (95% CI 1.92-6.18), and 4.00 (95% CI 2.09-7.66).,Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively).,The risk of AECOPD was 59%-78% higher in the hospital sample than in the population sample.,If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples.,Likewise, the effect of different AECOPD definitions should be taken into consideration.
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Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.,Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint.,Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment.,A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation.,In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators.,Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses.,Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers.,The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality.,The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.,NCT00563381; Study identifier: BI 205.389.
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Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life.,Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated.,We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD.,COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed.,Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness.,Diaphragm contractility was evaluated using thickening fraction (TFdi).,Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files.,Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion.,Fat-free mass index (FFMI) was assessed using bioelectrical impedance.,Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively).,Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%.,Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28).,Qci was significantly correlated to CAT score (rho=−0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002).,Qcsa and Qci were significantly lower in patients with frequent exacerbations.,In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values.,In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility.,As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population.,Further studies are required to better delineate its potential role as a prognostic marker in this population.
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Ultrasound (US) evaluation of diaphragmatic dysfunction (DD) has proved to be a reliable technique in critical care.,In this single-center prospective study, we investigated the impact of US-assessed DD on noninvasive ventilation (NIV) failure in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and its correlation with the transdiaphragmatic pressure assessed using the invasive sniff maneuver (Pdi sniff).,A population of 75 consecutive patients with AECOPD with hypercapnic acidosis admitted to our respiratory intensive care unit (RICU) were enrolled.,Change in diaphragm thickness (ΔTdi) < 20% during tidal volume was the predefined cutoff for identifying DD+/− status.,Correlations between ΔTdi < 20% NIV failure and other clinical outcomes were investigated.,Correlation between ΔTdi and Pdi sniff values was analyzed in a subset of ten patients.,DD+ patients had a higher risk for NIV failure than DD− patients (risk ratio, 4.4; p < 0.001), and this finding was significantly associated with higher RICU, in-hospital, and 90-day mortality rates; longer mechanical ventilation duration; higher tracheostomy rate; and longer RICU stay.,Huge increases in NIV failure (HR, 6.2; p < 0.0001) and 90-day mortality (HR, 4.7; p = 0.008) in DD+ patients were found by Kaplan-Meier analysis.,ΔTdi highly correlated with Pdi sniff (Pearson’s r = 0.81; p = 0.004).,ΔTdi < 20% showed better accuracy in predicting NIV failure than baseline pH value and early change in both arterial blood pH and partial pressure of carbon dioxide following NIV start (AUCs 0.84 to DTdi < 20%, 0.51 to pH value at baseline, 0.56 to early change in arterial blood pH following NIV start, and 0.54 to early change in partical pressure of carbon dioxide following NIV start, respectively; p < 0.0001).,Early and noninvasive US assessment of DD during severe AECOPD is reliable and accurate in identifying patients at major risk for NIV failure and worse prognosis.
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The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased.,Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD.,COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort.,ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/μL.,Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope.,Among 239 patients, 47 were diagnosed with ACO (19.7%).,During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting β2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO.,Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (− 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline.,Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.,The online version of this article (10.1186/s12931-018-0737-8) contains supplementary material, which is available to authorized users.
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The association between asthma-chronic obstructive pulmonary diseases (COPD) overlap syndrome (ACOS) and tuberculosis (TB) has yet to be studied.,The newly diagnosed TB patients (age > 20 y) treated from January 2000 to December 2008 were included (ACOS cohort, n = 10 751; non-ACOS cohort, n = 42 966).,The non-ACOS cohort involved patients with confirmed absence of ACOS.,We calculated incidence rate ratios (IRRs) for TB in the ACOS and non-ACOS cohorts by using poisson regression analysis.,Cox proportional hazards regression models were used to determine the adjusted HR (aHR) for TB in the ACOS cohort compared with the non-ACOS cohort.,The aHR for TB was 2.41 (95% confidence interval [CI], 2.19-2.66) in the ACOS cohort.,The TB risk was significantly higher in the ACOS cohort than in the non-ACOS cohort when stratified by age, sex, comorbidities, and atopy.,Within the ACOS cohort, the aHR was higher among patients receiving SABAs+SAMAs, LABAs+LAMAs, and ICSs (aHR [95% CI]: 3.06 [2.75-3.41], 3.68 [2.93-4.61], and 2.79 [1.25-6.22], respectively; all P < .05).,Furthermore, patients with more than 15 outpatient visits and hospitalizations per year demonstrated the highest aHR (8.09; 95% CI, 6.85-9.56).,ACOS cohort potentially develop incident TB, regardless of the age,sex, comorbidities and atopy; even without receiving the inhalers.This risk is higher, especially in the ACOS cohort have a high frequency of medical services or receiving the inhalers such as SABAs+SAMAs, LABAs+LAMAs and ICSs.
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Overlap syndrome (OVS) is the concurrence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), and is associated with poor outcomes.,We hypothesized that physiological changes in COPD may affect the pathogenesis of OSA in important ways.,We therefore sought to measure the anatomical and nonanatomical OSA traits in individuals with OVS and compare to those with OSA alone.,Patients with established OVS were recruited, along with age, gender, and BMI matched OSA only controls.,Smoking and relevant comorbidities or medications were excluded.,Subjects underwent baseline polysomnography followed by an overnight physiological research study to measure the OSA traits (Veupnea, Varousal, Vpassive, Vactive, and loop gain).,Fifteen subjects with OVS and 15 matched controls with OSA alone were studied (overall 66 ± 8 years, 20% women, BMI 31 ± 4 kg/m2, apnea‐hypopnea index 49 ± 36/hr).,Mixed‐modeling was used to incorporate each measurement (range 52-270 measures/trait), and account for age, gender, and BMI.,There were no significant differences in the traits between OVS and OSA subjects, although OVS subjects potentially tolerated a lower ventilation before arousal (i.e., harder to wake; p = .06).,Worsened lung function was significantly associated with worsened upper airway response and more unstable breathing (p < .05 for all).,Consistent differences in key OSA traits were not observed between OVS and OSA alone.,However, worse lung function does appear to exert an influence on several OSA traits.,These findings indicate that a diagnosis of OVS should not generally influence the approach to OSA, but that lung function might be considered if utilizing OSA trait‐specific treatment.,This is the first study to comprehensively measure both anatomical and non‐anatomical OSA traits during sleep in those with COPD + OSA (Overlap syndrome) and compare them to those with OSA alone.,No consistent differences were found between the two groups, while worsened lung function did impact upper airway function and control of breathing.,These findings have implications towards mechanisms underlying OSA, as well as management of sleep apnea.
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Acute hypercapnic respiratory failure (AHRF) treated with non-invasive ventilation in the ICU is frequently caused by chronic obstructive pulmonary disease (COPD) exacerbations and obesity-hypoventilation syndrome, the latter being most often associated with obstructive sleep apnea.,Overlap syndrome (a combination of COPD and obstructive sleep apnea) may represent a major burden in this population, and specific diagnostic pathways are needed to improve its detection early after ICU discharge.,To evaluate whether pulmonary function tests can identify a high probability of obstructive sleep apnea in AHRF survivors and outperform common screening questionnaires to identify the disorder.,Fifty-three patients surviving AHRF (31 males; median age 67 years (interquartile range: 62-74) participated in the study.,Anthropometric data were recorded and body plethysmography was performed 15 days after ICU discharge.,A sleep study was performed 3 months after ICU discharge.,The apnea-hypopnea index was negatively associated with static hyperinflation as measured by the residual volume to total lung capacity ratio in the % of predicted (coefficient = -0.64; standard error 0.17; 95% CI -0.97 to -0.31; p<0.001).,A similar association was observed in COPD patients only: coefficient = -0.65; standard error 0.19; 95% CI -1.03 to -0.26; p = 0.002.,Multivariate analysis with penalized maximum likelihood confirmed that the residual volume to total lung capacity ratio was the main contributor for apnea-hypopnea index variance in addition to classic predictors.,Screening questionnaires to select patients at risk for sleep-disordered breathing did not perform well.,In AHRF survivors, static hyperinflation is negatively associated with the apnea-hypopnea index in both COPD and non-COPD patients.,Measuring static hyperinflation in addition to classic predictors may help to increase the recognition of obstructive sleep apnea as common screening tools are of limited value in this specific population.
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There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD).,The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population.,The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.,A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.,We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2.,Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc.,Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation.,The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days.,The overall ICU mortality was 25%.,Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01).,The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe COPD were lower than those with other etiologies of acute respiratory failure.,A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated with a 45% decrease in ICU survival (P < .001).,A discharge home at the time of index admission was associated an increased overall survival compared with any other discharge location (P < .001).,We report good early outcomes, but significant long-term morbidity in patients with severe COPD requiring invasive mechanical ventilation for acute respiratory failure.,A higher APACHE score and presence of active malignancy are associated with a decrease in ICU survival, whereas a discharge home is associated with an increase in the overall survival.
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Cigarette smoking is the most commonly encountered and readily identifiable risk factor for COPD.,However, it is not clear which quantitative factors related to smoking influence the prognosis of COPD patients.,A total of 204 patients with a long-term history of smoking were enrolled into this study and followed up for 5 years.,Patients were divided into “death” or “survival” groups based on follow-up results and “quitting-smoking” or “continuing-smoking” groups based on whether they gave up smoking.,Patients in the death group had a longer smoking time, lower prevalence of quitting smoking, later onset of COPD symptoms, older age at quitting smoking, lower forced expiratory volume in one second (FEV1) % predicted, and lower ratio of FEV1/forced vital capacity.,Age, age at quitting smoking, and FEV1% predicted were independently associated with mortality from COPD.,Compared to the continuing-smoking group, the quitting-smoking group had a lower mortality rate, longer course of COPD, earlier onset of COPD symptoms, and lower residual volume percent predicted.,During the 5-year follow-up, 113 deaths were recorded (quitting-smoking group: n=92; 40 deaths; continuing-smoking group: n=112; 73 deaths).,The mortality risk remained significantly higher in the continuing-smoking group than the quitting-smoking group (log-rank test, 13.59; P=0.0002).,Smoking time may be related to the mortality rate from COPD.,Smoking cessation has the greatest capacity to influence the natural history of COPD.
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Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not.,Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD.,We hypothesized that-among COPD patients-the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1.,Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function.,BAL lymphocyte subsets were determined using flow cytometry.,The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019).,This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated.,No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function.,COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1.,Trial registration Clinicaltrials.gov identifier NCT02729220
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The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function.
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To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results.
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Bronchial hyperresponsiveness (BHR), sputum eosinophilia, and bronchial reversibility are often thought to be a hallmark of asthma, yet it has been shown to occur in COPD as well.,To evaluate the relationship between BHR, lung function, and airway inflammation in COPD patients.,Thirty-one, steroid-free patients with stable, mild and moderate COPD were studied.,The following tests were carried out: baseline lung function, reversibility, provocative dose of methacholine causing a 20% fall in forced expiratory volume in 1 second, a COPD symptom score, and sputum induction.,Twenty-nine patients completed the procedures.,About 41.4% had BHR, 31.0% had increased sputum eosinophils, and 37.9% had bronchial reversibility.,Some of the patients had only one of these characteristics while others had two or the three of them.,Patients with BHR had higher sputum eosinophils than patients without BHR (P=0.046) and those with sputum eosinophils ≥3% had more exacerbations in the previous year and a higher COPD symptom score than patients with sputum eosinophils <3% (P=0.019 and P=0.031, respectively).,In patients with BHR, the cumulative dose of methacholine was negatively related to the symptom score and the number of exacerbations in the previous year.,When patients with bronchial reversibility were considered, bronchodilation was positively related to sputum eosinophils.,Our study showed that BHR, sputum eosinophilia, and bronchial reversibility were not clustered in one single phenotype of COPD but could be present alone or together.,Of interest, BHR and airway eosinophilia were associated with clinical data in terms of exacerbations and symptoms.,Further investigation is needed to clarify this topic.
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Asthma-COPD overlap (ACO) is a term that encompasses patients with characteristics of two conditions, smoking asthmatics or COPD patients with asthma-like features such as high bronchodilator response or blood eosinophil count ≥300 cells/μL.,The aim of this study was to compare the different phenotypes inside the ACO definition in a real-life population cohort.,We analyzed patients from the MAJORICA cohort who had a diagnosis of asthma and/or COPD based on current guidelines, laboratory data in 2014 and follow-up until 2015.,Prevalence of ACO according to the different criteria, demographic, clinical and functional characteristics, prescriptions and use of health resources data were compared between three groups.,We included 603 patients.,Prevalence of smoking asthmatics was 14%, COPD patients with high bronchodilator response 1.5% and eosinophilic COPD patients 12%.,Smoking asthmatics were younger and used more rescue inhalers, corticosteroids and health resources.,Conversely, eosinophilic COPD patients were older than the other groups, often treated with corticosteroids and had lower use of health resources.,Most of the COPD patients with high bronchodilator response were included in the eosinophilic COPD group.,ACO includes two conditions (smoking asthmatics and eosinophilic COPD patients) with different medication requirement and prognosis that should not be pooled together.,Use of ≥300 blood eosinophils/μL as a treatable trait should be recommended.
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To examine quality of life, work productivity, and health care resource use among employed adults ages 40-64 years with chronic obstructive pulmonary disease (COPD) in the United States.,Data from the 2009 National Health and Wellness Survey were used.,All employed adults ages 40-64 years with or without a self-reported diagnosis of COPD were included in the study.,Impact on quality of life (using the mental and physical component summary scores and health utilities from the Short Form-12v2), work productivity and activity impairment (using the Work Productivity and Activity Impairment questionnaire), and resource use were analyzed using regression modeling.,There were 1112 employed adults with COPD versus 18,912 employed adults without COPD.,After adjusting for demographics and patient characteristics, adults with COPD reported significantly lower mean levels of mental component summary (46.8 vs 48.5), physical component summary (45.6 vs 49.2), and health utilities (0.71 vs 0.75) than adults without COPD.,Workers with COPD reported significantly greater presenteeism (18.9% vs 14.3%), overall work impairment (20.5% vs 16.3%), and impairment in daily activities (23.5% vs 17.9%) than adults without COPD.,Employed adults with COPD also reported more mean emergency room visits (0.21 vs 0.12) and more mean hospitalizations (0.10 vs 0.06) in the previous 6 months than employed adults without COPD.,All of the above differences were significant at two-sided P < 0.05.,After adjusting for various confounders, employed adults with COPD reported significantly lower quality of life and work productivity, and increased health care resource utilization than employed adults without COPD.,These results highlight the substantial impact and burden of COPD in the United States workforce.
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The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient’s airflow limitation, their history of exacerbations, and symptoms.,The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.,In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks.,The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.,Overall, 676 patients completed the study.,The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met.,QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001).,QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001).,QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use.,However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC.,Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%).,The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).,These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.
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NVA237 is a once-daily dry-powder formulation of the long-acting muscarinic antagonist glycopyrronium bromide in development for the treatment of chronic obstructive pulmonary disease (COPD).,The glycopyrronium bromide in COPD airways clinical study 1 (GLOW1) evaluated the efficacy, safety and tolerability of NVA237 in patients with moderate-to-severe COPD.,Patients with COPD with a smoking history of ≥ 10 pack-years, post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and ≥ 30% predicted normal and FEV1/forced vital capacity < 0.70 were enrolled.,Patients were randomized to double-blind treatment with NVA237 50 μg once daily or placebo for 26 weeks with inhaled/intranasal corticosteroids or H1 antagonists permitted in patients stabilized on them prior to study entry.,The primary outcome measure was trough FEV1 at Week 12.,A total of 822 patients were randomized to NVA237 (n = 552) or placebo (n = 270).,Least squares mean (± standard error) trough FEV1 at Week 12 was significantly higher in patients receiving NVA237 (1.408 ± 0.0105 L), versus placebo (1.301 ± 0.0137 L; treatment difference 108 ± 14.8 mL, p < 0.001).,Significant improvements in trough FEV1 were apparent at the end of Day 1 and sustained through Week 26.,FEV1 was significantly improved in the NVA237 group versus placebo throughout the 24-hour periods on Day 1 and at Weeks 12 and 26, and at all other visits and timepoints.,Transition dyspnoea index focal scores and St.,George's Respiratory Questionnaire scores were significantly improved with NVA237 versus placebo at Week 26, with treatment differences of 1.04 (p < 0.001) and-2.81 (p = 0.004), respectively.,NVA237 significantly reduced the risk of first moderate/severe COPD exacerbation by 31% (p = 0.023) and use of rescue medication by 0.46 puffs per day (p = 0.005), versus placebo.,NVA237 was well tolerated and had an acceptable safety profile, with a low frequency of cardiac and typical antimuscarinic adverse effects.,Once-daily NVA237 was safe and well tolerated and provided rapid, sustained improvements in lung function, improvements in dyspnoea, and health-related quality of life, and reduced the risk of exacerbations and the use of rescue medication.,ClinicalTrials.gov: NCT01005901
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Acute exacerbations are a leading cause of worsening COPD in terms of lung function decline, quality of life, and survival.,They also have a relevant economic burden on the health care system.,Determining the risk factors for acute exacerbation and early relapse could be a crucial element for a better management of COPD patients.,This review analyzes the current knowledge and underlines the main risk factors for recurrent acute exacerbations.,Comprehensive evaluation of COPD patients during stable phase and exacerbation could contribute to prevent treatment failure and relapses.
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National surveys have revealed significant differences in patient outcomes following admission to hospital with acute exacerbation of COPD which are likely to be due to variations in care.,We developed a care bundle, comprising a short list of evidence-based practices to be implemented prior to discharge for all patients admitted with this condition, based on a review of national guidelines and other relevant literature, expert opinion and patient consultation.,Implementation was then piloted using action research methodologies with patient input.,Actively involving staff was vital to ensure that the changes introduced were understood and the process followed.,Implementation of a care bundle has the potential to produce a dramatic improvement in compliance with optimum health care practice.
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The quality of care can be improved by the development and implementation of evidence-based treatment guidelines.,Different national guidelines for chronic obstructive pulmonary disease (COPD) exist in Europe and relevant differences may exist among them.,This was an evaluation of COPD treatment guidelines published in Europe and Russia in the past 7 years.,Each guideline was reviewed in detail and information about the most important aspects of patient diagnosis, risk stratification and pharmacotherapy was extracted following a standardised process.,Guidelines were available from the Czech Republic, England and Wales, Finland, France, Germany, Italy, Poland, Portugal, Russia, Spain and Sweden.,The treatment goals, criteria for COPD diagnosis, consideration of comorbidities in treatment selection and support for use of long-acting bronchodilators, were similar across treatment guidelines.,There were differences in measures used for stratification of disease severity, consideration of patient phenotypes, criteria for the use of inhaled corticosteroids and recommendations for other medications (e.g. theophylline and mucolytics) in addition to bronchodilators.,There is generally good agreement on treatment goals, criteria for diagnosis of COPD and use of long-acting bronchodilators as the cornerstone of treatment among guidelines for COPD management in Europe and Russia.,However, there are differences in the definitions of patient subgroups and other recommended treatments.,There are important differences between European national COPD guidelineshttp://ow.ly/U2P4y
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Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease.
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The COVID-19 pandemic is associated with severe pneumonia and acute respiratory distress syndrome leading to death in susceptible individuals.,For those who recover, post-COVID-19 complications may include development of pulmonary fibrosis.,Factors contributing to disease severity or development of complications are not known.,Using computational analysis with experimental data, we report that idiopathic pulmonary fibrosis (IPF)- and chronic obstructive pulmonary disease (COPD)-derived lung fibroblasts express higher levels of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 entry and part of the renin-angiotensin system that is antifibrotic and anti-inflammatory.,In preclinical models, we found that chronic exposure to cigarette smoke, a risk factor for both COPD and IPF and potentially for SARS-CoV-2 infection, significantly increased pulmonary ACE2 protein expression.,Further studies are needed to understand the functional implications of ACE2 on lung fibroblasts, a cell type that thus far has received relatively little attention in the context of COVID-19.
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Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions.
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Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile.,Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving usual-care background therapy.,Patients received olodaterol 5 μg or 10 μg or placebo once daily for 48 weeks.,Coprimary end points were forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0-3) response (change from baseline), and trough FEV1 response at 12 weeks.,Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks.,Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively.,In both studies, olodaterol 5 μg and 10 μg significantly improved the FEV1 AUC0-3 response (P<0.0001) and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo.,Secondary end points supported the efficacy of olodaterol.,These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 μg and 10 μg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy.
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Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide.,Developments in the understanding of COPD have led to standard guidelines for diagnosis, treatment, and spirometry assessments, which have in turn influenced trial designs and inclusion criteria.,Substantial clinical evidence has been gained from clinical trials and supports a positive approach to COPD management.,However, there appear to be changing trends in recent trials.,Large bronchodilator studies have reported lower improvements in trough forced expiratory volume in 1 second (FEV1) values versus placebo than were observed in earlier studies, while the rate of FEV1 decline seems to be lower in more recent trials.,In addition, recent evidence has called into question the usefulness of bronchodilator reversibility testing as a trial inclusion criterion.,Baseline patient populations and use of concomitant medications have also changed over recent years due to increased treatment options.,The impact of these many variables on clinical trial results is explored, with a particular focus on changes in inclusion criteria and patient baseline demographics.
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High-flow nasal cannula (HFNC) oxygen therapy in acute hypoxic respiratory failure is becoming increasingly popular.,However, evidence to support the use of HFNC in acute respiratory failure (ARF) with hypercapnia is limited.,Chronic obstructive pulmonary disease (COPD) patients with moderate hypercapnic ARF (arterial blood gas pH 7.25-7.35, PaCO2>50 mmHg) who received HFNC or non-invasive ventilation (NIV) in the intensive care uint from April 2016 to March 2018 were analyzed retrospectively.,The endpoint was treatment failure, defined as either invasive ventilation, or a switch to the other study treatment (NIV for patients in the NFNC group, and vice-versa), and 28-day mortality.,Eighty-two COPD patients (39 in the HFNC group and 43 in the NIV group) were enrolled in this study.,The mean age was 71.8±8.2 and 54 patients (65.9%) were male.,The treatment failed in 11 out of 39 patients with HFNC (28.2%) and in 17 of 43 patients with NIV (39.5%) (P=0.268).,No significant differences were found for 28-day mortality (15.4% in the HFNC group and 14% in the NIV group, P=0.824).,During the first 24 hrs of treatment, the number of nursing airway care interventions in the HFNC group was significantly less than in the NIV group, while the duration of device application was significantly longer in the HFNC group (all P<0.05).,Skin breakdown was significantly more common in the NIV group (20.9% vs 5.1%, P<0.05).,Among COPD patients with moderate hypercarbic ARF, the use of HFNC compared with NIV did not result in increased rates of treatment failure, while there were fewer nursing interventions and skin breakdown episodes reported in the HFNC group.
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Self-management support is one mechanism by which telehealth interventions have been proposed to facilitate management of long-term conditions.,The objectives of this metareview were to (1) assess the impact of telehealth interventions to support self-management on disease control and health care utilization, and (2) identify components of telehealth support and their impact on disease control and the process of self-management.,Our goal was to synthesise evidence for telehealth-supported self-management of diabetes (types 1 and 2), heart failure, asthma, chronic obstructive pulmonary disease (COPD) and cancer to identify components of effective self-management support.,We performed a metareview (a systematic review of systematic reviews) of randomized controlled trials (RCTs) of telehealth interventions to support self-management in 6 exemplar long-term conditions.,We searched 7 databases for reviews published from January 2000 to May 2016 and screened identified studies against eligibility criteria.,We weighted reviews by quality (revised A Measurement Tool to Assess Systematic Reviews), size, and relevance.,We then combined our results in a narrative synthesis and using harvest plots.,We included 53 systematic reviews, comprising 232 unique RCTs.,Reviews concerned diabetes (type 1: n=6; type 2, n=11; mixed, n=19), heart failure (n=9), asthma (n=8), COPD (n=8), and cancer (n=3).,Findings varied between and within disease areas.,The highest-weighted reviews showed that blood glucose telemonitoring with feedback and some educational and lifestyle interventions improved glycemic control in type 2, but not type 1, diabetes, and that telemonitoring and telephone interventions reduced mortality and hospital admissions in heart failure, but these findings were not consistent in all reviews.,Results for the other conditions were mixed, although no reviews showed evidence of harm.,Analysis of the mediating role of self-management, and of components of successful interventions, was limited and inconclusive.,More intensive and multifaceted interventions were associated with greater improvements in diabetes, heart failure, and asthma.,While telehealth-mediated self-management was not consistently superior to usual care, none of the reviews reported any negative effects, suggesting that telehealth is a safe option for delivery of self-management support, particularly in conditions such as heart failure and type 2 diabetes, where the evidence base is more developed.,Larger-scale trials of telehealth-supported self-management, based on explicit self-management theory, are needed before the extent to which telehealth technologies may be harnessed to support self-management can be established.
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Little is known about using electronic medical records to identify patients with chronic obstructive pulmonary disease to improve quality of care.,Our objective was to develop electronic medical record algorithms that can accurately identify patients with obstructive pulmonary disease.,A retrospective chart abstraction study was conducted on data from the Electronic Medical Record Administrative data Linked Database (EMRALD®) housed at the Institute for Clinical Evaluative Sciences.,Abstracted charts provided the reference standard based on available physician-diagnoses, chronic obstructive pulmonary disease-specific medications, smoking history and pulmonary function testing.,Chronic obstructive pulmonary disease electronic medical record algorithms using combinations of terminology in the cumulative patient profile (CPP; problem list/past medical history), physician billing codes (chronic bronchitis/emphysema/other chronic obstructive pulmonary disease), and prescriptions, were tested against the reference standard.,Sensitivity, specificity, and positive/negative predictive values (PPV/NPV) were calculated.,There were 364 patients with chronic obstructive pulmonary disease identified in a 5889 randomly sampled cohort aged ≥ 35 years (prevalence = 6.2%).,The electronic medical record algorithm consisting of ≥ 3 physician billing codes for chronic obstructive pulmonary disease per year; documentation in the CPP; tiotropium prescription; or ipratropium (or its formulations) prescription and a chronic obstructive pulmonary disease billing code had sensitivity of 76.9% (95% CI:72.2-81.2), specificity of 99.7% (99.5-99.8), PPV of 93.6% (90.3-96.1), and NPV of 98.5% (98.1-98.8).,Electronic medical record algorithms can accurately identify patients with chronic obstructive pulmonary disease in primary care records.,They can be used to enable further studies in practice patterns and chronic obstructive pulmonary disease management in primary care.,Researchers develop an algorithm that can accurately search through electronic health records to find patients with chronic lung disease.,Mining population-wide data for information on patients diagnosed and treated with chronic obstructive pulmonary disease (COPD) in primary care could help inform future healthcare and spending practices.,Theresa Lee at the University of Toronto, Canada, and colleagues used an algorithm to search electronic medical records and identify patients with COPD from doctors’ notes, prescriptions and symptom histories.,They carefully adjusted the algorithm to improve sensitivity and predictive value by adding details such as specific medications, physician codes related to COPD, and different combinations of terminology in doctors’ notes.,The team accurately identified 364 patients with COPD in a randomly-selected cohort of 5889 people.,Their results suggest opportunities for broader, informative studies of COPD in wider populations.
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We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.
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Chronic obstructive pulmonary disease (COPD) is associated with local and systemic inflammation.,The knowledge of interaction and co-variation of the inflammatory responses in different compartments is meagre.,Healthy controls (n = 23), smokers with (n = 28) and without (n = 29) COPD performed spirometry and dental examinations.,Saliva, induced sputum, bronchoalveolar lavage (BAL) fluid and serum were collected.,Inflammatory markers were assessed in all compartments using ELISA, flow cytometry and RT-PCR.,Negative correlations between lung function and saliva IL-8 and matrix metalloproteinase-9 (MMP-9) were found in smokers with COPD.,IL-8 and MMP-9 in saliva correlated positively with periodontal disease as assessed by gingival bleeding in non-smokers.,Tumor necrosis factor-α (TNF-α) in saliva, serum and TNF-α mRNA expression on macrophages in BAL-fluid were lower in smokers than in non-smokers.,There were positive correlations between soluble TNF-α receptor 1 (sTNFR1) and soluble TNF-α receptor 2 (sTNFR2) in sputum, BAL-fluid and serum in all groups.,Sputum interleukin-8 (IL-8) or interleukin-6 (IL-6) was positively correlated with sTNFR1 or sTNFR2 in non-smokers and with sTNFR2 in COPD.,Saliva which is convenient to collect and analyse, may be suitable for biomarker assessment of disease activity in COPD.,An attenuated TNF-α expression was demonstrated by both protein and mRNA analyses in different compartments suggesting that TNF-α response is altered in moderate and severe COPD.,Shedding of TNFR1 or TNFR2 is similarly regulated irrespective of airflow limitation.
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Matrix metalloproteinases (MMPs) and C-reactive protein (CRP) are involved in chronic obstructive pulmonary disease (COPD) pathogenesis.,The aim of the present work was to determine plasma concentrations of MMPs and CRP in COPD associated to biomass combustion exposure (BE) and tobacco smoking (TS).,Pulmonary function tests, plasma levels of MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP were measured in COPD associated to BE (n = 40) and TS (n =40) patients, and healthy non-smoking (NS) healthy women (controls, n = 40).,Plasma levels of MMP-1, MMP-7, MMP-9, and MMP-9/TIMP-1 and CRP were higher in BE and TS than in the NS healthy women (p <0.01).,An inverse correlation between MMP-1, MMP-7, MMP-9, MMP-9/TIMP-1 and CRP plasma concentrations and FEV1 was observed.,Increase of MMPs and CRP plasma concentrations in BE suggests a systemic inflammatory phenomenon similar to that observed in COPD associated to tobacco smoking, which may also play a role in COPD pathogenesis.
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There is a wide variability in measurement methodology of physical activity.,This study investigated the effect of different analysis techniques on the statistical power of physical activity outcomes after pulmonary rehabilitation.,Physical activity was measured with an activity monitor armband in 57 patients with COPD (mean ± SD age, 66 ± 7 years; FEV1, 46 ± 17% predicted) before and after 3 months of pulmonary rehabilitation.,The choice of the outcome (daily number of steps [STEPS], time spent in at least moderate physical activity [TMA], mean metabolic equivalents of task level [METS], and activity time [ACT]), impact of weekends, number of days of assessment, postprocessing techniques, and influence of duration of daylight time (DT) on the sample size to achieve a power of 0.8 were investigated.,The STEPS and ACT (1.6-2.3 metabolic equivalents of task) were the most sensitive outcomes.,Excluding weekends decreased the sample size for STEPS (83 vs 56), TMA (160 vs 148), and METS (251 vs 207).,Using 4 weekdays (STEPS and TMA) or 5 weekdays (METS) rendered the lowest sample size.,Excluding days with < 8 h wearing time reduced the sample size for STEPS (56 vs 51).,Differences in DT were an important confounder.,Changes in physical activity following pulmonary rehabilitation are best measured for 4 weekdays, including only days with at least 8 h of wearing time (during waking hours) and considering the difference in DT as a covariate in the analysis.,ClinicalTrials.gov; No.: NCT00948623; URL: www.clinicaltrials.gov
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Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable.
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The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.
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Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms.,Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections.,Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations.,Exogenous interferon-β reverses these effects.,FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways.,Mice deficient in the type I interferon-α/β receptor (IFNAR1−/−) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection.,This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production.,Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.,Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia.,Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ.
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Accurate prognosis information after a diagnosis of chronic obstructive pulmonary disease (COPD) would facilitate earlier and better informed decisions about the use of prevention strategies and advanced care plans.,We therefore aimed to develop and validate an accurate prognosis model for incident COPD cases using only information present in general practitioner (GP) records at the point of diagnosis.,Incident COPD patients between 2004-2012 over the age of 35 were studied using records from 396 general practices in England.,We developed a model to predict all-cause five-year mortality at the point of COPD diagnosis, using 47,964 English patients.,Our model uses age, gender, smoking status, body mass index, forced expiratory volume in 1-second (FEV1) % predicted and 16 co-morbidities (the same number as the Charlson Co-morbidity Index).,The performance of our chosen model was validated in all countries of the UK (N = 48,304).,Our model performed well, and performed consistently in validation data.,The validation area under the curves in each country varied between 0.783-0.809 and the calibration slopes between 0.911-1.04.,Our model performed better in this context than models based on the Charlson Co-morbidity Index or Cambridge Multimorbidity Score.,We have developed and validated a model that outperforms general multimorbidity scores at predicting five-year mortality after COPD diagnosis.,Our model includes only data routinely collected before COPD diagnosis, allowing it to be readily translated into clinical practice, and has been made available through an online risk calculator (https://skiddle.shinyapps.io/incidentcopdsurvival/).
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Chronic obstructive pulmonary disease (COPD) is a major cause of mortality.,Patients with advanced disease often have a poor quality of life, such that guidelines recommend providing palliative care in their last year of life.,Uptake and use of palliative care in advanced COPD is low; difficulty in predicting 1-year mortality is thought to be a major contributing factor.,We identified two primary care COPD cohorts using UK electronic healthcare records (Clinical Practice Research Datalink).,The first cohort was randomised equally into training and test sets.,An external dataset was drawn from a second cohort.,A risk model to predict mortality within 12 months was derived from the training set using backwards elimination Cox regression.,The model was given the acronym BARC based on putative prognostic factors including body mass index and blood results (B), age (A), respiratory variables (airflow obstruction, exacerbations, smoking) (R) and comorbidities (C).,The BARC index predictive performance was validated in the test set and external dataset by assessing calibration and discrimination.,The observed and expected probabilities of death were assessed for increasing quartiles of mortality risk (very low risk, low risk, moderate risk, high risk).,The BARC index was compared to the established index scores body mass index, obstructive, dyspnoea and exacerbations (BODEx), dyspnoea, obstruction, smoking and exacerbations (DOSE) and age, dyspnoea and obstruction (ADO).,Fifty-four thousand nine hundred ninety patients were eligible from the first cohort and 4931 from the second cohort.,Eighteen variables were included in the BARC, including age, airflow obstruction, body mass index, smoking, exacerbations and comorbidities.,The risk model had acceptable predictive performance (test set: C-index = 0.79, 95% CI 0.78-0.81, D-statistic = 1.87, 95% CI 1.77-1.96, calibration slope = 0.95, 95% CI 0.9-0.99; external dataset: C-index = 0.67, 95% CI 0.65-0.7, D-statistic = 0.98, 95% CI 0.8-1.2, calibration slope = 0.54, 95% CI 0.45-0.64) and acceptable accuracy predicting the probability of death (probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27).,The BARC compared favourably to existing index scores that can also be applied without specialist respiratory variables (area under the curve: BARC = 0.78, 95% CI 0.76-0.79; BODEx = 0.48, 95% CI 0.45-0.51; DOSE = 0.60, 95% CI 0.57-0.61; ADO = 0.68, 95% CI 0.66-0.69, external dataset: BARC = 0.70, 95% CI 0.67-0.72; BODEx = 0.41, 95% CI 0.38-0.45; DOSE = 0.52, 95% CI 0.49-0.55; ADO = 0.57, 95% CI 0.54-0.60).,The BARC index performed better than existing tools in predicting 1-year mortality.,Critically, the risk score only requires routinely collected non-specialist information which, therefore, could help identify patients seen in primary care that may benefit from palliative care.,The online version of this article (10.1186/s12916-019-1310-0) contains supplementary material, which is available to authorized users.
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Background: Chronic obstructive pulmonary disease (COPD) is a disease of increasing significance in terms of economic and social burden due to its increasing prevalence and high costs.,Direct costs of COPD are mostly associated with hospitalization expenditures.,In this study, our objective was to investigate the costs of hospitalization and factors affecting these costs in patients hospitalized due to acute exacerbation of COPD (AECOPD).,Methods: A total of 284 patients hospitalized AECOPD were included in the study.,Data were examined retrospectively using the electronic hospital charts.,Results: Mean duration of hospitalization was 11.38 ± 6.94 days among study patients.,Rates of admission to the intensive care unit, initiation of non-invasive mechanical ventilation (NIMV) and invasive mechanical ventilation (MIV) were 37.3% (n=106), 44.4% (n=126) and 18.3% (n=52) respectively.,The rate of mortality was 14.8% (n=42).,Mean cost of a single patient hospitalized for an AECOPD was calculated as $1765 ± 2139.,Mean cost of admission was $889 ± 533 in standard ward, and $2508 ± 2857 in intensive care unit (ICU).,The duration of hospitalization, a FEV1% predicted value below 30%, having smoked 40 package-years or more, the number of co-morbidities, NIMV, IMV, ICU, exitus and the number of hospitalizations in the past year were among the factors that increased costs significantly.,Hospital acquired pneumonia, chronic renal failure and anemia also increased the costs of COPD significantly.,Conclusion: The costs of treatment increase with the severity of COPD or with progression to a higher stage.,Efforts and expenditures aimed at preventing COPD exacerbations might decrease the costs in COPD.
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Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability.,The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea.,Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St.,Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI).,Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001).,Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ.,In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes.,ClinicalTrials.gov NCT00000606
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Chronic obstructive pulmonary disease (COPD) is linked to both cigarette smoking and genetic determinants.,We have previously identified iron-responsive element binding protein 2 (IRP2) as an important COPD susceptibility gene, with IRP2 protein increased in the lungs of individuals with COPD.,Here we demonstrate that mice deficient in Irp2 were protected from cigarette smoke (CS)-induced experimental COPD.,By integrating RIP-Seq, RNA-Seq, gene expression and functional enrichment clustering analysis, we identified IRP2 as a regulator of mitochondrial function in the lung.,IRP2 increased mitochondrial iron loading and cytochrome c oxidase (COX), which led to mitochondrial dysfunction and subsequent experimental COPD.,Frataxin-deficient mice with higher mitochondrial iron loading had impaired airway mucociliary clearance (MCC) and higher pulmonary inflammation at baseline, whereas synthesis of cytochrome c oxidase (Sco2)-deficient mice with reduced COX were protected from CS-induced pulmonary inflammation and impairment of MCC.,Mice treated with a mitochondrial iron chelator or mice fed a low-iron diet were protected from CS-induced COPD.,Mitochondrial iron chelation also alleviated CS-impairment of MCC, CS-induced pulmonary inflammation and CS-associated lung injury in mice with established COPD, suggesting a critical functional role and potential therapeutic intervention for the mitochondrial-iron axis in COPD.
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Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema.,The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known.,In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke.,Likewise, nCB intranasal administration induced emphysema in mouse lungs.,Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes.,Increasing the polarity or size of CB mitigated many adverse effects.,Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.,DOI:http://dx.doi.org/10.7554/eLife.09623.001,Smoking for many years damages the lungs and leads to a disease called emphysema that makes it difficult to breathe and is often deadly.,There are thousands of chemicals in cigarette smoke and many of them have been linked to the development of lung cancer, although it has been difficult to pinpoint those that are responsible for smoking-related emphysema.,Moreover, cigarette smoke also contains large numbers of small particles and relatively little is known about the role played by these particles in smoking-related disease.,One of the hallmarks of long-term smoking is a blackening of the lung tissue that persists even if someone stops smoking.,Previously, little was known about the composition of the substance that causes this blackening, or its significance in the development of emphysema.,Now, by studying lung tissue taken from smokers with emphysema, You et al. have shown that this black substance is made of nano-sized particles of a material called carbon black (which is also known as elemental carbon).,These nanoparticles are produced by the incomplete combustion of the cigarettes.,You et al. also confirmed that nanoparticles of carbon black can cause emphysema in mice.,Closer examination of the lung damage caused by the nanoparticles revealed that they trigger breakages in DNA, which leads to inflammation of the lung.,And because the nanoparticles cannot be cleared, they are released into the lung when cells die, which perpetuates lung inflammation and damage.,You et al. then went on to show that nanoparticles of carbon black can be modified in a way that allows them to be cleared from the lungs.,Such modifications could potentially protect people who are exposed to carbon black nanoparticles in the environment or in workplaces where carbon black is used, such as factories that produce automobile tires and other rubber products.,DOI:http://dx.doi.org/10.7554/eLife.09623.002
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To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD.
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Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease.
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Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD).,Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection.,Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation.,However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed.,We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD.,To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors.,Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors.,Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation.,Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects.,In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72-96 h post-infection.,Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.
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Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).,We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.,Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.,Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD.,While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella.,Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations.,Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations.,These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.,The online version of this article (10.1186/s12931-019-1085-z) contains supplementary material, which is available to authorized users.
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Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.
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Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO
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Few data exist on the understanding and adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in resource-limited settings, which are mostly in sub-Saharan Africa.,To assess physicians' understanding, adherence, and barriers to implementation of GOLD guidelines in Nigeria.,A questionnaire based on the recommendations of the guidelines was self-administered by 156 physicians in departments of internal and family medicine in selected hospitals to assess physician understanding of the GOLD guidelines and barriers to its implementation.,The medical records of patients with chronic obstructive pulmonary disease (COPD) were also reviewed to assess adherence to the guideline recommendations.,The performance score of all physicians was 22.37±0.39 (range 0-38).,Pulmonologists had the highest score (37.00±0.00) while medical officers had the lowest score (19.93±4.98) (F=10.16, df=5, p<0.001).,Forty one percent of physicians knew the spirometric criteria for diagnosing COPD and 26.9% could assess the severity.,In clinical practice, 32% of patients had brief smoking counselling despite 70% being smokers, 24% had spirometry and 18% had assessment of severity.,Almost 60% of patients were on oral aminophylline, 72% were on an inhaled long-acting β2-agonist and corticosteroid combination, 2% had pulmonary rehabilitation and no patients were vaccinated.,Self-reported adherence to the COPD guidelines was 23.7%.,Lack of familiarity (39.8%) was cited as the most common barrier to adherence to the guidelines.,The understanding of GOLD guidelines is satisfactory among Nigerian doctors managing patients with COPD but the level of adherence is poor.,Educational interventions are needed to improve the implementation of guideline-based management.
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Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely.,We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines.,Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included.,The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression.,A total 175 participants were included.,No significant postbronchodilator FEV1 decline was observed between the groups (−34.4±7.9 [group A]; −26.2±9.4 [group B]; −22.7±16.0 [group C]; and −24.0±8.7 mL/year [group D]) (P=0.79).,The group with less symptoms (−32.3±7.2 vs −25.0±6.5 mL/year) (P=0.44) and the low risk group (−31.0±6.1 vs −23.6±7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant.,However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline.,There was no significant difference in lung function decline rates according to the GOLD groups.,Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification.
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People with COPD have a decline in functional status, but little is known about the rate of decline and factors that contribute.,Of particular concern is the decline in cognitive and functional performance.,Decrease in cognitive and functional performance will finally lead to decreased health status, sedentary life style and premature frailty.,The aim of this study is to compare functional performance and cognitive status in patients with COPD of different ages and to examine the changes in extrapulmonary effects.,This study included 62 patients with COPD risk class D who were divided into two groups (<70 years, N=30 and >70 years, N=32).,Patients first completed the Montreal Cognitive Assessment (MoCA), which is a 30-point test that assesses different cognitive domains, while isometric knee extension (IKE) was measured using a digital handheld dynamometer, and functional exercise level was assessed using the 6-minute walking distance (6MWD) test.,The patients’ older age (age higher than 70 years) was associated with a significantly lower body mass index (BMI, 27.50 vs 24.24 kg/m2; P=0.020), higher vital capacity parameters, forced vital capacity (FVC, 2.74 vs 2.82 L; P=0.799), FVC (%) (73.00 vs 66.50, P=132), forced expiratory volume in the first second (FEV1, 0.93 vs 1.13 L; P=0.001) and FEV1 (%) (28.50 vs 30.50, P=0.605).,In addition, patients at older age presented a significantly reduced physical activity capacity, 6MWD (385.93 vs 320.84 m, P<0.001) and IKE (24.75 vs 22.55 kgf, P=0.005), as well as higher values for inflammatory biomarkers, C-reactive protein (8.77 vs 3.34 mg/L, P=0.022).,Moreover, patients at older age presented significantly lower score at the cognitive assessment, MoCA (23.50 vs 20.00, P<0.001).,Elderly COPD patients have reduced exercise capacity and muscle strength, deteriorated cognitive function and increased inflammatory markers.,Furthermore, inflammation markers were significantly correlated with muscle strength, walking distance and cognitive impairment.
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The aim of this study was to investigate the effects of high-intensity aerobic training (AT) and high-intensity aerobic training combined with resistance training (ie, combined training [CT]) on cognitive function in patients with COPD.,Twenty-eight Caucasian male patients (68.35±9.64 years; mean ± SD) with COPD were recruited and randomized into two groups, AT and CT.,Both groups performed physical reconditioning for 4 weeks, with a frequency of five training sessions per week.,The CT group completed two daily sessions of 30 minutes: one aerobic session and one strength session, respectively; The AT group performed two 30-minute aerobic endurance exercise sessions on treadmill.,Physical and cognitive function tests were performed before and after the training intervention performances.,Exercise training improved the following cognitive functions: long-term memory, verbal fluency, attentional capacity, apraxia, and reasoning skills (P<0.01).,Moreover, the improvements in the CT group were significantly greater than those in the AT group in long-term memory, apraxia, and reasoning skills (P<0.05).,CT may be a possible strategy to prevent cognitive decline and associated comorbidities in male patients with COPD.
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To explore the role of family with sequence similarity 13 member A (FAM13A) in TGF-β1-induced EMT in the small airway epithelium of patients with chronic obstructive pulmonary disease (COPD).,Small airway wall thickness and protein levels of airway remodeling markers, EMT markers, TGF-β1, and FAM13A were measured in lung tissue samples from COPD and non-COPD patients.,The correlations of FAM13A expression with COPD severity and EMT marker expression were evaluated.,Gain- and loss-of-function assays were performed to explore the functions of FAM13A in cell proliferation, motility, and TGF-β1-induced EMT marker alterations in human bronchial epithelial cell line BEAS-2B.,Independent of smoking status, lung tissue samples from COPD patients exhibited significantly increased small airway thickness and collagen fiber deposition, along with enhanced protein levels of remodeling markers (collagen I, fibronectin, and MMP-9), mesenchymal markers (α-SMA, vimentin, and N-cadherin), TGF-β1, and FAM13A, compared with those from non-COPD patients.,FAM13A expression negatively correlated with FEV1% and PO2 in COPD patients.,In small airway epithelium, FAM13A expression negatively correlated with E-cadherin protein levels and positively correlated with vimentin protein levels.,In BEAS-2B cells, TGF-β1 dose-dependently upregulated FAM13A protein levels.,FAM13A overexpression significantly promoted cell proliferation and motility in BEAS-2B cells, whereas FAM13A silencing showed contrasting results.,Furthermore, FAM13A knockdown partially reversed TGF-β1-induced EMT marker protein alterations in BEAS-2B cells.,FAM13A upregulation is associated with TGF-β1-induced EMT in the small airway epithelium of COPD patients independent of smoking status, serving as a potential therapeutic target for anti-EMT therapy in COPD.,The online version contains supplementary material available at 10.1186/s12931-021-01783-z.
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Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk.,We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.,After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37).,Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly.,By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively).,Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).,The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012.,Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not.,Patients were followed up to assess lung cancer risk or protective factors.,In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use.,The index date of statin use was the COPD confirmation date.,To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs).,Patients receiving < 28 cDDDs were defined as nonstatin users.,Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients.,Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.
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Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.
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To evaluate differentially expressed long noncoding RNAs (lncRNAs) and the potential role of lncRNA TUG1 in patients with chronic obstructive pulmonary disease (COPD).,Total RNA was extracted from both COPD and non-COPD lung tissues, and microarray analysis was performed with 25,628 lncRNA probes and 20,106 mRNA probes.,In addition, five up-regulated and five down-regulated lncRNAs were selected for identification using quantitative real-time polymerase chain reaction.,COPD cell model was established by transforming growth factor β (TGF-β) treatment.,Cell Counting Kit-8 assay was used to detect BEAS-2B and HFL1 cell proliferation after TUG-siRNA transfection with TGF-β treatment.,In addition, the expression levels of α-SMA and fibronectin proteins were determined using Western blot in BEAS-2B and HFL1 cells after TUG-siRNA transfection with TGF-β treatment.,There were 8,376 (32.7%) differentially expressed lncRNAs and 5,094 (25.3%) differentially expressed mRNAs in COPD lung tissues compared with non-COPD lung tissues.,Five of the analyzed lncRNAs (BC038205, BC130595, TUG1, MEG3, and LOC646329) were markedly increased, while five lncRNAs (LOC729178, PLAC2, LOC339529, LINC00229, and SNHG5) were significantly decreased in COPD lung tissues compared with non-COPD lung tissues (n=20) (***P<0.001).,Knockdown of lncRNA TUG1 promotes BEAS-2B and HFL1 cell proliferation after TGF-β treatment through inhibiting the expression levels of α-SMA and fibronectin.,Abundant, differentially expressed lncRNAs and mRNAs were identified by microarray analysis and these might play a partial or key role in the diagnosis of patients with COPD.,LncRNA TUG1 may become a very important class of biomarker and may act as a potential diagnostic and therapeutic target for patients with COPD.
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Adequate peak inspiratory flow rate (PIFR) is required for drug dispersion with dry powder inhalers (DPIs).,Prevalence of PIFR discordance (suboptimal PIFR with prescribed inhalers) and factors influencing device-specific PIFR are unclear in COPD.,The objective of this study was to determine the prevalence of PIFR discordance and associated clinical factors in a stable COPD population.,An observational, single-center, cohort study was conducted including 66 outpatients with COPD.,PIFR was measured using the In-Check™ Dial with applied resistance of prescribed inhalers.,Participants were defined as discordant if measured PIFR was <30 L/min and <60 L/min for high and low-medium resistance devices, respectively, using an inspiratory effort the participant normally used with their prescribed DPI.,The median age of the COPD participants was 69.4 years, 92% were white and 47% were female.,A total of 48% were using low-medium resistance DPIs (Diskus®/Ellipta®) and 76% used high-resistance DPI (Handihaler®).,A total of 40% of COPD participants were discordant to prescribed inhalers.,Female gender was the only factor consistently associated with lower PIFR.,Shorter height was associated with reduced PIFR for low-medium resistance (r=0.44; P=0.01), but not high resistance (r=0.20; P=0.16).,There was no correlation between PIFR by In-Check™ dial and PIFR measured by standard spirometer.,PIFR is reduced in stable COPD patients, with female gender being the only factor consistently associated with reduced PIFR.,Discordance with prescribed inhalers was seen in 40% of COPD patients, suggesting that many COPD patients do not generate adequate inspiratory force to overcome prescribed DPIs resistance in the course of normal use.
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Adherence to inhaled medications by COPD patients is a challenging issue, but relatively understudied.,The aim of this study is the characterization of adherence to inhaled medications by COPD patients, with a focus on patient-related determinants.,Stable COPD outpatients ≥40 years of age from a respiratory unit and diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria were included in a cross-sectional study.,The Measure of Treatment Adherence (MTA), the Beliefs about Medications Questionnaire (BMQ) and demographic, clinical, and COPD questionnaires were used.,After completing these questionnaires, semi-structured interviews were carried out and participants were encouraged to justify their opinions and behaviors.,Field notes were made during the interviews and each interview was analyzed before the next one.,Quantitative and qualitative analyses of the variables were then performed.,A total of 300 out of 319 participants (mean age =67.7 years, 78.1% males) completed the MTA questionnaire.,Of these, 31.3% were considered poorly adherent and 16.7% as non-adherent to the inhaled therapy.,A statistically significant negative association was found between adherence and current smoking status (P=0.044), and between adherence and FEV1% (P=0.000).,The mean BMQ Necessity score was higher in adherent patients (P=0.000), but the the mean Concern score was similar for both (P=0.877).,We found nine patterns of poor-adherence, six reasons given for poor-adherence behaviors, five reasons for good-adherence behaviors and three patient-related domains on adherence to medications.,Adherence is related to need perception and to the functional severity of the disease.,A non-adherent patient is usually a current smoker with lower degree of airflow limitation and lower perception of medication necessity.,New information obtained was related to the patterns and reasons for different adherence behaviors, which are based on three major groups of patient related-determinants: health-related experiences, health-related behaviors and health-related beliefs.
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Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease.,The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown.,To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described.,Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity.,In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models.,Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention.,While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.
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Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD).,Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology.,We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells.,Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined.,Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD.,Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ.,Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression.,Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR.,ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased.,Healthy smokers were intermediate between healthy nonsmokers and patients with COPD.,Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects.,MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release.,Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation.,Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD.
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Significant numbers of chronic obstructive respiratory disease patients are readmitted for Acute Exacerbation (AE) within 30 days of discharge.,And these early readmissions have serious clinical and socioeconomic consequences.,The objective of our study was to determine the rate of readmission within 30 days of discharge and it’s predictors among patients treated for acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD).,A prospective cohort study involving 130 patients (asthma = 59, COPD = 71) was conducted from April-September, 2019, in Jimma Medical Center (JMC), South-West Ethiopia.,Socio-demographic, clinical, laboratory, and drug-related data were recorded at admission and during hospital stay.,Cox regression analysis was performed to identify risk factors for readmissions following an AE of asthma and COPD.,During the study period, 130 (male, 78(60%)) patients were admitted with AE of asthma and COPD.,The median age was 59(IQR, 50-70) years.,Of 130 patients, 21(18.10%) had a new AE of asthma and COPD that required hospitalization in the 30 days after discharge.,The overall median survival time to 30-day readmission was 20 days (IQR, 16-29).,Multivariate analysis revealed prolonged use of oxygen therapy (AHR = 4.972, 95% CI [1.041-23.736] and frequent hospital admissions (AHR = 11.482 [1.308-100.793]) to be independent risk factors for early readmissions.,Early hospital readmission rates for AE of asthma and COPD were alarmingly high.,Frequent hospital admission and long-term oxygen therapy during hospital stay were independent predictors of 30-day readmission.
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One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days.,No tool has been developed specifically in this population to predict readmission or death.,Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement.,In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records.,A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort).,Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores.,Of 2417 patients, 936 were readmitted or died within 90 days of discharge.,The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL).,The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts.,Higher PEARL scores were associated with a shorter time to readmission.,The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting.,It is superior to other scores that have been used in this population.,UKCRN ID 14214.
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We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy.,Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US.,Eligible patients were aged ≥40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD.,As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes.,A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified.,Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively.,In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting β2-agonist only).,In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting β2-agonist only).,A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy.,Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination.,This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination.
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Pulmonary hypertension (PH) is the hemodynamic manifestation of various pathological processes that result in elevated pulmonary artery pressures (PAP).,The National Institutes of Health Registry defined pulmonary arterial hypertension as the mean PAP of more than 25 mm Hg with a pulmonary capillary wedge pressure or left atrial pressure equal to or less than 15 mm Hg.,This definition remains the currently accepted definition of PH that is used to define PH related to multiple clinical conditions including chronic obstructive pulmonary disease (COPD).,The estimated US prevalence of COPD by the National Health Survey in 2002 in people aged >25 was 12.1 million.,There is a lack of large population-based studies in COPD to document the correct prevalence of PH and outcome.,The major cause of PH in COPD is hypoxemia leading to vascular remodeling.,Echocardiogram is the initial screening tool of choice for PH.,This simple noninvasive test can provide an estimate of right ventricular systolic and right atrial pressures.,Right heart catheterization remains the gold standard to diagnose PH.,It provides accurate measurement of mean PAP and pulmonary capillary wedge pressure.,Oxygen therapy remains the cornerstone therapeutic for hypoxemia in COPD patients.,Anecdotal reports suggest utility of PDE5-inhibitors and prostacyclin to treat COPD-related PH.,Large randomized clinical trials are needed before the use of these drugs can be recommended.
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Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD).,However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear.,This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports.,Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000).,Respondents aged ≥40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions.,Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score ≥2).,Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively.,Adjusted mean activity impairment (55% vs 37%, P<0.001) and number of emergency room visits (0.61 vs 0.40, P=0.030) were higher in patients with greater dyspnea.,Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients’ ability to function across a multitude of domains.,These patients may benefit from more intense treatment of their symptoms.
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Patients with COPD often have multiple comorbidities requiring use of multiple medications, and adherence rates for maintenance COPD (mCOPD) medications are already known to be suboptimal.,Presence of comorbidities in COPD patients, and use of medications used to treat those comorbidities (non-COPD medications), may have an adverse impact on adherence to mCOPD medications.,The objective of the study was to evaluate the association between non-adherence to mCOPD medications and non-COPD medications in COPD patients.,COPD patients were identified using a large administrative claims database.,Selected patients were 40-89 years old and continuously enrolled for 12 months prior to and 24 months after the first identified COPD diagnosis (index date) during January 1, 2009 to December 31, 2010.,Patients were required to have ≥1 prescription for a mCOPD medication within 365 days of the index date and ≥1 prescription for one of 12 non-COPD medication classes within ±30 days of the first COPD prescription.,Adherence (proportion of days covered [PDC]) was measured during 365 days following the first COPD prescription.,The association between non-adherence (PDC <0.8) to mCOPD and non-adherence to non-COPD medications was determined using logistic regression, controlling for baseline patient characteristics.,A total of 14,117 patients, with a mean age of 69.9 years, met study criteria.,Of these, 40.9% were males and 79.2% were non-adherent to mCOPD medications with a mean PDC of 0.47.,Non-adherence to mCOPD medications was associated with non-adherence to 10 of 12 non-COPD medication classes (odds ratio 1.38-1.78, all P<0.01).,Adherence to mCOPD medications is low.,Non-adherence (or adherence) to mCOPD medications is positively related to non-adherence (or adherence) to non-COPD medications, implying that the need to take medications prescribed for comorbid conditions does not adversely impact adherence to mCOPD medications.
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Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem.,Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment.,This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action.,Several dietary options can be considered in terms of COPD prevention and/or progression.,Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD.,Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health.
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The association between body mass index (BMI) and mortality in patients suffering from chronic obstructive pulmonary disease (COPD) has been a subject of interest for decades.,However, the evidence is inadequate to draw robust conclusions because some studies were generally small or with a short follow-up.,We carried out a search in MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE database for relevant studies.,Relative risks (RRs) with 95% confidence interval (CI) were calculated to assess the association between BMI and mortality in patients with COPD.,In addition, a baseline risk-adjusted analysis was performed to investigate the strength of this association.,22 studies comprising 21,150 participants were included in this analysis.,Compared with patients having a normal BMI, underweight individuals were associated with higher mortality (RR = 1.34, 95% CI = 1.01-1.78), whereas overweight (RR = 0.47, 95% CI = 0.33-0.68) and obese (RR = 0.59, 95% CI = 0.38-0.91) patients were associated with lower mortality.,We further performed a baseline risk-adjusted analysis and obtained statistically similar results.,Our study showed that for patients with COPD being overweight or obese had a protective effect against mortality.,However, the relationship between BMI and mortality in different classes of obesity needed further clarification in well-designed clinical studies.
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Chronic obstructive pulmonary disease (COPD) affects over 250 million people globally, carrying a notable economic burden.,This systematic literature review aimed to highlight the economic burden associated with moderate-to-very severe COPD and to investigate key drivers of healthcare resource utilization (HRU), direct costs and indirect costs for this patient population.,Relevant publications published between January 1, 2006 and November 14, 2016 were captured from the Embase, MEDLINE and MEDLINE In-Process databases.,Supplemental searches from relevant 2015-2016 conferences were also performed.,Titles and abstracts were reviewed by two independent researchers against pre-defined inclusion and exclusion criteria.,Studies were grouped by the type of economic outcome presented (HRU or costs).,Where possible, data were also grouped according to COPD severity and/or patient exacerbation history.,In total, 73 primary publications were included in this review: 66 reported HRU, 22 reported direct costs and one reported indirect costs.,Most of the studies (94%) reported on data from either Europe or North America.,Trends were noted across multiple studies for higher direct costs (including mean costs per patient per year and mean costs per exacerbation) being associated with increasingly severe COPD and/or a history of more frequent or severe exacerbations.,Similar trends were noted according to COPD severity and/or exacerbation history for rate of hospitalization and primary care visits.,Multivariate analyses were reported by 29 studies and demonstrated the statistical significance of these associations.,Several other drivers of increased costs and HRU were highlighted for patients with moderate-to-very severe COPD, including comorbidities, and treatment history.,Moderate-to-very severe COPD represents a considerable economic burden for healthcare providers despite the availability of efficacious treatments and comprehensive guidelines on their use.,Further research is warranted to ensure cost-efficient COPD management, to improve treatments and ease budgetary pressures.
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The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR.,Randomised controlled feasibility trial.,Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes.,Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date.,103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)).,Participants had to be willing to participate in either arm of the trial, have internet access and be web literate.,Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material.,Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education).,Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected.,Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated.,A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0).,However, there were no significant differences between the groups in any outcome.,Dropout rates were higher in the web-based programme (57% vs 23%).,An interactive web-based PR programme is feasible and acceptable when compared with conventional PR.,Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care.,ISRCTN03142263; Results.
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In utero and/or childhood environmental tobacco smoke exposure is well known to adversely affect lung function and to depreciate child's health in many ways.,Fewer studies have assessed the long-term effects on COPD development and disease severity in later adulthood.,COPD patients were interviewed using a structured questionnaire regarding their personal as well as the smoking habits of their parents.,Data were compared with the disease history, e.g.,COPD exacerbation rate, and their lung function data.,Between 2003 and 2004 COPD patients were recruited a) in a private practice specialized in pulmonary medicine (n = 133) and b) in a hospital (n = 158). 75% of their fathers and only 15.4 of all mothers smoked regularly.,COPD patients from smoking mothers had lower FEV1 predicted than those raised in household without maternal smoking exposure: 39.4 ± 9.5% vs.,51.9 ± 6.0% (P = 0.037).,Fathers had no effect on FEV1 regardless if they are smokers or non-smokers.,Rate of severe exacerbations requiring hospitalization remained unaffected by parental second hand smoke exposure.,Maternal smoking negatively affects lung function of their offspring even in late adulthood when they develop COPD.,It even aggravates the cumulative effect of active cigarette consumption.,Clinical course of the COPD remained unaffected.
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Never smokers comprise a substantial proportion of patients with COPD.,Their characteristics and possible risk factors in this population are not yet well defined.,We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study.,Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors.,A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines.,In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.,Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD.,Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD.,This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio.,Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.,This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD.,Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.
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Cigarette smoking is the leading modifiable risk factor for disease and death worldwide.,Previous studies quantifying gene-level expression have documented the effect of smoking on mRNA levels.,Using RNA sequencing, it is possible to analyze the impact of smoking on complex regulatory phenomena (e.g. alternative splicing, differential isoform usage) leading to a more detailed understanding of the biology underlying smoking-related disease.,We used whole-blood RNA sequencing to describe gene and exon-level expression differences between 229 current and 286 former smokers in the COPDGene study.,We performed differential gene expression and differential exon usage analyses using the voom/limma and DEXseq R packages.,Samples from current and former smokers were compared while controlling for age, gender, race, lifetime smoke exposure, cell counts, and technical covariates.,At an adjusted p-value <0.05, 171 genes were differentially expressed between current and former smokers.,Differentially expressed genes included 7 long non-coding RNAs that have not been previously associated with smoking: LINC00599, LINC01362, LINC00824, LINC01624, RP11-563D10.1, RP11-98G13.1, AC004791.2.,Secondary analysis of acute smoking (having smoked within 2-h) revealed 5 of the 171 smoking genes demonstrated an acute response above the baseline effect of chronic smoking.,Exon-level analyses identified 9 exons from 8 genes with significant differential usage by smoking status, suggesting smoking-induced changes in isoform expression.,Transcriptomic changes at the gene and exon levels from whole blood can refine our understanding of the molecular mechanisms underlying the response to smoking.,The online version of this article (10.1186/s12920-017-0295-9) contains supplementary material, which is available to authorized users.
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CD8 cells may contribute towards an autoimmune process in COPD.,Down regulation of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with consequent T cell dysfunction.,We hypothesise that TCR signalling is abnormal in COPD pulmonary CD8 cells.,Micro-array gene expression analysis of blood and pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from smoker controls (S).,We focused on the TCR signalling pathway, with validation of key findings using polymerase chain reaction and immunofluorescence.,TCR signalling molecules in COPD pulmonary CD8 cells were down regulated compared to blood CD8 cells (CD247: fold change (FC) −2.43, Q = 0.001; LCK: FC −2.25, Q = 0.01).,Micro-array analysis revealed no significant differences between COPD and S pulmonary CD8 cells.,However, PCR revealed significantly lower gene expression levels of CD247 (FC −1.79, p = 0.04) and LCK (FC −1.77, p = 0.01) in COPD compared to S pulmonary CD8 cells.,CD247 down regulation in COPD CD8 cells was confirmed by immunofluorescent staining of bronchoalveolar lavage cells: Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non-smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR signalling molecules in COPD pulmonary CD8 cells.,This may cause T cell dysfunction.
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Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation.,Cardiovascular-related comorbidities are established to contribute to morbidity and mortality especially during exacerbations.,The aim of the current study was to determine alterations in hemorheology (erythrocyte aggregation, deformability) in newly diagnosed COPD patients and their response to medical treatment and to compare with values of COPD patients with exacerbations.,The study comprised 13 COPD patients, 12 controls, and 16 COPD patients with exacerbations.,The severity of COPD was determined according to Global Initiative for Chronic Obstructive Lung Disease guidelines.,Red blood cell (RBC) deformability and aggregation were measured by an ektacytometer.,RBC deformability of COPD patients with exacerbations was decreased compared to the other groups.,Erythrocyte aggregation and plasma fibrinogen of COPD patients determined during exacerbations were higher than control.,Decreased RBC deformability and increased aggregation associated with exacerbations of COPD may serve as unfavorable mechanisms to worsen oxygenation and thus clinical symptoms of the patient.,Treatment modalities that modify rheological parameters might be beneficial.
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Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD).,To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD.,The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition).,Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers.,Plasma levels of CRP, IL-6 and FG were measured in the total study group.,Differences in haplotype distributions were tested using the global and haplotype-specific statistics.,Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients.,However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile).,Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003).,Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005).,None of the genes were associated with COPD-related phenotypes.,Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation.
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Long-acting bronchodilators are the cornerstone of pharmacologic treatment of COPD.,The new combination of long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) has been introduced as fist line therapy for COPD.,This article analyses the evidence of efficacy and safety of the TIO/OLO combination.,A systematic review and metaanalysis of randomized controlled trials (RCT) with a period of treatment of at least 6 weeks, in patients with COPD confirmed by spirometry, comparing combined treatment with TIO/OLO (approved doses only), with any of the mono-components or any other active comparator administered as an inhalator.,A total of 10 Randomized controlled trials (RCT) were identified (N = 10,918).,TIO/OLO significantly improved trough FEV1 from baseline to week 12 versus TIO, OLO and LABA/ICS (0.06 L, 0.09 L and between 0.04 and 0.05 L, respectively).,TIO/OLO improved transitional dyspnea index (TDI) and St.,George’s Respiratory Questionnaire (SGRQ) compared with mono-components, with patients more likely to achieve clinically important improvements in TDI (risk ratio [RR]: 1.17, 95% confidence interval [CI]: [1.07, 1.28] versus TIO and RR: 1.14, 95%CI: [1.01, 1.28] versus OLO) and in SGRQ (RR: 1.21, 95%CI: [1.12, 1.30] versus TIO and RR: 1.28, 95%CI: [1.18, 1.40] versus OLO).,Patients treated with TIO/OLO showed a significant reduction in the use of rescue medication and no significant differences in frequency of general and serious adverse events were observed between TIO/OLO and mono-components.,Treatment with TIO/OLO provided significant improvements in lung function versus mono-components and LABA/ICS with more patients achieving significant improvements in dyspnea and health status.,No differences in adverse events were observed compared with other active treatments.,PROSPERO register of systematic reviews (CRD42016040162).,The online version of this article (10.1186/s12931-017-0683-x) contains supplementary material, which is available to authorized users.
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Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited.,This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).,A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs.,A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George’s Respiratory Questionnaire score, and rescue medication use.,Twenty-four studies (n=21,311) compared LAMAs with placebo/each other.,Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06-125.60]; 117.20 mL [104.50-129.90]; 114.10 mL [103.10-125.20]; 136.70 mL [104.20-169.20]); 24-week trough FEV1 (128.10 mL [84.10-172.00]; 135.80 mL [123.10-148.30]; 106.40 mL [95.45-117.30]; 115.00 mL [74.51-155.30]); 24-week St George’s Respiratory Questionnaire score (−4.60 [−6.76 to −2.54]; −3.14 [−3.83 to −2.45]; −2.43 [−2.92 to −1.93]; −4.69 [−7.05 to −2.31]); 24-week transitional dyspnea index score (1.00 [0.41-1.59]; 1.01 [0.79-1.22]; 0.82 [0.62-1.02]; 1.00 [0.49-1.51]); and 24-week rescue medication use (data not available; −0.41 puffs/day [−0.62 to −0.20]; −0.52 puffs/day [−0.74 to −0.30]; −0.30 puffs/day [−0.81 to 0.21]).,For 12-week trough FEV1, differences in change from baseline (95% credible interval) were −12.8 mL (−39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (−7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (−11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (−11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (−5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (−15.30 to 54.38), umeclidinium versus glycopyrronium.,Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.,The new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard.,Choice should depend on physician’s and patient’s preference.
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Sub-optimal chronic obstructive pulmonary disease (COPD) management has been found largely due to patients’ medication non-adherence and incorrect inhaler technique.,This study aimed to examine inhaler use technique and medication adherence among Vietnamese COPD patients as well as potential associated factors.,A cross-sectional study involving 70 COPD exacerbators was conducted.,Inhaler technique and adherence were evaluated by the 10-item and 12-item Test of Adherence to Inhaler (TAI).,Data on the history of COPD, home prescription of inhalers and duration of hospitalization were also collected.,Generalized linear regression models were used to determine the associated factors with inhaler use and medication adherence.,The results showed that the proportion of patients with good inhaler technique was 22.7% for metered-dose inhalers (MDI), 30.4% for dry powder inhalers (DPI) and 31.8% for soft-mist inhalers (SMI).,Full exhalation was the most common mistake.,The rates of non-compliance patterns were: “ignorant” (77.1%), “sporadic” (58.6%), and “deliberate” (55.7%).,Worse dyspnea, greater health condition impairment, and an increased frequency of exacerbations and hospitalizations were found to be associated negatively with correct inhaler use and treatment adherence.,Instructions to COPD patients about using inhalers should focus on correct inhaler technique and adherence even when feeling healthy.
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The study aims at investigating the influence of several factors on the probability of receiving one of the two tiotropium formulations (Respimat or Handihaler).,Drug utilisation study.,All residents in the Region Umbria, Italy, aged ≥45 years, who received prescriptions of tiotropium during 2011-2012.,Two groups of patients were studied: (1) incident users of the two tiotropium formulations (ie, without tiotropium prescriptions in the previous 6 months); (2) switchers from Handihaler to Respimat.,Users of the two formulations were compared with regard to baseline characteristics and medical history.,The adjusted OR of receiving Respimat was estimated for several factors.,Incident users of the two formulations (4390 participants) had similar characteristics.,They were older and with more comorbidities than patients included in randomised control trials (RCTs).,Among prevalent users of Handihaler, the probability of switching to Respimat was greater in patients with severe respiratory disease (users of ≥4 respiratory drugs: adjusted OR=4.62; 95% CI 2.46 to 8.69) and among β-blocker users (adjusted OR=1.76; 95% CI 1.13 to 2.75).,Age above 75 years and lipid-lowering drug use reduced the probability of switching.,A positive association was also found between neurological conditions and the use of Respimat.,When starting tiotropium treatment, the choice between the two formulations is weakly affected by comorbidities and chronic obstructive pulmonary disease severity.,Instead, these characteristics influence the likelihood of switching from Handihaler to Respimat.,Since tiotropium users in clinical practice are more severe than those included in RCTs, further aetiological studies are needed to compare the safety profile of the two formulations in routine care.
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Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD.
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The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.
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Metabolic syndrome is a common extrapulmonary comorbidity in patients with chronic obstructive pulmonary disease (COPD).,However, the reported relationship of COPD with dyslipidemia, an important component of metabolic syndrome, is ambiguous.,The aim of this meta-analysis is to investigate the association between COPD and the serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG).,The PubMed and Embase databases were searched to find potential studies using the search terms of (“dyslipidemia” or “HDL” or “LDL” or “cholesterol” or “triglyceride”) and COPD.,We also performed subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia.,Mean differences (MD) with 95% confidence intervals (CI) were estimated with random effects models.,A total of 11 studies comprising 615 cases and 471 controls were included in the study.,No significant differences were found in the HDL (MD = −2.55, 95% CI [−6.03, 0.93], P = 0.15), LDL (MD = −2.25, 95% CI [−13.36, 8.86], P = 0.69), TC (MD = −2.69, 95% CI [−13.30, 7.92], P = 0.62), and TG (MD = 6.90, 95% CI [−2.81, 16.60], P = 0.16) levels of the 2 groups.,However, subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia showed that TG levels were higher in patients with stable COPD than in healthy individuals (MD = 16.35, 95% CI [5.90, 26.80], P = 0.002).,Excluding the impact of hypolipidemic treatment on serum lipid profile, TG levels were higher in patients with COPD than in healthy individuals.,This meta-analysis suggested that physicians should screen COPD patients for elevated TG levels to reduce the risk of cardiovascular morbidity and mortality.
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Recently, variations in a component of high-density lipoprotein (HDL), namely apolipoprotein M (apoM), were found to be associated with chronic obstructive pulmonary disease (COPD).,The aim of this study was to evaluate the association between apoM and COPD severity.,Factors associated with apoM, COPD, or coronary artery disease (CAD) were also assessed.,A total of 110 COPD patients and 110 age- and sex-matched non-COPD controls were included.,Among them, thirty COPD patients and seven non-COPD controls had CAD.,ApoM and pentraxin-3 levels were measured by ELISA.,Additionally, the levels of high-sensitivity C-reactive protein (hs-CRP), cholesterol, and triglyceride were assessed using an automatic biochemical analyzer.,Serum apoM levels increased gradually with COPD severity, with the most prominent apoM elevation observed in very severe COPD cases.,In addition, ApoM was correlated with percent-predicted forced expiratory volume in one second (% predicted FEV1) (r = −0.38, P < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = 0.23, P < 0.017), and hs-CRP (r = 0.24, P = 0.01) in COPD patients.,Furthermore, apoM was shown to be a risk factor for COPD onset (OR = 1.095, 95 % CI = 1.034-1.160, P = 0.002), but not associated with CAD in COPD patients.,Serum apoM was elevated in COPD patients and increased gradually with COPD severity.,However, there was no association between apoM and CAD development in COPD patients.,The online version of this article (doi:10.1186/s12944-016-0228-1) contains supplementary material, which is available to authorized users.
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Until recently, there have been few clinical algorithms for the management of patients with COPD.,Current evidence-based clinical management guidelines can appear to be complex, and they lack clear step-by-step instructions.,For these reasons, we chose to create a simple and practical clinical algorithm for the management of patients with COPD, which would be applicable to real-world clinical practice, and which was based on clinical symptoms and spirometric parameters that would take into account the pathophysiological heterogeneity of COPD.,This optimized algorithm has two main fields, one for nonspecialist treatment by primary care and general physicians and the other for treatment by specialized pulmonologists.,Patients with COPD are treated with long-acting bronchodilators and short-acting drugs on a demand basis.,If the forced expiratory volume in one second (FEV1) is ≥50% of predicted and symptoms are mild, treatment with a single long-acting muscarinic antagonist or long-acting beta-agonist is proposed.,When FEV1 is <50% of predicted and/or the COPD assessment test score is ≥10, the use of combined bronchodilators is advised.,If there is no response to treatment after three months, referral to a pulmonary specialist is recommended for pathophysiological endotyping: 1) eosinophilic endotype with peripheral blood or sputum eosinophilia >3%; 2) neutrophilic endotype with peripheral blood neutrophilia >60% or green sputum; or 3) pauci-granulocytic endotype.,It is hoped that this simple, optimized, step-by-step algorithm will help to individualize the treatment of COPD in real-world clinical practice.,This algorithm has yet to be evaluated prospectively or by comparison with other COPD management algorithms, including its effects on patient treatment outcomes.,However, it is hoped that this algorithm may be useful in daily clinical practice for physicians treating patients with COPD in Russia.
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Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD).,The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem.,To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia.,A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation.,Common respiratory symptoms and risk factors were recorded.,Spirometry was performed in respondents with suspected CRD.,Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio <0.7 in symptomatic patients, following the Global Initiative for Obstructive Lung Disease guidelines.,The number of questionnaires completed was 7,164 (mean age 43.4 years; 57.2% female).,The prevalence of asthma symptoms was 25.7%, AR 18.2%, and CB 8.6%.,Based on patient self-reported diagnosis, 6.9% had asthma, 6.5% AR, and 22.2% CB.,The prevalence of COPD based on spirometry in patients with respiratory symptoms was estimated as 21.8%.,The prevalence of respiratory diseases and risk factors was high in Russia when compared to available data.,For bronchial asthma and AR, the prevalence for related symptoms was higher than self-reported previous diagnosis.
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To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection.,The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020.,Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected.,Patients with COPD were selected and compared to patients without COPD.,Factors associated with a poor prognosis were analyzed.,Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD.,Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male.,They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001).,The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001).,Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients.,Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037).,Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis.,COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients.
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Currently there is limited knowledge on medical comorbidities and COVID-19; we conducted a systematic review and meta-analysis to evaluate the impact of various morbidities on serious events in COVID 19.,PubMed, Cochrane Central Register of Clinical Trials were searched on April 28, 2020, to extract published articles that reported the outcomes of COVID-19 patients.,The search terms were “coronavirus” and “clinical characteristics”.,ICU admission, mechanical ventilation, ARDS, Pneumonia, death was considered serious events.,The comorbidities assessed in the study were Hypertension (HTN), Diabetes mellitus (DM), Cardiovascular diseases (CVD), Chronic obstructive pulmonary disease (COPD) and Chronic Kidney disease (CKD).,Subsequently, comparisons between comorbidity patient group and the non-comorbidity patient groups, in terms of serious events were made using the pooled estimates of odd’s ratio (OR),We identified 688 published results and 16 studies with 3994 patients were included in the systematic review.,Serious events were seen in 526(13.16%) patients.,Presence of hypertension with OR 2.95, diabetes mellitus with OR 3.07, Cardio vascular disease with OR 4.58, COPD with OR 6.66 and Chronic kidney disease with OR 5.32 had significant association in patients with COVID 19 on having serious events.,Presence of diabetes mellitus (OR 2.78)) had a significant impact on death in COVID 19 patients with a p-value 0.004.,Presence of medical comorbidities in COVID-19 leads to higher risk of developing serious events i.e.,ICU admission, mechanical intubation and mortality.,The presence of Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.,•Medical comorbidities in COVID-19 leads to higher morbidity and higher mortality rate.,•Patient with Comorbidities are likely to have high risk of severe events.,•Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.,Medical comorbidities in COVID-19 leads to higher morbidity and higher mortality rate.,Patient with Comorbidities are likely to have high risk of severe events.,Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.
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Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what “physical activity” means to COPD patients and how their perspective is best measured is poorly understood.,We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments).,116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III-IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised.,Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity.,The themes were similar irrespective of country, demographic or disease characteristics.,Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period.,For the first time, our approach provides comprehensive insight on physical activity from the COPD patients’ perspective.,The PROactive PRO instruments’ content validity represents the pivotal basis for empirically based item reduction and validation.,Conceptual framework as basis of PROactive PRO instruments to assess physical activity from COPD patient perspectivehttp://ow.ly/ytJoS
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The 65-item Functional Performance Inventory (FPI), developed to quantify functional performance in patients with chronic obstructive pulmonary disease (COPD), has been shown to be reliable and valid.,The purpose of this study was to create a shorter version of the FPI while preserving the integrity and psychometric properties of the original.,Secondary analyses were performed on qualitative and quantitative data used to develop and validate the FPI long form.,Seventeen men and women with COPD participated in the qualitative work, while 154 took part in the mail survey; 54 completed 2-week reproducibility assessment, and 40 relatives contributed validation data.,Following a systematic process of item reduction, performance properties of the 32-item short form (FPI-SF) were examined.,The FPI-SF was internally consistent (total scale α = 0.93; subscales: 0.76-0.89) and reproducible (r = 0.88; subscales: 0.69-0.86).,Validity was maintained, with significant (P < 0.001) correlations between the FPI-SF and the Functional Status Questionnaire (activities of daily living, r = 0.71; instrumental activities of daily living, r = 0.73), Duke Activity Status Index (r = 0.65), Bronchitis-Emphysema Symptom Checklist (r = −0.61), Basic Need Satisfaction Inventory (r = 0.61) and Cantril’s Ladder of Life Satisfaction (r = 0.63), and Katz Adjustment Scale for Relatives (socially expected activities, r = 0.51; free-time activities, r = −0.49, P < 0.01).,The FPI-SF differentiated patients with an FEVl% predicted greater than and less than 50% (t = 4.26, P < 0.001), and those with severe and moderate levels of perceived severity and activity limitation (t = 9.91, P < 0.001).,Results suggest the FPI-SF is a viable alternative to the FPI for situations in which a shorter instrument is desired.,Further assessment of the instrument’s performance properties in new samples of patients with COPD is warranted.
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