a
stringlengths 138
8.15k
| b
stringlengths 138
8.15k
| label
int64 1
1
|
|---|---|---|
COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling.
|
Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in those with chronic obstructive pulmonary disease (COPD).,Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD.,To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples from healthy nonsmokers, healthy smokers, and COPD patients.,BOEC from smokers and COPD patients showed increased DNA double-strand breaks and senescence compared to nonsmokers.,Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence.,Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence.,Treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or an ATM inhibitor (KU-55933) also rescued the senescent phenotype.,Using an in vivo mouse model of angiogenesis, we demonstrated that senescent BOEC from COPD patients are dysfunctional, displaying impaired angiogenic ability and increased apoptosis compared to cells from healthy nonsmokers.,Therefore, this study identifies epigenetic regulation of DNA damage and senescence as pathogenetic mechanisms linked to endothelial progenitors' dysfunction in smokers and COPD patients.,These defects may contribute to vascular disease and cardiovascular events in smokers and could therefore constitute therapeutic targets for intervention.
| 1 |
Valve implantation has evolved as a therapy for patients with advanced emphysema.,Although it is a minimally invasive treatment, it is associated with complications, the most common being pneumothorax.,Pneumothorax occurs due to the rapid target lobe volume reduction and may be a predictor of clinical benefit despite this complication.,The objective of this study was to conduct an exploratory data analysis of patients who developed a pneumothorax following endoscopic valve therapy for emphysema.,This study performed a retrospective evaluation of pneumothorax management and the impact of pneumothorax on clinical outcomes in 70 patients following valve therapy in 381 consecutive patients.,Pneumothorax rate following valve therapy was 18%.,Pneumothorax management consisted of chest tube insertion, valve removal, and surgical intervention in 87% (61/70), 44% (31/70), and 19% (13/70) of the patients, respectively.,Despite pneumothorax, patients experienced modest but significant improvements in lung function parameters (forced expiratory volume in 1 second: 55±148 mL, residual volume: −390±964 mL, total lung capacity: −348±876; all P<0.05).,Persistent lobar atelectasis 3 months after recovering from pneumothorax, which was associated with relevant clinical improvement, was observed in only 21% (15/70) of the patients.,Pneumothorax is a frequent severe complication following valve therapy that requires further intervention.,Nevertheless, the pneumothorax does not impair the clinical status in the majority of patients.,Patients with lobar atelectasis benefit after recovering from pneumothorax in terms of lung function parameters.
|
In patients with severe emphysema, bronchoscopic lung volume reduction using one-way valves is a promising therapeutic option to improve lung function and quality of life.,The goal of this treatment is to achieve a complete lobar atelectasis.,In a significant proportion of patients, this atelectasis cannot be achieved due to interlobar collateral ventilation.,This collateral ventilation is generated through incomplete lobar fissures.,Therefore, only patients with complete fissures and no collateral ventilation can be selected for endobronchial therapy with one-way valves.,Incomplete fissures are very common and exhibit a great variation in anatomy.,The reported prevalence is 17%-85% for the right major fissure, 19%-74% for the left major fissure, and 20%-90% for the minor fissure.,There are several methods of measuring or predicting the presence of collateral ventilation, with computed tomography (CT)-fissure analysis and the Chartis measurement being the most important.,CT-fissure analysis is an indirect method to measure the completeness of fissures as a surrogate for collateral ventilation.,The Chartis system is an endobronchial method to directly measure the presence of collateral ventilation.,Both methods have unique value, and the combination of both can accurately predict the treatment response to the bronchoscopic placement of endobronchial valves.,This review provides an in-depth view of lung fissure and collateral ventilation to help understand its importance in selecting the appropriate patients for new emphysema treatments and thus avoid useless treatment in unsuitable patients.
| 1 |
Growing evidence suggests that endothelial injury is involved in the pathophysiology of chronic obstructive pulmonary disease (COPD).,Circulating endothelial microparticles (EMPs) increase in patients with COPD because of the presence of endothelial injury.,We examined the relationship between EMP number and changes in forced expiratory volume in 1 s (FEV1) in patients with COPD.,Prospective study.,One hospital in Japan.,A total 48 outpatients with stable COPD coming to the hospital from September 2010 to September 2011.,Blood samples were collected and vascular endothelial (VE)-cadherin EMPs (CD144+ EMPs), E-selectin EMPs (CD62E+ EMPs) and platelet endothelial cell adhesion molecule EMPs (CD31+/CD41− EMPs) were measured using fluorescence-activated cell sorting.,Annual FEV1 changes were evaluated using FEV1 data acquired a year before and a year after sample collection.,The number of E-selectin and VE-cadherin EMPs showed significant negative correlations with annual FEV1 changes (rs=−0.65, p<0.001, rs=−0.43, p=0.003, respectively).,Leucocyte counts tended to be correlated with annual FEV1 changes, but this correlation was not significant (rs=−0.28, p=0.057).,There were significant differences in annual FEV1 changes between with and without history of frequent exacerbation (p=0.006), and among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages (p=0.009).,Multiple linear regression analysis revealed E-selectin EMP to be the only significant parameter associated with annual FEV1 changes, independent of VE-cadherin EMP, GOLD stages, leucocyte counts, and history of frequent exacerbation.,Receiver operating characteristic curves showed the optimum E-selectin EMP cut-off level for prediction of rapid FEV1 decline (>66 mL/year) to be 153.0/µL (areas under curve 0.78 (95% CI 0.60 to 0.89); sensitivity, 67%; specificity, 81%).,The high E-selectin EMP levels in stable patients with COPD are predictive of rapid FEV1 decline.,UMIN000005168.
|
In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of disease.,In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area.,Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis.,Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes.,Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators.,Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling.,The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD.,We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.
| 1 |
The aim of this study was to describe the impact of chronic obstructive pulmonary disease (COPD) on health status in the Burden of Obstructive Lung Disease (BOLD) populations.,We conducted a cross-sectional, general population-based survey in 11 985 subjects from 17 countries.,We measured spirometric lung function and assessed health status using the Short Form 12 questionnaire.,The physical and mental health component scores were calculated.,Subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity <0.70, n = 2269) had lower physical component scores (44±10 versus 48±10 units, p<0.0001) and mental health component scores (51±10 versus 52±10 units, p = 0.005) than subjects without COPD.,The effect of reported heart disease, hypertension and diabetes on physical health component scores (-3 to -4 units) was considerably less than the effect of COPD Global Initiative for Chronic Obstructive Lung Disease grade 3 (-8 units) or 4 (-11 units).,Dyspnoea was the most important determinant of a low physical and mental health component scores.,In addition, lower forced expiratory volume in 1 s, chronic cough, chronic phlegm and the presence of comorbidities were all associated with a lower physical health component score.,COPD is associated with poorer health status but the effect is stronger on the physical than the mental aspects of health status.,Severe COPD has a greater negative impact on health status than self-reported cardiovascular disease and diabetes.,COPD is related to worse health status: impairment is greater than in self-reported cardiovascular diseases or diabeteshttp://ow.ly/p1cIx
|
Chronic obstructive pulmonary disease (COPD) is an epidemic in many parts of the world.,Most patients with COPD demonstrate mild disease.,The cornerstone of management of mild disease is smoking cessation, which is the only proven intervention to relieve symptoms, modify its natural history and reduce mortality.,For asymptomatic patients, it is the only required therapy.,Short-acting bronchodilators can be added on an as needed basis for those with intermittent symptoms and regularly for those with persistent symptoms.,Long-acting bronchodilators can be substituted for those who remain symptomatic despite regular use of short-acting bronchodilators.,Inhaled corticosteroids do not modify the natural history of COPD and as such cannot be recommended as standalone therapy for mild COPD.,However, for patients with refractory and intractable symptoms, they may be used in combination with long-acting beta-2 agonists.,Influenza and pneumococcal vaccination and pulmonary rehabilitation are other therapies that may be considered for select patients with mild disease.,In this paper, we summarize the current standard of care for patients with mild COPD.
| 1 |
Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven.
|
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.
| 1 |
The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms.,Determining systemic mediators may help clarify the nature of inflammation in patients with ACO.,We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-α), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO.,This is a cross-sectional study of patients aged ≥40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity <0.70 recruited from outpatient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO.,ACO was defined by a history of smoking >10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD.,Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis.,In total, 109 ACO, 89 COPD, and 94 asthma patients were included.,Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p=0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p<0.001).,Their values in ACO were intermediate between those in asthma and in COPD.,Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD.,IL-13 was the most connected node in the network, with different weights among the three conditions.,Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern.,IL-13 could be central to the regulation of inflammation in these conditions.
|
Prior work suggests that asthma-COPD overlap syndrome (ACOS) has a greater health burden than asthma alone or COPD alone.,In the current study, we have further evaluated the health burden of ACOS in a nationally representative sample of the US population, focusing on patient-reported outcomes and health care utilization and on comparisons with asthma alone and COPD alone.,Patient-reported outcomes are especially meaningful, as these include functional activities that are highly valued by patients and are the basis for patient-centered care.,Using data from the Medical Expenditure Panel Survey (MEPS), we evaluated patient-reported outcomes and health care utilization among participants who were aged 40-85 years and had self-reported, physician-diagnosed asthma or COPD.,MEPS administered five rounds of interviews, at baseline and approximately every 6 months over 2.5 years.,Patient-reported outcomes included activities of daily living (ADLs), mobility, social/recreational activities, disability days in bed, and health status (Short Form 12, Version 2).,Health care utilization included outpatient and emergency department (ED) visits, and hospitalization.,Of 3,486 participants with asthma or COPD, 1,585 (45.4%) had asthma alone, 1,294 (37.1%) had COPD alone, and 607 (17.4%) had ACOS.,Relative to asthma alone, ACOS was significantly associated with higher odds of prevalent disability in ADLs and limitations in mobility and social/recreational activities (adjusted odds ratios [adjORs]: 1.91-3.98), as well as with higher odds of incident limitations in mobility and social/recreational activities, disability days in bed, and respiratory-based outpatient and ED visits, and hospitalization (adjORs: 1.86-2.35).,In addition, ACOS had significantly worse physical and mental health scores than asthma alone (P-values <0.0001).,Relative to COPD alone, ACOS was significantly associated with higher odds of prevalent limitations in mobility and social/recreational activities (adjORs: 1.68-2.06), as well as with higher odds of incident disability days in bed and respiratory-based outpatient and ED visits (adjORs: 1.48-1.74).,In addition, ACOS had a significantly worse physical health score, but similar mental health score, as compared with COPD alone (P-values 0.0025 and 0.1578, respectively).,In the US, ACOS is associated with a greater health burden, including patient-reported outcomes and health care utilization, relative to asthma alone and COPD alone.
| 1 |
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.
|
Sleep quality is often poor in patients with chronic obstructive pulmonary disease (COPD).,A cross-sectional European survey investigated the prevalence of night-time symptoms in COPD to evaluate the level of disconnect between physician and patient perceptions of the presence of night-time symptoms, and to compare the characteristics of patients with and without night-time symptoms.,A total of 251 primary care physicians and 251 respiratory specialists completed record forms on 2,807 patients with COPD.,The forms captured information on patient demographics, lung function, COPD severity, and symptoms.,Patients completed questionnaires on the time of day when their COPD symptoms bothered them, and the impact of COPD on their ability to get up in the morning and on sleep.,Data were compared between groups (those with and without night-time symptoms) using t-tests or Wilcoxon signed rank tests.,The kappa statistic was used to assess the level of disconnect between physician and patient perceptions of the impact of night-time symptoms.,Most patients (78%) reported night-time disturbance.,Patients with night-time symptoms experienced more daytime breathlessness (mean modified Medical Research Council dyspnea scale score 2.4 versus 1.1) and exacerbations in the previous 12 months (mean 1.7 versus 0.4), and received more maintenance therapy (mean of 2.8 versus 2.3 products) than those without.,Concordance between the frequency of physician-reported (67.9% of patients) and patient-reported (68.5% of patients) night-time symptoms was good.,Physicians significantly underestimated the impact of COPD on the patient’s ability to get up in the morning and on sleep (fair-moderate agreement).,Physician-reported night-time symptoms were present for 41.2% of patients who could be categorized by Global initiative for chronic Obstructive Lung Disease (GOLD) group (n=937), increasing from 20.9% of those in the low-risk group to 77.4% of those in the high-riskgroup.,Patients with COPD experience night-time symptoms regardless of GOLD group, that impact on their ability to get up in the morning and on their sleep quality.
| 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the world.,The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking.,Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease.,The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses.,In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD.,The complexity of COPD will necessitate a multi-target therapeutic approach.,It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies.
|
Chronic Obstructive Pulmonary Disease (COPD) is currently the fifth leading cause of death worldwide.,Neutrophilic inflammation is prominent, worsened during infective exacerbations and is refractory to glucocorticosteroids (GCs).,Deregulated neutrophilic inflammation can cause excessive matrix degradation through proteinase release.,Gelatinase and azurophilic granules within neutrophils are a major source of matrix metalloproteinase (MMP)-9 and neutrophil elastase (NE), respectively, which are elevated in COPD.,Secreted MMP-9 and NE activity in BALF were stratified according to GOLD severity stages.,The regulation of secreted NE and MMP-9 in isolated blood neutrophils was investigated using a pharmacological approach.,In vivo release of MMP-9 and NE in mice exposed to cigarette smoke (CS) and/or the TLR agonist lipopolysaccharide (LPS) in the presence of dexamethasone (Dex) was investigated.,Neutrophil activation as assessed by NE release was increased in severe COPD (36-fold, GOLD II vs.,IV).,MMP-9 levels (8-fold) and activity (21-fold) were also elevated in severe COPD, and this activity was strongly associated with BALF neutrophils (r = 0.92, p<0.001), but not macrophages (r = 0.48, p = 0.13).,In vitro, release of NE and MMP-9 from fMLP stimulated blood neutrophils was insensitive to Dex and attenuated by the PI3K inhibitor, wortmannin.,In vivo, GC resistant neutrophil activation (NE release) was only seen in mice exposed to CS and LPS.,In addition, GC refractory MMP-9 expression was only associated with neutrophil activation.,As neutrophils become activated with increasing COPD severity, they become an important source of NE and MMP-9 activity, which secrete proteinases independently of TIMPs.,Furthermore, as NE and MMP-9 release was resistant to GC, targeting of the PI3K pathway may offer an alternative pathway to combating this proteinase imbalance in severe COPD.
| 1 |
As of 11 July, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has infected over 12.7 million people around the world and caused more than 560,000 deaths [1].,Given the devastating impact that COVID-19 can have on the lung, it is natural to fear for patients with underlying COPD.,Estimating their excess risk for contracting COVID-19 and, in particular, its more severe respiratory manifestations has been a challenging exercise in this pandemic for various reasons.,First, the reporting on cases has concentrated on hospitalised and intensive care unit (ICU) patients, rather than on mild, outpatient cases.,This is in part also due to the variability in testing strategies across the world, where some nations with stricter testing requirements and scarce testing resources have focused on testing only those requiring hospitalisation.,COPD patients have increased risk of severe pneumonia and poor outcomes when they develop COVID-19.,This may be related to poor underlying lung reserves or increased expression of ACE-2 receptor in small airways.https://bit.ly/37dSB8l
|
Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation.,COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens.,Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections.,Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization.,Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD.,The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed.,As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus.,Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy.,Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality.
| 1 |
In patients with COPD, severe physical inactivity (SPI, which is defined as total daily energy expenditure/resting energy expenditure; physical activity level [PAL] ratio, <1.4) is associated with increased morbidity and mortality.,Pulmonary rehabilitation (PR) increases physical capacity in COPD, but the impact on SPI is unknown.,In this study, we aimed at elucidating the prevalence of SPI in COPD patients attending standard PR, the impact of PR on SPI prevalence, and the relationship between SPI and time spent in moderate physical activity thus whether American College of Sports Medicine (ACSM) recommendations are clinically useful in excluding SPI in COPD.,This is a prospective non-interventional pilot study on patients with COPD completing PR, consenting to wear an accelerometer (Sensewear© Armband) for a week before and after completing PR to assess changes in energy expenditure, time spent in physical activity, and number of daily steps.,Low level of daily physical activity was not an inclusion criterion.,In total, 57 patients completed the study and 31 (54%) had SPI at baseline.,In patients with SPI, baseline median FEV1 was 48 (range, 28-86) % of predicted and GOLD B, n=11 (35%)/GOLD D, n=20 (65%).,Surprisingly, 31 of SPI patients (97%) spent ≥150 minutes/week in moderate physical activity.,After rehabilitation, 24 (78%) did not change activity level and were persistently SPI.,We observed no differences at baseline between patient responding (n=7) vs not responding (n=24) to PR.,Responders increased number of daily steps and time spent in lighter but not moderate physical activity during rehabilitation.,In this pilot study, SPI was prevalent, and PR had limited impact.,Contraintui-tively, most patients with SPI complied with general recommendations of weekly hours spent in moderate physical activity.,Our study highlights that increasing time spent in light activity rather than improving time spent in moderate activity is important in COPD patients with chronic dyspnea.
|
Cardiopulmonary exercise test (CPET) has been gaining importance as a method of functional assessment in Brazil and worldwide.,In its most frequent applications, CPET consists in applying a gradually increasing intensity exercise until exhaustion or until the appearance of limiting symptoms and/or signs.,The following parameters are measured: ventilation; oxygen consumption (VO2); carbon dioxide production (VCO2); and the other variables of conventional exercise testing.,In addition, in specific situations, pulse oximetry and flow-volume loops during and after exertion are measured.,The CPET provides joint data analysis that allows complete assessment of the cardiovascular, respiratory, muscular and metabolic systems during exertion, being considered gold standard for cardiorespiratory functional assessment.1-6,The CPET allows defining mechanisms related to low functional capacity that can cause symptoms, such as dyspnea, and correlate them with changes in the cardiovascular, pulmonary and skeletal muscle systems.,Furthermore, it can be used to provide the prognostic assessment of patients with heart or lung diseases, and in the preoperative period, in addition to aiding in a more careful exercise prescription to healthy subjects, athletes and patients with heart or lung diseases.,Similarly to CPET clinical use, its research also increases, with the publication of several scientific contributions from Brazilian researchers in high-impact journals.,Therefore, this study aimed at providing a comprehensive review on the applicability of CPET to different clinical situations, in addition to serving as a practical guide for the interpretation of that test.
| 1 |
Chronic bronchitis (CB), emphysematous (EM) and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) phenotypes in COPD are well recognized.,This study aimed to investigate distinguishing characteristics of these phenotypes in COPD patients with frequent exacerbations (FE).,A retrospective study was carried out.,COPD patients with acute exacerbations were consecutively reviewed from November 2015 to October 2016.,Patients were divided into FE and infrequent exacerbations (iFE) subgroups.,A total of 142 eligible COPD subjects were reviewed.,In the CB phenotype subgroup, age, body mass index, forced expiratory volume in 1 second (FEV1) % predicted, COPD assessment test (CAT), modified Medical Research Council breathlessness measurement (mMRC) dyspnea scale, emphysema scores and arterial carbon dioxide pressure (PaCO2) were significantly different in subjects with FE when compared to those in subjects with iFE of CB.,In the EM phenotype subgroup, age, CAT, mMRC scores and history of COPD were different in subjects with FE when compared to those in CB subjects with iFE.,Multivariate analysis indicated that FEV1% predicted (odds ratio [OR] =0.90, P=0.04) and PaCO2 (OR =1.22, P=0.02) were independent risk factors for FE in COPD with CB phenotype, and CAT (OR =2.601, P=0.001) was the independent risk factor for FE in COPD with EM phenotype.,No significant differences in characteristics were observed in ACOS phenotype subgroups with FE or iFE.,In CB or EM phenotypes, COPD patients with FE present several differential clinical characteristics compared to patients with iFE, while the characteristics of ACOS phenotype in patients with FE need more investigation.
|
The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764
| 1 |
Evidence on the burden of chronic obstructive pulmonary disease (COPD) morbidity attributable to the interaction between ambient air pollution and temperature has been limited.,This study aimed to examine the modification effect of temperature on the association of ambient air pollutants (including particulate matter (PM) with aerodynamic diameter <10 μm (PM10) and <2.5 μm (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3)) with risk of hospital admissions (HAs) for COPD, as well as the associated morbidity burden in urban areas of Chengdu, China, from 2015 to 2016.,Based on the generalized additive model (GAM) with quasi-Poisson link, bivariate response surface model and stratification parametric model were developed to investigate the potential interactions between ambient air pollution and temperature on COPD HAs.,We found consistent interactions between ambient air pollutants (PM2.5, PM10 and SO2) and low temperature on COPD HAs, demonstrated by the stronger associations between ambient air pollutants and COPD HAs at low temperatures than at moderate temperatures.,Subgroup analyses showed that the elderly (≥80 years) and males were more vulnerable to this interaction.,The joint effect of PM and low temperature had the greatest impact on COPD morbidity burden.,Using WHO air quality guidelines as reference concentration, about 17.30% (95% CI: 12.39%, 22.19%) and 14.72% (95% CI: 10.38%, 19.06%) of COPD HAs were attributable to PM2.5 and PM10 exposures on low temperature days, respectively.,Our findings suggested that low temperature significantly enhanced the effects of PM and SO2 on COPD HAs in urban Chengdu, resulting in increased morbidity burden.,This evidence has important implications for developing interventions to reduce the risk effect of COPD morbidity.
|
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.
| 1 |
Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD).,We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.,We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.,We developed a custom array for UK Biobank to provide optimum genome-wide coverage of common and low-frequency variants, dense coverage of genomic regions already implicated in lung health and disease, and to assay rare coding variants relevant to the UK population.,We investigated whether there were shared genetic causes between different phenotypes defined by extremes of FEV1.,We also looked for novel variants associated with extremes of FEV1 and smoking behaviour and assessed regions of the genome that had already shown evidence for a role in lung health and disease.,We set genome-wide significance at p<5 × 10−8.,UK Biobank participants were recruited from March 15, 2006, to July 7, 2010.,Sample selection for the UK BiLEVE study started on Nov 22, 2012, and was completed on Dec 20, 2012.,We selected 50 008 unique samples: 10 002 individuals with low FEV1, 10 000 with average FEV1, and 5002 with high FEV1 from each of the heavy smoker and never smoker groups.,We noted a substantial sharing of genetic causes of low FEV1 between heavy smokers and never smokers (p=2·29 × 10−16) and between individuals with and without doctor-diagnosed asthma (p=6·06 × 10−11).,We discovered six novel genome-wide significant signals of association with extremes of FEV1, including signals at four novel loci (KANSL1, TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported loci (NPNT and HLA-DQB1/HLA-DQA2).,These variants also showed association with COPD, including in individuals with no history of smoking.,The number of copies of a 150 kb region containing the 5′ end of KANSL1, a gene that is important for epigenetic gene regulation, was associated with extremes of FEV1.,We also discovered five new genome-wide significant signals for smoking behaviour, including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2 (between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in brain tissue.,By sampling from the extremes of the lung function distribution in UK Biobank, we identified novel genetic causes of lung function and smoking behaviour.,These results provide new insight into the specific mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show substantial shared genetic architecture underlying airflow obstruction across individuals, irrespective of smoking behaviour and other airway disease.,Medical Research Council.
|
Smoking prevalence is frequently estimated on the basis of self-reported smoking status.,That can lead to an underestimation of smoking rates.,The aim of this study was to evaluate the difference between self-reported smoking status and that determined through the use of objective measures of smoking at a pulmonary outpatient clinic.,This was a cross-sectional study involving 144 individuals: 51 asthma patients, 53 COPD patients, 20 current smokers, and 20 never-smokers.,Smoking status was determined on the basis of self-reports obtained in interviews, as well as through tests of exhaled carbon monoxide (eCO) and urinary cotinine.,All of the asthma patients and COPD patients declared they were not current smokers.,In the COPD and asthma patients, the median urinary cotinine concentration was 167 ng/mL (range, 2-5,348 ng/mL) and 47 ng/mL (range, 5-2,735 ng/mL), respectively (p < 0.0001), whereas the median eCO level was 8 ppm (range, 0-31 ppm) and 5 ppm (range, 2-45 ppm), respectively (p < 0.05).,In 40 (38%) of the patients with asthma or COPD (n = 104), there was disagreement between the self-reported smoking status and that determined on the basis of the urinary cotinine concentration, a concentration > 200 ng/mL being considered indicative of current smoking.,In 48 (46%) of those 104 patients, the self-reported non-smoking status was refuted by an eCO level > 6 ppm, which is also considered indicative of current smoking.,In 30 (29%) of the patients with asthma or COPD, the urinary cotinine concentration and the eCO level both belied the patient claims of not being current smokers.,Our findings suggest that high proportions of smoking pulmonary patients with lung disease falsely declare themselves to be nonsmokers.,The accurate classification of smoking status is pivotal to the treatment of lung diseases.,Objective measures of smoking could be helpful in improving clinical management and counseling.
| 1 |
The relationship between serum biomarkers and clinical expressions of COPD is limited.,We planned to further describe this association using markers of inflammation and injury and repair.,We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years.,Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured.,We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot].,Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs.,4).,Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).,In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.
|
Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins.,We assessed the long term repeatability of Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) over one year and examined the relationships between these systemic markers in COPD.,Fifty-eight stable COPD patients completed a baseline and one-year visit.,Serum IL-6, plasma CRP, and plasma TNF-α were measured.,Repeatability was expressed by intraclass correlation coefficient (Ri) and the Bland-Altman method.,Pearson correlations were used to determine the relationships between the systemic markers at both visits.,There was moderate repeatability with a very high degree of statistical significance (p ≤ 0.001) between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-α).,CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively).,There were no other significant associations between the systemic markers at either of the visits.,Systemic inflammatory biomarkers IL-6, CRP, and TNF-α were moderately repeatable over a twelve month period in COPD patients.,We have also shown that a robust and repeatable association between IL-6 and CRP exists.
| 1 |
Cognitive dysfunction is a common impairment associated with COPD.,However, little is known about 1) its prevalence among those subjects referred for pulmonary rehabilitation (PR), 2) how it may affect the benefit of PR, 3) whether PR improves cognitive function and 4) whether cognitive dysfunction affects the usability of telehealth technology usually used to deliver in-home PR.,Fifty-six subjects with stable COPD (54% females, mean age 62 years (SD 9) and median FEV1 0.9 L (IQR 0.7 to 1.1)) participated in this multicenter observational study and performed 24 sessions of PR.,The Montreal Cognitive Assessment tool (MoCA) was used to assess the occurrence of mild cognitive dysfunction (using a screening cutoff <26) at baseline, completion of PR and 3 months of follow-up.,Mild cognitive dysfunction was found in 41 subjects (73% [95% CI: 60 to 83%]).,The MoCA score significantly improved following PR for those people with baseline mild cognitive dysfunction (p<0.01).,There was no significant difference in clinical outcomes between those people with or without mild cognitive dysfunction following PR nor in the proportion of subjects who were autonomous in using the telemonitoring system (83% compared with 71%, p=0.60).,Mild cognitive dysfunction is highly prevalent among those people with COPD referred for PR but does not affect the benefits of PR nor the usability of a telemonitoring system.,PR may improve short- and mid-term cognitive function for those people who experience mild cognitive dysfunction at the time they are referred to PR.
|
This retrospective, observational study of a routine clinical practice reports the feasibility and efficiency of home-based pulmonary rehabilitation (PR), including transcutaneous neuromuscular electrical stimulation (NMES) or usual endurance physical exercise (UEPE), on exercise tolerance, anxiety/depression, and health-related quality of life (HRQoL) in patients with COPD.,Seventy-one patients with COPD participated in home-based PR with NMES (Group NMES [GNMES]), while 117 patients participated in home-based PR with the UEPEs (Group UEPE [GUEPE]).,NMES was applied for 30 minutes twice a day, every day.,The endurance exercises in GUEPE began with a minimum 10-minute session at least 5 days a week, with the goal being 30-45 minutes per session.,Three upper and lower limb muscle strengthening exercises lasting 10-15 minutes were also proposed to both the groups for daily practice.,Moreover, PR in both the groups included a weekly 90-minute session based on an educational needs assessment.,The sessions comprised endurance physical exercise for GUEPE, NMES for GNMES, resumption of physical daily living activities, therapeutic patient education, and psychosocial support to facilitate health behavior changes.,Before and after PR, functional mobility and physical exercise capacity, anxiety, depression, and HRQoL were evaluated at home.,The study revealed that NMES significantly improved functional mobility (−18.8% in GNMES and −20.6% in GUEPE), exercise capacity (+20.8% in GNMES and +21.8% in GUEPE), depression (−15.8% in GNMES and −30.1% in GUEPE), and overall HRQoL (−7.0% in GNMES and −18.5% in GUEPE) in the patients with COPD, regardless of the group (GNMES or GUEPE) or severity of airflow obstruction.,Moreover, no significant difference was observed between the groups with respect to these data (P>0.05).,Home-based PR including self-monitored NMES seems feasible and effective for severely disabled COPD patients with severe exercise intolerance.
| 1 |
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.
|
Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage.
| 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users.
|
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.
| 1 |
Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.,To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.,We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.,We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes.,The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies.,Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated.,We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis.,Subtypes of COPD have distinct bacterial compositions and stabilities over time.,Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future.,This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient.,Results, NCT01360398.
|
There is a need for agents that suppress inflammation and progression of chronic obstructive pulmonary disease. p38 mitogen-activated protein kinase (p38 MAPK) has been associated with this disorder, and several inhibitors of this cascade are in clinical trials for its treatment, but their efficacy and utility are unknown.,This study evaluated the relationship between p38 MAPK activation and susceptibility to cigarette smoke (CS)-induced emphysema, and whether its inhibition ameliorated the lung inflammation and injury in murine models of cigarette smoke exposure.,In acute and chronic CS exposure, the activation and expression of p38 MAPK in the lungs, as well as lung inflammation and injury (proteinase production, apoptosis, and oxidative DNA damage), were compared between two mouse strains: C57BL/6 (emphysema-susceptible) and NZW (emphysema-resistant).,The selective p38 MAPK inhibitor SB203580 (45 mg/kg) was administrated intra-peritoneally to C57BL/6 mice, to examine whether it ameliorated cigarette smoke-induced lung inflammation and injury.,Acute CS-induced lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2), proteinase expression (MMP-12 mRNA), apoptosis, and oxidative DNA damage were significantly lower in NZW than C57BL/6 mice. p38 MAPK was significantly activated and up-regulated by both acute and chronic CS exposure in C57BL/6 but not NZW mice. mRNA expression of p38 MAPK was also upregulated in C57BL/6 by chronic CS exposure and tended to be constitutively suppressed in NZW mice.,SB203580 significantly attenuated lung inflammation (neutrophil infiltration, mRNA expressions of TNF-α and MIP-2, protein levels of KC, MIP-1α, IL-1β, and IL-6), proteinase expression (MMP-12 mRNA), oxidative DNA damage, and apoptosis caused by acute CS exposure.,Cigarette smoke activated p38 MAPK only in mice that were susceptible to cigarette smoke-induced emphysema.,Its selective inhibition ameliorated lung inflammation and injury in a murine model of cigarette smoke exposure. p38 MAPK pathways are a possible molecular target for the treatment of chronic obstructive pulmonary disease.
| 1 |
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.
|
Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD.,Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear.,A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE.,We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations.,Out of 77 patients, 61 patients (79.2%) had at least one comorbidity.,During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission.,Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids.,In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30-12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60-55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01-1.19, P=0.036) were associated with frequent severe AEs.,In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04-0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs.,Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients.
| 1 |
Elderly patients with impaired vision, cognitive decline or motor/sensory disturbances of their fingers suffering from chronic-obstructive pulmonary disease (COPD) encounter difficulties in handling inhaler devices used as the cornerstones of treatment of pulmonary obstruction.,Many elderly patients make severe mistakes which impede adequate drug delivery to the bronchioles.,This multimodal training program was designed to reduce the number of handling mistakes of inhaler devices.,From October 1, 2016 to September 30, 2017, a prospective intervention study was conducted in 38 in-patients > 65 years (median age 79 years) with previously diagnosed COPD.,The effect of an 8-day intervention comprising daily counselling and video demonstration according to the recommendations of the German Airway League on the frequency of mistakes during handling of inhaler devices, the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC) and the perception of symptoms (COPD Assessment Test, CAT) were studied.,Measurements on days 1 and 8 were compared by Wilcoxon signed rank test.,The number of handling mistakes per patient decreased as a consequence of the intervention from 3.0 (0-7) to 0.5 (0-6) [median (minimum-maximum; p < 0.0001)].,The CAT Score decreased from 19.5 (14/24) to 14.5 (10.75/21) [median (25.,/75. percentile; p < 0.0001) indicating a substantial reduction of clinical symptoms.,Conversely, FEV1 and FVC only slightly increased (difference statistically not significant).,At study entry, the number of handling mistakes was inversely correlated with the Mini Mental Status Test (MMST) score (p = 0.01).,The reduction of the number of handling mistakes during the intervention was not correlated with the MMST.,In COPD, intensive training for 8 days improved the handling of inhalers and reduced clinical symptoms in geriatric patients.,Patients with cognitive abnormalities also benefitted from this intervention.,German Clinical Trials Registry DRKS00023196, date of registration September 29, 2020 (retrospectively registered).
|
Nonadherence to medication and incorrect use of inhalers represent significant barriers to optimal disease management of patients with chronic obstructive pulmonary disease (COPD).,Thus, health care professionals (HCPs) play a critical role in educating their patients on appropriate inhaler use and in ensuring medication adherence.,However, many patients do not receive appropriate inhaler training or have not had their inhaler technique checked.,The Real-life Experience and Accuracy of inhaLer use (REAL) survey was a computer-assisted, telephonic survey consisting of 23 questions gathering real-world information on correct inhaler use, inhalation technique, device attributes, adherence, dosing accuracy, training, correct device use, ease of use, and factors that influence patient adherence in commercially available inhalers delivering COPD maintenance therapy.,All results are based on patient-reported data.,The survey was conducted between January 4, 2016 and February 2, 2016.,A total of 764 patients using various inhalers (Breezhaler® =186; Ellipta® =191; Genuair® =194; Respimat® =201) with mild to very severe COPD, with a mean ± SD age 56±9.8 years, completed the survey.,Patient self-reported adherence was significantly lower in younger patients compared to older patients (p=0.020).,Eighty-three percent of patients indicated that a demonstration (in-person) was “very helpful” versus 58% for video.,Patient preferences for training methods were as follows: demonstration of inhaler use (83%), video (58%), instructions for use (51%), and leaflet (34%).,Twenty-nine percent of patients had not been checked to see if they were using their device correctly by a HCP within the last two years.,Patients who were checked were significantly more adherent than unchecked patients (p=0.020).,The majority of the patients using Breezhaler reported either being very confident or confident of having taken a full dose, which was higher than those using Genuair, Ellipta (α=0.05), and Respimat (α=0.05).,Treatment adherence in the last 30 days was highest with Breezhaler followed by Respimat, Ellipta, and Genuair.,The REAL survey identified attributes that influenced patient adherence and optimal inhaler use.,Predictive attributes that influence patient adherence which HCPs should be aware of include age and disease severity.,Modifiable attributes which the HCP can influence include correct inhaler use training, choice of training methods, checking patient inhaler technique at subsequent visits, and device selection.,Inhalers are integral in the effective management of patients with COPD; it is therefore important that patients use the inhaler correctly and have full confidence in the dosage.
| 1 |
The high incidence of chronic obstructive pulmonary disease (COPD), one of the most prevalent diseases worldwide, has attracted growing attention.,Cigarette smoking is considered a major contributory factor in the pathogenesis and progression of COPD due to the tremendous oxidative burden that it causes, which induces an oxidant/antioxidant imbalance.,Excessive oxidation induced by the excessive generation of mitochondrial reactive oxygen species disturbs the antioxidant systems and plays an important role in triggering and promoting chronic inflammation of airways.,Given that mitochondria is one of the main sites of reactive oxygen species production by the oxidative phosphorylation process, oxidative stress may affect mitochondrial function by changing its structure and morphology and by affecting a series of mitochondrial proteins.,In particular, PTEN-induced putative kinase 1/Parkin and p62 play critical roles in mitophagy.,During the process, the Akt ubiquitin E3 ligase is an important mediator associated with cigarette smoke exposure-induced pulmonary endothelial cell death and dysfunction.,Thus, understanding the underlying mechanisms of the signaling pathway may provide important information regarding the therapeutic treatment of COPD by application of alternative PTEN-induced putative kinase 1 targets or ubiquitin E3 ligase.
|
Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction.,COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma.,Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression.,Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology.,Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress.,Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients.,For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status.
| 1 |
Our aim was to assess the impact of comorbidities on existing COPD prognosis scores.,A total of 543 patients with COPD (FEV1 <80% and FEV1/FVC <70%) were included between January 2003 and January 2004.,Patients were stable for at least 6 weeks before inclusion and were followed for 5 years without any intervention by the research team.,Comorbidities and causes of death were established from medical reports or information from primary care medical records.,The GOLD system and the body mass index, obstruction, dyspnea and exercise (BODE) index were used for COPD classification.,Patients were also classified into four clusters depending on the respiratory disease and comorbidities.,Cluster analysis was performed by combining multiple correspondence analyses and automatic classification.,Receiver operating characteristic curves and the area under the curve (AUC) were calculated for each model, and the DeLong test was used to evaluate differences between AUCs.,Improvement in prediction ability was analyzed by the DeLong test, category-free net reclassification improvement and the integrated discrimination index.,Among the 543 patients enrolled, 521 (96%) were male, with a mean age of 68 years, mean body mass index 28.3 and mean FEV1% 55%.,A total of 167 patients died during the study follow-up.,Comorbidities were prevalent in our cohort, with a mean Charlson index of 2.4.,The most prevalent comorbidities were hypertension, diabetes mellitus and cardiovascular diseases.,On comparing the BODE index, GOLDABCD, GOLD2017 and cluster analysis for predicting mortality, cluster system was found to be superior compared with GOLD2017 (0.654 vs 0.722, P=0.006), without significant differences between other classification models.,When cardiovascular comorbidities and chronic renal failure were added to the existing scores, their prognostic capacity was statistically superior (P<0.001).,Comorbidities should be taken into account in COPD management scores due to their prevalence and impact on mortality.
|
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.
| 1 |
Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management.,We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St.,George Respiratory Questionnaire (SGRQ).,We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits.,Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits.,Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.,We enrolled 90 COPD patients.,Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively).,Patients with severe COPD reported worse health status compared to milder subgroups.,CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01).,Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01).,Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98).,The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ.,Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations.,More than half of patients preferred CCQ instead of CAT.,The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients.
|
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability in all its stages, and death in patients with moderate or severe obstruction.,At present, COPD is suboptimally managed; current health is often not measured properly and hardly taken into account in management plans, and the future risk for patients with regard to health status and quality of life is not being evaluated.,This review addresses the effect of COPD on the lives of patients and examines ways in which existing assessment tools meet physicians’ needs for a standardized, simple method to measure consistently the full impact of COPD on patients in routine clinical practice.,Current assessment of COPD severity tends to focus on airflow limitation, but this does not capture the full impact of the disease and is not well correlated with patient perception of symptoms and health-related quality of life.,Qualitative studies have demonstrated that patients usually consider COPD impact in terms of frequency and severity of symptoms, and physical and emotional wellbeing.,However, patients often have difficulty expressing their disease burden and physicians generally have insufficient time to collect this information.,Therefore, it is important that methods are implemented to help generate a more complete understanding of the impact of COPD.,This can be achieved most efficiently using a quick, reliable, and standardized measure of disease impact, such as a short questionnaire that can be applied in daily clinical practice.,Questionnaires are precision instruments that contribute sensitive and specific information, and can potentially help physicians provide optimal care for patients with COPD.,Two short, easy-to-use, specific measures, ie, the COPD Assessment Test and the Clinical COPD Questionnaire, enable physicians to assess patients’ health status accurately and improve disease management.,Such questionnaires provide important measurements that can assist primary care physicians to capture the impact of COPD on patients’ daily lives and wellbeing, and improve long-term COPD management.
| 1 |
Functional respiratory imaging (FRI) uses high-resolution computed tomography (HRCT) scans to assess changes in airway volume and resistance.,In this randomized, double-blind, 2-week, crossover, Phase IIIB study, patients with moderate-to-severe COPD received twice-daily glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler (GFF MDI, 18/9.6 μg) and placebo MDI, formulated using innovative co-suspension delivery technology.,Co-primary endpoints included the following: specific image-based airway volume (siVaw) and specific image-based airway resistance (siRaw) at Day 15, measured using FRI.,Secondary and other endpoints included the following: change from baseline in post-dose forced expiratory volume in 1 second (FEV1) and inspiratory capacity (IC; spirometry) and ratio to baseline in post-dose functional residual capacity (FRC) and residual volume (RV; body plethysmography).,Twenty patients (46-78 years of age) were randomized and treated; of whom 19 completed the study.,GFF MDI treatment increased siVaw by 75% and reduced siRaw by 71% vs placebo MDI (both P<0.0001).,Image-based airway volume (iVaw) and image-based airway resistance (iRaw), without adjusting for lobe volume, demonstrated corresponding findings to the co-primary endpoint, as lobe volumes did not change with either treatment.,Approximately 48% of the delivered dose of glycopyrronium and formoterol fumarate was estimated to be deposited in the lungs.,Compared with placebo, GFF MDI treatment improved post-dose FEV1 and IC (443 mL and 454 mL, respectively; both P<0.001) and reduced FRC and RV (13% and 22%, respectively; both P<0.0001).,There were no significant safety findings.,GFF MDI demonstrated significant, clinically meaningful benefits on FRI-based airway volume and resistance in patients with moderate-to-severe COPD.,Benefits were associated with improvements in FEV1, IC, and hyperinflation.,ClinicalTrials.gov: NCT02643082.
|
Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD).,However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment.,A systematic review was conducted to define ‘critical’ errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2).,Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total).,Search-2 identified 9 studies.,We observed 299 descriptions of critical error.,Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency.,A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden.,We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes.,Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.,The online version of this article (10.1186/s12931-017-0710-y) contains supplementary material, which is available to authorized users.
| 1 |
While a subgroup of patients with exacerbations of chronic obstructive pulmonary disease (COPD) clearly benefit from antibiotics, their identification remains challenging.,We hypothesised that selective assessment of the balance between the two dominant bacterial groups (Gammaproteobacteria (G) and Firmicutes (F)) in COPD sputum samples might reveal a subgroup with a bacterial community structure change at exacerbation that was restored to baseline on recovery and potentially reflects effective antibiotic treatment.,Phylogenetically specific 16S rRNA genes were determined by quantitative real time PCR to derive a G:F ratio in serial sputum samples from 66 extensively-phenotyped COPD exacerbation episodes.,Cluster analysis based on Euclidean distance measures, generated across the 4 visit times (stable and exacerbation day: 0,14 and 42) for the 66 exacerbation episodes, revealed three subgroups designated HG, HF, and GF reflecting predominance or equivalence of the two target bacterial groups.,While the other subgroups showed no change at exacerbation, the HG cluster (n = 20) was characterized by G:F ratios that increased significantly at exacerbation and returned to baseline on recovery (p<0.00001); ratios in the HG group also correlated positively with inflammatory markers and negatively with FEV1.,At exacerbation G:F showed a significant receiver-operator-characteristic curve to identify the HG subgroup (AUC 0.90, p<0.0001).,The G:F ratio at exacerbation can be determined on a timescale compatible with decisions regarding clinical management.,We propose that the G:F ratio has potential for use as a biomarker enabling selective use of antibiotics in COPD exacerbations and hence warrants further clinical evaluation.
|
There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users.
| 1 |
Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD).,A prespecified spirometry substudy compared the lung function efficacy between treatment groups.,TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD.,In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial.,The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 μg (n = 461), 2.5 μg (n = 464), or tiotropium HandiHaler® 18 μg (n = 445).,Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups (difference versus HandiHaler® [95 % CI]: −10 [−38, 18] mL for Respimat® 5 μg and, −37 [−65, −9] mL for Respimat® 2.5 μg); achieving noninferiority to tiotropium HandiHaler® 18 μg for tiotropium Respimat® 5 but not for 2.5 μg (prespecified analysis).,Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 μg, 2.5 μg, and HandiHaler® 18 μg groups.,The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-μg, 2.5-μg, and HandiHaler® 18-μg groups).,The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not.,The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 μg was noninferior to tiotropium HandiHaler® 18 μg for trough FEV1, but Respimat® 2.5 μg was not.,Tiotropium Respimat® 5 μg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 μg with comparable rates of FEV1 decline.,The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction.,NCT01126437.,The online version of this article (doi:10.1186/s12931-015-0269-4) contains supplementary material, which is available to authorized users.
|
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.
| 1 |
Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.,Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts.,The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.,Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.,Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence.,Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.
|
Guidelines recommend inhaled corticosteroids (ICS) for patients with severe chronic obstructive pulmonary disease (COPD).,Most COPD patients are managed in primary care and receive ICS long-term and irrespective of severity.,The effect of withdrawing ICS from COPD patients in primary care is unknown.,In a pragmatic randomised, double-blind, placebo-controlled trial in 31 practices, 260 COPD patients stopped their usual ICS (median duration of use 8 years) and were allocated to 500 mcg fluticasone propionate twice daily (n = 128), or placebo (n = 132).,Follow-up assessments took place at three monthly intervals for a year at the patients' practice.,Our primary outcome was COPD exacerbation frequency.,Secondary outcomes were time to first COPD exacerbation, reported symptoms, peak expiratory flow rate and reliever inhaler use, and lung function and health related quality of life.,In patients randomised to placebo, COPD exacerbation risk over one year was RR: 1.11 (CI: 0.91-1.36).,Patients taking placebo were more likely to return to their usual ICS following exacerbation, placebo: 61/128 (48%); fluticasone: 34/132 (26%), OR: 2.35 (CI: 1.38-4.05).,Exacerbation risk whilst taking randomised treatment was significantly raised in the placebo group 1.48 (CI: 1.17-1.86).,Patients taking placebo exacerbated earlier (median time to first exacerbation: placebo (days): 44 (CI: 29-59); fluticasone: 63 (CI: 53-74), log rank 3.81, P = 0.05) and reported increased wheeze.,In a post-hoc analysis, patients with mild COPD taking placebo had increased exacerbation risk RR: 1.94 (CI: 1.20-3.14).,Withdrawal of long-term ICS in COPD patients in primary care increases risk of exacerbation shortens time to exacerbation and causes symptom deterioration.,Patients with mild COPD may be at increased risk of exacerbation after withdrawal.,ClinicalTrials.gov NCT00440687
| 1 |
Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.,This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.,Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care).,Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire.,Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items.,Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening.,Of 77 subjects, 50 participated in Phase I and 27 in Phase II.,Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity).,PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001).,Revisions were made to the draft items on the basis of cognitive interviews.,Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD.
|
Forced expiratory volume in 1s/forced expiratory volume in 6 s ( FEV1/FEV6) assessment with a microspirometer may be useful in the diagnostic work up of subjects who are suspected of having COPD in primary care.,To determine the diagnostic accuracy of a negative pre-bronchodilator (BD) microspirometry test relative to a full diagnostic spirometry test in subjects in whom general practitioners (GPs) suspect airflow obstruction.,Cross-sectional study in which the order of microspirometry and diagnostic spirometry tests was randomised.,Study subjects were (ex-)smokers aged ⩾50 years referred for diagnostic spirometry to a primary care diagnostic centre by their GPs.,A pre-BD FEV1/FEV6 value <0.73 as measured with the PiKo-6 microspirometer was compared with a post-BD FEV1/FVC (forced vital capacity) <0.70 and FEV1/FVC<lower limit of normal (LLN) from diagnostic spirometry.,One hundred and four subjects were analysed (59.6% males, 42.3% current smokers).,Negative predictive values from microspirometry for airflow obstruction based on the fixed and LLN cut-off points were 94.4% (95% confidence interval (CI), 86.4-98.5) and 96.3% (95% CI, 88.2-99.3), respectively.,In all, 18% of positive microspirometry results were not confirmed by a post-BD FEV1/FVC <0.70 and 44% of tests were false positive compared with the LLN criterion for airflow obstruction.,Pre-bronchodilator microspirometry seems to be able to reliably preselect patients for further assessment of airflow obstruction by means of regular diagnostic spirometry.,However, use of microspirometry alone would result in overestimation of airflow obstruction and should not replace regular spirometry when diagnosing COPD in primary care.
| 1 |
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.
|
The long-acting muscarinic antagonists umeclidinium (UMEC) and tiotropium (TIO) are approved once-daily maintenance therapies for COPD.,This study investigated the efficacy and safety of UMEC versus TIO in COPD.,This was a 12-week, multicenter, randomized, blinded, double-dummy, parallel-group, non-inferiority study.,Patients were randomized 1:1 to UMEC 62.5 μg plus placebo or TIO 18 μg plus placebo.,The primary end point was trough forced expiratory volume in 1 second (FEV1) at day 85 (non-inferiority margin −50 mL; per-protocol [PP] population).,Other end points included weighted mean FEV1 over 0-24 and 12-24 hours post-dose.,Patient-reported outcomes comprised Transition Dyspnea Index score, St George’s Respiratory Questionnaire total score, and COPD Assessment Test score.,Adverse events were also assessed.,In total, 1,017 patients were randomized to treatment.,In the PP population, 489 and 487 patients received UMEC and TIO, respectively.,In the PP population, change from baseline in trough FEV1 was greater with UMEC versus TIO at day 85, meeting non-inferiority and superiority margins (difference: 59 mL; 95% confidence interval [CI]: 29-88; P<0.001).,Similar results were observed in the intent-to-treat analysis of trough FEV1 at day 85 (53 mL, 95% CI: 25-81; P<0.001).,Improvements in weighted mean FEV1 over 0-24 hours post-dose at day 84 were similar with UMEC and TIO but significantly greater with UMEC versus TIO over 12-24 hours post-dose (70 mL; P=0.015).,Clinically meaningful improvements in Transition Dyspnea Index and St George’s Respiratory Questionnaire were observed with both treatments at all time points.,No differences were observed between UMEC and TIO in patient-reported outcomes.,Overall incidences of adverse events were similar for UMEC and TIO.,UMEC 62.5 μg demonstrated superior efficacy to TIO 18 μg on the primary end point of trough FEV1 at day 85.,Safety profiles were similar for both treatments.
| 1 |
Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs.,We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.,A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies.,Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61).,Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease.,There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia.,The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.,Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.,Long-term use of inhaled corticosteroids in COPD is associated with a significantly increased risk of side-effects, especially oral candidiasis, dysphonia, pneumonia, mycobacterial disease, diabetes and fractureshttps://bit.ly/3t0AGfO
|
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.
| 1 |
To explore the association between host serum 25-hydroxyvitamin D (25(OH)D) and the susceptibility and severity of COPD.,Previous studies on the association between host 25(OH)D and the susceptibility and severity of COPD were collected on the basis of a systematic literature search of PubMed and Web of Science up to June 2015.,Continuous variable data were presented as standard mean difference (SMD) or weighted mean difference with 95% confidence interval (CI).,The dichotomous variable data were analyzed as relative ratio (RR) or odds ratio with 95% CI for cohort and case-control studies.,A systematic review was conducted to understand the curative and side effects of vitamin D intake.,A total of 18 studies including eight cohort, five case-control, and five randomized studies met the inclusion criteria.,The serum level of 25(OH)D in COPD patients was comparable with controls with a pooled SMD of 0.191 (95% CI: −0.126 to 0.508, P=0.237) based on pooled analyses of cohort studies.,However, the serum level of 25(OH)D in COPD patients was lower with a pooled SMD of 0.961 (95% CI: 0.476-1.446, P<0.001) compared with controls based on pooled analyses of case-control studies.,The deficiency rates of 25(OH)D were comparable between controls and COPD patients with a pooled RR of 0.955 (95% CI: 0.754-1.211, P=0.705) based on analyses of cohort studies, and the same results were observed based on pooled analyses of case-control studies.,Interestingly, the deficiency rate of 25(OH)D was significantly lower in moderate or severe COPD patients with a pooled RR of 0.723 (95% CI: 0.632-0.828, P<0.001) compared with that in mild COPD patients.,The same results were obtained from the pooled analysis between moderate and severe COPD patients.,The four randomized studies showed that vitamin D intake provided benefit for COPD patients.,Low serum levels of 25(OH)D were not associated with COPD susceptibility, but the high deficiency rate of 25(OH)D was associated with COPD severity.,Vitamin D supplementation may prevent COPD exacerbation.
|
Osteoporosis is one of the systemic features of COPD.,A correlation between the emphysema phenotype of COPD and reduced bone mineral density (BMD) is suggested by some studies, however, the mechanisms underlying this relationship are unclear.,Experimental studies indicate that IL-1β, IL-6 and TNF-α may play important roles in the etiology of both osteoporosis and emphysema.,The OPG/RANK/RANKL system is an important regulator of bone metabolism, and participates in the development of post-menopausal osteoporosis.,Whether the OPG/RANK/RANKL pathway is involved in the pathogenesis of osteoporosis in COPD has not been studied.,Eighty male patients (current or former smokers) completed a chest CT scan, pulmonary function test, dual x-ray absorptiometry measurements and questionnaires.,Among these subjects, thirty patients with normal BMD and thirty patients with low BMD were selected randomly for measurement of IL-1β, IL-6, TNF-α (flow cytometry) and OPG/RANK/RANKL (ELISA).,Twenty age-matched healthy volunteers were recruited as controls.,Among these eighty patients, thirty-six had normal BMD and forty-four had low BMD.,Age, BMI and CAT score showed significant differences between these two COPD groups (p < 0.05).,The low-attenuation area (LAA%) in the lungs of COPD patients was negatively correlated with lumbar vertebral BMD (r = 0.741; p < 0.0001).,Forward logistic regression analysis showed that only LAA% (p = 0.005) and BMI (p = 0.009) were selected as explanatory variables.,The level of IL-1β was significantly higher in the COPD patients as compared to the normal controls (p < 0.05), but the difference between the two COPD groups did not reach significance.,The levels of IL-6 and TNF-α among the three groups were significantly different (p < 0.05).,The level of RANKL and the RANKL/OPG ratio were significantly higher in COPD patients with low BMD compared to those with normal BMD and the normal controls (p < 0.05), and correlated negatively with lumbar vertebral BMD, but positively with LAA%.,Radiographic emphysema is correlated with low BMD in current and former smokers with COPD.,IL-1β, IL-6, TNF-α, and the osteoporosis-related protein system OPG/RANK/RANKL may have some synergetic effects on emphysema and bone loss in COPD.
| 1 |
Rationale: In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate/formoterol fumarate (GFF).,However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses.,Objectives: To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses.,Methods: Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320/18/9.6 μg of BGF (BGF 320), 160/18/9.6 μg of BGF (BGF 160), 18/9.6 μg of GFF, or 320/9.6 μg of budesonide/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler).,Time to death (all-cause) was a prespecified secondary endpoint.,Measurements and Main Results: In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33-0.80; unadjusted P = 0.0035).,There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44-1.16; P = 0.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator.,Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis.,Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively.,Conclusions: Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD.,Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators.
|
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.
| 1 |
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.
|
Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
| 1 |
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.
|
COPD is a complex disease with multiple pathological components, which we unfortunately tend to ignore when spirometry is used as the only method to evaluate the disorder.,Additional measures are needed to allow a more complete and clinically relevant assessment of COPD.,The earliest potential risk factors of disease in COPD are variations in the genetic background.,Genetic variations are present from conception and can determine lifelong changes in enzyme activities and protein concentrations.,In contrast, measurements in blood, sputum, exhaled breath, broncho-alveolar lavage, and lung biopsies may vary substantially over time.,This review explores potential markers of early disease and prognosis in COPD by examining genetic markers in the α1-antitrypsin, cystic fibrosis transmembrane conductance regulator (CFTR), and MBL-2 genes, and by examining the biochemical markers fibrinogen and C-reactive protein (CRP), which correlate with degree of pulmonary inflammation during stable conditions of COPD.,Chronic lung inflammation appears to contribute to the pathogenesis of COPD, and markers of this process have promising predictive value in COPD.,To implement markers for COPD in clinical practice, besides those already established for the α1-antitrypsin gene, further research and validation studies are needed.
| 1 |
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.
|
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
| 1 |
Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively.,These mucosal tissues bear commonalities in embryology, structure and physiology.,Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients.,Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease.,Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation.,While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD.,Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota.,It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication.,While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD.,This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.
|
Exacerbations in Chronic obstructive pulmonary disease (COPD) are often accompanied by pulmonary and systemic inflammation, and are associated with an increased susceptibility to weight loss and muscle wasting.,As the emphysematous phenotype in COPD appears prone to skeletal muscle wasting, the aims of this study were to evaluate in emphysematous compared to control mice following repetitive exacerbations (1) changes in muscle mass and strength and, (2) whether muscle mass recovery and its underlying processes are impaired.,Emphysema was induced by intra-tracheal (IT) elastase instillations, followed by three weekly IT-LPS instillations to mimic repetitive exacerbations.,Loss of muscle mass and strength were measured, and related to analyses of muscle protein turnover and myogenesis signaling in tissue collected during and following recovery.,Emphysematous mice showed impaired muscle mass recovery in response to pulmonary inflammation-induced muscle atrophy.,Proteolysis and protein synthesis signaling remained significantly higher in emphysematous mice during recovery from LPS.,Myogenic signaling in skeletal muscle was altered, and fusion capacity of cultured muscle cells treated with plasma derived from LPS-treated emphysematous mice was significantly decreased.,In conclusion, repetitive cycles of pulmonary inflammation elicit sustained muscle wasting in emphysematous mice due to impaired muscle mass recovery, which is accompanied by aberrant myogenesis.
| 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation.
|
Objective: To explore the associations between decreased pulse oximetry values (SpO2) and clinical, laboratory, and demographic variables in general practice patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD), including those with both COPD and asthma in combination.,Design/setting: A cross-sectional study in seven Norwegian general practices of patients aged 40 years or over who were diagnosed by their general practitioner (GP) with asthma and/or COPD.,The patients were examined during a stable phase of their disease.,Patients diagnosed with COPD (including those with combined COPD/asthma) and those diagnosed with asthma only were analysed separately.,Main outcome measures: Decreased SpO2 values (≤ 95% and ≤ 92%).,Results: Of 372 patients included (mean age 61.5 years, 62% women), 82 (22.0%) had SpO2 ≤ 95%, of which 11 had SpO2 ≤ 92%.,In both asthma and COPD patients, SpO2 ≤ 95% was significantly associated with reduced lung function (spirometry), a diagnosis of coronary heart disease and older age (≥ 65 years).,In the COPD group, haemoglobin above normal was associated with SpO2 ≤ 95%.,These associations were confirmed by multivariable logistic regression, where FEV1% predicted < 50 was the strongest predictor of SpO2 ≤ 95% (odds ratio 6.8, 95% confidence interval 2.8-16.4).,Conclusion.,Pulse oximetry represents a useful diagnostic adjunct for assessing the severity of obstructive pulmonary disease.,Decreased pulse oximetry values in stable-phase patients with asthma and/or COPD should prompt the GP to consider revising the diagnosis and treatment and to look for co-morbidities.Key PointsDespite its common use in general practice, the diagnostic benefits of pulse oximetry remain to be established.Decreased pulse oximetry values are associated with both reduced lung function (spirometry) and with a diagnosis of coronary heart disease.Decreased pulse oximetry values may reflect suboptimal treatment and/or undiagnosed comorbidity.Pulse oximetry may therefore be a useful measure in the follow-up of asthma and COPD patients in general practice.,Despite its common use in general practice, the diagnostic benefits of pulse oximetry remain to be established.,Decreased pulse oximetry values are associated with both reduced lung function (spirometry) and with a diagnosis of coronary heart disease.,Decreased pulse oximetry values may reflect suboptimal treatment and/or undiagnosed comorbidity.,Pulse oximetry may therefore be a useful measure in the follow-up of asthma and COPD patients in general practice.
| 1 |
Most hospitalizations and costs related to COPD are due to exacerbations and insufficient disease management.,The COPD patient Management European Trial (COMET) is investigating a home-based multicomponent COPD self-management program designed to reduce exacerbations and hospital admissions.,Multicenter parallel randomized controlled, open-label superiority trial.,Thirty-three hospitals in four European countries.,A total of 345 patients with Global initiative for chronic Obstructive Lung Disease III/IV COPD.,The program includes extensive patient coaching by health care professionals to improve self-management (eg, develop skills to better manage their disease), an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring.,Comparator is the usual management as per the center’s routine practice.,Yearly number of hospital days for acute care, exacerbation number, quality of life, deaths, and costs.
|
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.
| 1 |
Chronic obstructive pulmonary disease (COPD) generates a high burden on health care, and hospital admissions represent a substantial proportion of the overall costs of the disease.,Integrated care (IC) has shown efficacy to reduce hospitalisations in COPD patients at a pilot level.,Deployment strategies for IC services require assessment of effectiveness at the health care system level.,The aim of this study was to explore the effectiveness of a community-based IC service in preventing hospitalisations and emergency department (ED) visits in stable frail COPD patients.,From April to December 2005, 155 frail community-dwelling COPD patients were randomly allocated either to IC (n=76, age 73 (8) years, forced expiratory volume during the first second, FEV1 41(19) % predicted) or usual care (n=84, age 75(9) years, FEV1 44 (20) % predicted) and followed up for 12 months.,The IC intervention consisted of the following: (a) patient’s empowerment for self-management; (b) an individualised care plan; (c) access to a call centre; and (d) coordination between the levels of care.,Thereafter, hospital admissions, ED visits and mortality were monitored for 6 years.,IC enhanced self-management (P=0.02), reduced anxiety-depression (P=0.001) and improved health-related quality of life (P=0.02).,IC reduced both ED visits (P=0.02) and mortality (P=0.03) but not hospital admission.,No differences between the two groups were seen after 6 years.,The intervention improved clinical outcomes including survival and decreased the ED visits, but it did not reduce hospital admissions.,The study facilitated the identification of two key requirements for adoption of IC services in the community: appropriate risk stratification of patients, and preparation of the community-based work force.
|
Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with usual care.,Design 24 month, multicentre, pragmatic cluster randomised controlled trial,Setting 40 general practices in the western part of the Netherlands,Participants Patients with COPD according to GOLD (Global Initiative for COPD) criteria.,Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse, and inability to fill in Dutch questionnaires.,Practices were included if they were willing to create a multidisciplinary COPD team.,Intervention General practitioners, practice nurses, and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice, including early recognition of exacerbations and self management, smoking cessation, physiotherapeutic reactivation, optimal diagnosis, and drug adherence.,Additionally, the course served as a network platform and collaborating healthcare providers designed an individual practice plan to integrate integrated disease management into daily practice.,The control group continued usual care (based on international guidelines).,Main outcome measures The primary outcome was difference in health status at 12 months, measured by the Clinical COPD Questionnaire (CCQ); quality of life, Medical Research Council dyspnoea, exacerbation related outcomes, self management, physical activity, and level of integrated care (PACIC) were also assessed as secondary outcomes.,Results Of a total of 1086 patients from 40 clusters, 20 practices (554 patients) were randomly assigned to the intervention group and 20 clusters (532 patients) to the usual care group.,No difference was seen between groups in the CCQ at 12 months (mean difference -0.01, 95% confidence interval -0.10 to 0.08; P=0.8).,After 12 months, no differences were seen in secondary outcomes between groups, except for the PACIC domain “follow-up/coordination” (indicating improved integration of care) and proportion of physically active patients.,Exacerbation rates as well as number of days in hospital did not differ between groups.,After 24 months, no differences were seen in outcomes, except for the PACIC follow-up/coordination domain.,Conclusion In this pragmatic study, an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care, except improved level of integrated care and a self reported higher degree of daily activities.,The contradictory findings to earlier positive studies could be explained by differences between interventions (provider versus patient targeted), selective reporting of positive trials, or little room for improvement in the already well developed Dutch healthcare system.,Trial registration Netherlands Trial Register NTR2268.
| 1 |
The prevalence rate of bronchiectasis in COPD is variable.,Coexisting bronchiectasis and COPD may influence COPD severity and exacerbation.,We investigated whether bronchiectasis is associated with frequent or severe COPD exacerbation.,Lower airway bacterial and mycobacterial infections are a possible mechanism for bronchiectasis.,A cross-sectional study was conducted in 2013-2014.,COPD exacerbations and hospitalizations were reviewed.,Spirometry and CT were performed.,COPD symptoms were assessed by using the COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale.,Sputum inductions were performed and specimens were sent for microbiology.,We recruited 72 patients.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) A, B, C, and D, were noted in 20%, 27.1%, 14.3%, and 38.6% of the patients, respectively.,Frequent exacerbations (≥2) and/or ≥1 hospitalization in the previous year were observed in 40.3% of patients.,Median mMRC of COPD with frequent and non-frequent exacerbations was 1.0 (range 1-2) and 2.0 (range 1-3), (p=0.002), respectively.,Median CAT of COPD with frequent and non-frequent exacerbations was 20.5 (3-37) and 11.0 (2-32), (p=0.004), respectively.,CT-detected bronchiectasis was observed in 47.2% of patients.,Median mMRC of COPD with and without bronchiectasis was 1.0 (0-4) and 1.0 (0-4) (p=0.22), respectively.,Median CAT of COPD with and without bronchiectasis was 16.2 (95% CI: 12.9-19.6) and 13.0 (3-37), (p=0.49), respectively.,The lower post-bronchodilator forced expiratory volume in 1 second (FEV1) of COPD with frequent exacerbations than those without was noted (p=0.007).,The post-bronchodilator forced expiratory volume at 1 second percent in patients with and without bronchiectasis was not different (p=0.91).,After adjusting for gender, severity of airflow obstruction, severity of COPD symptoms, the odds ratio for bronchiectasis with frequent and/or severe exacerbation was 4.99 (95% CI: 1.31-18.94), (p=0.018).,Neither bacterial nor mycobacterial airway infection was associated with bronchiectasis or frequent exacerbation.,Bronchiectasis is common in Thai COPD.,It was associated with frequent exacerbation or hospitalization.,Mycobacterial tuberculosis in COPD patients with bronchiectasis was uncommon.
|
Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease.,A defect in Th17 cytokines in response to Streptococcus pneumoniae, a bacteria associated with COPD exacerbations, has been recently reported.,Dendritic cells (DC) are professional antigen presenting cells that drive T-cells differentiation and activation.,In this study, we hypothesized that exposure to cigarette smoke, the main risk factor of COPD, might altered the pro-Th17 response to S. pneumoniae in COPD patients and human DC.,Pro-Th1 and -Th17 cytokine production by peripheral blood mononuclear cells (PBMC) from COPD patients was analyzed and compared to those from smokers and non-smokers healthy subjects.,The effect of cigarette smoke extract (CSE) was analyzed on human monocyte-derived DC (MDDC) from controls exposed or not to S. pneumoniae.,Bacteria endocytosis, maturation of MDDC and secretion of cytokines were assessed by flow cytometry and ELISA, respectively.,Implication of the oxidative stress was analyzed by addition of antioxidants and mitochondria inhibitors.,In parallel, MDDC were cocultured with autologous T-cells to analyze the consequence on Th1 and Th17 cytokine production.,PBMC from COPD patients exhibited defective production of IL-1β, IL-6, IL-12 and IL-23 to S. pneumoniae compared to healthy subjects and smokers.,CSE significantly reduced S. pneumoniae-induced MDDC maturation, secretion of pro-Th1 and -Th17 cytokines and activation of Th1 and Th17 T-cell responses.,CSE exposure was also associated with sustained CXCL8 secretion, bacteria endocytosis and mitochondrial oxidative stress.,Antioxidants did not reverse these effects.,Inhibitors of mitochondrial electron transport chain partly reproduced inhibition of S. pneumoniae-induced MDDC maturation but had no effect on cytokine secretion and T cell activation.,We observed a defective pro-Th1 and -Th17 response to bacteria in COPD patients.,CSE exposure was associated with an inhibition of DC capacity to activate antigen specific T-cell response, an effect that seems to be not only related to oxidative stress.,These results suggest that new therapeutics boosting this response in DC may be helpful to improve treatment of COPD exacerbations.,The online version of this article (doi:10.1186/s12931-016-0408-6) contains supplementary material, which is available to authorized users.
| 1 |
The prevalence of physical frailty and its clinical characteristics in advanced chronic obstructive pulmonary disease (COPD) is unknown, as well as the usefulness of functional capacity tests to screen for physical frailty.,The aim of the study was to evaluate the proportion and clinical portrait of COPD patients with chronic respiratory failure exhibiting physical frailty at the time of referral to home-based pulmonary rehabilitation.,We also evaluate the usefulness of the short physical performance battery (SPPB) and timed-up and go (TUG) as potential screening tools for physical frailty.,Finally, we evaluated the specific contribution of gait speed to the frailty Fried total score.,This was a prospective observational study in which physical frailty was defined using Fried criteria (body mass loss, exhaustion, low physical activity, slower walking and weakness).,Clinical portrait was documented from daily physical activity, exercise tolerance, functional capacity, anxiety and depressive symptoms, health-related quality of life, and fatigue scores.,The ability of the SPPB and TUG to predict physical frailty was investigated using receiver operating characteristic curves.,Contribution of each Fried criteria was evaluated with a principal component analysis (PCA).,Amongst the 44 included participants (FEV1, 33 ± 13% of predicted), 19 were physically frail.,Frail individuals had lower daily steps number, exercise tolerance and functional capacity, and higher fatigue, anxiety, and depressive symptom scores (p<0.05) compared to non-frail individuals.,SPPB and TUG did not have an acceptable detection accuracy for screening physical frailty.,PCA indicated that gait speed was the main contributor to the Fried total score of physical frailty.,Physical frailty affects a large proportion of COPD patients with chronic respiratory failure starting a home-based intervention and was associated with worse clinical status.,Although the present results need to be confirmed by adequately powered studies, gait speed seems to have the potential to become a simple screening tool for physical frailty in this population.
|
Lung cancer and chronic obstructive pulmonary disease have shared etiology, including key etiological changes (e.g., DNA damage and epigenetics change) and lung function impairment.,Focusing on those shared targets may help in the prevention of both.,Certain micronutrients (vitamins and minerals) and phytochemicals (carotenoids and phenols) have potent antioxidant or methyl-donating properties and thus have received considerable interest.,We reviewed recent papers probing into the potential of nutrients with respect to lung function preservation and prevention of lung cancer risk, and suggest several hypothetical intervention patterns.,Intakes of vitamins (i.e., A, C, D, E, B12), carotenoids, flavonoids, curcumins, resveratrol, magnesium, and omega-3 fatty acids all show protective effects against lung function loss, some mainly by improving average lung function and others through reducing decline rate.,Dietary interventions early in life may help lung function reserve over the lifespan.,Protective nutrient interventions among smokers are likely to mitigate the effects of cigarettes on lung health.,We also discuss their underlying mechanisms and some possible causes for the inconsistent results in observational studies and supplementation trials.,The role of the lung microbiome on lung health and its potential utility in identifying protective nutrients are discussed as well.,More prospective cohorts and well-designed clinical trials are needed to promote the transition of individualized nutrient interventions into health policy.
| 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy (long-acting muscarinic receptor antagonists, long-acting beta-2 agonists, and inhaled corticosteroids) for patients with only the most severe COPD.,Data on the proportion of COPD patients on triple therapy and their characteristics are sparse and dated.,Objective 1 of this study was to estimate the proportion of all, and all treated, COPD patients receiving triple therapy.,Objective 2 was to characterize those on triple therapy and assess the concordance of triple therapy use with GOLD guidelines.,This retrospective study used claims from the IMS PharMetrics Plus database from 2009 to 2013.,Cohort 1 was selected to assess Objective 1 only; descriptive analyses were conducted in Cohort 2 to answer Objective 2.,A validated claims-based algorithm and severity and frequency of exacerbations were used as proxies for COPD severity.,Of all 199,678 patients with COPD in Cohort 1, 7.5% received triple therapy after diagnosis, and 25.5% of all treated patients received triple therapy.,In Cohort 2, 30,493 COPD patients (mean age =64.7 years) who initiated triple therapy were identified.,Using the claims-based algorithm, 34.5% of Cohort 2 patients were classified as having mild disease (GOLD 1), 40.8% moderate (GOLD 2), 22.5% severe (GOLD 3), and 2.3% very severe (GOLD 4).,Using exacerbation severity and frequency, 60.6% of patients were classified as GOLD 1/2 and 39.4% as GOLD 3/4.,In this large US claims database study, one-quarter of all treated COPD patients received triple therapy.,Although triple therapy is recommended for the most severe COPD patients, spirometry is infrequently assessed, and a majority of the patients who receive triple therapy may have only mild/moderate disease.,Any potential overprescribing of triple therapy may lead to unnecessary costs to the patient and health care system.
|
Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven.
| 1 |
In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ ≥1, CAT ≥10, and mMRC scale ≥2 to indicate symptomatic patients.,The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George’s Respiratory Questionnaire (SGRQ) ≥25, as suggested by GOLD, following sensitivity and specificity analysis.,In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (≥25 and ≥20).,Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care.,Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires.,Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥25 were: study A, 0.99, 0.43, and 0.96 for CCQ ≥1, 0.92, 0.48, and 0.89 for CAT ≥10, and 0.68, 0.91, and 0.91 for mMRC ≥2; study B, 0.87, 0.77, and 0.9 for CCQ ≥1, 0.76, 0.73, and 0.82 for CAT ≥10, and 0.21, 1, and 0.81 for mMRC ≥2.,Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥20 were: study A, 0.99, 0.73, and 0.99 for CCQ ≥1, 0.91, 0.73, and 0.94 for CAT ≥10, and 0.66, 0.95, and 0.94 for mMRC ≥2; study B, 0.8, 0.89, and 0.89 for CCQ ≥1, 0.69, 0.78, and 0.8 for CAT ≥10, and 0.18, 1, and 0.81 for mMRC ≥2.,Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (≥25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels.,The correspondence with the mMRC scale seemed satisfactory, though not optimal.,The SGRQ threshold of ≥20 corresponded slightly better than SGRQ ≥25, recently suggested by GOLD 2015, with the established cutoff points for the CCQ, CAT, and mMRC scale.
|
Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin.,Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues.,Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA).,Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines.,Eosinophils are the major source of interleukin-5 and highly express the interleukin-5Rα on their surface.,Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5Rα (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD).,Overall, targeting interleukin-5/interleukin-5Rα is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma.,Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA.,A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD.,The review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD.,Interleukin-5/interleukin-5Rα-targeted treatments offer promises to patients with eosinophilic respiratory disorders.
| 1 |
Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users.
|
Treatment of chronic diseases such as chronic obstructive pulmonary disease (COPD) is complicated by the presence of comorbidities.,The objective of this analysis was to estimate the prevalence of comorbidity in COPD using nationally-representative data.,This study draws from a multi-year analytic sample of 14,828 subjects aged 45+, including 995 with COPD, from the National Health and Nutrition Examination Survey (NHANES), 1999-2008.,COPD was defined by self-reported physician diagnosis of chronic bronchitis or emphysema; patients who reported a diagnosis of asthma were excluded.,Using population weights, we estimated the age-and-gender-stratified prevalence of 22 comorbid conditions that may influence COPD and its treatment.,Subjects 45+ with physician-diagnosed COPD were more likely than subjects without physician-diagnosed COPD to have coexisting arthritis (54.6% vs.,36.9%), depression (20.6% vs.,12.5%), osteoporosis (16.9% vs.,8.5%), cancer (16.5% vs.,9.9%), coronary heart disease (12.7% vs.,6.1%), congestive heart failure (12.1% vs.,3.9%), and stroke (8.9% vs.,4.6%).,Subjects with COPD were also more likely to report mobility difficulty (55.6% vs.,32.5%), use of >4 prescription medications (51.8% vs.,32.1), dizziness/balance problems (41.1% vs.,23.8%), urinary incontinence (34.9% vs.,27.3%), memory problems (18.5% vs.,8.8%), low glomerular filtration rate (16.2% vs.,10.5%), and visual impairment (14.0% vs.,9.6%).,All reported comparisons have p < 0.05.,Our study indicates that COPD management may need to take into account a complex spectrum of comorbidities.,This work identifies which conditions are most common in a nationally-representative set of COPD patients (physician-diagnosed), a necessary step for setting research priorities and developing clinical practice guidelines that address COPD within the context of comorbidity.
| 1 |
The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects.,This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches.,In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%).,Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.).,Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ).,Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ).,The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ).,Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement.,MCID estimates differed depending on the method used.,Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients.,The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.
|
Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting β2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU.,We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry.,In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 μg, UMEC/VI 62.5/25 μg, or placebo.,The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1.,Additional end points and safety were also assessed.,Both UMEC/VI 125/25 μg and UMEC/VI 62.5/25 μg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 μg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 μg, 0.151 L, 95% CI 0.110-0.191; both P<0.001).,Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 μg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 μg, 0.7, 95% CI 0.1-1.2, P=0.016).,On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 μg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 μg, 0.160 L, 95% CI 0.139-0.181; both P<0.001).,Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001).,The incidence of adverse events was similar across groups.,In Asian patients with COPD, once-daily UMEC/VI 125/25 μg and UMEC 62.5/25 μg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo.,Symptomatic and quality of life measures also improved.,The safety profile of UMEC/VI was consistent with previous studies.
| 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.
|
The changes in grading of disease severity and treatment recommendations for patients with COPD in the 2017 GOLD strategy may present an opportunity for reducing treatment burden for the patients and costs to the health care system.,The aim of this study was to assess the implications of the GOLD 2017 grading system in terms of change in distribution across GOLD groups A-D for existing patients in UK primary care and estimate the potential cost savings of implementing GOLD 2017 treatment recommendations in UK primary care.,Using electronic health record data from the Clinical Practice Research Datalink (CPRD), patients aged ≥35 years with spirometry-confirmed COPD, receiving care during 2016, were included.,The cohort was graded according to the GOLD 2017 groups (A-D), and treatment costs were calculated, according to corresponding recommendations, to observe the difference in actual vs predicted costs.,When applying GOLD 2013 criteria, less than half of the cohort (46%) was assigned to GOLD A or B, as compared to 86% when applying the GOLD 2017 grading.,The actual mean annual maintenance treatment cost was £542 per patient vs a predicted £389 for treatment according to the 2017 GOLD strategy.,There is a potential to make significant cost savings by implementing the grading and treatment recommendations from the 2017 GOLD strategy.
| 1 |
Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement.,The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT).,Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1) <50% of predicted value from 27 secondary care respiratory units in Sweden.,Correlation analyses and multiple linear regression models were performed using EQ-5D index, EQ-5D visual analog scale (VAS), and CAT scores as response variables.,Having more comorbid conditions was associated with a worse HRQL as assessed by all instruments.,Chronic bronchitis was significantly associated with a worse HRQL as assessed by EQ-5D index (adjusted regression coefficient [95% confidence interval] −0.07 [−0.13 to −0.02]), EQ-5D VAS (−5.17 [−9.42 to −0.92]), and CAT (3.78 [2.35 to 5.20]).,Musculoskeletal symptoms were significantly associated with worse EQ-5D index (−0.08 [−0.14 to −0.02]), osteoporosis with worse EQ-5D VAS (−4.65 [−9.27 to −0.03]), and depression with worse EQ-5D index (−0.10 [−0.17 to −0.04]).,In stratification analyses, the associations of musculoskeletal symptoms, osteoporosis, and depression with HRQL were limited to female patients.,The instruments EQ-5D and CAT complement each other and emerge as useful for assessing HRQL in patients with COPD.,Chronic bronchitis, musculoskeletal symptoms, osteoporosis, and depression were associated with worse HRQL.,We conclude that comorbid conditions, in particular chronic bronchitis, depression, osteoporosis, and musculoskeletal symptoms, should be taken into account in the clinical management of patients with severe COPD.
|
Chronic obstructive pulmonary disease (COPD) includes pulmonary components with increased comorbidity rates, as well as being a systemic disease.,Comorbidities may frequently occur in COPD patients over 40 yr old.,We report the comorbidities of patients with COPD, diagnosed by spirometry, in a population-based epidemiologic survey in Korea.,Data were derived from the fourth Korean Health and Nutrition Examination Survey in 2008, a stratified multistage clustered probability design survey of a sample representing the entire population of Korea.,Results of spirometry and various health-related questionnaires were analyzed in 2,177 subjects aged ≥ 40 yr.,The prevalence of COPD (FEV1/FVC < 0.7) in subjects ≥ 40 yr of age was 14.1%.,Multivariate analysis showed that underweight (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.05-8.98), coronary heart disease (OR, 0.43; 95% CI, 0.20-0.93) and dyslipidemia (OR, 0.61; 95% CI, 0.45-0.82) were significantly associated with COPD, whereas allergic rhinitis, anemia, arthritis, chronic renal failure, depression, diabetes mellitus, hypertension, gastrointestinal ulcer, and osteoporosis were not.,Underweight might be more prevalent but coronary heart disease and dyslipidemia are less prevalent in Koreans with than without COPD in population setting.
| 1 |
This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung hyperinflation, and physical activity.,In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe airflow limitation received aclidinium 400 μg twice daily or placebo via Genuair®/Pressair®a for 3 weeks (2-week washout between treatment periods).,The primary endpoint was change from baseline to Week 3 in endurance time, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate.,Changes from baseline in intensity of exertional dyspnea (Borg CR10 Scale®) and trough inspiratory capacity were secondary endpoints.,Additional endpoints included changes from baseline in other spirometric, plethysmographic, and physical activity (assessed by objective accelerometer measurement) parameters.,Efficacy endpoints were analyzed using an analysis of covariance model.,In total, 112 patients were randomized and treated (mean age 60.3 years; mean post-bronchodilator forced expiratory volume in 1 s 1.7 L [56.7% predicted]; mean endurance time 485.7 s).,After 3 weeks, endurance time was significantly increased with aclidinium versus placebo (treatment difference 58.5 s; p < 0.05).,At Week 3, aclidinium significantly reduced dyspnea intensity at isotime during exercise (treatment difference -0.63; p < 0.05) and improved trough inspiratory capacity (treatment difference 78 mL; p < 0.05) versus placebo.,Significant improvements in spirometric, plethysmographic, and some physical activity parameters were observed with aclidinium versus placebo.,These results suggest that aclidinium significantly improves exercise endurance, exertional dyspnea, hyperinflation, and physical activity in patients with COPD.,ClinicalTrials.gov identifier: NCT01471171; URL: http://www.clinicaltrials.gov.,The online version of this article (doi:10.1186/1471-2466-14-209) contains supplementary material, which is available to authorized users.
|
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.
| 1 |
Studies report high in-hospital mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) especially for those requiring admission to an intensive care unit.,Recognizing factors associated with mortality in these patients could reduce health care costs and improve end-of-life care.,This retrospective study included AECOPD patients admitted to the respiratory intensive care unit of a tertiary hospital in Beijing from Jan 1, 2011 to Dec 31, 2018.,Patients demographic characteristics, blood test results and comorbidities were extracted from the electronic medical record system and compared between survivors and non-survivors.,We finally enrolled 384 AECOPD patients: 44 (11.5%) patients died in hospital and 340 (88.5%) were discharged.,The most common comorbidity was respiratory failure (294 (76.6%)), followed by hypertension (214 (55.7%)), coronary heart disease (115 (29.9%)) and chronic heart failure (76 (19.8%)).,Multiple logistic regression analysis revealed that independent risk factors associated with in-hospital mortality included lymphocytopenia, leukopenia, chronic heart failure and requirement for invasive mechanical ventilation.,The in-hospital mortality of patients with acute COPD exacerbation requiring RICU admission is high.,Lymphocytes < 0.8 × 109/L, leukopenia, requirement for invasive mechanical ventilation, and chronic heart failure were identified as risk factors associated with increased mortality rates.
|
The study aimed to investigate the demographic characteristics, clinical features, diagnoses, and treatments of hospitalized exacerbation COPD patients, as well as their disease prognoses and economic costs.,The study planned to enroll 7600 hospitalized patients (aged ≥18 years with main diagnosis as AECOPD).,Study patients were recruited since September 2017, followed up with a 3-year observing period.,In the baseline visit, information on demographic characteristics, clinical features, diagnoses, and treatments were collected.,In the following visits, treatments and examinations, recurrence of AECOPD, re-admission to hospital, complications, and mortality were recorded.,Several validated questionnaires were applied at specific visits.,This study included data from 1 September 2017 until 31 December 2022.,The data would be used to estimate all-cause mortality during hospital stay, AECOPD recurrence within 1 month after discharge, all-cause and cause-specific mortality, frequency of AECOPD recurrence, lung function, life quality, healthcare costs in the study period, etc.
| 1 |
Over the past two decades, there have been significant changes in the pharmacological management of COPD, due to an explosion of inhaler trials, and timely updation of national and international guidelines.,We sought to describe temporal changes in prescribing practices in the United Kingdom, and some of the factors that may have influenced them.,COPD patients were identified from UK primary care nationally representative electronic healthcare records (Clinical Practice Research Datalink), between 2000 and 2016.,Prescription data were described by the three maintenance inhaled medication classes used, inhaled corticosteroids (ICS), long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA), and their combinations, dual LABA-ICS, dual LAMA-LABA, or triple therapy LABA-ICS-LAMA.,Differing patient characteristics across the six different therapy regimens were measured in 2016.,COPD patients were identified: 187,588 prevalent and incident inhaler users and 169,511 incident inhaler users.,Since 2002, LAMA showed increasing popularity, while ICS alone exhibited an inverse trend.,Triple therapy prescriptions rapidly increased as the first-line therapy until 2014 when LAMA-LABA prescriptions started to increase.,By 2014, 41% of all COPD patients were maintained on triple therapy, and 13% were maintained on LAMA only.,Characterizing the patients in 2016 revealed that those on triple therapy were more likely to have more severe disease, yet, over a third of patients on triple therapy had only mild disease.,UK prescribing practices were not in keeping with national guidelines but did appear to align with evidence from major drug trials and updated international guidelines.,There has been a huge upsurge in triple therapy but incident data show this trend is beginning to reverse for initial management.
|
COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status.
| 1 |
Respiratory viruses are a common trigger for exacerbations of chronic obstructive pulmonary disease (COPD).,Human metapneumovirus (hMPV) is a paramyxovirus associated with respiratory tract infections and wheezing.,Our aim was to determine whether hMPV was associated with exacerbations of COPD.,The study was designed as an observational cohort study carried out in a 944-bed urban teaching hospital located in New Haven, Connecticut.,Between December 2002 and May 2003, patients hospitalized due to an exacerbation of COPD were identified.,Nasopharyngeal specimens obtained from these patients were tested for human metapneumovirus by RT-PCR and for respiratory syncytial virus, influenza A and B, parainfluenza-1, -2, and -3 and adenovirus by a cytospin-enhanced direct immunofluorescence assay and/or viral culture.,Fifty individuals met enrollment criteria and hMPV was identified in 6 (12%), respiratory syncytial virus in 4 (8%), influenza A in 2 (4%) and parainfluenza type 3 in 1 (2%) patients.,Both A and B hMPV genotypes were identified in patients hospitalized due to exacerbations of COPD.,hMPV was frequently identified in patients hospitalized due to an exacerbation of COPD.,Further studies are necessary to determine the epidemiology and the impact of hMPV in COPD patients.
|
Acute exacerbations of COPD are a major cause of morbidity, mortality and hospitalisation.,Respiratory viruses are associated with the majority of exacerbations but a causal relationship has not been demonstrated and the mechanisms of virus-induced exacerbations are poorly understood.,Development of a human experimental model would provide evidence of causation and would greatly facilitate understanding mechanisms, but no such model exists.,We aimed to evaluate the feasibility of developing an experimental model of rhinovirus induced COPD exacerbations and to assess safety of rhinovirus infection in COPD patients.,We carried out a pilot virus dose escalating study to assess the minimum dose of rhinovirus 16 required to induce experimental rhinovirus infection in subjects with COPD (GOLD stage II).,Outcomes were assessed by monitoring of upper and lower respiratory tract symptoms, lung function, and virus replication and inflammatory responses in nasal lavage.,All 4 subjects developed symptomatic colds with the lowest dose of virus tested, associated with evidence of viral replication and increased pro-inflammatory cytokines in nasal lavage.,These were accompanied by significant increases in lower respiratory tract symptoms and reductions in PEF and FEV1.,There were no severe exacerbations or other adverse events.,Low dose experimental rhinovirus infection in patients with COPD induces symptoms and lung function changes typical of an acute exacerbation of COPD, appears safe, and provides preliminary evidence of causation.
| 1 |
The number of patients with chronic obstructive pulmonary disease (COPD) has been rising with continued exposure to environmental risk factors and aging of populations around the world.,Frailty is a geriatric syndrome with a decline in physiological reserve and often coexists with chronic diseases such as COPD.,Frailty is an independent risk factor for the development and progression of COPD, and COPD can lead to frailty; treating one might improve the other.,Thus, there is an increasing interest in the assessment of frailty in patients with COPD.,Furthermore, early identification and assessment of frailty in patients with COPD may affect the choice of intervention and improve its effectiveness.,Based on the current literature, the intent of this review was to summarize and discuss frailty assessment tools used for COPD patients and the relevant clinical practices for predicting outcomes.,We ascertain that using suitable frailty assessment tools could facilitate physicians to screen and stratify physically frail patients with COPD.,Screening appropriately targeted population can achieve better intervention outcomes and pulmonary rehabilitation among frail COPD patients.
|
Frailty is a state of increased risk of unfavorable outcomes when exposed to stressors, and COPD is one of the several chronic illnesses associated with the condition.,However, few studies have been conducted regarding the prevalence of COPD and its related factors in Southeast Asia.,The objectives of this study were to determine the prevalence of frailty in COPD patients and to identify the associated factors in these populations.,A cross-sectional study of COPD patients who attended a COPD clinic was conducted from May 2015 to December 2016.,Baseline characteristics were collected, and the diagnosis of frailty was based on the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale.,Descriptive statistics were used to analyze baseline data.,Factors associated with frailty were analyzed using univariate and multivariate regression analyses.,The results showed that the prevalence rates of frailty and pre-frailty were 6.6% (eight out of 121 cases) and 41.3% (50 out of 121 cases), respectively, among COPD patients.,Fatigue was the most common component of the FRAIL scale that was found more frequently in frail patients than in non-frail patients (odds ratio [OR] 91.9).,Factors associated with frailty according to multivariate analyses were comorbid cancer (adjusted OR [AOR] 45.8), at least two instances of nonelective admission over the past 12 months (AOR 112.5), high waist circumference (WC) (AOR 1.3), and presence of sarcopenia (AOR 29.5).,In conclusion, frailty affected 6.6% of stable COPD patients.,Cancer, two or more instances of nonelective hospitalization over the past 12 months, high WC, and presence of sarcopenia were associated with frailty.,Early identification and intervention in high-risk patients is recommended to prevent or delay the adverse outcomes of frailty.
| 1 |
To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population.,One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited.,The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.,Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment.,We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group.,We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot.,Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population.,In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production.
|
Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function.,Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD).,Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study.,Mean annual decline in FEV1 % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status.,Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line).,AQP5 abundance and localization were assessed by immunoblots and confocal immunofluoresence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization.,Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers.,Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results.,In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid.,Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD.,A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress.,These results suggest that AQP5 may be an important candidate gene for COPD.
| 1 |
Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) seem to have several symptoms in common that impact health.,However, methodological differences make this difficult to compare.,Comparisons of symptoms, impact of symptoms on function and health between patients with COPD and CHF in primary health care (PHC).,The study is cross sectional, including patients with COPD (n=437) and CHF (n=388), registered in the patient administrative systems of PHC.,The patients received specific questionnaires - the Memorial Symptom Assessment Scale, the Medical Research Council dyspnea scale, and the Fatigue Impact Scale - by mail and additional questions about psychological and physical health.,The mean age was 70±10 years and 78±10 years for patients with COPD and CHF respectively (P=0.001).,Patients with COPD (n=273) experienced more symptoms (11±7.5) than the CHF patients (n=211) (10±7.6).,The most prevalent symptoms for patients with COPD were dyspnea, cough, and lack of energy.,For patients with CHF, the most prevalent symptoms were dyspnea, lack of energy, and difficulty sleeping.,Experience of dyspnea, cough, dry mouth, feeling irritable, worrying, and problems with sexual interest or activity were more common in patients with COPD while the experience of swelling of arms or legs was more common among patients with CHF.,When controlling for background characteristics, there were no differences regarding feeling irritable, worrying, and sexual problems.,There were no differences in impact of symptoms or health.,Patients with COPD and CHF seem to experience similar symptoms.,There were no differences in how the patients perceived their functioning according to their cardinal symptoms; dyspnea and fatigue, and health.,An intervention for both groups of patients to optimize the management of symptoms and improve function is probably more relevant in PHC than focusing on separate diagnosis groups.
|
Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.
| 1 |
Objectives: To understand the key characteristics of Asthma and Chronic Obstructive Pulmonary Disease Overlap Syndrome (ACOS) and to identify evidence gaps relating to the identification, treatment and management of ACOS patients.,Methods: A structured literature review and 1-hour telephone interviews with specialist respiratory physicians were conducted (n=10; China, France, Germany, Japan and the USA).,Results: All 10 physicians used the term ACOS in clinical practice.,ACOS was not clearly defined in the literature.,Prevalence of ACOS among adult patients with COPD or asthma ranged from 12-55%.,ACOS patients had severe disease, with increased exacerbations and hospitalisations compared to some asthma and COPD patients.,ACOS represented a clinical challenge due to a lack of evidence-based guidelines distinguishing between asthma, COPD and ACOS.,Published data quantifying ACOS costs were limited.,Conclusions: There is a need for consensus evidence-based guidance to facilitate earlier diagnosis and to optimise the management of ACOS patients.
|
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD).,However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing.,In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study.,Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014.,When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD.,When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD.,To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers.,The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS.
| 1 |
Clinical outcomes among COVID-19 patients vary greatly with age and underlying comorbidities.,We aimed to determine the demographic and clinical factors, particularly baseline chronic conditions, associated with an increased risk of severity in COVID-19 patients from a population-based perspective and using data from electronic health records (EHR).,Retrospective, observational study in an open cohort analyzing all 68,913 individuals (mean age 44.4 years, 53.2% women) with SARS-CoV-2 infection between 15 June and 19 December 2020 using exhaustive electronic health registries.,Patients were followed for 30 days from inclusion or until the date of death within that period.,We performed multivariate logistic regression to analyze the association between each chronic disease and severe infection, based on hospitalization and all-cause mortality.,5885 (8.5%) individuals showed severe infection and old age was the most influencing factor.,Congestive heart failure (odds ratio -OR- men: 1.28, OR women: 1.39), diabetes (1.37, 1.24), chronic renal failure (1.31, 1.22) and obesity (1.21, 1.26) increased the likelihood of severe infection in both sexes.,Chronic skin ulcers (1.32), acute cerebrovascular disease (1.34), chronic obstructive pulmonary disease (1.21), urinary incontinence (1.17) and neoplasms (1.26) in men, and infertility (1.87), obstructive sleep apnea (1.43), hepatic steatosis (1.43), rheumatoid arthritis (1.39) and menstrual disorders (1.18) in women were also associated with more severe outcomes.,Age and specific cardiovascular and metabolic diseases increased the risk of severe SARS-CoV-2 infections in men and women, whereas the effects of certain comorbidities are sex specific.,Future studies in different settings are encouraged to analyze which profiles of chronic patients are at higher risk of poor prognosis and should therefore be the targets of prevention and shielding strategies.
|
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.
| 1 |
Genetic factors play a role in the development and severity of chronic obstructive pulmonary disease (COPD).,The pathogenesis of COPD is a multifactorial process including an inflammatory cell profile.,Recent studies revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the susceptibility to COPD through changing the airway inflammatory process and lung function.,In this paper, we investigated associations of four polymorphisms (T1, T2, S2 and Q-1) of ADAM33 as well as their haplotypes with pulmonary function and airway inflammatory process in an East Asian population of patients with COPD.,We found that T1, T2 and Q-1 were significantly associated with the changes of pulmonary function and components of cells in sputum of COPD, and T1 and Q-1 were significantly associated with cytokines and mediators of inflammation in airway of COPD in recessive models. 10 haplotypes were significantly associated with transfer factor of the lung for carbon monoxide in the disease state, 4 haplotypes were significantly associated with forced expiratory volume in one second, and other haplotypes were associated with airway inflammation.,We confirmed for the first time that ADAM33 was involved in the pathogenesis of COPD by affecting airway inflammation and immune response in an East Asian population.,Our results made the genetic background of COPD, a common and disabling disease, more apparent, which would supply genetic support for the study of the mechanism, classification and treatment for this disease.,The online version of this article (doi:10.1186/1471-2466-14-173) contains supplementary material, which is available to authorized users.
|
There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer.
| 1 |
Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcoholic Fatty Liver Disease (NAFLD) both independently increase cardiovascular risk.,We hypothesized that NAFLD might increase the incidence of cardiovascular disease and death in COPD patients.,The relationship between NAFLD, incident cardiovascular events, and death was assessed in a prospective cohort of COPD patients with 5-year follow-up.,Noninvasive algorithms combining biological parameters (FibroMax®) were used to evaluate steatosis, non-alcoholic steatohepatitis (NASH) and liver fibrosis.,Univariate and multivariate Cox regression models were used to assess the hazard for composite outcome at the endpoint (death or cardiovascular event) for each liver pathology.,In 111 COPD patients, 75% exhibited liver damage with a prevalence of steatosis, NASH and fibrosis of 41%, 37% and 61%, respectively.,During 5-year follow-up, 31 experienced at least one cardiovascular event and 7 died.,In univariate analysis, patients with liver fibrosis had more cardiovascular events and higher mortality (Hazard ratio [95% CI]: 2.75 [1.26; 6.03]) than those with no fibrosis; this remained significant in multivariate analysis (Hazard ratio [95% CI]: 2.94 [1.18; 7.33]).,We also found that steatosis and NASH were not associated with increased cardiovascular events or mortality.,To conclude, early assessment of liver damage might participate to improve cardiovascular outcomes in COPD patients.
|
Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD.,Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD.,Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”.,These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation.,In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells.,Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs).,Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD.,This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.
| 1 |
The impacts of high blood eosinophil count (HBEC) at admission for COPD exacerbation on posthospitalization outcomes are still unclear.,Previous studies have focused on its associations with first readmission rates; yet, its impacts on longitudinal outcomes such as subsequent readmissions still have to be explored.,The main objective of this study is to investigate outcomes associated with HBEC following a first hospitalization for COPD exacerbation.,This is an observational cohort study design.,We retrospectively analyzed data of patients with a first hospitalization within 5 years for COPD exacerbation between April 2006 and March 2013.,Patients were stratified into the HBEC group if the blood eosinophil count at admission was ≥200 cells/µL and/or ≥2% of the total white blood cells.,With information on exact dates of subsequent hospitalizations and death, we modeled readmissions and death as states in a multi-state Markov model and estimated transition probabilities to the next states.,Sensitivity analyses were performed by varying thresholds for the definition of HBEC (≥300 cells/µL and/or ≥3%).,A total of 479 patients were included, of which 173 had HBEC.,The transition probabilities for a first readmission was 74% (95% CI, 66%-83%) for patients with HBEC vs 70% (95% CI, 63%-77%) for patients with normal blood eosinophil count (NBEC).,The transition probabilities for a second readmission were 91% (95% CI, 84%-100%) for HBEC patients in contrast with 83% (95% CI, 74%-92%) for NBEC patients.,Meanwhile, transition probability for death was lower in patients with HBEC.,The differences enlarged in sensitivity analyses with higher cutoff.,Greater blood eosinophil cell counts during a first hospitalization for COPD predict increased susceptibility to up to two readmissions.,These patients may however have a lower risk of death.
|
Blood eosinophils have been suggested as a potential biomarker in chronic obstructive pulmonary disease (COPD), and their stability over time has been investigated in a few studies.,However, the association between the stability of blood eosinophils and long-term clinical outcomes in COPD patients has yet to be fully elucidated.,This study aimed to evaluate the stability of blood eosinophils and its association with clinical outcomes in COPD patients.,In total, 299 COPD patients from the Korean Obstructive Lung Disease cohort with at least two blood eosinophil measurements were included.,Patients were stratified according to a cut-off of 300 cells/μL, and the association between eosinophil changes and all-cause mortality was analysed.,The annual decline in forced expiratory volume in 1 s (FEV1), serial changes in St George’s Respiratory Questionnaire score (SGRQ), and exacerbations during follow-up were compared among eosinophil groups.,Patients were stratified into three groups according to the blood eosinophil cut-off: persistently < 300 cells/μL (PL; n = 175), variable (V; n = 68), and persistently ≥300 cells/μL (PH; n = 56).,There were no significant differences in baseline characteristics (age, sex, smoking, body mass index, use of inhaled corticosteroids, exacerbations in the previous year, FEV1 (L or % predicted), or emphysema score) among the groups.,During a median follow-up of 6.0 years, the PH group had a better survival rate than the PL group (adjusted mortality rate ratio, 0.29; 95% confidence interval, 0.09-0.97; P = 0.045).,The PH group also showed improved symptoms and impact domains of SGRQ score compared to the PL group.,No difference was found in annual FEV1 decline or exacerbations during follow-up among the groups.,Patients with persistently high blood eosinophils had a better survival rate than those with persistently low blood eosinophils.,Serial follow-up of blood eosinophils could help to predict outcomes in COPD patients.,The online version of this article (10.1186/s12931-018-0840-x) contains supplementary material, which is available to authorized users.
| 1 |
Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays.
|
► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.
| 1 |
Undiagnosed Chronic Obstructive Pulmonary Disease (COPD) results in high morbidity, disability and mortality in India.,Effective strategies for active COPD screening in community settings are needed to increase early identification, risk reduction and timely management.,The objective of this study was to test the diagnostic accuracy of a sequential two-step screening strategy to detect COPD, implemented by community health workers (CHWs), among adults aged ≥40 years in a rural area of North India.,Trained CHWs screened all consenting (n=3256) eligible adults in two villages using the Lung Function Questionnaire (LFQ) to assess their COPD risk and conducted pocket spirometry on 268 randomly selected (132 with high risk ie LFQ score ≤18 and 136 with low risk ie LFQ score >18) individuals.,Subsequently, trained researchers conducted post-bronchodilator spirometry on these randomly selected individuals using a diagnostic quality spirometer and confirmed the COPD diagnosis according to the Global Initiative for Obstructive Lung Disease (GOLD) criteria (FEV1/FVC ratio <0.7).,This strategy of using LFQ followed by pocket spirometry was sensitive (78.6%) and specific (78.8%), with a positive predictive value of 66% and negative predictive value of 88%.,It could accurately detect 67% of GOLD Stage 1, 78% of GOLD Stage 2, 82% of GOLD Stage 3 and 100% of GOLD Stage 4 individuals with airflow limitation.,COPD can be accurately detected by trained CHWs using a simple sequential screening strategy.,This can potentially contribute to accurate assessment of COPD and thus its effective management in low-resource settings.
|
Socioeconomic status (SES) is a strong social determinant of health.,There remains a limited understanding of the association between SES and COPD prevalence among low- and middle-income countries where the majority of COPD-related morbidity and mortality occurs.,We examined the association between SES and COPD prevalence using data collected in Argentina, Bangladesh, Chile, Peru, and Uruguay.,We compiled lung function, demographic, and SES data from three population-based studies for 11,042 participants aged 35-95 years.,We used multivariable alternating logistic regressions to study the association between COPD prevalence and SES indicators adjusted for age, sex, self-reported daily smoking, and biomass fuel smoke exposure.,Principal component analysis was performed on monthly household income, household size, and education to create a composite SES index.,Overall COPD prevalence was 9.2%, ranging from 1.7% to 15.4% across sites.,The adjusted odds ratio of having COPD was lower for people who completed secondary school (odds ratio [OR] =0.73, 95% CI 0.55-0.98) and lower with higher monthly household income (OR =0.96 per category, 95% CI 0.93-0.99).,When combining SES factors into a composite index, we found that the odds of having COPD was greater with lower SES (interquartile OR =1.23, 95% CI 1.05-1.43) even after controlling for subject-specific factors and environmental exposures.,In this analysis of multiple population-based studies, lower education, lower household income, and lower composite SES index were associated with COPD.,Since household income may be underestimated in population studies, adding household size and education into a composite index may provide a better surrogate for SES.
| 1 |
Implementation of noninvasive ventilation (NIV) as an add-on treatment has been routinely used in a non-intensive care setting since 2004 for patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure at a university hospital in Denmark.,Although randomized controlled trials show lowered mortality rates in highly selected patients with acute exacerbation and respiratory failure, there are only few reports on long-term survival after receiving NIV.,We present long-term all-cause mortality data from patients receiving NIV for the first time.,Data from medical records were retrospectively retrieved from all patients receiving NIV for the first time after being admitted acutely to an acute medical ward and further transfer to a respiratory ward with respiratory failure and a diagnosis of COPD in the period January 1, 2005 to December 31, 2007; patients were followed until January 2012.,Demographic data collected included age, sex, diagnoses at discharge, and, when present, FEV1; a “not-to-intubate” order was also registered when listed.,In total, 253 patients (143 female, 110 male) received NIV for the first time.,The median age was 72 years (range 46-91 years).,The 30-day mortality rate was 29.3%.,The 5-year survival rate was 23.7%.,Women showed a trend towards better survival than men (25.7% vs 19.2%, P = 0.25), and the trend was even more pronounced for patients with COPD.,The mortality rate of patients receiving NIV is high, as expected in a real-life setting, but with a 5-year survival rate of 23.7% with a trend towards more female than male long-term survivors.
|
Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects.
| 1 |
We examined whether systemic cytokine signaling via interleukin (IL)-17 and growth-related oncogene-α (GRO-α) is impaired in smokers with obstructive pulmonary disease including chronic bronchitis (OPD-CB).,We also examined how this systemic cytokine signaling relates to bacterial colonization in the airways of the smokers with OPD-CB.,Currently smoking OPD-CB patients (n=60, corresponding to Global initiative for chronic Obstructive Lung Disease [GOLD] stage I-IV) underwent recurrent blood and sputum sampling over 60 weeks, during stable conditions and at exacerbations.,We characterized cytokine protein concentrations in blood and bacterial growth in sputum.,Asymptomatic smokers (n=10) and never-smokers (n=10) were included as control groups.,During stable clinical conditions, the protein concentrations of IL-17 and GRO-α were markedly lower among OPD-CB patients compared with never-smoker controls, whereas the asymptomatic smoker controls displayed intermediate concentrations.,Notably, among OPD-CB patients, colonization by opportunistic pathogens was associated with markedly lower IL-17 and GRO-α, compared with colonization by common respiratory pathogens or oropharyngeal flora.,During exacerbations in the OPD-CB patients, GRO-α and neutrophil concentrations were increased, whereas protein concentrations and messenger RNA for IL-17 were not detectable in a reproducible manner.,In smokers with OPD-CB, systemic cytokine signaling via IL-17 and GRO-α is impaired and this alteration may be linked to colonization by opportunistic pathogens in the airways.,Given the potential pathogenic and therapeutic implications, these findings deserve to be validated in new and larger patient cohorts.
|
We have previously shown that the defective ability of alveolar macrophages (AM) to phagocytose apoptotic cells (‘efferocytosis’) in chronic obstructive pulmonary disease/emphysema (COPD) could be therapeutically improved using the C-type lectin, mannose binding lectin (MBL), although the exact mechanisms underlying this effect are unknown.,An S-type lectin, galectin-3, is also known to regulate macrophage phenotype and function, via interaction with its receptor CD98.,We hypothesized that defective expression of galectin/CD98 would be associated with defective efferocytosis in COPD and that mechanisms would include effects on cytoskeletal remodeling and macrophage phenotype and glutathione (GSH) availability.,Galectin-3 was measured by ELISA in BAL from controls, smokers and current/ex-smokers with COPD.,CD98 was measured on AM using flow cytometry.,We assessed the effects of galectin-3 on efferocytosis, CD98, GSH, actin polymerisation, rac activation, and the involvement of PI3K (using β-actin probing and wortmannin inhibition) in vitro using human AM and/or MH-S macrophage cell line.,Significant decreases in BAL galectin-3 and AM CD98 were observed in BAL from both current- and ex-smoker COPD subjects vs controls.,Galectin 3 increased efferocytosis via an increase in active GTP bound Rac1.,This was confirmed with β-actin probing and the role of PI3K was confirmed using wortmannin inhibition.,The increased efferocytosis was associated with increases in available glutathione and expression of CD98.,We provide evidence for a role of airway lectins in the failed efferocytosis in COPD, supporting their further investigation as potential macrophage-targeted therapies.
| 1 |
Comorbidities are associated with the severity of coronavirus disease 2019 (COVID‐19).,This meta‐analysis aimed to explore the risk of severe COVID‐19 in patients with pre‐existing chronic obstructive pulmonary disease (COPD) and ongoing smoking history.,A comprehensive systematic literature search was carried out to find studies published from December 2019 to 22 March 2020 from five databases.,The languages of literature included English and Chinese.,The point prevalence of severe COVID‐19 in patients with pre‐existing COPD and those with ongoing smoking was evaluated with this meta‐analysis.,Overall 11 case series, published either in Chinese or English language with a total of 2002 cases, were included in this study.,The pooled OR of COPD and the development of severe COVID‐19 was 4.38 (fixed‐effects model; 95% CI: 2.34‐8.20), while the OR of ongoing smoking was 1.98 (fixed‐effects model; 95% CI: 1.29‐3.05).,There was no publication bias as examined by the funnel plot and Egger's test (P = not significant).,The heterogeneity of included studies was moderate for both COPD and ongoing smoking history on the severity of COVID‐19.,COPD and ongoing smoking history attribute to the worse progression and outcome of COVID‐19.
|
The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) a pandemic [1].,COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,COVID-19 displays symptoms ranging from mild to severe (pneumonia) that can lead to death in some individuals [2-4].,As of 18 April 2020, there have been 2 280 945 cases of COVID-19 worldwide and 156 354 deaths [5].,SARS-CoV-2 uses the angiotensin-converting enzyme II (ACE-2) as the cellular entry receptor [6].,While the virus can infect individuals of any age, to date, most of the severe cases have been described in those >55 years of age and with significant comorbidities, such as COPD [7].,Here, we determined whether patients with COPD have increased expression of ACE-2 in bronchial epithelial cells in the lower respiratory tract.,Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus.,This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.https://bit.ly/3bC29es
| 1 |
Studies have suggested that chronic obstructive pulmonary disease (COPD) is commonly misdiagnosed and misclassified in primary care, but less is known about the quality of diagnosis in specialist respiratory care.,To measure the accuracy of COPD diagnosis and classification of airway obstruction in primary care and at a specialist respiratory centre, and to explore associations between misdiagnosis and misclassification and a range of explanatory factors.,Data were obtained for 1,205 referrals to a specialist respiratory centre between 2007 and 2010.,Standard analysis methods were used.,The majority of patients were referred for pulmonary rehabilitation (676/1,205, 56%).,Of 1,044 patients with a primary care diagnosis of COPD, 211 (20%) had spirometry inconsistent with COPD.,In comparison, of 993 specialist centre diagnoses, 65 (6.5%) had inconsistent spirometry.,There was poor agreement between the airflow obstruction grade recorded on the referral and that based on spirometry (kappa=0.26, n=448), whereas agreement between the respiratory centre assessment of airflow obstruction and spirometry was good (kappa=0.88, n=1,016).,Referral by practice nurse was associated with accuracy of airflow obstruction classification in primary care (OR 1.85, 95% CI 1.33 to 2.57).,Males were more likely than females to have an accurate specialist care classification of airway obstruction (OR 1.40, 95% CI 1.01 to 1.93).,Grade of airway obstruction changed between referral and assessment in 56% of cases.,In primary care, a proportion of patients diagnosed with COPD do not have COPD, and misclassification of grade of airflow obstruction is common.,Misdiagnosis and misclassification is less common in the specialist care setting of BreathingSpace.
|
Geographic clusters in prevalence and hospitalizations for COPD have been identified at national, state, and county levels.,The study objective is to identify county-level geographic accessibility to pulmonologists for adults with COPD.,Service locations of 12,392 practicing pulmonologists and 248,160 primary care physicians were identified from the 2013 National Provider Identifier Registry and weighted by census block-level populations within a series of circular distance buffer zones.,Model-based county-level population counts of US adults ≥ 18 years of age with COPD were estimated from the 2013 Behavioral Risk Factor Surveillance System.,The percentages of all estimated adults with potential access to at least one provider type and the county-level ratio of adults with COPD per pulmonologist were estimated for selected distances.,Most US adults (100% in urbanized areas, 99.5% in urban clusters, and 91.7% in rural areas) had geographic access to a primary care physician within a 10-mile buffer distance; almost all (≥ 99.9%) had access to a primary care physician within 50 miles.,At least one pulmonologist within 10 miles was available for 97.5% of US adults living in urbanized areas, but only for 38.3% in urban clusters and 34.5% in rural areas.,When distance increased to 50 miles, at least one pulmonologist was available for 100% in urbanized areas, 93.2% in urban clusters, and 95.2% in rural areas.,County-level ratios of adults with COPD per pulmonologist varied greatly across the United States, with residents in many counties in the Midwest having no pulmonologist within 50 miles.,County-level geographic variations in pulmonologist access for adults with COPD suggest that those adults with limited access will have to depend on care from primary care physicians.
| 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence.,Its underdiagnosis and hence under-treatment is a general feature across all countries.,This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease.,A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms.,Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV1% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV1 ≥80% predicted.,In recent years, an elegant series of studies has shown that “exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment”.,In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation.,Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy.,This is an essential issue in COPD.,In fact, on one hand, airflow limitation, even mild, can unduly limit the patient’s physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease.,Therefore, we thought that it was worthwhile to analyze further and discuss this stage of “mild COPD”.,To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with “mild” airflow limitation.,The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind “mild” COPD.,Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both.
|
A high prevalence of bronchiectasis was found by chest computed tomography (CT) in patients with moderate-severe chronic obstructive pulmonary disease (COPD), and it was shown to be associated with more severe symptoms, higher frequency of exacerbations and mortality.,The risk factors for bronchiectasis in COPD are not yet clarified.,High-resolution computed tomography (HRCT) of chest was performed in patients with moderate-severe COPD, and the presence and the extent of bronchiectasis were evaluated by two radiologists.,Demographic data, respiratory symptoms, lung function, previous pulmonary tuberculosis, serum inflammatory markers, serum total immunoglobulin E (T-IgE), and sputum culture of Pseudomonas aeruginosa were compared between those with and without bronchiectasis.,Multivariate logistic regression analysis was used to determine the independent factors associated with bronchiectasis.,We enrolled 190 patients with stable COPD, of which 87 (87/190, 45.8%) had bronchiectasis on HRCT.,Compared with those without bronchiectasis, COPD patients with bronchiectasis were more likely to be males (P = 0.021), had a lower body mass index (BMI) (P = 0.019), a higher prevalence of previous tuberculosis (P = 0.005), longer history of dyspnea (P < 0.001), more severe dyspnea (P = 0.041), higher frequency of acute exacerbation (P = 0.002), higher serum concentrations of C-reactive protein (CRP) (P = 0.017), fibrinogen (P = 0.016), and T-IgE [P = 0.004; for log10(T-IgE), P <0.001].,COPD patients with bronchiectasis also showed poorer lung function (for FEV1/FVC, P = 0.013; for FEV1%predicted, P = 0.012; for global initiative for chronic obstructive lung disease (GOLD) grades, P = 0.035), and a higher positive rate of sputum P aeruginosa (P = 0.020).,Logistic regression analysis demonstrated that male gender (P = 0.021), previous tuberculosis (P = 0.021), and increased level of serum T-IgE [for log10(T-IgE), P < 0.001] were risk factors for coexistent bronchiectasis.,More notably, the level of serum T-IgE [log10(T-IgE)] was positively correlated with the extent of bronchiectasis in COPD patients (r = 0.208, P = 0.05).,Higher serum T-IgE, male gender, and previous tuberculosis are independent risk factors for coexistent bronchiectasis in COPD.,The association of T-IgE with the extent of bronchiectasis also suggests that further investigations are needed to explore the potential role of IgE in the pathogenesis of bronchiectasis in COPD.
| 1 |
Hospitalization brings considerable economic pressure on COPD patients in China.,A clear understanding of hospitalization costs for patients with COPD is warranted to improve treatment strategies and to control costs.,Currently, investigation on factors contributing to hospitalization costs for patients with COPD in China is limited.,This study aimed to measure the hospitalization costs of COPD and to determine the contributing factors.,Medical record data from the First Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2016 were used for a retrospective analysis.,Patients who were hospitalized with a diagnosis of COPD were included.,Patient characteristics, medical treatment, and hospitalization costs were analyzed by descriptive statistics and multivariable regression.,Among the 1,943 patients included in this study, 87.85% patients were male; the mean (SD) age was 71.15 (9.79) years; 94.49% patients had comorbidities; and 82.30% patients had health insurance.,Regarding medical treatment, the mean (SD) length of stay was 9.38 (7.65) days; 11.12% patients underwent surgery; 87.91% used antibiotics; and 4.53% underwent emergency treatment.,For hospitalization costs, the mean (SD) of the total costs per COPD patient per admission was 24,372.75 (44,173.87) CNY (3,669.33 [6,650.38] USD), in which Western medicine fee was the biggest contributor (45.53%) followed by diagnosis fee (27.00%) and comprehensive medical fee (12.04%).,Regression found that reimbursement (−0.032; 95% CI −0.046 to 0.007), length of stay (0.738; 95% CI 0.832-0.892), comorbidity (0.044; 95% CI 0.029-0.093), surgery (0.145; 95% CI 0.120-0.170), antibiotic use (0.086; 95% CI 0.060-0.107), and emergency treatment (0.121; 95% CI 0.147-0.219) were significantly (P<0.01) associated with total hospitalization costs.,To control hospitalization costs for COPD patients in China, the significance of comorbidity, length of stay, antibiotic use, surgery, and emergency treatment suggests the importance of controlling the COPD progression and following clinical guidelines for inpatients.,Interventions such as examination of pulmonary function for early detection, quality control of medical treatment, and patient education warrant further investigation.
|
The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management.,A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD.,The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management.,Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation.,Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD.,Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations.,Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD.,In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence.,Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration.
| 1 |
Risk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke.,To investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts.,In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β′) of tobacco smoke exposure ≥10 pack-years (β = − 0.13 and β′ = − 0.14).,We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass.,The main outcome was the incidence of moderate or severe exacerbations.,Among 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%).,The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56-1.89; P = 0.921).,No interaction between sex and tobacco and biomass smoke was observed.,When propensity score matching with available covariates including age and sex was applied, a similar result was observed.,Patients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations.,This suggests that patients with COPD associated with biomass smoke should be treated actively.,The online version of this article (10.1186/s12890-019-0833-7) contains supplementary material, which is available to authorized users.
|
Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction.,We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain.,We interviewed 576 subjects of both sexes aged 20-70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire.,Forced spirometry was performed by 497 subjects according to ATS normative.,Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women).,Textile industry was the most frequently reported job in relation to these exposures (39%).,Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3).,Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits.,Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV1 -80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV1/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed.,Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry.,Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking.
| 1 |
To improve the care of patients with advanced COPD and be able to address their palliative needs a new outpatient organization (CAPTAIN) was developed and implemented.,CAPTAIN was inspired by best practice and existing guidelines and changed the traditional organization of an outpatient structure including the roles of nurses and doctors.,Only sparse knowledge exists of the health professionals’ expectations and experiences to organizational changes in an outpatient setting.,This insight is necessary as health professionals are key stakeholders in implementing new structures and successfully transforming knowledge into practice.,The aim of this study was to explore the health professionals’ expectations and experiences of a new palliative out-patients structure for patients with advanced COPD.,The design was interpretive description as described by Thorne.,Focus groups and individual interviews were conducted with pulmonary nurses, pulmonary doctors and municipality nurses from 2014 to 2016.,The overall theme was dualism.,Both nurses and doctors were pending between aspiration and concern in their expectations to the new structure, meanwhile their actual experiences were pending between perceived gain and improvements versus consequences with the new structure.,Nurses’ and doctors’ existing practice was altered and the new structure required new ways for them to cooperate and ways in which skills from each profession were most efficiently utilized.,Nurses and doctors considered the new structure as a quality boost and it fulfilled their hope of improving the quality of care offered to patients with advanced COPD, however with increased work-related stress as a derived consequence.
|
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.
| 1 |
Lipid metabolism plays an important role in many lung functions.,Disorders of lipid metabolism are part of the pathogenesis of chronic obstructive pulmonary disease (COPD).,Lipids are involved in numerous cross-linkages with inflammation.,Recent studies strongly support the involvement of fatty acids as participants in inflammation.,They are involved in the initiation and resolution of inflammation, including acting as a substrate for the formation of lipid mediators of inflammation resolution.,Specialized pro-inflammatory mediators (SPMs) belonging to the classes of lipoxins, resolvins, maresins, and protectins, which are formed enzymatically from unsaturated fatty acids, are now described.,Disorders of their production and function are part of the pathogenesis of COPD.,SPMs are currently the subject of active research in order to find new drugs.,Short-chain fatty acids are another important participant in metabolic and immune processes, and their role in the pathogenesis of COPD is of great clinical interest.
|
Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease.
| 1 |
BackgroundThe clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition,MethodsHCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction.,Laboratory-documented influenza (LDI) was detected by serologic assay and culture.,HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998-99 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were ⩾50 years old and who received influenza vaccines,ResultsHCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses.,In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13-0.58]).,A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness.,Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization.,A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1,ConclusionsThe frequencies of HCoV and LDI illnesses were similar.,HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization
|
Respiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations.,Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown.,We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection.,Nine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus.,Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages.,In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured.,Rhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD.,O&NS markers correlated with virus load and inflammatory markers.,Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress.,Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation.,Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines.,O&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations.,Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations.
| 1 |
Circulating endothelial microparticles (EMPs) and progenitor cells (PCs) are biological markers of endothelial function and endogenous repair capacity.,The study was aimed to investigate whether COPD patients have an imbalance between EMPs to PCs compared to controls and to evaluate the effect of cigarette smoke on these circulating markers.,Circulating EMPs and PCs were determined by flow cytometry in 27 nonsmokers, 20 smokers and 61 COPD patients with moderate to severe airflow obstruction.,We compared total EMPs (CD31+CD42b-), apoptotic if they co-expressed Annexin-V+ or activated if they co-expressed CD62E+, circulating PCs (CD34+CD133+CD45+) and the EMPs/PCs ratio between groups.,COPD patients presented increased levels of total and apoptotic circulating EMPs, and an increased EMPs/PCs ratio, compared with nonsmokers.,Women had less circulating PCs than men through all groups and those with COPD showed lower levels of PCs than both control groups.,In smokers, circulating EMPs and PCs did not differ from nonsmokers, being the EMPs/PCs ratio in an intermediate position between COPD and nonsmokers.,We conclude that COPD patients present an imbalance between endothelial damage and repair capacity that might explain the frequent concurrence of cardiovascular disorders.,Factors related to the disease itself and gender, rather than cigarette smoking, may account for this imbalance.
|
Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown.,We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS.,CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells.,CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium.,CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice.,The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis.,Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages.,These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers.
| 1 |
Familial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees.,The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents.,Historic cohort study.,80 214 (50% females).,The Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932-2004 (n=80 214) between 1 January 1964 and 31 December 2010 for COPD (n=1978).,The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD.,The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162).,COPD in adoptees.,Adoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)).,The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00).,Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)).,The findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD.
|
Cigarette smoking is the major risk factor for COPD, leading to chronic airway inflammation.,We hypothesized that cigarette smoke induces structural and functional changes of airway epithelial mitochondria, with important implications for lung inflammation and COPD pathogenesis.,We studied changes in mitochondrial morphology and in expression of markers for mitochondrial capacity, damage/biogenesis and fission/fusion in the human bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD stage IV patients to age-matched smoking and never-smoking controls.,We observed that long-term CSE exposure induces robust changes in mitochondrial structure, including fragmentation, branching and quantity of cristae.,The majority of these changes were persistent upon CSE depletion.,Furthermore, long-term CSE exposure significantly increased the expression of specific fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress (Mn-SOD) markers.,These changes were accompanied by increased levels of the pro-inflammatory mediators IL-6, IL-8, and IL-1β.,Importantly, COPD primary bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial morphology as observed in long-term CSE-exposure BEAS-2B cells.,Moreover, expression of specific OXPHOS proteins was higher in PBECs from COPD patients than control smokers, as was the expression of mitochondrial stress marker PINK1.,The observed mitochondrial changes in COPD epithelium are potentially the consequence of long-term exposure to cigarette smoke, leading to impaired mitochondrial function and may play a role in the pathogenesis of COPD.
| 1 |
Comparative effects on physical activity of mono and dual bronchodilators remain unclear in patients with treatment-naïve chronic obstructive pulmonary disease (COPD).,We sought to compare the changes in physical activity before and after tiotropium and tiotropium/olodaterol treatment in treatment-naïve COPD patients.,A prospective, multicenter, randomized, open-labeled, and parallel interventional study was conducted.,Eighty Japanese patients with treatment-naïve COPD were randomized to receive either tiotropium or tiotropium/olodaterol treatment for 12 weeks.,Spirometry and dyspnea index were assessed, and COPD assessment test (CAT) and the 6-minute walk distance (6MWD) were conducted before and after treatment.,Evaluation of physical activity was assessed by a triaxle accelerometer over a 2-week period before and after treatment.,There were no differences in the mean age (69.8 vs 70.4 years), body mass index (BMI) (22.5 vs 22.6 kg/m2) and mean % forced expiratory volume in 1 second (%FEV1) at baseline (61.5 vs 62.6%) between the two groups.,Changes in FEV1 (mean±standard error, 242.8±28.8 mL) and transient dyspnea index (TDI) (2.4±0.3 points) before and after tiotropium/olodaterol treatment were greater than with tiotropium treatment (104.1±31.9 mL, p<0.01 and 1.5±0.3, p=0.02, respectively).,Changes in the duration of physical activity with 1.0-1.5 metabolic equivalents (METs) estimated in the sedentary position following tiotropium/olodaterol treatment (−38.7±14.7 min) tended to be reduced more than with tiotropium treatment (−4.6±10.6 min) (p=0.06), although those with ≥2.0 METs numerically increased with both treatments (+10.8±7.6 min for tiotropium/olodaterol vs +8.3±7.6 min for tiotropium, p=0.82).,Tiotropium/olodaterol treatment reduced the duration of physical activity with 1.0-1.5 METs (regression coefficient, −43.6 [95% CI −84.1, −3.1], p=0.04) in a multiple regression model adjusted for cofounding factors such as age, FEV1, total CAT scores, 6MWD, and TDI.,This is the first study to report the impact of dual bronchodilator on physical activity in treatment-naïve COPD patients of Japanese with low BMI.
|
In 2013, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) updated the management strategy on COPD based on severity using a combined assessment of symptoms, degree of airflow limitation, and number of exacerbations.,This study quantified prevalence and incidence of COPD in the United Kingdom and estimated disease severity by GOLD 2013 categories A/B (low risk) and C/D (high risk).,The Clinical Practice Research Datalink was used to identify COPD patients ≥40 years.,Patient characteristics were described, and prevalence was calculated on December 31, 2013.,Five-year incidence (2009-2013) was estimated, with rates standardized using 2011 UK population age and sex.,To classify patients by GOLD categories, spirometry results, the modified British Medical Research Council grade, and history of exacerbations were used.,The prevalent cohort comprised 49,286 patients with COPD with mean age 70 years; 51.0% were male.,Overall prevalence was 33.3 per 1,000 persons (95% confidence interval [CI]: 33.1-33.6); 66.4% were classified as GOLD A/B and 33.6% as C/D.,The standardized prevalence of GOLD A/B was 21.9 per 1,000 persons (95% CI: 21.7-22.1) and of C/D was 11.1 (95% CI: 10.9-11.2).,A total of 27,224 newly diagnosed COPD patients were identified with mean age 67 years at diagnosis; 53.0% were male.,Incidence was 2.2 per 1,000 person-years (95% CI: 2.2-2.3); 68.7% were classified in categories A/B and 31.3% in C/D, of which 17.2% did not receive COPD maintenance medication.,A third of COPD patients in the UK are considered high risk (GOLD 2013 categories C/D), and a third of patients are diagnosed for the first time at these severe stages.,Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD in the UK is warranted.
| 1 |
Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear.,This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD.,Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers.,Serum concentrations of PAI-1, suPAR, tissue inhibitor of metalloproteinase-1 (TIMP-1), Matrix metalloproteinase-9 (MMP-9), and C-reactive protein (CRP) were detected with Magnetic Luminex Screening Assay.,Differences between groups were statistically analyzed using one-way analysis of variance or chi-square test.,Pearson’s partial correlation test (adjusted for age, sex, body mass index, cigarette status, and passive smoke exposure) and multivariable linear analysis were used to explore the relationships between circulating PAI-1 and indicators of COPD.,First, we found that serum PAI-1 levels but not suPAR levels were significantly increased in COPD patients compared with healthy volunteers (125.56±51.74 ng/mL versus 102.98±36.62 ng/mL, P=0.007).,Then, the correlation analysis showed that circulating PAI-1 was inversely correlated with pulmonary function parameters including the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC), FEV1/Pre (justified r=−0.308, P<0.001; justified r=−0.295, P=0.001, respectively) and SAO indicators such as FEV3/FVC, MMEF25-75/Pre (justified r=−0.289, P=0.001; justified r=−0.273, P=0.002, respectively), but positively related to the inflammatory marker CRP (justified r=0.351, P<0.001), the small airway remolding biomarker TIMP-1, and MMP-9 (justified r=0.498, P<0.001; justified r=0.267, P=0.002, respectively).,Besides, multivariable linear analysis showed that FEV1/FVC, CRP, and TIMP-1 were independent parameters associated with PAI-1.,Our findings first illustrate that elevated serum PAI-1 levels are related to the lung function decline, systemic inflammation, and SAO in COPD, suggesting that PAI-1 may play critical roles in the pathogenesis of COPD.
|
Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
| 1 |
The clinical value of blood eosinophils and their stability in chronic obstructive pulmonary disease (COPD) remains controversial.,There are limited studies on association between the stability of blood eosinophils in acute exacerbation of COPD (AECOPD) and clinical outcomes.,This study aimed to evaluate the stability of blood eosinophils in hospitalized AECOPD and its relationship to clinical outcomes.,This prospective observational study recruited patients hospitalized with AECOPD from November 2016 to July 2020.,The eligible patients were divided into four groups according to their blood eosinophil counts at admission and discharge: persistently < 300 cells/μl (LL), < 300 cells/μl at admission but ≥ 300 cells/µl at discharge (LH), ≥ 300 cells/μl at admission but < 300 cells/µl at discharge (HL), and persistently ≥ 300 cells/μl (HH).,Cox hazard analyses were used to study the association between eosinophil changes and exacerbations or mortality.,In 530 patients included, 90 (17.0%) had a high blood eosinophil count (BEC) ≥ 300 cells/µl at admission but 32 (35.6%) of them showed a decreased BEC at discharge.,The proportions and distribution for group LL, LH, HL, and HH were 381 (71.9%), 59 (11.1%), 32 (6.0%), and 58 (10.9%), respectively.,During hospitalization, the LH group had a higher C-reactive protein level, higher rate of intensive care unit (ICU) admission, and higher total cost.,The length of hospital stay of the LH group was longer compared with group LL, HL, or HH (P = 0.002, 0.017, and 0.001, respectively).,During a follow-up of 12 months, the HH group was associated with a higher risk of moderate-to-severe exacerbations compared to the LL group (hazard ratio 2.00, 95% confidence interval 1.30-3.08, P = 0.002).,Eosinophil changes had no significant association with mortality at 12 months.,Sensitivity analyses in patients without asthma and without use of systemic corticosteroids prior to admission did not alter the results.,More attention should be paid to the LH group when evaluating the short-term prognosis of AECOPD.,A persistently high BEC was a risk factor for long-term exacerbations.,Eosinophil changes during hospitalization could help to predict outcomes.,The online version contains supplementary material available at 10.1186/s12931-021-01888-5.
|
Asthma and chronic obstructive pulmonary disease (COPD) are both highly prevalent conditions that can coexist in the same individual: the so-called ‘asthma -COPD overlap’ (ACO).,Its prevalence and prognosis vary widely depending on how ACO is defined in each publication, the severity of bronchial obstruction of patients included and the treatment they are receiving.,Although there is a lack of evidence about the biology of ACO, the overlap of both diseases should express a mixture of a Th1 inflammatory pattern (characteristic of COPD) and a Th2 signature (characteristic of asthma).,In this review we support a novel algorithm for ACO diagnosis proposed by the Spanish Respiratory Society (SEPAR), based on a sequential evaluation that considers: (a) the presence of chronic airflow limitation in a smoker or ex-smoker patient ⩾35 years old; (b) a current diagnosis of asthma; and (c) the existence of a very positive bronchodilator test (PBT; ⩾15% and ⩾400 ml) or the presence of eosinophilia in blood (⩾300 eosinophils/μl).,This algorithm can identify those patients who may benefit from a treatment with inhaled corticosteroids (ICSs) and maybe from biological drugs in a near future.,In addition, it is easily applicable in clinical practice.,The major disadvantage is that it groups patients with very different characteristics under the ACO’s umbrella.,In view of this heterogeneity, we recommend a strategy of defining specific and measurable therapeutic objectives for every single patient and identifying the traits that can be treated to achieve those objectives.
| 1 |
Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results.,Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.,Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years.,Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.,Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB−) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB+).,CB+ subjects were older, more frequently current smokers and had more pack-years than CB− subjects.,During a median 6.5 years of follow-up, CB+ subjects had greater decline in lung function (−38 mL·year−1, 95% CI −61.7-−14.6; p=0.024).,CB+ subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001).,In females, survival was significantly worse in CB+ subjects compared to CB− subjects.,Regarding cause-specific mortality, CB+ subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).,COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.,Chronic bronchitis increases the risk of exacerbations and mortality among patients with COPDhttp://ow.ly/o1fq30bFf9Q
|
Symptoms, particularly dyspnea, and activity limitation, have an impact on the health status and the ability to function normally in patients with chronic obstructive pulmonary disease (COPD).,To develop an electronic patient diary (eDiary), qualitative patient interviews were conducted from 2009 to 2010 to identify relevant symptoms and degree of bother due to symptoms.,The eDiary was completed by a subset of 209 patients with moderate-to-severe COPD in the 26-week QVA149 SHINE study.,Two morning assessments (since awakening and since the last assessment) and one evening assessment were made each day.,Assessments covered five symptoms (“shortness of breath,” “phlegm/mucus,” “chest tightness,” “wheezing,” and “coughing”) and two impact items (“bothered by COPD” and “difficulty with activities”) and were scored on a 10-point numeric scale.,Patient compliance with the eDiary was 90.4% at baseline and 81.3% at week 26.,Correlations between shortness of breath and impact items were >0.95.,Regression analysis showed that shortness of breath was a highly significant (P<0.0001) predictor of impact items.,Exploratory factor analysis gave a single factor comprising all eDiary items, including both symptoms and impact items.,Shortness of breath, the total score (including five symptoms and two impact items), and the five-item symptom score from the eDiary performed well, with good consistency and reliability.,The eDiary showed good sensitivity to change, with a 0.6 points reduction in the symptoms scores (on a 0-10 point scale) representing a meaningful change.,The eDiary was found to be valid, reliable, and responsive.,The high correlations obtained between “shortness of breath” and the ratings of “bother” and “difficulty with activities” confirmed the relevance of this symptom in patients with COPD.,Future studies will be required to explore further psychometric properties and their ability to differentiate between COPD treatments.
| 1 |
Microspirometry may be useful as the second stage of a screening pathway among patients reporting respiratory symptoms.,We assessed sensitivity and specificity of the Vitalograph® lung monitor compared with post-bronchodilator confirmatory spirometry (ndd Easy on-PC) among primary care chronic obstructive pulmonary disease (COPD) patients within the Birmingham COPD cohort.,We report a case-control analysis within 71 general practices in the UK.,Eligible patients were aged ≥40 years who were either on a clinical COPD register or reported chronic respiratory symptoms on a questionnaire.,Participants performed pre- and post-bronchodilator microspirometry, prior to confirmatory spirometry.,Out of the 544 participants, COPD was confirmed in 337 according to post-bronchodilator confirmatory spirometry.,Pre-bronchodilator, using the LLN as a cut-point, the lung monitor had a sensitivity of 50.5% (95% CI 45.0%, 55.9%) and a specificity of 99.0% (95% CI 96.6%, 99.9%) in our sample.,Using a fixed ratio of FEV1/FEV6 < 0.7 to define obstruction in the lung monitor, sensitivity increased (58.8%; 95% CI 53.0, 63.8) while specificity was virtually identical (98.6%; 95% CI 95.8, 99.7).,Within our sample, the optimal cut-point for the lung monitor was FEV1/FEV6 < 0.78, with sensitivity of 82.8% (95% CI 78.3%, 86.7%) and specificity of 85.0% (95% CI 79.4%, 89.6%).,Test performance of the lung monitor was unaffected by bronchodilation.,The lung monitor could be used in primary care without a bronchodilator using a simple ratio of FEV1/FEV6 as part of a screening pathway for COPD among patients reporting respiratory symptoms.
|
Chronic obstructive pulmonary disease prevalence rates are still high.,However, the majority of subjects are not diagnosed.,Strategies have to be implemented to overcome the problem of under-diagnosis.,Questionnaires could be used to pre-select subjects for spirometry and thereby help reducing under-diagnosis.,We report a brief, simple, self-administrable and validated chronic obstructive pulmonary disease questionnaire to increase the pre-test probability for chronic obstructive pulmonary disease diagnosis in subjects undergoing confirmatory spirometry.,In 2005, we completed the Austrian Burden of Obstructive Lung Disease-study in 1258 subjects aged >40 years.,Post-bronchodilator spirometry was performed, and non-reversible airflow limitation defined by FEV1/FVC ratio below the lower limit of normal.,Questions from the Salzburg chronic obstructive pulmonary disease screening-questionnaire were selected using a logistic regression model, and risk scores were based on regression-coefficients.,A training sub-sample (n = 800) was used to create the score, and a test sub-sample (n = 458) was used to test it.,In 2008, an external validation study was done, using the same protocol in 775 patients from primary care.,The Salzburg chronic obstructive pulmonary disease screening questionnaire was composed of items related to “breathing problems”, “wheeze”, “cough”, “limitation of physical activity”, and “smoking”.,At the >=2 points cut-off of the Salzburg chronic obstructive pulmonary disease screening questionnaire, sensitivity was 69.1% [95%CI: 56.6%; 79.5%], specificity 60.0% [95%CI: 54.9%; 64.9%], the positive predictive value 23.2% [95%CI: 17.7%; 29.7%] and the negative predictive value 91.8% [95%CI: 87.5%; 95.7%] to detect post bronchodilator airflow limitation.,The external validation study in primary care confirmed these findings.,The Salzburg chronic obstructive pulmonary disease screening questionnaire was derived from the highly standardized Burden of Obstructive Lung Disease study.,This validated and easy to use questionnaire can help to increase the efficiency of chronic obstructive pulmonary disease case-finding.,Scientists in Austria have developed a brief, simple questionnaire to identify patients likely to have early-stage chronic lung disease.,Chronic obstructive pulmonary disease (COPD) is notoriously difficult to diagnose, and the condition often causes irreversible lung damage before it is identified.,Finding a simple, cost-effective method of pre-screening patients with suspected early-stage COPD could potentially improve treatment responses and limit the burden of extensive lung function (‘spirometry’) tests on health services.,Gertraud Weiss at Paracelsus Medical University, Austria, and co-workers have developed and validated an easy-to-use, self-administered questionnaire that could prove effective for pre-screening patients.,The team trialed the five-point Salzburg COPD-screening questionnaire on 1258 patients.,Patients scoring 2 points or above on the questionnaire underwent spirometry tests.,The questionnaire seems to provide a sensitive and cost-effective way of pre-selecting patients for spirometry referral.
| 1 |
This systematic review details symptom clusters, their compositions, and associated factors and appraises the methodologies of studies that reported symptom clusters in patients with chronic obstructive pulmonary disease (COPD).,Ten studies were eligible for inclusion in this study.,Four common symptom clusters were identified.,Two theoretical frameworks, four statistical methods, and various symptom assessment tools were used to identify symptom clusters.,Factors associated with symptom clusters included demographic, clinical, and biological factors.,No studies examined the subjective experiences of symptom clusters.,Overall, inconsistencies were identified in the composition of symptom clusters across studies.,This may be due to variations in study design, assessment tools, and statistical methods.,Future studies should attempt to arrive at a common definition, especially that is theoretically derived, for symptom clusters, standardize the criteria for symptoms for inclusion in the clusters, and focus on patients’ subjective experience to inform which clusters are clinically relevant.
|
During 2007-2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data for the subset of adults with airflow limitation.,The goals of this study were to 1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD) using pre-bronchodilator and post-bronchodilator spirometry measurements and fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine the potential impact of nonresponse on the estimates.,This analysis was limited to those aged 40-79 years who were eligible for NHANES pre-bronchodilator spirometry (n=7,104).,Examinees with likely airflow limitation were further eligible for post-bronchodilator testing (n=1,110).,Persons were classified as having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of normal (LLN) based on person’s age, sex, height, and race/ethnicity.,Those without spirometry but self-reporting both daytime supplemental oxygen therapy plus emphysema and/or current chronic bronchitis were also classified as having COPD.,The final analytic samples for pre-bronchodilator and post-bronchodilator analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively.,To account for non-response, NHANES examination weights were adjusted to the eligible pre-bronchodilator and post-bronchodilator subpopulations.,In 2007-2010, using the fixed ratio criterion and pre-bronchodilator test results, COPD prevalence was 20.9% (SE 1.1) among US adults aged 40-79 years.,Applying the same criterion to post-bronchodilator test results, prevalence was 14.0% (SE 1.0).,Using the LLN criterion and pre-bronchodilator test results, the COPD prevalence was 15.4% (SE 0.8), while applying the same criterion to post-bronchodilator test results, prevalence was 10.2% (SE 0.8).,The overall COPD prevalence among US adults aged 40-79 years varied from 10.2% to 20.9% based on whether pre- or post-bronchodilator values were used and which diagnostic criterion (fixed ratio or LLN) was applied.,The overall prevalence decreased by approximately 33% when airflow limitation was based on post-bronchodilator as compared to pre-bronchodilator spirometry, regardless of which diagnostic criterion was used.
| 1 |
Chronic obstructive pulmonary disease (COPD) is associated with exercise limitation and physical inactivity, which are believed to have significant long-term negative health consequences for patients.,While a number of COPD treatments and exercise training programmes increase exercise capacity, there is limited evidence for their effects on physical activity levels, with no clear association between exercise capacity and physical activity in clinical trials.,Physical activity depends on a number of behaviour, environmental and physiological factors.,We describe the design of the PHYSACTO trial, which is investigating the effects of bronchodilators, either alone or with exercise training, in combination with a standardised behaviour-change self-management programme, on exercise capacity and physical activity in patients with COPD.,It is hypothesised that bronchodilators in conjunction with a behaviour-change self-management programme will improve physical activity and that this effect will be amplified by the addition of exercise training.,Patients are being recruited from 34 sites in Australia, New Zealand, the USA, Canada and Europe.,Patients receiving a multicomponent intervention designed to support behaviour change related to physical activity are randomised to four treatment arms: placebo, tiotropium, tiotropium+olodaterol, and tiotropium+olodaterol+exercise training.,The primary outcome is improvement in exercise capacity after 8 weeks, measured by endurance time during a shuttle walk test.,The secondary outcome is improvement in physical activity, including objective accelerometer assessment and patient-reported functioning using the Functional Performance Inventory-Short Form and the novel hybrid PROactive instrument.,Additionally, the influence of moderating variables (ie, factors influencing a patient's choice to be physically active) on increases in physical activity is also explored.,The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations.,The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.,NCT02085161.
|
Despite being a major public health problem, chronic obstructive pulmonary disease (COPD) remains underdiagnosed, and only 2.4% COPD patients are aware of their disease in Korea.,The objective of this study was to estimate the prevalence of COPD detected by spirometry performed as a preoperative screening test and to determine the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group distribution and self-awareness of COPD.,We reviewed the medical records of adults (age, ≥40 years) who had undergone spirometry during preoperative screening between April and August 2013 at a tertiary hospital in Korea.,COPD was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio of <0.7.,We analyzed self-administered COPD questionnaires for the assessment of the frequency of acute exacerbation over the previous year and dyspnea severity using the modified Medical Research Council dyspnea scale and COPD assessment test.,Among 3029 patients aged >40 years who had undergone spirometry as a preoperative screening test, 474 (15.6%; 404 men; median age, 70 years; range, 44-93 years) were diagnosed with COPD.,Only 26 (5.5%) patients reported previous diagnosis of COPD (2.1%), emphysema (0.8%), or chronic bronchitis (2.5%).,The GOLD group distribution was as follows: 63.3% in group A, 31.2% in group B, 1.7% in group C, and 3.8% in group D.,The prevalence of COPD diagnosed by preoperative spirometry was 15.6%, and only 5.5% patients were aware of their disease.,Approximately one-third of the COPD patients belonged to GOLD groups B, C, and D, which require regular treatment.
| 1 |
To evaluate the effectiveness of telephone health coaching delivered by a nurse to support self management in a primary care population with mild symptoms of chronic obstructive pulmonary disease (COPD).,Multicentre randomised controlled trial.,71 general practices in four areas of England.,577 patients with Medical Research Council dyspnoea scale scores of 1 or 2, recruited from primary care COPD registers with spirometry confirmed diagnosis.,Patients were randomised to telephone health coaching (n=289) or usual care (n=288).,Telephone health coaching intervention delivered by nurses, underpinned by Social Cognitive Theory.,The coaching promoted accessing smoking cessation services, increasing physical activity, medication management, and action planning (4 sessions over 11 weeks; postal information at weeks 16 and 24).,The nurses received two days of training.,The usual care group received a leaflet about COPD.,The primary outcome was health related quality of life at 12 months using the short version of the St George’s Respiratory Questionnaire (SGRQ-C).,The intervention was delivered with good fidelity: 86% of scheduled calls were delivered; 75% of patients received all four calls. 92% of patients were followed-up at six months and 89% at 12 months.,There was no difference in SGRQ-C total score at 12 months (mean difference −1.3, 95% confidence interval −3.6 to 0.9, P=0.23).,Compared with patients in the usual care group, at six months follow-up, the intervention group reported greater physical activity, more had received a care plan (44% v 30%), rescue packs of antibiotics (37% v 29%), and inhaler use technique check (68% v 55%).,A new telephone health coaching intervention to promote behaviour change in primary care patients with mild symptoms of dyspnoea did lead to changes in self management activities, but did not improve health related quality of life.,Current controlled trials ISRCTN 06710391
|
COPD has significant psychosocial impact.,Self-management support improves quality of life, but programs are not universally available.,IT-based self-management interventions can provide home-based support, but have mixed results.,We conducted a case series of an off-the-shelf Internet-based health-promotion program, The Preventive Plan (TPP), coupled with nurse-coach support, which aimed to increase patient activation and provide self-management benefits.,A total of 19 COPD patients were recruited, and 14 completed 3-month follow-up in two groups: groups 1 and 2 with more and less advanced COPD, respectively.,Change in patient activation was determined with paired t-tests and Wilcoxon signed-rank tests.,Benefits and user experience were explored in semistructured interviews, analyzed thematically.,Only group 1 improved significantly in activation, from a lower baseline than group 2; group 1 also improved significantly in mastery and anxiety.,Both groups felt significantly more informed about COPD and reported physical functioning improvements.,Group 1 reported improvements in mood and confidence.,Overall, group 2 reported fewer benefits than group 1.,Both groups valued nurse-coach support; for group 1, it was more important than TPP in building confidence to self-manage.,The design of TPP and lack of motivation to use IT were barriers to use, but disease severity and poor IT skills were not.,Our findings demonstrate the feasibility of combining nurse-coach support aligned to an Internet-based health resource, TPP, in COPD and provide learning about the challenges of such an approach and the importance of the nurse-coach role.
| 1 |
Chinese herbal medicine is widely used in combination with usual care for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China.,Chinese patent medicine Shufeng Jiedu (SFJD) capsules is widely used for respiratory infectious diseases.,This review aims to evaluate effectiveness and safety of SFJD for AECOPD.,A systematic review of randomised controlled trials (RCTs) in patients with AECOPD, who received SFJD as a single intervention or as add-on treatment to usual care.,PubMed, the Cochrane Library, EMBASE, Scopus, Web of Science and four Chinese databases were searched from inception to April 2019.,Two authors screened trials, extracted data, and assessed risk of bias, independently.,Meta-analysis was performed using RevMan 5.3 software.,We performed subgroup analyses and sensitivity analyses according to the predefined protocol.,Quality of evidence was assessed using GRADE.,Thirteen RCTs (1036 patients, with 936 inpatients) were included, all compared SFJD in combination with usual care (including antibiotics) to usual care alone.,The mean age of participants ranged from 52 to 67 years, with approximately 60% male.,Due to lack of blinding and other factors, all trials were of high risk of bias.,SFJD was associated with a significant reduction in treatment failure, from 20.1 to 8.3% (11 trials; 815 patients; relative risk 0.43, 95% confidence interval [CI] 0.30 to 0.62), and duration of hospital stay (2 trials; 79 patients; mean difference − 4.32 days, 95% CI − 5.89 to − 2.75 days).,No significant difference in adverse events was found between SFJD and control groups.,Low certainty evidence suggests SFJD may bring additional benefit in reducing treatment failure, shorten hospital stay, and improving symptoms.,Further large, high quality RCTs are needed to confirm its benefit and safety.,PROSPERO CRD42019133682.
|
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality.,Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy.,This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs.,A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted.,A total of 244 patients were divided into the intervention group (n = 122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n = 122, treated with conventional medicine and placebo).,Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded.,Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment.,A total of 242 patients completed the study.,The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229.,After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P < .001; PPS: mean difference -1.87, 95% CI -2.71 to -1.03, P < .001).,FEV1, FVC, and FEV1%pred were significantly higher over time in the Xuan Bai Cheng Qi group compared with those in the control group (day 10, FAS and PPS: P < .05).,PaO2 and PaCO2 were significantly improved in the Xuan Bai Cheng Qi group (day 10, FAS and PPS: P < .05).,Xuan Bai Cheng Qi was also found to ameliorate cytokine levels and oxidation/antioxidant index compared with placebo.,There were no differences in safety variables and adverse events between the two groups.,Xuan Bai Cheng Qi formula appears to be a safe and beneficial treatment for AECOPD of phlegm-heat obstructing the lungs syndrome type.
| 1 |
The coexistence of COPD and asthma is widely recognized but has not been well described.,This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.,We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.,119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma.,These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001).,More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001).,Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001).,Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT.,There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.,Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life.,They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.,ClinicalTrials.gov: NCT00608764
|
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among US adults and is projected to be the third by 2020.,In anticipation of the increasing burden imposed on healthcare systems and payers by patients with COPD, a means of identifying COPD patients who incur higher healthcare utilization and costs is needed.,This retrospective, cross-sectional analysis of US managed care administrative claims data describes a practical way to identify COPD patients.,We analyze 7.79 million members for potential inclusion in the COPD cohort, who were continuously eligible during a 1-year study period.,A younger commercial population (7.7 million) is compared with an older Medicare population (0.115 million).,We outline a novel approach to stratifying COPD patients using "complexity" of illness, based on occurrence of claims for given comorbid conditions.,Additionally, a unique algorithm was developed to identify and stratify COPD exacerbations using claims data.,A total of 42,565 commercial (median age 56 years; 51.4% female) and 8507 Medicare patients (median 75 years; 53.1% female) were identified as having COPD.,Important differences were observed in comorbidities between the younger commercial versus the older Medicare population.,Stratifying by complexity, 45.0%, 33.6%, and 21.4% of commercial patients and 36.6%, 35.8%, and 27.6% of older patients were low, moderate, and high, respectively.,A higher proportion of patients with high complexity disease experienced multiple (≥2) exacerbations (61.7% commercial; 49.0% Medicare) than patients with moderate- (56.9%; 41.6%), or low-complexity disease (33.4%; 20.5%).,Utilization of healthcare services also increased with an increase in complexity.,In patients with COPD identified from Medicare or commercial claims data, there is a relationship between complexity as determined by pulmonary and non-pulmonary comorbid conditions and the prevalence of exacerbations and utilization of healthcare services.,Identification of COPD patients at highest risk of exacerbations using complexity stratification may facilitate improved disease management by targeting those most in need of treatment.
| 1 |
Existing data on COPD prevalence are limited or totally lacking in many regions of Europe.,The geographic information system inverse distance weighted (IDW) interpolation technique has proved to be an effective tool in spatial distribution estimation of epidemiological variables, when real data are few and widely separated.,Therefore, in order to represent cartographically the prevalence of COPD in Europe, an IDW interpolation mapping was performed.,The point prevalence data provided by 62 studies from 19 countries (21 from 5 Northern European countries, 11 from 3 Western European countries, 14 from 5 Central European countries, and 16 from 6 Southern European countries) were identified using validated spirometric criteria.,Despite the lack of data in many areas (including all regions of the eastern part of the continent), the IDW mapping predicted the COPD prevalence in the whole territory, even in extensive areas lacking real data.,Although the quality of the data obtained from some studies may have some limitations related to different confounding factors, this methodology may be a suitable tool for obtaining epidemiological estimates that can enable us to better address this major public health problem.
|
To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions.
| 1 |
The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research.,The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls.,Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups.,Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO.,Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values.,To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile.,While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters.,Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r = −0.52, p = 0.005 and r = −0.61, p = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r = −0.25, p = 0.47 and r = −0.15, p = 0.96, respectively), and may be driving overall associations in the general cohort.,In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO.,These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD.
|
Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects.
| 1 |
The multi‐drug resistant‐1 (MDR‐1) gene is located on human chromosome 7 and encodes a glycosylated membrane protein that is a member of the ATP‐binding cassette transporters superfamily.,The aim of the study was to reveal the role of the C3435T MDR‐1 gene polymorphism in chronic obstructive pulmonary disease.,DNA samples from 41 patients with chronic obstructive pulmonary disease and 50 healthy control participants were used to compare MDR‐1 gene profiles.,Genotyping assays were performed using the StripAssay technique that is based on reverse‐hybridization.,The T allele polymorphism in the MDR‐1 gene located at position 3435 in exon 26 was shown to correlate with chronic obstructive pulmonary disease.,These preliminary results suggest that the T allele polymorphism of the MDR‐1 gene is associated with chronic obstructive pulmonary disease.
|
Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function.,This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers.,We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.,Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33.,COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287).,The control group had an FEV1/FVC ratio ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 20 pack years of smoking.,Logistic and linear regressions were used for the analysis.,Age, sex, and smoking status were considered as potential confounders.,Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007).,Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25-75 (p values 0.001 - 0.02).,S2 was associated with FEV1/FVC ratio (p < 0.05).,The association between S1 and residual volume revealed a trend toward significance (p value < 0.07).,Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.,Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers.,Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD.
| 1 |
The medico-economic impact of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) is poorly documented.,To estimate the effectiveness and cost-effectiveness of pulmonary rehabilitation in a hypothetical cohort of COPD patients.,We used a multi-state Markov model, adopting society’s perspective.,Simulated cohorts of French GOLD stage 2 to 4 COPD patients with and without pulmonary rehabilitation were compared in terms of life expectancy, quality-adjusted life years (QALY), disease-related costs, and the incremental cost-effectiveness ratio (ICER).,Sensitivity analyses included variations of key model parameters.,At the horizon of a COPD patient’s remaining lifetime, pulmonary rehabilitation would result in mean gain of 0.8 QALY, with an over disease-related costs of 14 102 € per patient.,The ICER was 17 583 €/QALY.,Sensitivity analysis showed that pulmonary rehabilitation was cost-effective in every scenario (ICER <50 000 €/QALY).,These results should provide a useful basis for COPD pulmonary rehabilitation programs.
|
Chronic obstructive pulmonary disease (COPD) is an obstructive and progressive airway disease associated with an important reduction in daily physical activity and psychological problems that contribute to the patient’s disability and poor health-related quality of life (HRQoL).,Nowadays, pulmonary rehabilitation (PR) plays an essential role in the management of symptomatic patients with COPD, by breaking the vicious circle of dyspnea-decreased activity-deconditioning-isolation.,Indeed the main benefits of comprehensive PR programs for patients with COPD include a decrease in symptoms (dyspnea and fatigue), improvements in exercise tolerance and HRQoL, reduction of health care utilization (particularly bed-days), as well as an increase in physical activity.,Several randomized studies and meta-analyses greatly established the benefits of PR, which additionally, is recommended in a number of influential guidelines.,This review aimed to highlight the impact of PR on COPD patients, focusing on the clinical usefulness of PR, which provides patients a good support for change.
| 1 |
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.
|
While adverse effects of exposure to air pollutants on respiratory health are well studied, little is known about the effect of a reduction in air pollutants on chronic respiratory symptoms and diseases.,We investigated whether different declines in air pollution levels in industrialised and rural areas in Germany were associated with changes in respiratory health over a period of about 20 years.,We used data from the SALIA cohort study in Germany (Study on the influence of Air pollution on Lung function, Inflammation and Aging) to assess the association between the prevalence of chronic obstructive pulmonary disease (COPD) and chronic respiratory symptoms and the decline in air pollution exposure.,In 1985-1994, 4874 women aged 55-years took part in the baseline investigation.,Of these, 2116 participated in a questionnaire follow-up in 2006 and in a subgroup of 402 women lung function was tested in 2008-2009.,Generalized estimating equation (GEE) models were used to estimate the effect of a reduction in air pollution on respiratory symptoms and diseases.,Ambient air concentrations of particulate matter with aerodynamic size < 10 μm (PM10) declined in average by 20 μg/m3.,Prevalence of chronic cough with phlegm production and mild COPD at baseline investigation compared to follow-up was 9.5% vs.,13.3% and 8.6% vs.,18.2%, respectively.,A steeper decline of PM10 was observed in the industrialized areas in comparison to the rural area, this was associated with a weaker increase in prevalence of respiratory symptoms and COPD.,Among women who never smoked, the prevalence of chronic cough with phlegm and mild COPD was estimated at 21.4% and 39.5%, respectively, if no air pollution reduction was assumed, and at 13.3% and 17.5%, respectively, if air pollution reduction was assumed.,We concluded that parallel to the decline of ambient air pollution over the last 20 years in the Ruhr area the age-related increase in chronic respiratory diseases and symptoms appears to attenuate in the population of elderly women.
| 1 |
Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness.,The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD.,We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD.,A cross-sectional study was performed on stable outpatients with COPD.,PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale.,Ninety-eight patients were recruited.,Significant differences in PA duration were observed at all intensities according to the mMRC grade.,Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day.,COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4).,PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL.,Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD.
|
To study patients’ levels of exercise activity and the clinical characteristics that relate to physical activity and inactivity among patients with chronic obstructive pulmonary disease (COPD).,A postal questionnaire was administered to 719 patients with COPD in 2010; patients were recruited from the Helsinki and Turku University Central Hospitals in Finland and have been followed since 2005.,The questionnaire asked participants about their exercise routines and other daily activities, potential restrictions to exercise, health-related quality of life, and subjective sensations of dyspnea upon exertion.,A total of 50% of the participants reported exercising > 2 times a week throughout the year.,The proportion of the exercise inactive patients increased in parallel with disease progression, but the participants exhibited great variation in the degree of activity as well as in sport choices.,Year-round activity was better maintained among patients who exercised both indoors and outdoors.,Training activity was significantly correlated with patients’ reported subjective dyspnea (r = 0.32, P < 0.001), health-related quality of life (r = 0.25, P < 0.001), mobility score (r = 0.37, P < 0.001), and bronchial obstruction (r = 0.18, P < 0.001).,Active patients did not differ from inactive patients in terms of sex, age, smoking status, somatic comorbidities, or body mass index.,Irrespective of the level of severity of patients’ COPD, the most significant barrier to exercising was the subjective sensation of dyspnea.,When a patient with COPD suffers from dyspnea and does not have regular exercise routines, the patient will most likely benefit from an exercise program tailored to his or her physical capabilities.
| 1 |
Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD).,The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.,A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.,One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]).,In univariate analyses, health-related quality of life (Saint George’s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety.,All four domains introduced separately were independently associated with health-related quality of life.,When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60).,With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).,This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.
|
The course of chronic obstructive pulmonary disease (COPD) is frequently aggravated by exacerbations, and changes in the composition and activity of the microbiome may be implicated in their appearance.,The aim of this study was to analyse the composition and the gene content of the microbial community in bronchial secretions of COPD patients in both stability and exacerbation.,Taxonomic data were obtained by 16S rRNA gene amplification and pyrosequencing, and metabolic information through shotgun metagenomics, using the Metagenomics RAST server (MG-RAST), and the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) programme, which predict metagenomes from 16S data.,Eight severe COPD patients provided good quality sputum samples, and no significant differences in the relative abundance of any phyla and genera were found between stability and exacerbation.,Bacterial biodiversity (Chao1 and Shannon indexes) did not show statistical differences and beta-diversity analysis (Bray-Curtis dissimilarity index) showed a similar microbial composition in the two clinical situations.,Four functional categories showed statistically significant differences with MG-RAST at KEGG level 2: in exacerbation, Cell growth and Death and Transport and Catabolism decreased in abundance [1.6 (0.2-2.3) vs 3.6 (3.3-6.9), p = 0.012; and 1.8 (0-3.3) vs 3.6 (1.8-5.1), p = 0.025 respectively], while Cancer and Carbohydrate Metabolism increased [0.8 (0-1.5) vs 0 (0-0.5), p = 0.043; and 7 (6.4-9) vs 5.9 (6.3-6.1), p = 0.012 respectively].,In conclusion, the bronchial microbiome as a whole is not significantly modified when exacerbation symptoms appear in severe COPD patients, but its functional metabolic capabilities show significant changes in several pathways.
| 1 |
Conflicting data exist on the role of pulmonary dendritic cells (DCs) and their maturation in patients with chronic obstructive pulmonary disease (COPD).,Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer.,A total of 75 consecutive patients were included.,Spirometry testing was used to identify COPD.,Lung parenchyma sections anatomically distant from the primary lesion were examined.,We used flow cytometry to identify different DCs subtypes-including BDCA1-positive myeloid DCs (mDCs), BDCA3-positive mDCs, and plasmacytoid DCs (pDCs)-and determine their maturation markers (CD40, CD80, CD83, and CD86) in all participants.,We also identified follicular DCs (fDCs), Langerhans DCs (LDCs), and pDCs in 42 patients by immunohistochemistry.,COPD was diagnosed in 43 patients (16 current smokers and 27 former smokers), whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers).,The number and maturation of DCs did not differ significantly between COPD and non-COPD patients.,However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively).,Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects.,Cigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung.
|
We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke.,The exact mechanisms for this defect are unknown.,Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P) are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function.,We compared mRNA expression of sphingosine kinases (SPHK1/2), S1P receptors (S1PR1-5) and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1) in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers) using Real-Time PCR.,Phagocytosis of apoptotic cells was investigated using flow cytometry.,Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD.,To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5.,The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model.,We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively), S1PR2 and 5 (4.3- and 14.6-fold increases respectively), and SGPL1 (4.5-fold increase) in COPD vs. controls.,S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD “disease effect” rather than smoke effect per se.,Significant associations were noted between S1PR5 and both lung function and phagocytosis.,Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient-derived macrophages.,Antagonising SIPR5 significantly improved phagocytosis.,Our results suggest a potential link between the S1P signalling system and defective macrophage phagocytic function in COPD and advise therapeutic targets.
| 1 |
Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD).,We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD.,This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation.,Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models.,The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69-84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM.,All components contributed to the CID event rate.,Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events.,The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count.,Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels.,CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.
|
Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials.
| 1 |
To clarify how low BMI and weight loss were associated with risk of chronic obstructive pulmonary disease (COPD) mortality, in a large prospective cohort of the general population across Japan, the Japan Collaborative Cohort Study, conducted between 1988 and 2009.,A total of 45,837 male residents were observed for a median period of 19.1 years.,Self-administered questionnaires, collecting information on BMI, weight loss since the age of 20, lifestyles, history of diseases, as well as records of COPD mortality, were analysed at 2019.,During follow-up, 268 participants died from COPD.,The multivariate-adjusted hazard ratio (95% confidence interval) of COPD mortality associated with a 1-SD increment of body mass index (BMI) was 0.48 (0.41-0.57), while for weight change from age of 20 (+ 2.0 kg) it was 0.63 (0.59-0.68).,These associations were persistently observed after stratifications with smoking status, excluding those having airway symptoms in the baseline survey, and excluding early COPD deaths within 5, 10 and 15 years.,Our study suggests that BMI and weight change since the age of 20 could be markers for COPD prognosis, indicated by risk of COPD mortality.
|
Alpha-1-antitrypsin deficiency is a relatively prevalent, but under-diagnosed, genetic disease.,The objective of this study was to assess whether the systematic screening for alpha-1-antitrypsin deficiency in all patients with chronic obstructive pulmonary disease from a tertiary service has an impact on the number of patients being diagnosed with this condition.,Chronic obstructive pulmonary disease patients were screened for alpha-1-antitrypsin deficiency using immunonephelometry.,The presence of a mutation was confirmed by molecular study of the SERPINA1 gene or by genetic sequencing, as needed.,A total of 551 patients with chronic obstructive pulmonary disease were analyzed.,Among these, 40 (7.2%) had some genetic mutation, while 11 (2%) had a Pi*ZZ genotype, resulting in severe respiratory illness.,The systematic evaluation of chronic obstructive pulmonary disease patients revealed that screening is an effective method to diagnose alpha-1-antitrypsin deficiency.,Early diagnosis may facilitate smoking cessation and initiation of treatment to maintain lung function.
| 1 |
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.
|
The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early.
| 1 |
COPD often coexists with chronic conditions that may influence disease prognosis.,We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients.,Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices.,Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes.,Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions.,Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years.,At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5.,The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%).,Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45).,From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36).,Chronic comorbidities are highly prevalent in primary care COPD patients.,Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk.
|
Background: Surfactant protein D (SP-D) is a lung-specific protein proposed to predict clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).,However, the changes in serum SP-D during acute exacerbation (AECOPD) episodes and the relationship of serum SP-D with the overall severity of the disease in stable COPD (SCOPD) remain unclear.,Methods: Serum SP-D levels were analyzed in three groups, including AECOPD (n=40), SCOPD (n=71), and controls (n=60).,In AECOPD group, serum SP-D levels were determined at 1, 5, 14, and 30 days post-exacerbation.,In SCOPD group, BODE (body mass index, airflow obstruction, dyspnea, exercise capacity) index was evaluated for severity assessment.,Results: Serum SP-D levels were sequentially elevated from the controls to the SCOPD, and then to the AECOPD (p < 0.001).,During an AECOPD episode, the raised serum SP-D levels subsided at day 5 (p > 0.05), fell markedly at day 14 (p < 0.001), and continued to decline at day 30 (p < 0.001).,Among patients with SCOPD, serum SP-D levels correlated positively with the BODE index (p < 0.01).,Conclusions: The longitudinal changes in serum SP-D levels during an AECOPD episode suggest that SP-D may be a potential systemic biomarker for COPD exacerbation.,The correlation of serum SP-D levels with the BODE index suggests that circulating SP-Ds can reflect the overall severity of SCOPD.
| 1 |
Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown.,We examined whether the treatment given for exacerbations predicted subsequent outcomes.,This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®).,Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan-Meier plots.,Of 8,061 patients with moderate to severe exacerbation(s), demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization.,Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively), and a greater risk of having a hospitalized (severe) exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively) or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively) compared with exacerbations treated with antibiotics alone.,Initial hospitalization led to the highest risk of subsequent hospitalization (all-cause or COPD related [severe exacerbation], HR: 3.35 and 4.31, P<0.0001, respectively) or death (all-cause or COPD related, HR: 3.53 and 5.54, P<0.0001, respectively) versus antibiotics alone.,These data indicate that the way exacerbations are treated initially is a useful guide to the patient’s subsequent clinical course.,Factors that clinicians consider when making treatment choices require further clarification.
|
It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD).,The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients.,Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study.,The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS).,The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models.,Among a total of 854 patients, the BDR-positive cases varied according to the criteria used.,There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria.,Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93).,This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants.,Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients.,Increase use of ICS/LABA may have affected this relationship.,The online version of this article (doi:10.1186/s12931-017-0587-9) contains supplementary material, which is available to authorized users.
| 1 |
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation that is not fully reversible.,Bronchodilator therapy is the cornerstone in COPD treatment.,Bronchodilation in COPD is mainly achieved via administration of long- and ultralong-acting β2-agonists and with long-acting muscarinic antagonists.,New combinations of bronchodilators with dual-acting muscarinic antagonist and β2-agonist properties have been licensed, and others are currently being developed with the aim of achieving once-daily dosing, and therefore may improve the likelihood of treatment compliance.,These combination bronchodilators include glycopyrronium bromide/indacaterol maleate, umeclidinium (UMEC) bromide/vilanterol trifenatate (VI), aclidinium bromide/formoterol and tiotropium bromide/olodaterol (Boehringer Ingelheim, Germany).,This review will focus mainly on studies and clinical trials involving the novel fixed-dose combination of UMEC/VI at doses of 125/25 μg and 62.5/25 μg in patients with COPD.,Data from large clinical trials involving more than 4,500 COPD patients indicate that UMEC/VI is an effective once-daily treatment in COPD with improved pulmonary function.,Future studies assessing the impact of this combination on exacerbations, delay in disease progression, and health status in patients with COPD are warranted.
|
The combination of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a selective long-acting β2 agonist, is in development for the treatment of chronic obstructive pulmonary disease (COPD).,This study evaluated the pharmacokinetics, safety and tolerability, and pharmacodynamics of once-daily, inhaled UMEC and UMEC/VI when co-administered with oral verapamil, a moderate P-glycoprotein transporter and moderate cytochrome P450 3A4 (CYP3A4) inhibitor frequently used by patients with COPD and cardiovascular comorbidities.,Subjects were randomized to one of two 13-day treatment regimens: UMEC 500 μg or UMEC 500 μg/VI 25 μg.,All subjects received a single tablet containing 240 mg verapamil on each of days 9-13.,Repeat doses of UMEC and UMEC/VI in combination with and without verapamil were safe and well tolerated.,There was no increase in systemic exposure of UMEC when administered in combination with VI compared to UMEC alone.,UMEC maximum concentration was similar with or without verapamil; a moderate increase in UMEC area under the curve (approximately 1.4-fold) was observed with verapamil.,Verapamil did not increase systemic exposure to VI following administration of the UMEC/VI combination.,Administration of UMEC and UMEC/VI combination was well tolerated and did not show clinically relevant increases in systemic exposure for either drug.,The UMEC/VI combination is unlikely to have a clinically meaningful drug-drug interaction with moderate P-glycoprotein transporter and CYP3A4 inhibitor drugs.
| 1 |
Introduction.,Chronic obstructive pulmonary disease (COPD) is associated with comorbidities such as cardiovascular disease, metabolic disease, osteoporosis, and anxiety and/or depression.,Although pulmonary rehabilitation programs are proven to be beneficial in patients with COPD, it is unclear whether comorbidities influence pulmonary rehabilitation outcomes.,The aim of the present review was to investigate to what extent the presence of comorbidities can affect pulmonary rehabilitation outcomes.,Methods.,The systematic literature search (Pubmed, EMBASE, and PEDro) resulted in 4 articles meeting the inclusion criteria.,The odds ratios (95% confidence intervals) of the logistic regression analyses, with comorbidities as independent variables and pulmonary rehabilitation outcomes (dyspnea, functional exercise capacity, and quality of life) as dependent variables, were used for data extraction.,Results.,Patients with anxiety and/or depression less likely improve in dyspnea.,Osteoporosis is associated with less improvements in functional exercise capacity, while cardiovascular disease does not seem to negatively impact on this outcome.,Patients with cardiovascular comorbidity will experience less positive changes in quality of life.,Conclusion.,Evidence from literature suggests that comorbidities can have a negative influence on pulmonary rehabilitation outcomes.,Screening for comorbidities in pulmonary rehabilitation settings seems useful to readdress the right patients for individually tailored pulmonary rehabilitation.
|
Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases.,The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid.,An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid).,The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population.,Patients were deemed to have COPD if this diagnosis appeared on their clinical histories.,Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated.,Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%).,After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity.,Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs.
| 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most prevalent and debilitating diseases in adults worldwide and is associated with a deleterious effect on the quality of life of affected patients.,Although it remains one of the leading causes of global mortality, the prognosis seems to have improved in recent years.,Even so, the number of patients with COPD and multiple comorbidities has risen, hindering their management and highlighting the need for futures changes in the model of care.,Together with standard medical treatment and therapy adherence - essential to optimizing disease control - several nonpharmacological therapies have proven useful in the management of these patients, improving their health-related quality of life (HRQoL) regardless of lung function parameters.,Among these are improved diagnosis and treatment of comorbidities, prevention of COPD exacerbations, and greater attention to physical disability related to hospitalization.,Pulmonary rehabilitation reduces symptoms, optimizes functional status, improves activity and daily function, and restores the highest level of independent physical function in these patients, thereby improving HRQoL even more than pharmacological treatment.,Greater physical activity is significantly correlated with improvement of dyspnea, HRQoL, and mobility, along with a decrease in the loss of lung function.,Nutritional support in malnourished COPD patients improves exercise capacity, while smoking cessation slows disease progression and increases HRQoL.,Other treatments such as psychological and behavioral therapies have proven useful in the treatment of depression and anxiety, both of which are frequent in these patients.,More recently, telehealthcare has been associated with improved quality of life and a reduction in exacerbations in some patients.,A more multidisciplinary approach and individualization of interventions will be essential in the near future.
|
1) To estimate the annual cost of patients with stable chronic obstructive pulmonary disease (COPD) followed in primary care in Spain; 2) To analyze the possible cost predictor variables.,A multicenter, epidemiological, observational, descriptive study.,Sociodemographic data, severity of disease, associated comorbidity, treatment followed by patients, quality of life (SF-12 questionnaire), health care resource utilization in the previous 12 months and duration of working disability due to COPD were collected.,A total of 10,711 patients (75.6% men; 24.4% women) with a mean age of 67.1 ± 9.66 years were evaluated.,The mean forced expiratory volume in one second (FEV1) value was 57.4 ± 13.4%.,The total cost per patient per year was €1,922.60 ± 2,306.44.,The largest component of this cost was hospitalization (€788.72 ± 1,766.65), followed by cost of drugs (€492.87 ± 412.15) and visits to emergency rooms (€134.32 ± 195.44).,Linear regression analysis found associated heart disease, FEV1, physical component of quality of life, number of medical visits (primary care physician, pneumologist and emergency room), hospital admissions (frequency and duration of stay) and duration of working disability to be significant predictors of the total annual cost.,The total annual cost of a COPD patient followed in primary care in Spain was considered high in this study.,The presence of associated heart disease, severity of airflow obstruction, physical component of quality of life, health care resource utilization and duration of work disability were found to be predictor of cost.
| 1 |
According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting β2 agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations.,However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy.,Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations.,This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice.,Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks.
|
Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy.
| 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.