a
stringlengths 138
8.15k
| b
stringlengths 138
8.15k
| label
int64 1
1
|
|---|---|---|
Quantifying physical activity in chronic obstructive pulmonary disease (COPD) is important as physical inactivity is related to poor health outcomes.,This study analyzed the relationship between patients’ self-reported daily walking time and relevant characteristics related to COPD severity.,Pooled analysis was performed on data from four observational studies on which daily walking time was gathered from a personal interview.,Patients were classified as physically inactive if walking time was <30 min/day.,Walking times were described and compared according to several markers of disease severity.,The mean daily walking time of 5,969 patients was 66 (standard deviation [SD] 47) min/day; 893 (15%) patients were inactive.,A linear dose-response relationship was observed between walking time and the modified Medical Research Council (mMRC) dyspnea score, admissions, COPD assessment test (CAT), body mass index, airway obstruction, dyspnea, exacerbation (BODEx) index, and Charlson index (P<0.001).,Daily walking times were lower in patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B and D (P<0.001).,Often, inactive patients had mMRC or Charlson index >3, post-bronchodilator forced expiratory volume in the first second <30% predicted, at least one hospitalization for COPD, classified as GOLD B or D, BODEx >4, and CAT score >30.,Lower self-reported walking times are related to worse markers of disease severity in COPD.
|
COPD is currently the fourth cause of morbidity and mortality in the developed world.,Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL).,The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease.,It is a multicenter, epidemiological, observational, descriptive study.,Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included.,Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected.,All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores.,10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66).,The mean value of FEV1 was 35.9 ± 10.0%.,Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively.,Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease.,The correlation with FEV1 was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12).,Predictors for both HRQoL components were sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.,Other independent predictors of PCS-12 were age, body mass index and educational level.,Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease.,The factors determining the HRQoL include sex, FEV1, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.
| 1 |
Lung cancer and chronic obstructive pulmonary disease (COPD) are two major lung diseases.,Epidermal growth factor receptor (EGFR) mutations, v‐Ki‐ras2 Kirsten rat sarcoma (KRAS) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements represent driver mutations that are frequently assessed on initial evaluation of non-small-cell lung cancer (NSCLC).,The present study focused on the expression of driver mutations in NSCLC patients presenting with COPD and further evaluated the association between NSCLC and COPD.,Data from 501 consecutive patients with histologically proven recurrent or metastatic NSCLC were analyzed retrospectively.,The patients underwent spirometry and genotyping of EGFR, ALK, and KRAS in tissue samples.,Patient characteristics and expression of driver mutations were compared between the COPD and non-COPD groups.,Among 350 patients with spirometric results, 106 (30.3%) were diagnosed with COPD, 108 (30.9%) had EGFR mutations, 31 (8.9%) had KRAS mutations, and 34 (9.7%) showed ALK rearrangements.,COPD was independently associated with lower prevalences of EGFR mutations (95% confidence interval [CI], 0.254-0.931, p = 0.029) and ALK rearrangements (95% CI, 0.065-0.600, p = 0.004).,The proportions of EGFR mutations and ALK rearrangements decreased as the severity of airflow obstruction increased (p = 0.001).,In never smokers, the prevalence of EGFR mutations was significantly lower in the COPD group than in the non-COPD group (12.7% vs.,49.0%, p = 0.002).,COPD-related NSCLC patients exhibited low prevalences of EGFR mutations and ALK rearrangements compared with the non-COPD group.,Further studies are required regarding the molecular mechanisms underlying lung cancer associated with COPD.
|
Lung cancer and chronic obstructive pulmonary disease (COPD) share a common risk factor in cigarette smoking and a large portion of patients with lung cancer suffer from COPD synchronously.,We therefore hypothesized that COPD is an independent risk factor for lung cancer.,Our aim was to investigate the intrinsic linkage of COPD (or emphysema, chronic bronchitis and asthma) and lung cancer.,The present hospital-based case-control study included 1,069 patients with newly diagnosed lung cancer and 1,132 age frequency matched cancer-free controls.,The odds ratios (ORs) for the associations between each previous pulmonary disease and lung cancer were estimated with logistic regression models, adjusting for age, sex, family history of cancer, BMI and pack year smoking.,In meta-analysis, the pooled effects of previous pulmonary diseases were analyzed with random effects models; and stratification analyses were conducted on smoking status and ethnicity.,In the case-control study, previous COPD was associated with the odds for increased risk of lung cancer (OR = 1.29, 95% confidence interval [CI] = 1.00∼1.68); so were emphysema (OR = 1.55, 95%CI = 1.03∼2.32) and chronic bronchitis (OR = 1.22, 95%CI = 0.99∼1.67); while asthma was associated with odds for decreased risk of lung cancer (OR = 0.29, 95%CI = 0.16∼0.53).,These associations were more pronounced in smokers (P<.05 for all strata), but not in non-smokers.,In meta-analysis, 35 studies (22,010 cases and 44,438 controls) were identified.,COPD was significantly associated with the odds for increased risk of lung cancer (pooled OR = 2.76; 95% CI = 1.85-4.11), so were emphysema (OR = 3.02; 95% CI = 2.41-3.79) and chronic bronchitis (OR = 1.88; 95% CI = 1.49-2.36); and these associations were more pronounced in smokers than in non-smokers (P<.001 respectively).,No significant association was observed for asthma.,Previous COPD could increase the risk of lung cancer, especially in smokers.
| 1 |
To review and summarize existing literature on the indirect burden of chronic obstructive pulmonary disease (COPD) in the US.,Medline, Scopus, and OvidSP databases were searched using defined search terms to identify relevant studies.,Eligible studies were published in English between January 2000 and April 2012 and calculated the indirect burden of COPD in a US population in terms of prevalence, incidence or costs of productivity loss, disability, morbidity, or mortality.,Of 53 studies identified, eleven met eligibility criteria, with data years spanning 1987-2009.,Estimates of workforce participation range from 56% to 69% among individuals with COPD and from 65% to 77% among individuals without COPD.,Approximately 13%-18% of those with COPD are limited in the amount or type of work they can do and one-third or more experience general activity limitation.,Estimates of restricted activity days range from 27-63 days per year.,Estimates of mean annual sick leave and/or disability days among employed individuals with COPD range from 1.3-19.4 days.,Estimates of bed confinement range from 13-32 days per year.,Estimated mean annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521-$3,348 in 2010 [US dollars]) and varied with the population studied, specific cost outcomes, and economic inputs.,In studies that assessed total (direct and indirect) costs, indirect costs accounted for 27%-61% of total costs, depending on the population studied.,COPD is associated with substantial indirect costs.,The disease places a burden on employers in terms of lost productivity and associated costs and on individuals in terms of lost income related to absenteeism, activity limitation, and disability.,Consideration of indirect as well as direct costs is necessary to gain a more complete view of the societal burden of COPD.
|
Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world.,Although smoking is the main risk factor for this disease, only a minority of smokers develop COPD.,Why this happens is largely unknown.,Recent discoveries by the human microbiome project have shed new light on the importance and richness of the bacterial microbiota at different body sites in human beings.,The microbiota plays a particularly important role in the development and functional integrity of the immune system.,Shifts or perturbations in the microbiota can lead to disease.,COPD is in part mediated by dysregulated immune responses to cigarette smoke and other environmental insults.,Although traditionally the lung has been viewed as a sterile organ, by using highly sensitive genomic techniques, recent reports have identified diverse bacterial communities in the human lung that may change in COPD.,This review summarizes the current knowledge concerning the lung microbiota in COPD and its potential implications for pathogenesis of the disease.
| 1 |
To determine distribution of COPD assessment categories and physicians’ adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 strategy in Turkish COPD patients.,A total of 1,610 COPD patients (mean [standard deviation] age: 62.6 [9.9] years, 85.7% were males) were included in this multicenter, non-interventional, cross-sectional study.,Patients were categorized via GOLD 2013 strategy document.,Consistency between reported and re-classified GOLD categories, and measures used for symptom evaluation and exacerbation was analyzed.,Overall, 41.1% of patients were assigned to GOLD A, while 13.2% were assigned to GOLD C categories.,Long-acting beta-2 agonist + long-acting muscarinic antagonist + inhaled corticosteroid regimen was the most common treatment (62.0%).,Over-treatment was noted in >70% of GOLD A, B, and C patients.,A high consistency between measures of symptom evaluation (Kappa coefficient =0.993, P<0.0001) and a low-moderate consistency between exacerbation risk measures (Kappa coefficient =0.237, P<0.0001) were noted.,Our findings revealed GOLD A as the most prevalent category in Turkish cohort of COPD patients.,Group assignment was altered depending on the chosen measure for symptom and risk assessment.,Physician non-adherence to treatment recommendations in GOLD 2013 document leading to over-treatment in patients assigned to GOLD A, B, and C categories was also detected.
|
Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.
| 1 |
Tai Chi is a traditional Chinese mind-body exercise that has been widely practiced in the People’s Republic of China for many centuries.,This exercise has also been applied as a training modality in pulmonary rehabilitation programs for stable chronic obstructive pulmonary disease (COPD).,This systematic review and meta-analysis aimed to assess the effects of Tai Chi on exercise capacity and health-related quality of life (HRQoL) in COPD patients.,Electronic databases (PubMed, Embase, Web of Science, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, China National Knowledge Infrastructure, and China Biology Medicine disc) were searched.,Entries published from January 1980 to March 2014 were included in the search.,Eligible studies included those that involved randomized controlled trials and those that lasted for at least 12 weeks.,The primary outcome measures were six-minute walking distance (6MWD), St George’s Respiratory Questionnaire (SGRQ), and Chronic Respiratory Disease Questionnaire (CRQ).,Effect estimates were pooled with random-effects meta-analysis.,Eleven articles involving 824 patients met the inclusion criteria.,All included articles compared COPD patients in a Tai Chi group versus COPD patients in nonexercise and/or physical exercise groups.,The meta-analysis showed that compared with the nonexercise group, the COPD patients practicing Tai Chi demonstrated significantly enhanced 6MWD (mean difference 35.99, 95% confidence interval [CI] 15.63-56.35, P=0.0005), decreased SGRQ total score (mean difference −10.02, 95% CI −17.59, −2.45, P=0.009), and increased CRQ total score (mean difference 0.95, 95% CI 0.22-1.67, P=0.01).,Compared with the physical exercise group, the Tai Chi group showed significantly reduced SGRQ total score (mean difference −3.52, 95% CI −6.07, −0.97, P=0.007), but no statistical significance was found for 6MWD between the two groups (mean difference 13.65, 95% CI −1.06, 28.37, P=0.07) in COPD patients.,Preliminary evidence suggests that Tai Chi has beneficial effects on exercise capacity and HRQoL in COPD patients.,This exercise can be recommended as an effective alternative training modality in pulmonary rehabilitation programs.,Further studies are required to support the preliminary evidence and to observe the long-term effects of Tai Chi.
|
Currently, several studies assessed the role of Tai Chi (TC) in management of chronic obstructive pulmonary disease, but these studies have wide variation of sample and convey inconclusive results.,We therefore undertook a meta-analysis to assess the effects of TC.,A computerized search through electronic databases was performed to obtain sample studies.,The primary outcomes were 6-min walking distance (6MWD) and dyspnea.,Secondary outcomes included health-related quality of life and pre-bronchodilator spirometry.,Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I2 test.,A random-effects meta-analysis model was applied.,Eight randomized controlled trials involving 544 patients met the inclusion criteria.,The pooled WMDs were 34.22 m (95% CI 21.25-47.20, P<0.00001) for 6 MWD, -0.86 units (95% CI -1.44--0.28, P = 0.004) for dyspnea, 70 ml (95% CI 0.02-0.13, P = 0.01) for FEV1, 120 ml (95% CI 0.00-0.23, P = 0.04) for FVC.,TC significantly improved the Chronic Respiratory Disease Questionnaire total score, and the St George’s Respiratory Questionnaire score except impact score.,Findings suggest that TC may provide an effective alternative means to achieve results similar to those reported following participation in pulmonary rehabilitation programs.,Further studies are needed to substantiate the preliminary findings and investigate the long-term effects of TC.
| 1 |
Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303.
|
To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD, using St.George’s Respiratory questionnaire (SGRQ), the 6-minutes walking test (6-MWT) and BODE index as the primary outcome measures.,A prospective, parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD (67 men and 13 women; mean age 64.8 ± 10.6 years; FEV1, 42.8% ± 7.6% of the predicted value.,The active group (n = 40) took part in a 14-week rehabilitation program [3 h/wk, 1.5 h of education and exercise and 1.5 h of cycling].,The control group (n = 40) was reviewed routinely as medical outpatients.,The following evaluations were carried out at study entry and after14 weeks: (1) pulmonary function studies; (2) 6-minutes walking test 6MWT; (3) quality of life; and (4) BODE index.,The following patients completed the study: 35 patients (87.5%) from the active group (mean age, 63.7 ± 11.9 years; mean forced expiratory volume in one second (FEV1), 41.9 ± 2.6% of the predicted value); and 36 patients (88%) from the control group (mean age, 65.9 ± 10.3 years; mean FEV1, 43.33 ± 3.6% of the predicted value).,We found no changes in pulmonary function parameters in the active group and the control one at 14weeks.,On the other hand, there were significant changes within the components of the SGRQ (12.3 for the score total) for the patients of the active group but not for the patients of the control one (only 1.5 for the score total), we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one, and finally a decrease of two points (from 6 to 4) was noted in the score of the active group’s BODE index without any change in the control group’s one.,An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD, and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index.
| 1 |
Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries.,However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown.,This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE.,The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE.,Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks.,Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded.,The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494.,The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications.,Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries.,There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD.,The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.
|
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations.
| 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM).,Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elastin, the signature protein of the lungs.,During pathological remodeling driven by inflammatory cells and proteases, fragments of these proteins are released into the bloodstream, where they may serve as biomarkers for disease phenotypes.,The aim of this study was to investigate the lung ECM remodeling in healthy controls and COPD patients in the COPDGene study.,The COPDGene study recruited 10,300 COPD patients in 21 centers.,A subset of 89 patients from one site (National Jewish Health), including 52 COPD patients, 12 never-smoker controls and 25 smokers without COPD controls, were studied for serum ECM biomarkers reflecting inflammation-driven type I and VI collagen breakdown (C1M and C6M, respectively), type VI collagen formation (Pro-C6), as well as elastin breakdown mediated by neutrophil elastase (EL-NE).,Correlation of biomarkers with lung function, the SF-36 quality of life questionnaire, and other clinical characteristics was also performed.,The circulating concentrations of biomarkers C6M, Pro-C6, and EL-NE were significantly elevated in COPD patients compared to never-smoking control patients (all p < 0.05).,EL-NE was significantly elevated in emphysema patients compared to smoking controls (p < 0.05) and never-smoking controls (p < 0.005), by more than 250%.,C1M was inversely associated with forced expiratory volume in 1 s (FEV1) (r = −0.344, p = 0.001), as was EL-NE (r = −0.302, p = 0.004) and Pro-C6 (r = −0.259, p = 0.015).,In the patients with COPD, Pro-C6 was correlated with percent predicted Forced Vital Capacity (FVC) (r = 0.281, p = 0.046) and quality of life using SF-36.,C6M and Pro-C6, were positively correlated with blood eosinophil numbers in COPD patients (r = 0.382, p = 0.006 and r = 0.351, p = 0.012, respectively).,These data suggest that type VI collagen turnover and elastin degradation by neutrophil elastase are associated with COPD-induced inflammation (eosinophil-bronchitis) and emphysema.,Serological assessment of type VI collagen and elastin turnover may assist in identification of phenotypes likely to be associated with progression and amenable to precision medicine for clinical trials.
|
Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.,Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity.,In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling.,The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.,Patients scheduled for lung resection were prospectively recruited.,Demographic, clinical data and pulmonary function tests results were recorded.,Emphysema was visually scored and histological remodeling features were noted.,Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.,We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding.,In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.,13 COPD and 7 non COPD patients were included.,The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03] respectively).,Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD, p = 0.04).,The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs 12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]).,Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI [0.09;0.87] respectively).,Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels.,Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).,Our results showed an abnormal bronchial epithelial wound closure process in severe COPD.,Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.,The online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users.
| 1 |
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation.,COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity.,The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia.,COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode.,Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations.,Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD.,Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis.,Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity.,Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease.,Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations.
|
COPD exacerbations are responsible for the morbidity and mortality of this disease.,The relationship between exacerbations and patient-related clinical outcomes is not clearly understood.,A retrospective analysis of two 1-year, placebo-controlled clinical trials with tiotropium 18 μg daily was conducted to examine relationships between exacerbations and other clinical outcomes.,The relationship between FEV1, St.,George’s Respiratory Questionnaire (SGRQ), and the transition dyspnea index (TDI) were examined based on the frequency of exacerbations (0, 1, 2, >2).,921 patients participated in the trials (mean age 65 years, mean FEV1 = 1.02 L (39% predicted).,The percent change from baseline in FEV1 in the tiotropium group was +12.6%, +12.0%, +2.1% and +8.9%; and in the placebo group was −3.4%, −3.4%, −5.7% and −6.7% for exacerbation frequencies of 0, 1, 2, >2, respectively.,Compared with baseline, the largest improvement in SGRQ occurred in patients with no exacerbations.,In the placebo group, there was a significant association between an increased frequency of exacerbations and worsening SGRQ scores.,A reduction in exacerbation rates of 4.4% to 42.0% such as that shown in this study cohort was associated with meaningful changes in questionnaire based instruments.,In the placebo-treated patients increased frequency of exacerbations was associated with larger decrements in FEV1, TDI, and SGRQ.,A reduction in the frequency of exacerbations is associated with changes that are considered meaningful in these clinical outcomes.
| 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally.
|
Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms.
| 1 |
COPD is a significant cause of morbidity and mortality.,In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation.,Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy.,In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention.,In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13.,The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions.,We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD.
|
Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease where treatment decisions should be based on disease severity and also should be equally distributed across age, gender, and social situation.,The aim of this study was to determine to what extent patients with COPD are offered evidence-based interventions and how the interventions are distributed across demographic and clinical factors in the sample.,Baseline registrations of demographic, disease-related, and management-related variables of 7,810 patients in the Swedish National Airway Register are presented.,One-third of the patients were current smokers.,Patient-reported dyspnea and health-related quality of life were more deteriorated in elderly patients and patients living alone.,Only 34% of currently smoking patients participated in the smoking cessation programs, and 22% of all patients were enrolled in any patient education program, with women taking part in them more than men.,Less than 20% of the patients had any contact with physiotherapists or dieticians, with women having more contact than men.,Men had more comorbidities than women, except for depression and osteoporosis.,Women were more often given pharmacological treatments.,With increasing severity of dyspnea, participation in patient education programs was more common.,Dietician contact was more common in those with lower body mass index and more severe COPD stage.,Both dietician contact and physiotherapist contact increased with deteriorated health-related quality of life, dyspnea, and increased exacerbation frequency.,The present study showed that COPD management is mostly equally distributed across demographic characteristics.,Only a minority of the patients in the present study had interdisciplinary team contacts.,Thus, this data shows that the practical implementation of structured guidelines for treatment of COPD varies, to some extent, with regard to age and gender.,Also, disease characteristics influence guideline implementation for each individual patient.,Quality registers have the strength to follow-up on compliance with guidelines and show whether an intervention needs to be adapted prior to implementation in health care practice.
| 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.
|
COPD remains a major health problem in Japan.,Patients with COPD experience a reduced quality of life (QoL) and have a higher chance of work impairment and productivity loss.,However, there is a lack of data on the impact of COPD in terms of QoL and work activity impairment in Japan.,This study assessed the socioeconomic burden of COPD in Japan and the impact it may have on the working age population.,This was a 2-year retrospective chart review in COPD patients aged ≥40 years, with at least one health care visit to clinic or hospital in the previous 12 months.,Patients were required to have available medical charts for at least the previous 24 months.,Symptoms were assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L) and work productivity and activity impairment general health questionnaires were used to evaluate health-related QoL and work productivity, and health care resource utilization data were obtained from clinical charts.,In total, 71 patients aged <65 years, and 151 patients aged ≥65 years were included; the majority of patients had moderate or severe airflow limitation.,Exacerbations (moderate or severe) were reported by ~35% of patients in both age groups; 52.1% and 62.9% of patients in the <65-year and ≥65-year age groups had COPD assessment test scores ≥10.,EQ-5D-5L index scores in the <65-year and ≥65-year age groups were 0.79 and 0.77, respectively.,Work productivity and activity impairment scores were higher in <65-year age group.,Annual costs of health care resource use per patient in the <65-year and ≥65-year age groups were ¥438,975 (US$4,389) and ¥467,871 (US$4,678), respectively.,Costs due to productivity loss were estimated to be ¥5,287,024 (US$52,870) in the <65-year age group and ¥3,018,974 (US$30,187) in the ≥65-year age group.,COPD represents a significant socioeconomic burden in Japan.,Patients with COPD report significant use of health care resources.,Higher impact on work impairment and productivity loss was observed frequently in the working age population.
| 1 |
Current evidence suggests that roflumilast is efficacious in treating COPD, especially in preventing the acute exacerbation of COPD.,This study was designed to evaluate the clinical effects and safety of roflumilast in the treatment of stable COPD using randomized clinical trial (RCT) data.,A MEDLINE, EMBASE, and Cochrane Controlled Trials Register search was carried out.,RCTs reporting the treatment effects of roflumilast in COPD were identified.,Relevant data were extracted and a meta-analysis was performed.,A total of nine articles and 13 RCT studies were identified.,Overall, 29.1% of the subjects in the roflumilast group showed evidence of exacerbation.,The corresponding figure was 32.2% in the placebo group.,According to pooled analysis, the use of roflumilast reduced COPD exacerbations in comparison to placebo (odds ratio [OR] =0.82, 95% confidence interval [CI] =0.75-0.9).,The quality of life and spirometry were improved.,For patients receiving baseline pre-bronchodilators, their average forced expiratory volume in the first second showed evidence of change when they took roflumilast (64.88 mL; 95% CI =54.09-75.66).,Those who took placebo showed no evidence of change.,Similar result was observed in patients receiving baseline (54.49 mL; 95% CI =44.04-64.94).,As for the safety of roflumilast treatment, the overall cumulative incidence of adverse drug reaction was 54.2% in the roflumilast group and 48.2% in the placebo group (OR =1.36, 95% CI =1.13-1.65).,The adverse effects included diarrhea, headache, nausea, weight loss, and insomnia.,The efficacy of roflumilast in the prevention of acute exacerbation of COPD is obvious.,Roflumilast is proved to be able to improve spirometry of COPD patients.,The adverse drug reaction did not increase significantly in the roflumilast group compared with the control group.,COPD patients can benefit from roflumilast therapy.,However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them; hence, more randomized trials are needed to further support this conclusion.
|
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD.
| 1 |
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.
|
A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use.,Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice.,We performed a systematic literature search in both Pubmed and Embase up to September 2010.,Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only.,Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies.,Of 7,028 articles screened, 13 studies comprising 15 indices were included.,Only 1 index had been explored for its application in daily practice.,We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation.,Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea.,The quality of the studies underlying the indices varied between fairly poor and good.,Statistical methods to assess the predictive abilities of the indices were heterogenic.,They generally revealed moderate to good discrimination, when measured.,Limitations: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity.,We identified 15 prognostic COPD indices.,Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation.,Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this.
| 1 |
Background and objectives: Inhalers mishandling remain an important clinical issue worldwide.,The aim of this study was to evaluate inhalation technique in stable COPD out-patients.,The variables under study were type of inhaler device (ID), patients’ preference for an inhaler, number of IDs used by each patient, beliefs about inhaler medication and some demographic, clinical and functional patients' characteristics.,We aim to assess how they are related to inhalation technique.,Methods: A cross-sectional study was conducted in a hospital outpatient respiratory care.,COPD patients over 40 years old, diagnosed according to GOLD criteria, and using IDs were included consecutively.,The Beliefs about Medicines Questionnaire (BMQ), a demographic and a clinical survey were applied.,The number of IDs used by each patient and the patients’ preference for some IDs were recorded.,Patients were asked to demonstrate the use of their prescribed inhalation devices, and inhaler technique was assessed by using previously defined checklists, including essential steps and critical errors.,A statistics analysis was then performed.,Results: We studied 300 subjects performing a total of 521 inhalation manoeuvers with 10 different IDs.,At least one step incorrectly performed was found in 48.2% of demonstrations and in 29.9% critical errors were observed.,Misuse was related to priming/loading in 6.9%, to inhalation manoeuver in 13.1% and to both in 10%.,There was a statistically significant association between critical errors and type of ID (P<0.001).,No significant relationship was found between correct performance of key manoeuvers and patients’ preference or number of inhalers used per patient.,Misuse due to critical errors was observed in 39.3% of patients and was positively related to female gender, age ≥65, lower education level and lower socioeconomic status (higher Graffar classification score), but not to patients’ clinical or functional characteristics.,In the sub-group of patients presenting critical errors when using IDs, there was a statistically significant inverse association between BMQ Necessity score and number of critical errors.,Conclusions: Inhalers mishandling remains disappointingly common.,A good inhalation technique depends on the type of ID, and failure of inhalation manoeuver was the main cause of ID misuse.,It was not associated to multiple inhalers’ use nor to patient’s preference, but to the patient’s beliefs about the necessity to use them.,Elderly patients, women and those with lower education level or lower socioeconomic status demonstrate a worse inhalation technique.
|
Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy.,The ELLIPTA® DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease.,It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication.,Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration.,There are three principal operating steps to administer a dose: open, inhale, close.,This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler.,Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (≥30 L/min) and over its 30-day in-use life.,Data from the human factors validation tests demonstrated that almost all participants (≥97%) were able to complete each of the steps required to prepare a dose for inhalation without error.,Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options.,It also improves patient ease-of-use when compared with the DISKUS® DPI.
| 1 |
Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS).,Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function.,In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity.,In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression.,In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit.,This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases.
|
Chronic obstructive pulmonary disease (COPD) is a disease characterised by persistent airflow limitation that is not fully reversible and is currently the fourth leading cause of death globally.,It is now well established that cardiovascular-related comorbidities contribute to morbidity and mortality in COPD, with approximately 50% of deaths in COPD patients attributed to a cardiovascular event (e.g. myocardial infarction).,Cardiovascular disease (CVD) and COPD share various risk factors including hypertension, sedentarism, smoking and poor diet but the underlying mechanisms have not been fully established.,However, there is emerging and compelling experimental and clinical evidence to show that increased oxidative stress causes pulmonary inflammation and that the spill over of pro-inflammatory mediators from the lungs into the systemic circulation drives a persistent systemic inflammatory response that alters blood vessel structure, through vascular remodelling and arterial stiffness resulting in atherosclerosis.,In addition, regulation of endothelial-derived vasoactive substances (e.g. nitric oxide (NO)), which control blood vessel tone are altered by oxidative damage of vascular endothelial cells, thus promoting vascular dysfunction, a key driver of CVD.,In this review, the detrimental role of oxidative stress in COPD and comorbid CVD are discussed and we propose that targeting oxidant-dependent mechanisms represents a novel strategy in the treatment of COPD-associated CVD.
| 1 |
Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century.,The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD.,Our understanding of the key molecular mechanisms which drive the pathological changes are not complete.,In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation.,We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations.,We discuss the need to specifically target SAD to attenuate the progression of COPD.
|
High blood eosinophil count is a predictive biomarker for response to inhaled corticosteroids in prevention of acute exacerbation of COPD, and low blood eosinophil count is associated with pneumonia risk in COPD patients taking inhaled corticosteroids.,However, the prognostic role of blood eosinophil count remains underexplored.,Therefore, we investigated the associated factors and mortality based on blood eosinophil count in COPD.,Patients with COPD were recruited from 16 hospitals of the Korean Obstructive Lung Disease cohort (n=395) and COPD in Dusty Area cohort (n=234) of Kangwon University Hospital.,The two merged cohorts were divided based on blood eosinophil count into three groups: high (≥5%), middle (2%-5%), and low (<2%).,The high group had longer six-minute walk distance (high =445.8±81.4, middle =428.5±88.0, and low =414.7±86.3 m), higher body mass index (23.3±3.1, 23.1±3.1, and 22.5±3.2 kg/m2), lower emphysema index (18.5±14.1, 22.2±15.3, and 23.7±16.3), and higher inspiratory capacity/total lung capacity ratio (32.6±7.4, 32.4±9.2, and 29.9% ± 8.9%) (P<0.05).,The survival period increased with increasing blood eosinophil count (high =9.52±0.23, middle =8.47±1.94, and low =7.42±0.27 years, P<0.05).,Multivariate linear regression analysis revealed that the emphysema index was independently and negatively correlated with blood eosinophil count (P<0.05).,In COPD, the severity of emphysema was independently linked with low blood eosinophil count and the longer survival period was associated with increased blood eosinophil count, though it was not proven in the multivariate analysis.
| 1 |
Caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function.,However, no systematic review has examined how the caregiver role has been operationalized in interventions to improve outcomes of individuals with COPD or the quality or effectiveness of these interventions.,The aims of this review were to 1) determine whether caregivers have been involved as part of interventions to improve outcomes of individuals with COPD; 2) determine the risk of bias within included intervention studies; and 3) examine the effectiveness of interventions that have involved caregivers in improving outcomes of individuals with COPD.,The electronic databases of Medline, Embase, PsycINFO, and Cochrane Library were searched from January 2000 to November 2015.,Experimental studies testing interventions that involved a caregiver to improve COPD patient outcomes were eligible.,Nine studies involving caregivers met inclusion criteria.,No studies reported any intervention components targeted solely at caregivers, with most instead including caregivers in dyadic or group education sessions about COPD delivered by health care professionals.,The risk of bias identified in included studies was mixed.,Seven of the nine studies were effective in improving a broad range of outcomes.,These findings highlight that there is an urgent need for methodologically rigorous interventions to examine the effectiveness of strategies to assist caregivers to provide direct care, encourage adherence to health care provider recommendations, act as a health care advocate, and provide emotional and psychosocial support to individuals with COPD.
|
Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO
| 1 |
Chronic obstructive pulmonary disease (COPD), especially in severe forms, is commonly associated with systemic inflammation and balance impairment.,The aim of our study was to evaluate the impact on equilibrium of stable and exacerbation (acute exacerbation of COPD [AECOPD]) phases of COPD and to investigate if there is a connection between lower extremity muscle weakness and systemic inflammation.,We enrolled 41 patients with COPD (22 stable and 19 in AECOPD) and 20 healthy subjects (control group), having no significant differences regarding the anthropometric data.,We analyzed the differences in balance tests scores: Falls Efficacy Scale-International (FES-I) questionnaire, Berg Balance Scale (BBS), Timed Up and Go (TUG) test, Single Leg Stance (SLS), 6-minute walking distance (6MWD), isometric knee extension (IKE) between these groups, and also the correlation between these scores and inflammatory biomarkers.,The presence and severity of COPD was associated with significantly decreased score in IKE (P<0.001), 6MWD (P<0.001), SLS (P<0.001), and BBS (P<0.001), at the same time noting a significant increase in median TUG score across the studied groups (P<0.001).,The AECOPD group vs stable group presented a significant increase in high-sensitive C-reactive protein (hs-CRP) levels (10.60 vs 4.01; P=0.003) and decrease in PaO2 (70.1 vs 59.1; P<0.001).,We observed that both IKE scores were significantly and positive correlated with all the respiratory volumes.,In both COPD groups, we observed that fibrinogen reversely and significantly correlated with the 6MWD, and FES-I questionnaire is correlated positively with TUG test.,Hs-CRP correlated reversely with the walking test and SLS test, while correlating positively with TUG test and FES-I questionnaire.,According to this study, COPD in advanced and acute stages is associated with an increased history of falls, systemic inflammation, balance impairment, and lower extremity muscle weakness.
|
Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD).,However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD.,The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness.,Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision.,Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control.,Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p = 0.037).,Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p = 0.047), decreased anterior body sway during back muscle vibration (p = 0.025), and increased posterior body sway during simultaneous ankle-muscle vibration (p = 0.002).,Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p = 0.037).,Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls.,These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability.,Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle training improve postural balance and reduce the fall risk in individuals with COPD.
| 1 |
Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress.,Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD.,Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins.,Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction.,Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible.,Other sirtuin isoforms were not affected by miR-34a.,Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.
|
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease involving a wide variety of cells and inflammatory mediators.,The most important etiological factor in the development of this disease is cigarette smoking.,Much of the research into the mechanisms of COPD has been concerned with the induction of inflammation and the role of neutrophils and macrophages in the pathophysiology of the disease.,The possible contribution of the epithelium to the development of COPD has only recently become apparent and remains unclear.,In this article we review research into the effect of cigarette smoke on the pulmonary epithelium with particular emphasis on oxidative stress, proteolytic load, pro-inflammatory cytokine and chemokine profile and epithelial secretions.,In addition, we have also reviewed how cigarette smoke may affect epithelial damage and repair processes.
| 1 |
With increasing choice of medications and devices for asthma and chronic obstructive pulmonary disease (COPD) treatment, comparative evidence may inform treatment decisions.,This systematic literature review assessed clinical and economic evidence for using a single combination inhaler versus multiple inhalers to deliver the same medication for patients with asthma or COPD.,In 2016, Embase, PubMed and the Cochrane library were searched for publications reporting studies in asthma or COPD comparing a single-inhaler combination medicine with multiple inhalers delivering the same medication.,Publications included English-language articles published since 1996 and congress abstracts since 2013.,Clinical, economic and adherence endpoints were assessed.,Of 2031 abstracts screened, 18 randomized controlled trials (RCTs) in asthma and four in COPD, nine retrospective and three prospective observational studies in asthma, and four observational studies in COPD were identified.,Of these, five retrospective and one prospective study in asthma, and two retrospective studies in COPD reported greater adherence with a single inhaler than multiple inhalers.,Nine observational studies reported significantly (n=7) or numerically (n=2) higher rates of adherence with single- versus multiple-inhaler therapy.,Economic analyses from retrospective and prospective studies showed that use of single-inhaler therapies was associated with reduced healthcare resource use (n=6) and was cost-effective (n=5) compared with multiple-inhaler therapies.,Findings in 18 asthma RCTs and one prospective study reporting lung function, and six RCTs reporting exacerbation rates, showed no significant differences between a single inhaler and multiple inhalers.,This was in contrast to several observational studies reporting reductions in healthcare resource use or exacerbation events with single-inhaler treatment, compared with multiple inhalers.,Retrospective and prospective studies showed that single-inhaler use was associated with decreased healthcare resource utilization and improved cost-effectiveness compared with multiple inhalers.,Lung function and exacerbation rates were mostly comparable in the RCTs, possibly due to study design.
|
Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392.
| 1 |
Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus disease (COVID-19).,Early data suggest elevated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) receptor angiotensin converting enzyme 2 (ACE2) expression, but relationships to disease phenotype and downstream regulators of inflammation in the Renin-Angiotensin system (RAS) are unknown.,We aimed to determine the relationship between RAS gene expression relevant to SARS-CoV-2 infection in the lung with disease characteristics in COPD, and the regulation of newly identified SARS-CoV-2 receptors and spike-cleaving proteases, important for SARS-CoV-2 infection.,We quantified gene expression using RNA sequencing of epithelial brushings and bronchial biopsies from 31 COPD and 37 control subjects.,ACE2 gene expression (log2-fold change (FC)) was increased in COPD compared to ex-smoking (HV-ES) controls in epithelial brushings (0.25, p = 0.042) and bronchial biopsies (0.23, p = 0.050), and correlated with worse lung function (r = − 0.28, p = 0.0090).,ACE2 was further increased in frequent exacerbators compared to infrequent exacerbators (0.51, p = 0.00045) and associated with use of ACE inhibitors (ACEi) (0.50, p = 0.0034), having cardiovascular disease (0.23, p = 0.048) or hypertension (0.34, p = 0.0089), and inhaled corticosteroid use in COPD subjects in bronchial biopsies (0.33, p = 0.049).,Angiotensin II receptor type (AGTR)1 and 2 expression was decreased in COPD bronchial biopsies compared to HV-ES controls with log2FC of -0.26 (p = 0.033) and − 0.40, (p = 0.0010), respectively.,However, the AGTR1:2 ratio was increased in COPD subjects compared with HV-ES controls, log2FC of 0.57 (p = 0.0051).,Basigin, a newly identified potential SARS-CoV-2 receptor was also upregulated in both brushes, log2FC of 0.17 (p = 0.0040), and bronchial biopsies, (log2FC of 0.18 (p = 0.017), in COPD vs HV-ES.,Transmembrane protease, serine (TMPRSS)2 was not differentially regulated between control and COPD.,However, various other spike-cleaving proteases were, including TMPRSS4 and Cathepsin B, in both epithelial brushes (log2FC of 0.25 (p = 0.0012) and log2FC of 0.56 (p = 5.49E−06), respectively) and bronchial biopsies (log2FC of 0.49 (p = 0.00021) and log2FC of 0.246 (p = 0.028), respectively).,This study identifies key differences in expression of genes related to susceptibility and aetiology of COVID-19 within the COPD lung.,Further studies to understand the impact on clinical course of disease are now required.,The online version contains supplementary material available at 10.1186/s12931-021-01755-3.
|
Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.
| 1 |
Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders.,In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach).,Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece.,This was a cross-sectional observational study.,Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece).,The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2).,Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach.,The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A.,Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.,The online version contains supplementary material available at 10.1186/s12890-021-01576-6.
|
Nighttime symptoms can negatively impact the quality of life of patients with chronic obstructive pulmonary disease (COPD).,The Nighttime Symptoms of COPD Instrument (NiSCI) was designed to measure the occurrence and severity of nighttime symptoms in patients with COPD, the impact of symptoms on nighttime awakenings, and rescue medication use.,The objective of this study was to explore item reduction, inform scoring recommendations, and evaluate the psychometric properties of the NiSCI.,COPD patients participating in a Phase III clinical trial completed the NiSCI daily.,Item analyses were conducted using weekly mean and single day scores.,Descriptive statistics (including percentage of respondents at floor/ceiling and inter-item correlations), factor analyses, and Rasch model analyses were conducted to examine item performance and scoring.,Test-retest reliability was assessed for the final instrument using the intraclass correlation coefficient (ICC).,Correlations with assessments conducted during study visits were used to evaluate convergent and known-groups validity.,Data from 1,663 COPD patients aged 40-93 years were analyzed.,Item analyses supported the generation of four scores.,A one-factor structure was confirmed with factor analysis and Rasch analysis for the symptom severity score.,Test-retest reliability was confirmed for the six-item symptom severity (ICC, 0.85), number of nighttime awakenings (ICC, 0.82), and rescue medication (ICC, 0.68) scores.,Convergent validity was supported by significant correlations between the NiSCI, St George’s Respiratory Questionnaire, and Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Respiratory Symptoms scores.,The results suggest that the NiSCI can be used to determine the severity of nighttime COPD symptoms, the number of nighttime awakenings due to COPD symptoms, and the nighttime use of rescue medication.,The NiSCI is a reliable and valid instrument to evaluate these concepts in COPD patients in clinical trials and clinical practice.,Scoring recommendations and steps for further research are discussed.
| 1 |
COPD is a disease associated with significant economic burden.,It was reported that Global initiative for chronic Obstructive Lung Disease (GOLD) guideline-oriented pharmacotherapy improves airflow limitation and reduces health care costs.,However, several studies showed a significant dissociation between international recommendations and clinicians’ practices.,The consequent reduced diagnostic and therapeutic inappropriateness has proved to be associated with an increase in costs and a waste of economic resources in the health sector.,The aim of the study was to evaluate COPD management in the Puglia region.,The study was performed in collaboration with the pulmonology centers and the Regional Health Agency (AReS Puglia).,An IT platform allowed the pulmonologists to enter data via the Internet.,All COPD patients who visited a pneumological outpatient clinic for the first time or for regular follow-ups or were admitted to a pneumological department for an exacerbation were considered eligible for the study.,COPD’s diagnosis was confirmed by a pulmonologist at the moment of the visit.,The project lasted 18 months and involved 17 centers located in the Puglia region.,Six hundred ninety-three patients were enrolled, evenly distributed throughout the region.,The mean age was 71±9 years, and 85% of them were males.,Approximately 23% were current smokers, 63% former smokers and 13.5% never smokers.,The mean post-bronchodilator forced expiratory volume in 1 second was 59%±20% predicted.,The platform allowed the classification of patients according to the GOLD guidelines (Group A: 20.6%, Group B: 32.3%, Group C: 5.9% and Group D: 39.2%), assessed the presence and severity of exacerbations (20% of the patients had an exacerbation defined as mild [13%], moderate [37%] and severe [49%]) and evaluated the appropriateness of inhalation therapy at the time of the visit.,Forty-nine percent of Group A patients were following inappropriate therapy; in Group B, 45.8% were following a therapy in contrast with the guidelines.,Among Group C patients, 41.46% resulted in triple combination therapy, whilê14% of Group D patients did not have a therapy or were following an inappropriate therapy.,In conclusion, 30% of all patients evaluated had been following an inadequate therapy.,Subsequently, an online survey was developed to inquire about the reasons for the results obtained.,In particular, we investigated the reasons why 30% of our population did not follow the therapy suggested by the GOLD guidelines: 1) why was there an excessive use of inhaled corticosteroids, 2) why a significantly high percentage was inappropriately treated with triple therapy and 3) why a consistent percentage (11%) of Group D patients were not treated at all.,The data provides an overview on the management of COPD in the region of Puglia (Italy) and represents a resource in order to improve appropriateness and reduce the waste of health resources.
|
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.
| 1 |
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.
|
Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce.,Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint.,Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment.,A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation.,In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators.,Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses.,Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers.,The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality.,The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival.,NCT00563381; Study identifier: BI 205.389.
| 1 |
Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).,Methods: The multidisciplinary panel created six research questions using a modified Delphi approach.,A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.,Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).,Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.
|
Long term oxygen therapy (LTOT) has a strong evidence base in COPD patients with respiratory failure, but prescribing practices are recognized to need reform to ensure appropriate use and minimize costs.,In the UK, since February 2006, all Home Oxygen prescription is issued by hospitals, making respiratory specialists totally in charge of home oxygen prescription.,It has been widely noted that inappropriate home oxygen, often for intermittent use (“short burst”), is frequently prescribed in patients with COPD and related conditions with the intention to prevent hospital admissions outside of evidence based LTOT guidelines.,We participated in a national Lung Improvement Project aimed at making LTOT use more evidence based.,We utilised this unique opportunity of studying the effect of removal of oxygen from COPD patients (who did not meet LTOT criteria) on hospital admission rates.,Primary and secondary care data sources were used to identify patients with COPD in a single primary care trust who were admitted to hospital at least once due to COPD between April 2007 and November 2010.,Admission rates were compared between LTOT users and non-users, adjusted for age and COPD severity.,LTOT users were further studied for predictors of admission in those appropriately or inappropriately given oxygen according to NICE guidance, and for admissions before and after oxygen receipt, adjusting further for co-morbidity.,Mortality and economic analyses were also conducted.,Readmission was more likely in LTOT users (3.18 v 1.67 per patient, p < 0.001) after adjustment for FEV1 and age by multiple regression.,When stratifying by appropriateness of LTOT prescription, adjusting also for Charlson index and other covariates, FEV1 predicted admission in appropriate users but there were no predictors in inappropriate users.,In longitudinal analyses admission rates did not differ either side of oxygen prescription in appropriate or inappropriate LTOT users.,Specialist assessment resulted in cost savings due to reduced use of oxygen.,Admission to hospital is more likely in LTOT users, independent of COPD severity.,Oxygen use outside NICE guidance does not appear to prevent admissions.
| 1 |
Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology.,Accurate detection of COPD subtypes by image biomarkers are urgently needed to enable individualized treatment thus improving patient outcome.,We adapted the Parametric Response Map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype.,We analyzed whole lung CT scans of 194 COPD individuals acquired at inspiration and expiration from the COPDGene Study.,PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity.,PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype, while providing detailed spatial information of disease distribution and location.,PRMs ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients complementing standard clinical techniques.
|
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the small airways.,The effect of inhaled corticosteroids (ICS) on lung inflammation in COPD remains uncertain.,We sought to determine the effects of ICS on inflammatory indices in bronchial biopsies and bronchoalveolar lavage fluid of patients with COPD.,We searched Medline, Embase, Cinahl, and the Cochrane database for randomized, controlled clinical trials that used bronchial biopsies and bronchoalveolar lavage to evaluate the effects of ICS in stable COPD.,For each chosen study, we calculated the mean differences in the concentrations of inflammatory cells before and after treatment in both intervention and control groups.,These values were then converted into standardized mean differences (SMD) to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across the original studies.,If significant heterogeneity was present (P < 0.1), then a random effects model was used to pool the original data; otherwise, a fixed effects model was used.,We identified eight original studies that met the inclusion criteria.,Four studies used bronchial biopsies (n =102 participants) and showed that ICS were effective in reducing CD4 and CD8 cell counts (SMD, −0.52 units and −0.66 units, 95% confidence interval).,The five studies used bronchoalveolar lavage fluid (n =309), which together showed that ICS reduced neutrophil and lymphocyte counts (SMD, −0.64 units and −0.64 units, 95% confidence interval).,ICS on the other hand significantly increased macrophage counts (SMD, 0.68 units, 95% confidence interval) in bronchoalveolar lavage fluid.,ICS has important immunomodulatory effects in airways with COPD that may explain its beneficial effect on exacerbations and enhanced risk of pneumonia.
| 1 |
We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year.,Eighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO); inflammatory variables were measured in venous blood.,Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.,Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%) had greater serum concentration (median (25th-75th quartile)) of serum amyloid A (SAA; 134 (84-178) vs 71 (38-116) ng/mL; P=0.024), surfactant protein D (SP-D; 15.6 (9.0-19.3) vs 8.5 (3.6-14.9) ng/mL; P=0.049) and interleukin-4 (IL-4; 0.12 (0.08-1.44) vs 0.03 (0.01-0.10) pg/mL; P=0.001).,SAA, SP-D and IL-4 were not significantly correlated with FEV1%predicted or FVC %predicted.,After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012).,The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (≥124.1 ng/mL) than the lowest SAA quartile (≤44.1 ng/mL) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008).,For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators; an SAA cut-off of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity.,In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD.
|
Metabolic syndrome is a common extrapulmonary comorbidity in patients with chronic obstructive pulmonary disease (COPD).,However, the reported relationship of COPD with dyslipidemia, an important component of metabolic syndrome, is ambiguous.,The aim of this meta-analysis is to investigate the association between COPD and the serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG).,The PubMed and Embase databases were searched to find potential studies using the search terms of (“dyslipidemia” or “HDL” or “LDL” or “cholesterol” or “triglyceride”) and COPD.,We also performed subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia.,Mean differences (MD) with 95% confidence intervals (CI) were estimated with random effects models.,A total of 11 studies comprising 615 cases and 471 controls were included in the study.,No significant differences were found in the HDL (MD = −2.55, 95% CI [−6.03, 0.93], P = 0.15), LDL (MD = −2.25, 95% CI [−13.36, 8.86], P = 0.69), TC (MD = −2.69, 95% CI [−13.30, 7.92], P = 0.62), and TG (MD = 6.90, 95% CI [−2.81, 16.60], P = 0.16) levels of the 2 groups.,However, subgroup analysis enrolling patients who were not receiving treatment for dyslipidemia showed that TG levels were higher in patients with stable COPD than in healthy individuals (MD = 16.35, 95% CI [5.90, 26.80], P = 0.002).,Excluding the impact of hypolipidemic treatment on serum lipid profile, TG levels were higher in patients with COPD than in healthy individuals.,This meta-analysis suggested that physicians should screen COPD patients for elevated TG levels to reduce the risk of cardiovascular morbidity and mortality.
| 1 |
Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation.,Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD.,Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication.,Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.,In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD.,EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis.,As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs.,Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining.,Gene expression in the lung tissue was assessed using microarray analysis.,Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA).,Student’s t test was used to compare between 2 groups.,Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA).,Data presented as median ± standard deviation (SD).,Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells.,Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue.,Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD.,In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation.,Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.,The online version contains supplementary material available at 10.1186/s13287-020-02088-6.
|
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.
| 1 |
Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD.
|
Clinical manifestations of chronic obstructive pulmonary disease (COPD), including airflow limitation, dyspnea, and activity limitation, ultimately lead to impaired health-related quality of life (HRQoL).,This 9-month, randomized, double-blind, multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL, spirometric parameters, and exacerbations in 554 patients with moderate-to-severe COPD.,HRQoL was assessed using the St.,George’s Respiratory Questionnaire (SGRQ) and the new 8-item Visual Simplified Respiratory Questionnaire (VSRQ), which is currently being validated.,The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end (Month 9).,Mean ± SD baseline SGRQ total score was 47.4 ± 18.1.,Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end (59.1% vs 48.2%, respectively; p = 0.029).,Tiotropium significantly improved spirometric parameters (forced expiratory volume in 1 second [FEV1]: 0.11 ± 0.02 L vs 0.01 ± 0.02 L; between-group difference: 0.10 ± 0.03 L, p = 0.0001) and reduced exacerbations vs placebo.,Maintenance treatment with tiotropium provided significant and clinically relevant improvements in HRQoL, as measured by the SGRQ.
| 1 |
COPD exacerbations accelerate disease progression.,To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation (AECOPD) frequency and duration.,403 COPD patients, GOLD stage II-IV, aged 44-76 years were included in the Bergen COPD Cohort Study in 2006/07, and followed for 3 years.,Examined baseline predictors were sex, age, body composition, smoking, AECOPD the last year, GOLD stage, Charlson comorbidity score (CCS), hypoxemia (PaO2<8 kPa), cough, use of inhaled steroids, and the inflammatory markers leucocytes, C-reactive protein (CRP), neutrophil gelatinase associated lipocalin (NGAL), soluble tumor necrosis factor receptor 1 (sTNF-R1), and osteoprotegrin (OPG).,Negative binomial models with random effects were fitted to estimate the annual incidence rate ratios (IRR).,For analysis of AECOPD duration, a generalized estimation equation logistic regression model was fitted, also adjusting for season, time since inclusion and AECOPD severity.,After multivariate adjustment, significant predictors of AECOPD were: female sex [IRR 1.45 (1.14-1.84)], age per 10 year increase [1.23 (1.03-1.47)], >1 AECOPD last year before baseline [1.65 (1.24-2.21)], GOLD III [1.36 (1.07-1.74)], GOLD IV [2.90 (1.98-4.25)], chronic cough [1.64 (1.30-2.06)] and use of inhaled steroids [1.57 (1.21-2.05)].,For AECOPD duration more than three weeks, significant predictors after adjustment were: hypoxemia [0.60 (0.39-0.92)], years since inclusion [1.19 (1.03-1.37)], AECOPD severity; moderate [OR 1.58 (1.14-2.18)] and severe [2.34 (1.58-3.49)], season; winter [1.51 (1.08-2.12)], spring [1.45 (1.02-2.05)] and sTNF-R1 per SD increase [1.16 (1.00-1.35)].,Several COPD characteristics were independent predictors of both AECOPD frequency and duration.
|
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death.
| 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation.,An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes.,T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses.,This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD).,Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study.,In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls.,The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits.,Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies.,Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of “inflammation adjustment” and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.,Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment.,There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups.,Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient.,Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.,These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating.,Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation.,All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated.
|
There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling.,No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation.,Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions.,VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD.,Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes.,The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD.,This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases.
| 1 |
In Tunisia, there is a paucity of population-based data on Chronic Obstructive Pulmonary Disease (COPD) prevalence.,To address this problem, we estimated the prevalence of COPD following the Burden of Lung Disease Initiative.,We surveyed 807 adults aged 40+ years and have collected information on respiratory history and symptoms, risk factors for COPD and quality of life.,Post-bronchodilator spirometry was performed and COPD and its stages were defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,Six hundred and sixty one (661) subjects were included in the final analysis.,The prevalence of GOLD Stage I and II or higher COPD were 7.8% and 4.2%, respectively (Lower Limit of Normal modified stage I and II or higher COPD prevalence were 5.3% and 3.8%, respectively).,COPD was more common in subjects aged 70+ years and in those with a BMI < 20 kg/m2.,Prevalence of stage I+ COPD was 2.3% in <10 pack years smoked and 16.1% in 20+ pack years smoked.,Only 3.5% of participants reported doctor-diagnosed COPD.,In this Tunisian population, the prevalence of COPD is higher than reported before and higher than self-reported doctor-diagnosed COPD.,In subjects with COPD, age is a much more powerful predictor of lung function than smoking.
|
Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution.,However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far.,Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women.,We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.,In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany.,NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data.,Lung function was determined and COPD was defined by using the GOLD criteria.,Chronic respiratory symptoms and possible confounders were defined by questionnaire data.,Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.,The prevalence of COPD (GOLD stages 1-4) was 4.5%.,COPD and pulmonary function were strongest affected by PM10 and traffic related exposure.,A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD.,Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away.,Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.,Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.
| 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are associated with lung function decline, lower quality of life, and increased mortality, and can be prevented by pharmacological treatment and rehabilitation.,To examine management including examination, treatment, and planned follow-up of COPD exacerbation visits in primary care patients and to explore how measures and management at exacerbation visits are related to subsequent exacerbation risk.,A clinical population of 775 COPD patients was randomly selected from 56 Swedish primary healthcare centres.,Data on patient characteristics and management of COPD exacerbations were obtained from medical record review and a patient questionnaire.,In the study population of 458 patients with at least one exacerbation, Cox regression analyses estimated the risk of a subsequent exacerbation with adjustment for age and sex.,During a follow-up period of 22 months, 238 patients (52%) had a second exacerbation.,A considerable proportion of the patients were not examined and treated as recommended by guidelines.,Patients with a scheduled extra visit to an asthma/COPD nurse following an exacerbation had a decreased risk of further exacerbations compared with patients with no extra follow-up other than regularly scheduled visits (adjusted hazard ratio 0.60 (95% confidence interval 0.37 to 0.99), p=0.045).,Guidelines for examination and emergency treatment at COPD exacerbation visits are not well implemented.,Scheduling an extra visit to an asthma/COPD nurse following a COPD exacerbation may be associated with a decreased risk of further exacerbations in primary care patients.
|
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations.
| 1 |
Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression.,A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs).,PQTLs consistently replicated between the two cohorts.,Features of pQTLs were compared to previously reported expression QTLs (eQTLs).,Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests.,We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested.,Most pQTL SNPs were novel with low overlap to eQTL SNPs.,The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC).,Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.,Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins.,The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates.,Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema.,In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms.,Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.
|
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.
| 1 |
Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are important clinical events, with many patients experiencing multiple AECOPDs annually.,The terms used in the literature to define recurring AECOPD events are inconsistent and may impact the ability to describe the true burden of these events.,We undertook a systematic review to identify and summarize terms and definitions used in observational studies to describe AECOPD-related events occurring after an initial AECOPD (hereafter “subsequent AECOPD”).,PubMed was searched (2000-2019) for observational studies on subsequent AECOPD events using broad search strings for “COPD”, “exacerbation”, and “subsequent exacerbation events”.,Only English-language studies were included.,Small studies (n<50) and studies focusing on hospital re-admission only were excluded.,Extracted data were analyzed descriptively to generate a narrative summary, using a thematic approach to group studies utilizing similar terms for subsequent AECOPD.,Forty-seven studies were included.,No single, distinct terms or definitions were used to define and identify multiple occurrences of AECOPDs, though most (46) studies used one or more of four clustered terms and definitions: reapse (n = 13), recurrence/re-exacerbation (n = 11), treatment failure (n = 12) and non-recovery/time to recovery (n = 16).,Heterogeneity was observed within and between the four clusters with respect to study setting, starting point for observing subsequent AECOPDs, time frame to identify a subsequent AECOPD (except for studies using “time to recovery”), and basis for identifying a subsequent exacerbation.,Our review demonstrates that subsequent AECOPDs (including events such as relapse, recurrence/re-exacerbation, treatment failure, non-recovery/time to recovery) are ill-defined in the observational study literature, emphasizing the need to reach consensus on precise and objective definitions (for example, when one AECOPD ends and another begins).,Use of standardized terminology and definitions may aid comparability between, and synthesis of, studies, thus improving the understanding of the natural history and burden of exacerbations in COPD patients.
|
The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD).,We previously developed a score (‘2008 score’, based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs).,External validity of this score remained to be assessed.,To test the predictive properties of the ‘2008 score’ in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance.,Data from a cohort study in 1824 patients hospitalized in a medical ward for an AECOPD were analyzed.,Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed.,A new score was developed using multivariate logistic regression modeling in a randomly selected derivation population sample followed by testing in the remaining population (validation sample).,Robustness of results was assessed by case-by-case validation.,The 2008 score was characterized by a c-statistic at 0.77, a sensitivity of 69% and a specificity of 76% for prediction of in-hospital mortality.,The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78, a sensitivity of 77% and specificity of 66%.,A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AECOPD.,Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity.,The online version of this article (doi:10.1186/s12931-014-0099-9) contains supplementary material, which is available to authorized users.
| 1 |
The Coronavirus disease 2019 (COVID-19) pandemic has led to widespread implementation of public health measures, such as stay-at-home orders, social distancing, and masking mandates.,In addition to decreasing spread of severe acute respiratory syndrome coronavirus 2, these measures also impact the transmission of seasonal viral pathogens, which are common triggers of chronic obstructive pulmonary disease (COPD) exacerbations.,Whether reduced viral prevalence mediates reduction in COPD exacerbation rates is unknown.,We performed retrospective analysis of data from a large, multicenter health care system to assess admission trends associated with community viral prevalence and with initiation of COVID-19 pandemic control measures.,We applied difference-in-differences analysis to compare season-matched weekly frequency of hospital admissions for COPD prior to and after implementation of public health measures for COVID-19.,Community viral prevalence was estimated using regional Centers for Disease Control and Prevention test positivity data and correlated to COPD admissions.,Data involving 4422 COPD admissions demonstrated a season-matched 53% decline in COPD admissions during the COVID-19 pandemic, which correlated to community viral burden (r = 0.73; 95% confidence interval, 0.67-0.78) and represented a 36% greater decline over admission frequencies observed in other medical conditions less affected by respiratory viral infections (incidence rate ratio 0.64; 95% confidence interval, 0.57-0.71, P < .001).,The post-COVID-19 decline in COPD admissions was most pronounced in patients with fewer comorbidities and without recurrent admissions.,The implementation of public health measures during the COVID-19 pandemic was associated with decreased COPD admissions.,These changes are plausibly explained by reduced prevalence of seasonal respiratory viruses.
|
Previous studies suggested that the prevalence of chronic respiratory disease in patients hospitalised with COVID-19 was lower than its prevalence in the general population.,The aim of this study was to assess whether chronic lung disease or use of inhaled corticosteroids (ICS) affects the risk of contracting severe COVID-19.,In this population cohort study, records from 1205 general practices in England that contribute to the QResearch database were linked to Public Health England's database of SARS-CoV-2 testing and English hospital admissions, intensive care unit (ICU) admissions, and deaths for COVID-19.,All patients aged 20 years and older who were registered with one of the 1205 general practices on Jan 24, 2020, were included in this study.,With Cox regression, we examined the risks of COVID-19-related hospitalisation, admission to ICU, and death in relation to respiratory disease and use of ICS, adjusting for demographic and socioeconomic status and comorbidities associated with severe COVID-19.,Between Jan 24 and April 30, 2020, 8 256 161 people were included in the cohort and observed, of whom 14 479 (0·2%) were admitted to hospital with COVID-19, 1542 (<0·1%) were admitted to ICU, and 5956 (0·1%) died.,People with some respiratory diseases were at an increased risk of hospitalisation (chronic obstructive pulmonary disease [COPD] hazard ratio [HR] 1·54 [95% CI 1·45-1·63], asthma 1·18 [1·13-1·24], severe asthma 1·29 [1·22-1·37; people on three or more current asthma medications], bronchiectasis 1·34 [1·20-1·50], sarcoidosis 1·36 [1·10-1·68], extrinsic allergic alveolitis 1·35 [0·82-2·21], idiopathic pulmonary fibrosis 1·59 [1·30-1·95], other interstitial lung disease 1·66 [1·30-2·12], and lung cancer 2·24 [1·89-2·65]) and death (COPD 1·54 [1·42-1·67], asthma 0·99 [0·91-1·07], severe asthma 1·08 [0·98-1·19], bronchiectasis 1·12 [0·94-1·33], sarcoidosis 1·41 [0·99-1·99), extrinsic allergic alveolitis 1·56 [0·78-3·13], idiopathic pulmonary fibrosis 1·47 [1·12-1·92], other interstitial lung disease 2·05 [1·49-2·81], and lung cancer 1·77 [1·37-2·29]) due to COVID-19 compared with those without these diseases.,Admission to ICU was rare, but the HR for people with asthma was 1·08 (0·93-1·25) and severe asthma was 1·30 (1·08-1·58).,In a post-hoc analysis, relative risks of severe COVID-19 in people with respiratory disease were similar before and after shielding was introduced on March 23, 2020.,In another post-hoc analysis, people with two or more prescriptions for ICS in the 150 days before study start were at a slightly higher risk of severe COVID-19 compared with all other individuals (ie, no or one ICS prescription): HR 1·13 (1·03-1·23) for hospitalisation, 1·63 (1·18-2·24) for ICU admission, and 1·15 (1·01-1·31) for death.,The risk of severe COVID-19 in people with asthma is relatively small.,People with COPD and interstitial lung disease appear to have a modestly increased risk of severe disease, but their risk of death from COVID-19 at the height of the epidemic was mostly far lower than the ordinary risk of death from any cause.,Use of inhaled steroids might be associated with a modestly increased risk of severe COVID-19.,National Institute for Health Research Oxford Biomedical Research Centre and the Wellcome Trust.
| 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.
|
To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD.,We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo.,Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization.,The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects.,The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage.,Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations.,Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD.,Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively.,For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively.,Study duration or type of study (cohort versus trial) did not significantly affect the outcomes.,This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes.
| 1 |
Genome-wide mRNA profiling in lung tissue from human and animal models can provide novel insights into the pathogenesis of chronic obstructive pulmonary disease (COPD).,While 6 months of smoke exposure are widely used, shorter durations were also reported.,The overlap of short term and long-term smoke exposure in mice is currently not well understood, and their representation of the human condition is uncertain.,Lung tissue gene expression profiles of six murine smoking experiments (n = 48) were obtained from the Gene Expression Omnibus (GEO) and analyzed to identify the murine smoking signature.,The “human smoking” gene signature containing 386 genes was previously published in the lung eQTL study (n = 1,111).,A signature of mild COPD containing 7 genes was also identified in the same study.,The lung tissue gene signature of “severe COPD” (n = 70) contained 4,071 genes and was previously published.,We detected 3,723 differentially expressed genes in the 6 month-exposure mice datasets (FDR <0.1).,Of those, 184 genes (representing 48% of human smoking) and 1,003 (representing 27% of human COPD) were shared with the human smoking-related genes and the COPD severity-related genes, respectively.,There was 4-fold over-representation of human and murine smoking-related genes (P = 6.7 × 10−26) and a 1.4 fold in the severe COPD -related genes (P = 2.3 × 10−12).,There was no significant enrichment of the mice and human smoking-related genes in mild COPD signature.,These data suggest that murine smoke models are strongly representative of molecular processes of human smoking but less of COPD.
|
This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity.,A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study.,Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups.,We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores.,Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment.,This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.
| 1 |
Cycle ergometer training (CET) has been shown to improve exercise performance of the quadriceps muscles in patients with COPD, and inspiratory muscle training (IMT) may improve the pressure-generating capacity of the inspiratory muscles.,However, the effects of combined CET and IMT remain unclear and there is a lack of comprehensive assessment.,Eighty-one patients with COPD were randomly allocated to three groups: 28 received 8 weeks of CET + IMT (combined training group), 27 received 8 weeks of CET alone (CET group), and 26 only received 8 weeks of free walking (control group).,Comprehensive assessment including respiratory muscle strength, exercise capacity, pulmonary function, dyspnea, quality of life, emotional status, nutritional status, and body mass index, airflow obstruction, and exercise capacity index were measured before and after the pulmonary rehabilitation program.,Respiratory muscle strength, exercise capacity, inspiratory capacity, dyspnea, quality of life, depression and anxiety, and nutritional status were all improved in the combined training and CET groups when compared with that in the control group (P<0.05) after pulmonary rehabilitation program.,Inspiratory muscle strength increased significantly in the combined training group when compared with that in the CET group (ΔPImax [maximal inspiratory pressure] 5.20±0.89 cmH2O vs 1.32±0.91 cmH2O; P<0.05).,However, there were no significant differences in the other indices between the two groups (P>0.05).,Patients with weakened respiratory muscles in the combined training group derived no greater benefit than those without respiratory muscle weakness (P>0.05).,There were no significant differences in these indices between the patients with malnutrition and normal nutrition after pulmonary rehabilitation program (P>0.05).,Combined training is more effective than CET alone for increasing inspiratory muscle strength.,IMT may not be useful when combined with CET in patients with weakened inspiratory muscles.,Nutritional status had slight impact on the effects of pulmonary rehabilitation.,A comprehensive assessment approach can be more objective to evaluate the effects of combined CET and IMT.
|
The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users.
| 1 |
Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD.,This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.,Data from LANTERN and ILLUMINATE studies were pooled and analyzed.,In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 μg/50 μg or twice-daily SFC 50 μg/500 μg.,End points were pre-dose trough forced expiratory volume in one second (FEV1), standardized area under the curve for FEV1 from 0 to 12 hours (FEV1 AUC0-12 hours), peak FEV1, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George’s Respiratory Questionnaire total score, rescue medication use and safety.,A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454).,At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups.,TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups.,IND/GLY also reduced the rate of exacerbations in the pooled population.,Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.,In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients.
|
The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460.
| 1 |
The role of IL-27 in the pathogenesis of airway inflammatory diseases remains elusive.,We, therefore, have studied its concentrations in the sputum and plasma of patients with COPD and patients with pulmonary TB (PTB), and further investigated the mechanism-of-action effects of IL-27 on bronchial epithelial cells in vitro.,Human bronchial epithelial cells grown on air-liquid interface culture were activated by IL-27, alone, or in combination with other inflammatory cytokines in the presence or absence of various signaling molecule inhibitors.,The expression of CXCL10 was detected by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA).,The underlying signaling pathways were studied by intracellular staining using flow cytometry, Western blot, ELISA, or siRNA.,Significantly higher sputum and plasma concentrations of IL-27 were found in patients with COPD (n = 34; P < .01 and P < .001, respectively) or patients with PTB (n = 31; P < .01 and P < .001, respectively) than in healthy control subjects (n = 48).,Sputum, but not plasma, IL-27 levels in patients with COPD correlated negatively with FEV1 (r = −0.51, P < .01).,Sputum, but not plasma, IL-27 in patients with PTB correlated positively with mycobacterial load in sputum (r = 0.48, P < .05).,Further in vitro studies demonstrated that IL-27 could induce gene and protein expression of CXCL10 in bronchial epithelial cells, which was regulated by the activation of the phosphatidylinositol 3-OH kinase (PI3K)-Akt signaling pathway.,The production of IL-27 is related to the pathogenesis of COPD and PTB, and IL-27 induces the expression of CXCL10 in bronchial epithelial cells through the activation of the PI3K-Akt signaling pathway.
|
CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor.,This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD).,This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study.,Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months.,Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler).,Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32.,Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32.,Of 61 randomised patients, 54 (88.5%) completed the study.,There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes.,CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo.,In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα).,In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo.,CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide).,The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy.,The study is registered on ClinicalTrials.gov (NCT03004417).,The online version of this article (10.1186/s12931-019-1142-7) contains supplementary material, which is available to authorized users.
| 1 |
Purpose: Assess the clinical and economic consequences associated with an early versus late diagnosis in patients with COPD.,Patients and methods: In a retrospective, observational cohort study, electronic medical record data (2000-2014) were collected from Swedish primary care patients with COPD.,COPD indicators (pneumonia, other respiratory diseases, oral corticosteroids, antibiotics for respiratory infections, prescribed drugs for respiratory symptoms, lung function measurement) registered prior to diagnosis were applied to categorize patients into those receiving early (2 or less indicators) or late diagnosis (3 or more indicators registered >90 days preceding a COPD diagnosis).,Outcome measures included annual rate of and time to first exacerbation, mortality risk, prevalence of comorbidities and health care utilization.,Results: More patients with late diagnosis (n=8827) than with early diagnosis (n=3870) had a recent comorbid diagnosis of asthma (22.0% vs 3.9%; P<0.0001).,Compared with early diagnosis, patients with late diagnosis had a higher exacerbation rate (hazard ratio [HR] 1.89, 95% confidence interval [CI]: 1.83-1.96; P<0.0001) and shorter time to first exacerbation (HR 1.61, 95% CI: 1.54-1.69; P<0.0001).,Mortality was not different between groups overall but higher for late versus early diagnosis, after excluding patients with past asthma diagnosis (HR 1.10, 95% CI: 1.02-1.18; P=0.0095).,Late diagnosis was also associated with higher direct costs than early diagnosis.,Conclusion: Late COPD diagnosis is associated with higher exacerbation rate and increased comorbidities and costs compared with early diagnosis.,The study highlights the need for accurate diagnosis of COPD in primary care in order to reduce exacerbations and the economic burden of COPD.
|
Although chronic obstructive pulmonary disease (COPD) is a major global health burden there is a lack of patient awareness of disease severity, particularly in relation to exacerbations.,We conducted a global patient survey using an innovative, internet-based methodology to gain insight into patient perceptions of COPD and exacerbations in a real-world sample typical of today’s working-age COPD population.,Two thousand patients with COPD (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries completed an online questionnaire developed by the authors.,The Medical Research Council (MRC) breathlessness scale was used to delineate symptom severity.,Over three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC 1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as a result of an exacerbation.,While a majority of MRC 1 and 2 patients (51%) reported being back to normal within a few days of an exacerbation, 23% of MRC 3, 4 and 5 patients took several weeks to return to normal and 6% never fully recovered.,A high proportion of patients (39%) took a ‘wait and see’ approach to exacerbations.,Despite the high prevalence of exacerbations and their negative impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5 patients felt that they had control of their COPD.,However, 77% of all patients were worried about their long-term health, and 38% of MRC 1 and 2 patients and 59% of MRC 3, 4 and 5 patients feared premature death due to COPD.,To reduce the adverse effects of COPD on patients’ quality of life and address their fears for the future, we need better patient education and improved prevention and treatment of exacerbations.
| 1 |
Coronavirus disease 2019 (COVID-19) was rapidly expanded worldwide within a short period.,Its relationship with chronic comorbidities is still unclear.,We aimed to determine the effects of chronic comorbidities on clinical outcomes of patients with and without COVID-19.,This was an analysis of 65,535 patients with suspicion of viral respiratory disease (38,324 SARS-CoV-2 positive and 27,211 SARS-CoV-2 negative) from January 01 to May 12, 2020 using the national administrative healthcare open data of Mexico.,SARS-CoV-2 infection was confirmed by reverse-transcriptase-polymerase-chain-reaction.,General characteristics and chronic comorbidities were explored.,Clinical outcomes of interest were hospital admission, pneumonia, intensive care unit admission, endotracheal intubation and mortality.,Prevalence of chronic comorbidities was 49.4%.,Multivariate logistic regression analysis showed that the effect of age, male sex, bronchial asthma, diabetes mellitus and chronic kidney disease on clinical outcomes was similar for both SARS-CoV-2 positive and negative patients.,Adverse clinical outcomes were associated with the time from symptoms onset to medical contact, chronic obstructive pulmonary disease, hypertension and obesity in SARS-CoV-2 positive patients, but with cardiovascular disease in SARS-CoV-2 negative patients (p value < 0.01 for all comparisons).,Chronic comorbidities are commonly found in patients with suspicion of viral respiratory disease.,The knowledge of the impact of comorbidities on adverse clinical outcomes can better define those COVID-19 patients at higher risk.,The different impact of the specific type of chronic comorbidity on clinical outcomes in patients with and without SARS-CoV-2 infection requires further researches.,These findings need confirmation using other data sources.,The online version contains supplementary material available at 10.1007/s11739-020-02597-5.
|
The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).,Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities.,COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities.,Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD.,First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection?,Secondly, do inhaled corticosteroids offer protection against COVID-19?,And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients?,This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.,This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19https://bit.ly/36PKzEO
| 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important measure of disease severity in terms of impaired disease progression, increased recovery time, healthcare resource utilization, overall morbidity and mortality.,We aimed to quantify exacerbation and healthcare resource utilization rates among COPD patients in Sweden with respect to baseline treatments, exacerbation history, and comorbidities.,Patients with a COPD or chronic bronchitis (CB) diagnosis in secondary care at age of ≥40 years on 1.7.2009 were identified and followed until 1.7.2010 or death.,Severe exacerbations were defined as hospitalizations due to respiratory disease, and healthcare resource utilization was measured by all-cause hospitalizations and secondary care visits.,Poisson regression was used adjusting for age, gender, time since COPD/CB diagnosis, and Charlson comorbidity index.,In 88,548 patients (54% females, mean age 72 years), previous respiratory hospitalizations and current high use of COPD medication (double or triple therapy) predicted an 8.3-fold increase in severe exacerbation rates and 1.8-fold increase in healthcare resource utilization rates in the following year, compared to patients without combination treatment and/or history of severe exacerbations.,COPD/CB patients with history of severe exacerbations and high use of COPD medication experienced a significantly increased rate of severe exacerbations and healthcare resource utilization during the one-year follow-up.,The online version of this article (10.1186/s12890-018-0573-0) contains supplementary material, which is available to authorized users.
|
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use.
| 1 |
Objective To investigate the association between the Alternate Healthy Eating Index 2010 (AHEI-2010)-a measure of diet quality-and the risk of chronic obstructive pulmonary disease (COPD).,Design Prospective cohort study.,Setting Participants in the Nurses’ Health Study and the Health Professionals Follow-up Study, United States.,Participants 73 228 female nurses from 1984 to 2000 and 47 026 men from 1986 to 1998, who completed biennial questionnaires.,Main outcome measures The primary outcome was the self report of newly diagnosed COPD.,Multivariable Cox proportional hazards models were adjusted for age, physical activity, body mass index, total energy intake, smoking, second hand tobacco exposure (only in the Nurses’ Health Study), race/ethnicity, physician visits, US region, spouse’s highest educational attainment (only in the Nurses’ Health Study), and menopausal status (only in the Nurses’ Health Study).,Results Over the study period, 723 cases of newly diagnosed COPD occurred in women and 167 in men.,In the pooled analysis, a significant negative association was seen between the risk of newly diagnosed COPD and fifths of the AHEI-2010: hazard ratios were 0.81 (95% confidence interval 0.51 to 1.29) for the second fifth, 0.98 (0.80 to 1.18) for the third fifth, 0.74 (0.59 to 0.92) for the fourth fifth, and 0.67 (0.53 to 0.85) for participants who ate the healthiest diet according to the AHEI-2010 (that is, were in the highest fifth), compared with those who ate the less healthy diet (participants in the lowest fifth).,Similar findings were observed among ex-smokers and current smokers.,Conclusions A higher AHEI-2010 diet score (reflecting high intakes of whole grains, polyunsaturated fatty acids, nuts, and long chain omega-3 fats and low intakes of red/processed meats, refined grains, and sugar sweetened drinks) was associated with a lower risk of COPD in both women and men.,These findings support the importance of a healthy diet in multi-interventional programs to prevent COPD.
|
The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7.,Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative.,We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.,In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years.,Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated.,The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.,Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively.,The GOLD classification led to more false positives, the LLNs to more false negative diagnoses.,The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC).,Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses.,The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.,GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis.,Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.
| 1 |
Although there is growing evidence linking chronic obstructive pulmonary disease (COPD) hospital admissions to the exposure to ambient air pollution, the effect can vary depending on the local geography, pollution type, and pollution level.,The number of large-scale multicity studies remains limited in China.,This study aims to assess the short-term effects of ambient air pollution (PM2.5, PM10, SO2, NO2) on chronic obstructive pulmonary disease hospital admissions from 2015 to 2016, with a total of 216,159 records collected from 207 hospitals in 17 cities all over the Shandong province, east China.,Generalized additive models and penalized splines were applied to study the data whilst controlling for confounding meteorological factors and long-term trends.,The air pollution was analyzed with 0-6 day lag effects and the percentage change of hospital admissions was assessed for a 10-μg/m3 increase in the air pollution levels.,We also examined the percentage changes for different age groups and gender, respectively.,The results showed that air pollution was significantly associated with adverse health outcomes and stronger effects were observed for females.,The air pollution health effects were also impacted by geographical factors such that the air pollution had weaker health effects in coastal cities.
|
Exacerbations of chronic obstructive pulmonary disease (COPD) contribute greatly to increased morbidity, mortality and diminished quality of life.,Recent studies report moderately strong positive associations between exposures to several air pollutants and COPD-related emergency department (ED) visits and hospital admissions (HA).,Studies that use clinically defined exacerbations rather than counting ED visits and HA may be more sensitive to environmental triggers like air pollution, but very few such studies exist.,Participants in a COPD disease management group living in an area of low air pollution and who were followed closely for the earliest signs of an exacerbation provided an opportunity to study associations between air pollution and COPD exacerbation.,Associations between short term exposures to air pollutants, including sulfur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter < 2.5 microns (PM2.5), and COPD exacerbation were assessed among 168 patients residing in central Massachusetts, a region with air pollution levels well below USEPA National Ambient Air Quality Standards (NAAQS).,Case-crossover analyses and multivariate conditional logistic regression were used to estimate associations between 7-day average concentrations of each air pollutant, as measured at central site monitors, and COPD exacerbation experienced in the patients’ homes during the period 2012-2013, while controlling for temperature and self-reported influenza.,We found that short-term exposures to SO2 were associated with an increase in COPD exacerbation risk (odds ratio (OR) = 2.45, 95 % CI: 1.75-3.45 per 1 ppb increase) after adjustment for PM2.5.,Short-term exposures to NO2 concentrations showed a weaker association, (OR = 1.17, 95 % CI: 1.05-1.30 per 1 ppb increase) after adjustment for PM2.5.,An unexpectedly modest negative association was seen for short-term exposures to PM2.5.,Despite living in an area with air pollution concentrations below current USEPA NAAQS, these COPD patients appeared to suffer increased risk of COPD exacerbation following short-term exposures to increased concentrations of SO2 and NO2.,An unexpected negative association with PM2.5 may result from the complex air chemistry of low level PM in this region.
| 1 |
The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD.,Differentially expressed genes (DEGs) were screened using the Limma package in R.,A protein-protein interaction (PPI) network of DEGs was built based on the STRING database.,Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID.,Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software.,In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened.,Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes.,The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction.,Additionally, 39 key AECOPD-related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a.,In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD.
|
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world.,It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD.,The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected.,The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors.,In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity.,In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke.,We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress.
| 1 |
To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting.,A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009.,Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed.,Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations.,At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up.,A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis.,At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%).,Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months.,Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months.,Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months.,Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline.,The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state.
|
Chronic obstructive pulmonary disease (COPD) is a common disease in the general population and it places a considerable burden on patients, with the disease negatively affecting quality of life.,In practice, patients with COPD generally seek medical attention because of symptoms, particularly breathlessness, and the resulting physical limitations, which affect the health-related quality of life (HR-QOL) in patients.,The defining feature of COPD is airflow limitation that causes air trapping and increased hyperinflation as the ventilation rate increases during physical effort.,Hyperinflation causes or worsens breathlessness as breathing becomes inefficient, with the end result being an avoidance of physical exertion and a cycle of increasing dyspnea caused by inactivity and deconditioning, with deleterious effects on HR-QOL.,Current published guidelines for COPD state that the goals of pharmacologic therapy should be to control symptoms, improve health status and exercise tolerance, and reduce the frequency of COPD exacerbations.,Effective and sustained bronchodilation has emerged as a key strategy for improving dyspnea and ability to exercise.,As there is no cure for COPD, a major goal of treatment and of research into new therapies is to improve HR-QOL in COPD patients.,More recently, indacaterol, an inhaled ultra-long-acting β2-agonist (24-hour action), has been approved in many countries at different doses (between 75 and 300 μg once daily) for treatment of patients with stable but symptomatic COPD.,The aim of this review was to explore once-daily indacaterol clinical data as related to improvement in HR-QOL in COPD.,Indacaterol studies have shown significant improvements in lung function of COPD patients, and these improvements have also translated into clinically meaningful improvements in patient symptoms and HR-QOL.
| 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.
|
Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by nonreversible airway obstruction.,Well-characterized symptoms such as exertional dyspnea and fatigue have a negative impact on patients’ quality of life (QoL) and restrict physical activity in daily life.,The impact of COPD symptoms on QoL is often underestimated; for example, 36% of patients who describe their symptoms as being mild-to-moderate also admit to being too breathless to leave the house.,Additionally, early morning and nighttime symptoms are a particular problem.,Methods are available to allow clinicians to accurately assess COPD symptoms, including patient questionnaires.,Integrated approaches to COPD management, particularly pulmonary rehabilitation, are effective strategies for addressing symptoms, improving exercise capacity and, potentially, also increasing physical activity.,Inhaled bronchodilators continue to be the mainstay of drug therapy in COPD, where options can be tailored to meet patients’ needs with careful selection of the inhaled medication and the device used for its delivery.,Overall, an integrated approach to disease management should be considered for improving QoL and subsequent patient outcomes in COPD.
| 1 |
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.
|
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.
| 1 |
COPD is a disease associated with significant economic burden.,It was reported that Global initiative for chronic Obstructive Lung Disease (GOLD) guideline-oriented pharmacotherapy improves airflow limitation and reduces health care costs.,However, several studies showed a significant dissociation between international recommendations and clinicians’ practices.,The consequent reduced diagnostic and therapeutic inappropriateness has proved to be associated with an increase in costs and a waste of economic resources in the health sector.,The aim of the study was to evaluate COPD management in the Puglia region.,The study was performed in collaboration with the pulmonology centers and the Regional Health Agency (AReS Puglia).,An IT platform allowed the pulmonologists to enter data via the Internet.,All COPD patients who visited a pneumological outpatient clinic for the first time or for regular follow-ups or were admitted to a pneumological department for an exacerbation were considered eligible for the study.,COPD’s diagnosis was confirmed by a pulmonologist at the moment of the visit.,The project lasted 18 months and involved 17 centers located in the Puglia region.,Six hundred ninety-three patients were enrolled, evenly distributed throughout the region.,The mean age was 71±9 years, and 85% of them were males.,Approximately 23% were current smokers, 63% former smokers and 13.5% never smokers.,The mean post-bronchodilator forced expiratory volume in 1 second was 59%±20% predicted.,The platform allowed the classification of patients according to the GOLD guidelines (Group A: 20.6%, Group B: 32.3%, Group C: 5.9% and Group D: 39.2%), assessed the presence and severity of exacerbations (20% of the patients had an exacerbation defined as mild [13%], moderate [37%] and severe [49%]) and evaluated the appropriateness of inhalation therapy at the time of the visit.,Forty-nine percent of Group A patients were following inappropriate therapy; in Group B, 45.8% were following a therapy in contrast with the guidelines.,Among Group C patients, 41.46% resulted in triple combination therapy, whilê14% of Group D patients did not have a therapy or were following an inappropriate therapy.,In conclusion, 30% of all patients evaluated had been following an inadequate therapy.,Subsequently, an online survey was developed to inquire about the reasons for the results obtained.,In particular, we investigated the reasons why 30% of our population did not follow the therapy suggested by the GOLD guidelines: 1) why was there an excessive use of inhaled corticosteroids, 2) why a significantly high percentage was inappropriately treated with triple therapy and 3) why a consistent percentage (11%) of Group D patients were not treated at all.,The data provides an overview on the management of COPD in the region of Puglia (Italy) and represents a resource in order to improve appropriateness and reduce the waste of health resources.
|
This study aimed to examine the distribution of predefined phenotypes, demographic data, clinical outcomes, and treatment of patients who were included in the Polish cohort of the Phenotypes of COPD in Central and Eastern Europe (POPE) study.,This was a sub-analysis of the data from the Polish cohort of the POPE study, an international, multicenter, observational cross-sectional survey of COPD patients in Central and Eastern European countries.,The study included patients aged >40 years, with a confirmed diagnosis of COPD, and absence of exacerbation for at least 4 weeks before study inclusion.,A total of seven Polish centers participated in the study.,Among the 430 Polish COPD patients enrolled in the study, 61.6% were non-exacerbators (NON-AE), 25.3% were frequent exacerbators with chronic bronchitis (AE CB), 7.9% were frequent exacerbators without chronic bronchitis (AE NON-CB), and 5.1% met the definition of asthma-COPD overlap syndrome (ACOS).,There were statistically significant differences among these phenotypes in terms of symptom load, lung function, comorbidities, and treatment.,Patients with the AE CB phenotype were most symptomatic with worse lung function, and more frequently reported anxiety and depression.,Patients with the ACOS phenotype were significantly younger and were diagnosed with COPD earlier than those with other COPD phenotypes; those with the ACOS phenotype were also more often atopic and obese.,There is significant heterogeneity among COPD patients in the Polish population in terms of phenotype and clinical outcome.,The non-exacerbator phenotype is observed most frequently in Poland, while the frequent exacerbator with chronic bronchitis phenotype is the most symptomatic.
| 1 |
COPD is characterized by an ongoing inflammatory process of the airways that leads to obstruction or limitation of airflow.,It is mainly associated with exposure to cigarette smoke.,In addition, it is considered, at present, a serious public health problem, ranking fourth in mortality worldwide.,Many cells participate in the pathophysiology of COPD, the most important are neutrophils, macrophages and CD4+ and CD8+ T cells.,Neutrophil migration to the inflammation area could be mediated largely by cytokines related to CD4+ Th17 lymphocytes, because it has been shown that IL-17A, IL-17F and IL-22 act as inducers for CXCL8, CXCL1, CXCL5, G-CSF, and GM-CSF secretion by epithelial cells of the airways.,The aims of these molecules are differentiation, proliferation and recruitment of neutrophils.,Furthermore, it is believed that CD4+ lymphocytes Th17 may be involved in protection against pathogens for which Th1 and Th2 are not prepared to fight.,In COPD exacerbations, there is an increased cellularity in the lung region and respiratory tract.,Therefore, the increase in the number of neutrophils and macrophages in the airways and the increase in proinflammatory cytokines are directly related to the severity of exacerbations and that is the importance of the functions of Th17 profile in this entity.
|
Asthma and COPD are characterized by airway dysfunction and inflammation.,Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease.,The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain.,We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects.,Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD.,The median (interquartile range) IL-17A cells/mm2 submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04).,In COPD, IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046).,IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD.,IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005).,The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV1% predicted (r = −0.5, P = .008) and FEV1/FVC (r = −0.4, P = .04).,Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation.
| 1 |
For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction.,The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies.,The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD.,Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use.,Patients’ preference was assessed after completion of both study periods.,Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler.,For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively.,In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01).,Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities.,Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler.,These are important factors for optimum dose delivery and successful COPD management.
|
Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven.
| 1 |
Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear.,The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated.,The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD.,Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition.,Eighty-six patients (mean age, 72 years; male, 64%) were included.,During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three.,A dual infection was present in three patients.,After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase).,In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up.,During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection.,Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract.,In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others.,clinicaltrials.gov; Identifier: NCT00448604.
|
ICAM-1 is a major receptor for ~60% of human rhinoviruses, and non-typeable Haemophilus influenzae, two major pathogens in COPD.,Increased cell-surface expression of ICAM-1 in response to tobacco smoke exposure has been suggested.,We have investigated epithelial ICAM-1 expression in both the large and small airways, and lung parenchyma in smoking-related chronic airflow limitation (CAL) patients.,We evaluated epithelial ICAM-1 expression in resected lung tissue: 8 smokers with normal spirometry (NLFS); 29 CAL patients (10 small-airway disease; 9 COPD-smokers; 10 COPD ex-smokers); Controls (NC): 15 normal airway/lung tissues.,Immunostaining with anti-ICAM-1 monoclonal antibody was quantified with computerized image analysis.,The percent and type of cells expressing ICAM-1 in large and small airway epithelium and parenchyma were enumerated, plus percentage of epithelial goblet and submucosal glands positive for ICAM- 1.,A major increase in ICAM-1 expression in epithelial cells was found in both large (p < 0.006) and small airways (p < 0.004) of CAL subjects compared to NC, with NLFS being intermediate.,In the CAL group, both basal and luminal areas stained heavily for ICAM-1, so did goblet cells and sub-mucosal glands, however in either NC or NLFS subjects, only epithelial cell luminal surfaces stained.,ICAM-1 expression on alveolar pneumocytes (mainly type II) was slightly increased in CAL and NLFS (p < 0.01).,Pack-years of smoking correlated with ICAM-1 expression (r = 0.49; p < 0.03).,Airway ICAM-1 expression is markedly upregulated in CAL group, which could be crucial in rhinoviral and NTHi infections.,The parenchymal ICAM-1 is affected by smoking, with no further enhancement in CAL subjects.,The online version of this article (doi:10.1186/s12931-016-0483-8) contains supplementary material, which is available to authorized users.
| 1 |
Plasma soluble Receptor for Advanced Glycation End Product (sRAGE) is considered as a biomarker in COPD.,The contribution of endogenous sRAGE (esRAGE) to the pool of plasma sRAGE and the implication of both markers in COPD pathogenesis is however not clear yet.,The aim of the current study was therefore to measure plasma levels of esRAGE comparative to total sRAGE in patients with COPD and a control group.,Further, we established the relations of esRAGE and total sRAGE with disease specific characteristics such as lung function and DLCO, and with different circulating AGEs.,Plasma levels of esRAGE and sRAGE were measured in an 88 patients with COPD and in 55 healthy controls.,FEV1 (%predicted) and FEV1/VC (%) were measured in both groups; DLCO (%predicted) was measured in patients only.,In this study population we previously reported that the AGE Nϵ-(carboxymethyl) lysine (CML) was decreased, Nϵ-(carboxyethyl) lysine (CEL) increased and pentosidine was not different in plasma of COPD patients compared to controls.,Plasma esRAGE (COPD: 533.9 ± 412.4, Controls: 848.7 ± 690.3 pg/ml; p = 0.000) was decreased in COPD compared to controls.,No significant correlations were observed between plasma esRAGE levels and lung function parameters or plasma AGEs.,A positive correlation was present between esRAGE and total sRAGE levels in the circulation.,Confirming previous findings, total sRAGE (COPD: 512.6 ± 403.8, Controls: 1834 ± 804.2 pg/ml; p < 0.001) was lower in patients compared to controls and was positively correlated FEV1 (r = 0.235, p = 0.032), FEV1/VC (r = 0.218, p = 0.047), and DLCO (r = 0.308, p = 0.006). sRAGE furthermore did show a significant positive association with CML (r = 0.321, p = 0.003).,Although plasma esRAGE is decreased in COPD patients compared to controls, only total sRAGE showed a significant and independent association with FEV1, FEV1/VC and DLCO, indicating that total sRAGE but not esRAGE may serve as marker of COPD disease state and severity.
|
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability internationally.,Alveolar hypoxia and consequent hypoxemia increase in prevalence as disease severity increases.,Ventilation/perfusion mismatch resulting from progressive airflow limitation and emphysema is the key driver of this hypoxia, which may be exacerbated by sleep and exercise.,Uncorrected chronic hypoxemia is associated with the development of adverse sequelae of COPD, including pulmonary hypertension, secondary polycythemia, systemic inflammation, and skeletal muscle dysfunction.,A combination of these factors leads to diminished quality of life, reduced exercise tolerance, increased risk of cardiovascular morbidity, and greater risk of death.,Concomitant sleep-disordered breathing may place a small but significant subset of COPD patients at increased risk of these complications.,Long-term oxygen therapy has been shown to improve pulmonary hemodynamics, reduce erythrocytosis, and improve survival in selected patients with severe hypoxemic respiratory failure.,However, the optimal treatment for patients with exertional oxyhemoglobin desaturation, isolated nocturnal hypoxemia, or mild-to-moderate resting daytime hypoxemia remains uncertain.
| 1 |
Chronic obstructive pulmonary disease (COPD) is a widespread disease.,It produces some night symptoms such as nighttime cough and dyspnea.,Then subjective and objective changes in sleep pattern are expected.,Present study was conducted to determine frequency of sleepiness and quality of sleep in patients with COPD.,Present case-control study has been performed on 120 patients with diagnosis of COPD who had been referred to pulmonary disease clinic in a University teaching hospital.,One hundred twenty age- and sex- matched healthy individuals were recruited in the study and served as control.,Spirometry (PFT) was performed for all patients.,Patients were categorized under 3 groups in relation to their PFT as follow: mild COPD (FEV1/FVC<70% and FEV1≥80%), moderate COPD (FEV1/FVC<70% and 50%≤FEV1<80%), and severe COPD (FEV1/FVC<70% and FEV1<50%).,Pittsburgh Sleep Quality questionnaire (PSQI) and Epworth Sleepiness Scale (ESS) were used to estimate quality of sleep and daytime sleepiness in the patients and control group.,The collected data were analyzed using version 16 SPSS software.,Student’s T- test, Chi- square and multiple logistic regressions were used as appropriated.,120 patients with COPD (79 males and 41 females) and 120 normal individuals responded to the questionnaires.,Mean scores of quality of sleep were 8.03±3.66 and 4.2±2.8 in COPD patients and control group respectively.,32.1% of the patients had good sleep quality (PSQI score less than 5) and 67.9% had poor sleep quality.,Daytime sleepiness (ESS≥ 10) was present in 34.8% of the patients and 15% of control people.,Multiple logistic regressions showed that the patients reported significantly worse sleep quality and more daytime sleepiness than control group [OR=2.9; 95% CI (1.6-3.7) & OR=3.5; 95% CI (2.5-4.3) respectively].,Results of present study confirmed that COPD is associated with daytime sleepiness and poor quality of sleep, possibly attributable to nighttime respiratory difficulties and concomitant sleep apnea.,Assessment of the patients for symptoms of sleep apnea, daytime sleepiness should be a part of regular follow up visits of patients with COPD.
|
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.
| 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation.,Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes.,Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.,This post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies.,Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study.,Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.,Exacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150-300 cells/μL and 20.1% with > 300 cells/μL.,The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count.,When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150-300 cells/μL and 0.44 for > 300 cells/μL respectively).,A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively.,For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150-300 cells/μL) and 1.07 (> 300 cells/μL).,Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).,We found no clinically important relationship between baseline blood eosinophil count and exacerbation rate.,Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.,ClinicalTrials.gov Identifiers: NCT00168844, NCT00168831, NCT00387088, NCT00782210, NCT00782509, NCT00793624, NCT00796653, NCT01431274, NCT01431287, NCT02296138 and NCT00975195.
|
The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA) in a single inhaler is a viable treatment option for patients with chronic obstructive pulmonary disease (COPD).,Here, we systematically review the current knowledge on double bronchodilation for the treatment of COPD, with a specific focus on its efficacy versus placebo and/or monotherapy bronchodilation.,A systematic review of clinical trials investigating LABA/LAMA combination therapies was conducted.,Articles were retrieved from PubMed, Embase, and Scopus on June 26, 2016.,We specifically selected clinical trials with a randomized controlled or crossover design published in any scientific journal showing the following characteristics: 1) comparison of different LABA/LAMA combinations in a single inhaler for patients with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo and/or bronchodilator monotherapy) in terms of lung function, respiratory symptoms, or exacerbations.,We analyzed 26 clinical trials conducted on 24,338 patients.,All LABA/LAMA combinations were consistently able to improve lung function compared with both placebo and bronchodilator monotherapy.,Improvements in symptoms were also consistent versus placebo, showing some lack of correlation for some clinical end points and combinations versus monotherapy bronchodilation.,Albeit being an exploratory end point, exacerbations showed an improvement with LABA/LAMA combinations over placebo in some trials; however, scarce information was available in comparison with bronchodilator monotherapy in most studies.,Our data show consistent improvements for LABA/LAMA combinations, albeit with some variability (depending on the clinical end point, the specific combination, and the comparison group).,Clinicians should be aware that these are average differences.,All treatments should be tailored at the individual level to optimize clinical outcomes.
| 1 |
Krasnoyarsk region is a territory with the widespread risk factors for chronic obstructive pulmonary disease (COPD) such as tobacco smoke, air pollution, and occupational exposure.,An assessment of COPD prevalence based on medical diagnosis statistics underestimates the true COPD prevalence.,This study aims to evaluate how medical examinations may increase the accuracy of estimates of COPD prevalence.,True COPD prevalence was estimated as a number of patients with the established disease diagnosis supplemented by the additional disease cases detected during medical examinations per 1,000 inhabitants of the region.,Official medical statistics data and the data collected from the Global Alliance against Chronic Respiratory Diseases program 2011 among 15,000 inhabitants of the region aged 18 years and older were analyzed.,This study revealed the COPD cases without official medical diagnosis.,The true prevalence of COPD is estimated to be two times higher than the prevalence estimates based on medical diagnosis statistics.,Undiagnosed and untreated cases of COPD result in severe COPD forms as well as addition of severe comorbidities.,Because of this, there is an increase in the index of potential years of life lost.,Conducting special medical examinations may increase the number of COPD cases detected at the early stages of the disease.,This, in turn, may reduce the overall burden of the disease for the population of the region.
|
The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented.,However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.,TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers).,To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: ≥ 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).,Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV.,SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage.,Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV.,The rates of adverse events were similar across treatment arms and increased with disease severity.,Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.,In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages.,Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease.,The effects were similar to those reported for the study as a whole.,Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.,Clinicaltrial.gov registration NCT00268216; Study number: SCO30003
| 1 |
Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress.,Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD.,Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins.,Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction.,Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible.,Other sirtuin isoforms were not affected by miR-34a.,Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.
|
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 |
The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.,Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1).,All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained.,Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and transitional dyspnea index at 12 weeks.,Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV1 at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [−0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [−0.04-0.05]).,For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (−0.49 points [−1.87-0.89]).,Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function.,In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.
|
Pooled data were analyzed to evaluate the safety and tolerability of indacaterol, a once-daily inhaled long-acting β2-agonist for chronic obstructive pulmonary disease (COPD).,Data were pooled from clinical studies of 3-12 months’ duration in patients with moderate-to-severe COPD receiving double-blind indacaterol 75 μg (n = 449), 150 μg (n = 2611), 300 μg (n = 1157), or 600 μg once daily (n = 547); formoterol 12 μg twice daily (n = 556); salmeterol 50 μg twice daily (n = 895); placebo (n = 2012); or tiotropium 18 μg once daily, given open label or blinded (n = 1214).,Outcomes were adverse events, serious adverse events and deaths, plasma potassium, blood glucose, and QTc interval and vital signs.,The commonest adverse events with indacaterol were COPD worsening, nasopharyngitis, and headache; most cases were mild or moderate and incidence was generally similar to placebo and other active treatments.,The risk of acute respiratory serious adverse events (leading to hospitalization, intubation, or death) was not significantly increased with any of the active treatments compared with placebo.,COPD exacerbation rates (analyzed in the intent-to-treat population) were significantly reduced with all active treatments versus placebo.,Hazard ratios versus placebo for major cardiovascular adverse events were <1 for all indacaterol doses.,Notable values for vital signs and measures of systemic β2-adrenoceptor activity were rare with indacaterol.,The number of deaths adjusted per patient-year was lower with indacaterol (all doses combined) than with placebo (relative risk 0.21 [95% confidence interval 0.07-0.660], P = 0.008).,Indacaterol has a good profile of safety and tolerability that is appropriate for the maintenance treatment of patients with COPD.
| 1 |
A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear.,Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable.,To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases.,We recruited 59 outpatients with MetS and 76 outpatients with COPD.,After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29).,A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%.,More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease.,MetS+COPD patients exhibited significantly higher C-peptide levels.,We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers.,Finally, a negative association emerged between smoking and vitamin D.,We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance.,Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development.
|
Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved.,We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased.,Associations with other subphenotypes were examined.,The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease.,Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry.,COPD was defined by standard spirometric criteria.,Emphysema was assessed qualitatively and quantitatively on CT.,Full pulmonary function testing and expiratory CTs were measured in a subset.,Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD.,The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent.,Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity.,Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI.,There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping.,These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.
| 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
|
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.
| 1 |
Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer.,Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls.,Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers.,We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type.,From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history.,Genome-wide miRNA profiles were generated and evaluated using machine learning techniques.,For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family.,The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5).,We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis.,For selected miRNAs, qRT-PCR analysis was applied to validate the results.,In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.
|
Cigarette smoke-induced release of pro-inflammatory cytokines including interleukin-8 (IL-8) from inflammatory as well as structural cells in the airways, including airway smooth muscle (ASM) cells, may contribute to the development of chronic obstructive pulmonary disease (COPD).,Despite the wide use of pharmacological treatment aimed at increasing intracellular levels of the endogenous suppressor cyclic AMP (cAMP), little is known about its exact mechanism of action.,We report here that next to the β2-agonist fenoterol, direct and specific activation of either exchange protein directly activated by cAMP (Epac) or protein kinase A (PKA) reduced cigarette smoke extract (CSE)-induced IL-8 mRNA expression and protein release by human ASM cells.,CSE-induced IκBα-degradation and p65 nuclear translocation, processes that were primarily reversed by Epac activation.,Further, CSE increased extracellular signal-regulated kinase (ERK) phosphorylation, which was selectively reduced by PKA activation.,CSE decreased Epac1 expression, but did not affect Epac2 and PKA expression.,Importantly, Epac1 expression was also reduced in lung tissue from COPD patients.,In conclusion, Epac and PKA decrease CSE-induced IL-8 release by human ASM cells via inhibition of NF-κB and ERK, respectively, pointing at these cAMP effectors as potential targets for anti-inflammatory therapy in COPD.,However, cigarette smoke exposure may reduce anti-inflammatory effects of cAMP elevating agents via down-regulation of Epac1.
| 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization.,Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function.,A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated.,COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy.,Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations.,For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate.,Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis.,Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids.,A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations.
|
Natural history of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations; however, little is known about prognosis of the first-ever COPD exacerbation and variables predicting its outcomes.,A population-based cohort study among COPD patients with their first-ever exacerbations requiring hospitalizations was conducted.,Main outcomes were in-hospital mortality and one-year mortality after discharge.,Demographics, comorbidities, medications and in-hospital events were obtained to explore outcome predictors.,The cohort comprised 4204 hospitalized COPD patients, of whom 175 (4%) died during the hospitalization.,In-hospital mortality was related to higher age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.03-1.06) and Charlson comorbidity index score (OR: 1.08 per point; 95% CI: 1.01-1.15); angiotensin II receptor blockers (OR: 0.61; 95% CI: 0.38-0.98) and β blockers (OR: 0.63; 95% CI: 0.41-0.95) conferred a survival benefit.,At one year after discharge, 22% (871/4029) of hospital survivors were dead.,On multivariate Cox regression analysis, age and Charlson comorbidity index remained independent predictors of one-year mortality.,Longer hospital stay (hazard ratio [HR] 1.01 per day; 95% CI: 1.01-1.01) and ICU admission (HR: 1.33; 95% CI: 1.03-1.73) during the hospitalization were associated with higher mortality risks.,Prescription of β blockers (HR: 0.79; 95% CI: 0.67-0.93) and statins (HR: 0.66; 95% CI: 0.47-0.91) on hospital discharge were protective against one-year mortality.,Even the first-ever severe COPD exacerbation signifies poor prognosis in COPD patients.,Comorbidities play a crucial role in determining outcomes and should be carefully assessed.,Angiotensin II receptor blockers, β blockers and statins may, in theory, have dual cardiopulmonary protective properties and probably alter prognosis of COPD patients.,Nevertheless, the limitations inherent to a claims database study, such as the diagnostic accuracy of COPD and its exacerbation, should be born in mind.
| 1 |
We recently reported that current smokers and those with COPD had higher airway epithelial cell expression of the angiotensin-converting enzyme II (ACE-2) viral entry receptor [1].,We thus read with great interest the work of P.,Russo and co-workers, which proposes a mechanism for this finding, namely that this upregulation is mediated by nicotine exposure specifically through the α7 subtype of nicotine acetylcholine receptors (α7-nAChR).,While exposure to increasing concentrations of nicotine caused epithelial cells to increase ACE-2 levels, subsequent gene silencing of α7-nAChR appeared to significantly dampen this response.,A secondary transcriptome sequencing analysis of our cohort (consisting of 42 subjects who underwent bronchoscopy for epithelial cell brushings [1]) reveals evidence in support of this hypothesis.,α7-nAChR may upregulate ACE-2https://bit.ly/2xS0cfT
|
Self-management strategies have the potential to support patients with chronic obstructive pulmonary disease (COPD).,Telehealth interventions may have a role in delivering this support along with the opportunity to monitor symptoms and physiological variables.,This paper reports findings from a six-month, clinical, cohort study of COPD patients’ use of a mobile telehealth based (mHealth) application and how individually determined alerts in oxygen saturation levels, pulse rate and symptoms scores related to patient self-initiated treatment for exacerbations.,The development of the mHealth intervention involved a patient focus group and multidisciplinary team of researchers, engineers and clinicians.,Individual data thresholds to set alerts were determined, and the relationship to exacerbations, defined by the initiation of stand-by medications, was measured.,The sample comprised 18 patients (age range of 50-85 years) with varied levels of computer skills.,Patients identified no difficulties in using the mHealth application and used all functions available. 40 % of exacerbations had an alert signal during the three days prior to a patient starting medication.,Patients were able to use the mHealth application to support self- management, including monitoring of clinical data.,Within three months, 95 % of symptom reporting sessions were completed in less than 100 s.,Home based, unassisted, daily use of the mHealth platform is feasible and acceptable to people with COPD for reporting daily symptoms and medicine use, and to measure physiological variables such as pulse rate and oxygen saturation.,These findings provide evidence for integrating telehealth interventions with clinical care pathways to support self-management in COPD.
| 1 |
The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD).,The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD.,This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD.,It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers.,The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report.,This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations.,The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient.,The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma-COPD overlap syndrome (ACOS).,These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions.,For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol-ipratropium) is recommended in patients with less symptoms.,If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended.,For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice.,Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic.,If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast.,ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD.,Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD.,Thus, evidence-based recommendation of treatment cannot be given.,The treatment should cover both diseases.,Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both).
|
Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence.
| 1 |
The present study aimed to analyze the effects of physical training on an antioxidant canonical pathway and metalloproteinases activity in diaphragm muscle in a model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD).,Male mice were randomized into control, smoke, exercise, and exercise + smoke groups, which were maintained in trial period of 24 weeks.,Gene expression of kelch-like ECH-associated protein 1; nuclear factor erythroid-2 like 2; and heme-oxygenase1 by polymerase chain reaction was performed.,Metalloproteinases 2 and 9 activities were analyzed by zymography.,Exercise capacity was evaluated by treadmill exercise test before and after the protocol.,Aerobic training inhibited diaphragm muscle wasting induced by cigarette smoke exposure.,This inhibition was associated with improved aerobic capacity in those animals that were submitted to 24 weeks of aerobic training, when compared to the control and smoke groups, which were not submitted to training.,The aerobic training also downregulated the increase of matrix metalloproteinases (MMP-2 and MMP-9) and upregulated antioxidant genes, such as nuclear factor erythroid-2 like 2 (NRF2) and heme-oxygenase1 (HMOX1), in exercise + smoke group compared to smoke group.,Treadmill aerobic training protects diaphragm muscle wasting induced by cigarette smoke exposure involving upregulation of antioxidant genes and downregulation of matrix metalloproteinases.
|
In general, smoking increases the risk of mortality.,However, it is less clear how the relative risk varies by cause of death.,The exact impact of changes in smoking habits throughout life on different mortality risks is less studied.,We studied the impact of baseline and lifetime smoking habits, and duration of smoking on the risk of all-cause mortality, mortality of cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), any cancer and of the four most common types of cancer (lung, colorectal, prostate, and breast cancer) in a cohort study (Vlagtwedde-Vlaardingen 1965-1990, with a follow-up on mortality status until 2009, n = 8,645).,We used Cox regression models adjusted for age, BMI, sex, and place of residence.,Since previous studies suggested a potential effect modification of sex, we additionally stratified by sex and tested for interactions.,In addition, to determine which cause of death carried the highest risk we performed competing-risk analyses on mortality due to CVD, cancer, COPD and other causes.,Current smoking (light, moderate, and heavy cigarette smoking) and lifetime persistent smoking were associated with an increased risk of all-cause, CVD, COPD, any cancer, and lung cancer mortality.,Higher numbers of pack years at baseline were associated with an increased risk of all-cause, CVD, COPD, any cancer, lung, colorectal, and prostate cancer mortality.,Males who were lifetime persistent pipe/cigar smokers had a higher risk of lung cancer [HR (95% CI) = 7.72 (1.72-34.75)] as well as all-cause and any cancer mortality.,A longer duration of smoking was associated with a higher risk of COPD, any and lung cancer [HR (95% CI) = 1.06 (1.00-1.12), 1.03 (1.00-1.06) and 1.10 (1.03-1.17) respectively], but not with other mortality causes.,The competing risk analyses showed that ex- and current smokers had a higher risk of cancer, CVD, and COPD mortality compared to all other mortality causes.,In addition, heavy smokers had a higher risk for COPD mortality compared to cancer, and CVD mortality.,Our study indicates that lifetime numbers of cigarettes smoked and the duration of smoking have different impacts for different causes of mortality.,Moreover, our findings emphasize the importance of smoking-related competing risks when studying the smoking-related cancer mortality in a general population and that smoking cessation immediately effectively reduces the risk of all-cause and any cancer mortality.
| 1 |
COPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality.,However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading.,Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension.,This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests.,The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients.,PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension.,A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure.,This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD.,Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs.,•Pulmonary hypertension is common in COPD.,•Right ventricular remodeling occurs at pressures below the diagnostic threshold of PH.,•Pulmonary arterial stiffening occurs early in the development of PH.,•Non-invasive measurement of pulmonary stiffness may serve as an early biomarker of PH.,Pulmonary hypertension is common in COPD.,Right ventricular remodeling occurs at pressures below the diagnostic threshold of PH.,Pulmonary arterial stiffening occurs early in the development of PH.,Non-invasive measurement of pulmonary stiffness may serve as an early biomarker of PH.
|
It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia.,Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure.,Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise.,Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure.,Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output.,Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume.,The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure.,During exercise, a similar decline in pulmonary artery pressure was observed.,This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure.,We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.
| 1 |
Cytokines are key players in the initiation and propagation of inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis and allergic asthma.,This makes them attractive targets for specific novel anti-inflammatory treatment strategies.,Recently, both interleukin-1 (IL-1) and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD.,IL-6 in COPD was shown to correlate negatively with lung function, and IL-1beta was induced by cigarette smoke in the bronchial epithelium, causing airway inflammation.,Furthermore, IL-8 has been shown to be a pro-inflammatory marker in bronchiectasis, COPD and allergic asthma.,Clinical trials using specific cytokine blockade therapies are currently emerging and have contributed to reduce exacerbations and steroid use in COPD.,Here, we present a review of the current understanding of the roles of cytokines in the pathophysiology of chronic inflammatory airway diseases.,Furthermore, outcomes of clinical trials in cytokine blockade as novel treatment strategies for selected patient populations with those diseases will be discussed.
|
The aim of this study was to investigate the plasma inflammatory cytokine levels and their correlations with pulmonary function in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS).,Between January 2013 and December 2014, a total of 96 patients with asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or ACOS were enrolled, and 35 healthy people were included as a control group.,Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA).,Correlations between the plasma inflammatory cytokine levels and forced expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and FEV1/forced vital capacity (FVC) were analyzed.,IL-4 and IL-8 levels showed statistically significant differences among the 3 groups of patients (both P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly higher in the AECOPD group and ACOS group than those in the asthma group (all P<0.05).,IL-10 level and TNF-α level were significantly different among the 3 patient groups (both P<0.001).,IL-10 level was significantly different between each of the 2 groups (all P<0.001).,TNF-α level in the asthma group was higher than in the AECOPD group and ACOS group (both P<0.001).,IL-4 and IL-10 were positively and IL-8 and TNF-α were negatively related with FEV1, FEV1%pred, and FEV1/FVC.,Plasma levels of inflammatory cytokines IL-4, IL-8, IL-10, and TNF-α are related with severity of airway diseases and could be potential markers for the evaluation of asthma, COPD, and ACOS.
| 1 |
Optimal peak inspiratory flow rate (PIFR) is crucial for optimizing dry powder inhaler (DPI) effectiveness for chronic obstructive pulmonary disease (COPD).,This study provide an insight that there was a substantial proportion of improper PIFRs (not only insufficient but also excessive) among COPD patients using DPIs.,We enrolled 138 COPD patients from a medical center in Taiwan and measured PIFRs against different internal resistances of DPIs.,Proportion of excessive, optimal, suboptimal, and insufficient PIFRs were 2%, 54%, 41%, 3%, respectively, against medium-high resistance; 2%, 77%, 20%, 1%, respectively, against medium resistance; 27%, 63%, 9%, 1%, respectively, against medium-low resistance; and 42%, 57%, 1%, 0%, respectively, against low resistance (p < 0.01).,Although most PIFRs against medium-high (54%), medium (77%), medium-low (63%) and low (57%) resistance were optimal, a substantial proportion of PIFRs against low resistance were excessive (42%, p < 0.01), irrespective of age, body-mass index, dyspnea severity score, and COPD severity.,Insufficient PIFRs were infrequent, but suboptimal/insufficient PIFRs were most prevalent in patients older than 75 years than in younger patients (36% vs. 56%, p = 0.036) against medium-high resistance.,Regularly monitoring PIFRs against the specific resistance of the DPIs and instructing patients to employ a proper inspiration effort may help to optimize the effects of DPIs.
|
Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA® dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo.,Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast.,A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler.,Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only).,Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6-136.9 L/min), pressure drops (1.2-13.8 kPa), and inhaled volumes through the inhaler (0.7-4.2L).,DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed.,Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy.,Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy.,Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency.
| 1 |
With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever.,We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success.,Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions.,Inclusion eligibility, quality appraisal (Cochrane’s risk of bias tool) and data extraction were performed by two independent reviewers.,Regression analyses were performed to identify characteristics contributing to inhaler technique improvement.,Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique.,However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates.,Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p < 0.05), were shown to have an impact on effectiveness of the intervention, explaining up to 91% of the effectiveness variation.,Other factors, such as disease (asthma vs. chronic obstructive pulmonary disease), education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role.,Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time.,In conclusion, educational interventions to improve inhaler technique are effective on the short-term.,Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended.
|
Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care.
| 1 |
To investigate the association between inhaled corticosteroid (ICS) exposure patterns and the risk of pneumonia in chronic obstructive pulmonary disease (COPD) patients, we performed a nested case-control study.,Between 1998 and 2010, 51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849 control subjects selected from a cohort of COPD patients using ICSs via risk-set sampling of the database constructed by the National Health Research Institutes of Taiwan.,After adjusting for covariates, the current use of ICSs was associated with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95% confidence interval [CI] =1.20-1.30), and there was an increase in the OR with increase in the average daily dosage.,Additionally, users of fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95% CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39, respectively).,In contrast, there were no statistically significant associations between the risk of pneumonia and the use of budesonide/formoterol, budesonide, or either budesonide/formoterol or budesonide.,In conclusion, ICSs are significantly associated with an increased risk of pneumonia in COPD patients.,The effect is prominent for fluticasone-containing ICSs but not for budesonide-containing ICSs.
|
Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.,Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.,Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.,Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.,Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.,Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each.,In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up.,Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively.,The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6).,The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003).,All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).,Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.,Trial registration Clinical Trials.gov NCT01146392.
| 1 |
Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear.,We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.,Sputum was collected from 174 stable COPD subjects longitudinally over 12 months.,Microbial sampling using culture and qPCR was performed.,Spirometry and sputum measures of airway inflammation were assessed.,Sputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]).,Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL.,Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts.,H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive.,Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.,qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods.
|
Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD).,Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation.,The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1β (IL-1β) to its active form.,Since inflammasome activation has been described for a variety of inflammatory diseases, we investigated whether this pathway plays a role in NTHi infection of the airways.,A murine macrophage cell line (RAW 264.7), human alveolar macrophages and human lung tissue (HLT) were stimulated with viable or non-viable NTHi and/or nigericin, a potassium ionophore.,Secreted cytokines were measured with ELISA and participating proteins detected via Western Blot or immunohistochemistry.,Western Blot analysis of cells and immunohistochemistry of lung tissue detected the inflammasome key components NLRP3 and caspase-1 after stimulation, leading to a significant induction of IL-1β expression (RAW: control at the lower detection limit vs.,NTHi 505±111pg/ml, p<0.01).,Inhibition of caspase-1 in human lung tissue led to a significant reduction of IL-1β and IL-18 levels (IL-1β: NTHi 24 h 17423±3198pg/ml vs.,NTHi+Z-YVAD-FMK 6961±1751pg/ml, p<0.01).,Our data demonstrate the upregulation of the NRLP3-inflammasome during NTHi-induced inflammation in respiratory cells and tissues.,Our findings concerning caspase-1 dependent IL-1β release suggest a role for the inflammasome in respiratory tract infections with NTHi which may be relevant for the pathogenesis of bacterial exacerbations in COPD.
| 1 |
Some beverages and smoking cause an inflammatory response in the lungs and airways in a similar way, ultimately affecting chronic obstructive pulmonary disease (COPD) occurrence.,Using a nationally representative health survey database, this study investigates the individual and joint effects of consumption of different beverages and smoking on COPD.,This study is a cross-sectional analysis of 15,961 Korean adults in the Korea National Health and Nutritional Examination Survey of 2008-2015.,COPD was defined as forced expiratory volume in 1 s (FEV1) divided by forced vital capacity (FVC) <0.70.,We used multiple linear and logistic regression models to examine the association of beverage consumption and smoking with an FEV1/FVC ratio and odds ratio (OR) for COPD.,The mean FEV1/FVC ratio decreased with increasing soda intake (p = 0.016), coffee intake (p = 0.031), and smoking status; however, the mean FEV1/FVC ratio increased with increasing green tea intake frequency (p = 0.029).,When soda intake increased to 10 times/month, the OR of having COPD increased to 1.04 times (95% CI: 1.01, 1.07).,The positive joint effect of soda intake and smoking on COPD was marginally significant (p = 0.058).,We found that soda intake, coffee intake, and smoking increased airflow limitation while green tea intake decreased it.,In addition, soda intake and smoking had a positive joint effect on COPD in the Korean population.
|
Objectively measuring daily physical activity (PA) using an accelerometer is a relatively expensive and time-consuming undertaking.,In routine clinical practice it would be useful to estimate PA in patients with chronic obstructive pulmonary disease (COPD) with more simple methods.,To evaluate whether PA can be estimated by simple tests commonly used in clinical practice in patients with COPD.,The average number of steps per day was measured for 7 days with a SenseWear Pro™ accelerometer and used as gold standard for PA.,A physical activity level (PAL) of <1.4 was considered very inactive.,Univariate and multivariate analyses were used to examine the relationship between the 6-minute walking distance (6MWD), the number of stands in the Sit-to-Stand Test (STST), hand-grip strength and the total energy expenditure as assessed by the Zutphen Physical Activity Questionnaire (TEEZPAQ).,ROC curve analysis was used to identify patients with an extremely inactive lifestyle (PAL<1.4).,In 70 patients with COPD (21 females) with a mean [SD] FEV1 of 43.0 [22.0] %predicted, PA was found to be significantly and independently associated with the 6MWD (r = 0.69, 95% CI 0.54 to 0.80, p<0.001), STST (r = 0.51, 95% CI 0.31 to 0.66, p = 0.001) and TEEZPAQ (r = 0.50, 95% CI 0.30 to 0.66, p<0.001) but not with hand-grip strength.,However, ROC curve analysis demonstrated that these tests cannot be used to reliably identify patients with an extremely inactive lifestyle.,In patients with COPD simple tests such as the 6-Minute Walk Test, the Sit-to-Stand Test and the Zutphen Physical Activity Questionnaire cannot be used to reliably predict physical inactivity.
| 1 |
Although the age range of chronic obstructive pulmonary disease (COPD) patients is broad, few studies have focused on the effects of age on disease characteristics.,Keio University and affiliated hospitals established an observational COPD cohort.,Patients were assessed using high resolution computed tomography (CT) to quantify emphysema, health status using the COPD assessment test (CAT) and the St.,George’s Respiratory Questionnaire (SGRQ), spirometry, echocardiogram, dual X-ray absorption of bone, biomarkers and comorbid diagnoses.,We examined the characteristics of COPD patients aged 75 and over compared with patients below 75.,A total of 443 patients comprising 252 patients aged <75 years and 191 patients aged ≥75 years, were enrolled.,Emphysematous changes on CT and prevalence of possible pulmonary hypertension were greater in late-elderly patients.,The slope of the relationship between CT emphysema densitometry score and forced expiratory volume in 1 s was significantly less steep in the late-elderly than the younger patients (p = 0.002).,CAT and total SGRQ scores and the frequency of long-term oxygen therapy were significantly higher in the late-elderly with moderate airflow obstruction compared to those of the younger in the same grade, although the opposite was seen in late-elderly patients with very severe airflow obstruction.,Hypertension, aortic aneurysm, prostatic hypertrophy, anemia, and cataract are more prevalent in late-elderly patients.,Elderly COPD patients show a varied age-related pattern of disease that warrants specific attention in clinical practice above and beyond assessment of airflow limitation.,Trial registration Clinical trial registered with the University Hospital Medical Information Network (UMIN000003470, April 10, 2010),The online version of this article (doi:10.1186/s13104-015-1810-8) contains supplementary material, which is available to authorized users.
|
Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI).,Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated.,Methods: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies.,Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity.,Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion.,Results: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9).,Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD.,Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity.,Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants.,Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker.,Conclusions: All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler.,Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability.,Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler.
| 1 |
Acute exacerbation of COPD (AECOPD) is associated with an increased hospitalization and mortality.,Azithromycin and erythromycin are the recommended drugs to reduce the risk of exacerbations.,However, the most suitable duration of therapy and drug-related adverse events are still a matter of debate.,The aim of this meta-analysis was to assess the current evidence regarding the efficacy and safety of long-term macrolide treatment for COPD.,We comprehensively searched PubMed, Embase, the Cochrane Library, and the Web of Science and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and retrospective studies.,Eleven RCTs and one retrospective study including a total of 2,151 cases were carried out.,Long-term macrolide treatment significantly reduced the total number of cases with one or more exacerbations (OR=0.40; 95% CI=0.24-0.65; P<0.01) and the rate of exacerbations per patient per year (risk ratio [RR]=0.60; 95% CI=0.45-0.78; P<0.01).,Subgroup analyses showed that the minimum duration for drug efficacy for both azithromycin and erythromycin therapy was 6 months.,In addition, macrolide therapy could improve the St George Respiratory Questionnaire (SGRQ) total score (P<0.01) but did not achieve the level of clinical significance.,The frequency of hospitalizations was not significantly different between the treatment and control groups (P=0.50).,Moreover, chronic azithromycin treatment was more likely to increase adverse events (P<0.01).,Prophylactic azithromycin or erythromycin treatment has a significant effect in reducing the frequency of AECOPD in a time-dependent manner.,However, long-term macrolide treatment could increase the occurrence of adverse events and macrolide resistance.,Future large-scale, well-designed RCTs with extensive follow-up are required to identify patients in whom the benefits outweigh risks.
|
We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD.,We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects.,Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages.,Multiplex ELISA measured BAL cytokines.,Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles.,We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups.,However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects.,BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs.,The mouse-model of COPD showed similar increase in mRNA for M2 markers.,Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance.,There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD.
| 1 |
Forecasting hospitalization in patients with COPD has gained significant interest in the field of COPD care.,There is a need to find simple tools that can help clinicians to stratify the risk of hospitalization in these patients at the time of care.,The perception of quality of life has been reported to be independently associated with hospitalizations, but questionnaires are impractical for daily clinical use.,Individual questions from valid questionnaires can have robust predictive abilities, as has been suggested in previous reports, as a way to use patient-reported outcomes to forecast important events like hospitalizations in COPD.,Our primary aim was to assess the predictive value of individual questions from the Chronic Respiratory Questionnaire Self-Assessment Survey (CRQ-SAS) on the risk of hospitalization and to develop a clinically relevant and simple algorithm that clinicians can use in routine practice to identify patients with an increased risk of hospitalization.,A total of 493 patients with COPD prospectively recruited from an outpatient pulmonary clinic completed the CRQ-SAS, demographic information, pulmonary function testing, and clinical outcomes.,The cohort had a mean age of 70 years, was 54% male, with forced expiratory volume in 1 second percentage predicted 42.8±16.7, and modified Medical Research Council dyspnea scale score of 2±1.13.,Our analysis validated the original CRQ-SAS domains.,Importantly, recursive partitioning analysis identified three CRQ-SAS items regarding fear or panic of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms that were highly predictive of hospitalization.,We propose a robust (area under the curve =0.70) but short and easy algorithm for daily clinical care to forecast hospitalizations in patients with COPD.,We identified three themes - fear of breathlessness, dyspnea with basic activities of daily living, and depressive symptoms - as important patient-reported outcomes to predict hospitalizations, and propose a short and easy algorithm to forecast hospitalizations in patients with COPD.
|
Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear.,We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.,Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007).,COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal.,Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry.,Model performance was assessed using standard criteria.,4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70.,The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76).,Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78).,The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).,Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD.,Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.
| 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.
|
Emphysematous smokers with normal spirometry form a considerable proportion of the clinical population.,However, despite presenting with respiratory symptoms and activity limitation, they cannot be diagnosed with chronic obstructive lung disease (COPD) according to current criteria.,Thus, we aimed to determine whether emphysema in smokers has a different pathogenesis from that in patients with COPD.,We compared 12 pairs of lung tissue samples from emphysematous patients with normal spirometry and COPD, and determined the degree of emphysema using computed tomography.,With a focus on COPD-related pathogenesis, we independently assessed inflammatory response, protease-antiprotease balance, oxidative stress, and apoptosis in both groups.,Both groups showed similar pathological changes at a comparable degree of emphysema; the expression of inflammatory factors was comparable, with overexpression of proteases and decreased levels of antiproteases.,Moreover, there was no significant difference in the activities of glutathione and superoxide dismutase, and expression of apoptosis-related factors.,In conclusion, emphysema in smokers with normal spirometry and in patients with COPD had similar pathogenesis.,Forced expiratory volume in 1 second cannot be used as the sole diagnostic criterion in patients with COPD; early intervention is of great importance to such patients.
| 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.
|
The changes in the microbial community structure during acute exacerbations of severe chronic obstructive pulmonary disease (COPD) in hospitalized patients remain largely uncharacterized.,Therefore, further studies focused on the temporal dynamics and structure of sputum microbial communities during acute exacerbation of COPD (AECOPD) would still be necessary.,In our study, the use of molecular microbiological techniques provided insight into both fungal and bacterial diversities in AECOPD patients during hospitalization.,In particular, we examined the structure and varieties of lung microbial community in 6 patients with severe AECOPD by amplifying 16S rRNA V4 hyper-variable and internal transcribed spacer (ITS) DNA regions using barcoded primers and the Illumina sequencing platform.,Sequence analysis showed 261 bacterial genera representing 20 distinct phyla, with an average number of genera per patient of >157, indicating high diversity.,Acinetobacter, Prevotella, Neisseria, Rothia, Lactobacillus, Leptotrichia, Streptococcus, Veillonella, and Actinomyces were the most commonly identified genera, and the average total sequencing number per sputum sample was >10000 18S ITS sequences.,The fungal population was typically dominated by Candia, Phialosimplex, Aspergillus, Penicillium, Cladosporium and Eutypella.,Our findings highlight that COPD patients have personalized structures and varieties in sputum microbial community during hospitalization periods.
| 1 |
Co-morbidities are common in chronic obstructive pulmonary disease (COPD).,We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients.,Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis.,The prevalence of their co-morbidities was compared with those of 5000 population controls.,The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients.,Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls.,Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments.,Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1.,FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted).,Poor HRQoL also predicted death during the next five years.,The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD.
|
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airway obstruction and inflammation but also accompanied by several extrapulmonary consequences, such as skeletal muscle weakness and osteoporosis.,Skeletal muscle weakness is of major concern, since it leads to poor functional capacity, impaired health status, increased healthcare utilization, and even mortality, independently of lung function.,Osteoporosis leads to fractures and is associated with increased mortality, functional decline, loss of quality of life, and need for institutionalization.,Therefore, the presence of the combination of these comorbidities will have a negative impact on daily life in patients with COPD.,In this review, we will focus on these two comorbidities, their prevalence in COPD, combined risk factors, and pathogenesis.,We will try to prove the clustering of these comorbidities and discuss possible preventive or therapeutic strategies.
| 1 |
Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users.
|
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 |
Worldwide, nearly 3 million people die of chronic obstructive pulmonary disease (COPD) every year.,Integrated disease management (IDM) improves disease-specific quality of life and exercise capacity for people with COPD, but can also reduce hospital admissions and hospital days.,Self-management of COPD through eHealth interventions has shown to be an effective method to improve the quality and efficiency of IDM in several settings, but it remains unknown which factors influence usage of eHealth and change in behavior of patients.,Our study, e-Vita COPD, compares different levels of integration of Web-based self-management platforms in IDM in three primary care settings.,The main aim of this study is to analyze the factors that successfully promote the use of a self-management platform for COPD patients.,The e-Vita COPD study compares three different approaches to incorporating eHealth via Web-based self-management platforms into IDM of COPD using a parallel cohort design.,Three groups integrated the platforms to different levels.,In groups 1 (high integration) and 2 (medium integration), randomization was performed to two levels of personal assistance for patients (high and low assistance); in group 3 there was no integration into disease management (none integration).,Every visit to the e-Vita and Zorgdraad COPD Web platforms was tracked objectively by collecting log data (sessions and services).,At the first log-in, patients completed a baseline questionnaire.,Baseline characteristics were automatically extracted from the log files including age, gender, education level, scores on the Clinical COPD Questionnaire (CCQ), dyspnea scale (MRC), and quality of life questionnaire (EQ5D).,To predict the use of the platforms, multiple linear regression analyses for the different independent variables were performed: integration in IDM (high, medium, none), personal assistance for the participants (high vs low), educational level, and self-efficacy level (General Self-Efficacy Scale [GSES]).,All analyses were adjusted for age and gender.,Of the 702 invited COPD patients, 215 (30.6%) registered to a platform.,Of the 82 patients in group 1 (high integration IDM), 36 were in group 1A (personal assistance) and 46 in group 1B (low assistance).,Of the 96 patients in group 2 (medium integration IDM), 44 were in group 2A (telephone assistance) and 52 in group 2B (low assistance).,A total of 37 patients participated in group 3 (no integration IDM).,In all, 107 users (49.8%) visited the platform at least once in the 15-month period.,The mean number of sessions differed between the three groups (group 1: mean 10.5, SD 1.3; group 2: mean 8.8, SD 1.4; group 3: mean 3.7, SD 1.8; P=.01).,The mean number of sessions differed between the high-assistance and low-assistance groups in groups 1 and 2 (high: mean 11.8, SD 1.3; low: mean 6.7, SD 1.4; F1,80=6.55, P=.01).,High-assistance participants used more services (mean 45.4, SD 6.2) than low-assistance participants (mean 21.2, SD 6.8; F1,80=6.82, P=.01).,No association was found between educational level and usage and between GSES and usage.,Use of a self-management platform is higher when participants receive adequate personal assistance about how to use the platform.,Blended care, where digital health and usual care are integrated, will likely lead to increased use of the online program.,Future research should provide additional insights into the preferences of different patient groups.,Nederlands Trial Register NTR4098; http://www.trialregister.nl/trialreg/admin/rctview.asp?,TC=4098 (Archived by WebCite at http://www.webcitation.org/6qO1hqiJ1)
|
Patients with COPD experience respiratory symptoms, impairments of daily living and recurrent exacerbations.,The aim of integrated disease management (IDM) is to establish a programme of different components of care (ie, self-management, exercise, nutrition) in which several healthcare providers (ie, nurses, general practitioners, physiotherapists, pulmonologists) collaborate to provide efficient and good quality of care.,The aim of this Cochrane systematic review was to evaluate the effectiveness of IDM on quality of life, exercise tolerance and exacerbation related outcomes.,Searches for all available evidence were carried out in various databases.,Included randomised controlled trials (RCTs) consisted of interventions with multidisciplinary (≥2 healthcare providers) and multitreatment (≥2 components) IDM interventions with duration of at least 3 months.,Two reviewers independently searched, assessed and extracted data of all RCTs.,A total of 26 RCTs were included, involving 2997 patients from 11 different countries with a follow-up varying from 3 to 24 months.,In all 68% of the patients were men, with a mean age of 68 years and a mean forced expiratory volume in 1 s (FEV1) predicted value of 44.3%.,Patients treated with an IDM programme improved significantly on quality of life scores and reported a clinically relevant improvement of 44 m on 6 min walking distance, compared to controls.,Furthermore, the number of patients with ≥1 respiratory related hospital admission reduced from 27 to 20 per 100 patients.,Duration of hospitalisation decreased significantly by nearly 4 days.
| 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users.
|
Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations.,A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome.,The Respimat® Soft Mist™ Inhaler (SMI) generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs) or some dry powder inhalers (DPIs).,We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients.,Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics.,In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI.,In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI.,Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven.
| 1 |
In patients with COPD, self-management skills are important to reduce the impact of exacerbations.,However, both detection and adequate response to exacerbations appear to be difficult for some patients.,Little is known about the underlying process of exacerbation-related self-management.,Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior.,A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated.,Fifteen patients (male n=8; age range 59-88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015.,Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed.,Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management.,Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms.,Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions.,This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients.,The conceptual model can be used as a framework for health care professionals providing self-management support.,In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account.
|
Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303.
| 1 |
Assessing risk of future exacerbations is an important component in COPD management.,History of exacerbation is a strong and independent predictor of future exacerbations, and the criterion of ≥2 nonhospitalized or ≥1 hospitalized exacerbation is often used to identify high-risk patients in whom therapy should be intensified.,However, other factors or “treatable traits” also contribute to risk of exacerbation.,The objective of the study was to develop and externally validate a novel clinical prediction model for risk of hospitalized COPD exacerbations based on both exacerbation history and treatable traits.,A total of 237 patients from the COPD Registry of Changi General Hospital, Singapore, aged 75±9 years and with mean post-bronchodilator FEV1 60%±20% predicted, formed the derivation cohort.,Hospitalized exacerbation rate was modeled using zero-inflated negative binomial regression.,Calibration was assessed by graphically comparing the agreement between predicted and observed annual hospitalized exacerbation rates.,Predictive (discriminative) accuracy of the model for identifying high-risk patients (defined as experiencing ≥1 hospitalized exacerbations) was assessed with area under the curve (AUC) and receiver operating characteristics analyses, and compared to other existing risk indices.,We externally validated the prediction model using a multicenter dataset comprising 419 COPD patients.,The final model included hospitalized exacerbation rate in the previous year, history of acute invasive/noninvasive ventilation, coronary artery disease, bronchiectasis, and sputum nontuberculous mycobacteria isolation.,There was excellent agreement between predicted and observed annual hospitalized exacerbation rates.,AUC was 0.789 indicating good discriminative accuracy, and was significantly higher than the AUC of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) risk assessment criterion (history of ≥1 hospitalized exacerbation in the previous year) and the age, dyspnea, and obstruction index.,When applied to the independent multicenter validation cohort, the model was well-calibrated and discrimination was good.,We have derived and externally validated a novel risk prediction model for COPD hospitalizations which outperforms several other risk indices.,Our model incorporates several treatable traits which can be targeted for intervention to reduce risk of future hospitalized exacerbations.
|
The objective of the study is to develop a scoring system for predicting a 90-day re-exacerbation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,A total of 176 consecutive hospitalized patients with AECOPD were included.,The sociodemographic characteristics, status before acute exacerbation (AE), presentations of and treatment for the current AE, and the re-exacerbation in 90 days after discharge from hospital were collected.,The re-exacerbation rate in 90 days was 48.9% (86 out of 176).,It was associated with the degree of lung function impairment (Global initiative for chronic Obstructive Lung Disease [GOLD] grades), frequency of AE in the previous year, and parameters of the current AE, including pleural effusion, use of accessory respiratory muscles, inhaled long-acting β-2-agonists, inhaled corticosteroids, controlled oxygen therapy, noninvasive mechanical ventilation, and length of hospital stay, but was not associated with body mass index, modified Medical Research Council scale, or chronic obstructive pulmonary disease assessment test.,A subgroup of ten variables was selected and developed into the re-exacerbation index scoring system (age grades, GOLD grades, AE times in the previous year, pleural effusion, use of accessory respiratory muscles, noninvasive mechanical ventilation, controlled oxygen therapy, inhaled long-acting β-2-agonists and inhaled corticosteroids, and length of hospital stay).,The re-exacerbation index showed good discrimination for re-exacerbation, with a C-statistic of 0.750 (P<0.001).,A comprehensive assessment integrating parameters of stable chronic obstructive pulmonary disease, clinical presentations at exacerbation, and treatment showed a strong predictive capacity for short-term outcome in patients with AECOPD.,Further studies are required to verify these findings.
| 1 |
Both stable chronic obstructive pulmonary disease (COPD) and acute exacerbations represent leading causes of death, disability and healthcare expenditure.,They are complex, heterogeneous and their mechanisms are poorly understood.,The role of respiratory viruses has been studied extensively but is still not adequately addressed clinically.,Through a rigorous evidence update, we aim to define the prevalence and clinical burden of the different respiratory viruses in stable COPD and exacerbations, and to investigate whether viral load of usual respiratory viruses could be used for diagnosis of exacerbations triggered by viruses, which are currently not diagnosed or treated aetiologically.,Based on a prospectively registered protocol, we will systematically review the literature using standard methods recommended by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group.,We will search Medline/PubMed, Excerpta Medica dataBASE (EMBASE), the Cochrane Library, the WHO’s Clinical Trials Registry and the proceedings of relevant international conferences on 2 March 2020.,We will evaluate: (A) the prevalence of respiratory viruses in stable COPD and exacerbations, (B) differences in the viral loads of respiratory viruses in stable COPD vs exacerbations, to explore whether the viral load of prevalent respiratory viruses could be used as a diagnostic biomarker for exacerbations triggered by viruses and (C) the association between the presence of respiratory viruses and clinical outcomes in stable COPD and in exacerbations.,Ethics approval is not required since no primary data will be collected.,Our findings will be presented in national and international scientific conferences and will be published in peer reviewed journals.,Respiratory viruses currently represent a lost opportunity to improve the outcomes of both stable COPD and exacerbations.,Our work aspires to ‘demystify’ the prevalence and clinical burden of viruses in stable COPD and exacerbations and to promote clinical and translational research.,CRD42019147658.
|
The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries.,Using data from this survey we evaluated the economic impact of COPD.,This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology.,Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications.,Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale.,Combined direct and indirect costs estimated the total societal costs per patient.,The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs.,The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%.,Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities.,The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities.,Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs.
| 1 |
Chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure (HF) in clinical practice since they share the same pathogenic mechanism.,Both conditions incur significant morbidity and mortality.,Therefore, the prognosis of COPD and HF combined is poorer than for either disease alone.,Nevertheless, usually only one of them is diagnosed.,An active search for each condition using clinical examination and additional tests including plasma natriuretic peptides, lung function testing, and echocardiography should be obtained.,The combination of COPD and HF presents many therapeutic challenges.,The beneficial effects of selective β1-blockers should not be denied in stable patients who have HF and coexisting COPD.,Additionally, statins, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers may reduce the morbidity and mortality of COPD patients.,Moreover, caution is advised with use of inhaled β2-agonists for the treatment of COPD in patients with HF.,Finally, noninvasive ventilation, added to conventional therapy, improves the outcome of patients with acute respiratory failure due to hypercapnic exacerbation of COPD or HF in situations of acute pulmonary edema.,The establishment of a combined and integrated approach to managing these comorbidities would seem an appropriate strategy.,Additional studies providing new data on the pathogenesis and management of patients with COPD and HF are needed, with the purpose of trying to improve quality of life as well as survival of these patients.
|
Several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment.,These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group.,This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD.,In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy.,We used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD.,Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points.,Disease severity was using Forced Expiratory Volume in one second (FEV1); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index.,Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking.,COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64).,Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases).,Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048).,Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001).,COPD is a major risk factor for cognitive impairment.,Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective.,Health care providers should consider screening their COPD patients for cognitive impairment.
| 1 |
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system affecting primarily distal respiratory pathways and lung parenchyma.,This study was aimed at investigating the association of COPD with IREB2, CHRNA5, CHRNA3, FAM13A and hedgehog interacting protein (HHIP) genes in a Tatar population from Russia.,Six single nucleotide polymorphisms (SNPs) (rs13180, rs16969968, rs1051730, rs6495309, rs7671167, rs13118928) were genotyped by the real-time polymerase chain reaction in this study (511 COPD patients and 508 controls).,Logistic regression was used to detect the association of SNPs and haplotypes of linked loci in different models.,Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years.,The rs13180 (IREB2), rs16969968 (CHRNA5) and rs1051730 (CHRNA3) were significantly associated with COPD in additive model [Padj=0.00001, odds ratio (OR)=0.64; Padj=0.0001, OR=1.41 and Padj=0.0001, OR=1.47].,The C-G haplotype by rs13180 and rs1051730 was a protective factor for COPD in our population (Padj=0.0005, OR=0.61).,These results were confirmed only in smokers.,The rs16969968 and rs1051730 were associated with decrease of forced expiratory volume in 1 sec % predicted (Padj=0.005 and Padj=0.0019).,Our study showed the association of rs13180, rs16969968 and rs1051730 with COPD and lung function in Tatar population from Russia.,Further studies need to be done in other ethnic populations.
|
Genome-wide association studies have identified loci at 15q25 (IREB2) and 4q22 (FAM13A), associated with lung cancer (LC) and chronic obstructive pulmonary disease (COPD).,The aim of our research was to determine the association of IREB2 and FAM13A SNPs with LC and severe/very severe COPD patients.,We examined IREB2 variants (rs2568494, rs2656069, rs10851906, rs13180) and FAM13A (rs1903003, rs7671167, rs2869967) among 1.141 participants (468 LC, 149 COPD, 524 smoking controls).,The frequency of the minor IREB2 rs2568494 AA genotype, was higher in LC vs controls (P = 0.0081, OR = 1.682).,The FAM13A rs2869967 was associated with COPD (minor CC genotype: P = 0.0007, OR = 2.414).,The rs1903003, rs7671167 FAM13A variants confer a protective effect on COPD (both P < 0.002, OR < 0.405).,Haplotype-based tests identified an association of the IREB2 AAAT haplotype with LC (P = 0.0021, OR = 1.513) and FAM13A TTC with COPD (P = 0.0013, OR = 1.822).,Cumulative genetic risk score analyses (CGRS), derived by adding risk alleles, revealed that the risk for COPD increased with the growing number of the FAM13A risk alleles.,OR (95% CI) for carriers of ≥5 risk alleles reached 2.998 (1.8 to 4.97) compared to the controls.,This study confirms that the IREB2 variants contribute to an increased risk of LC, whereas FAM13A predisposes to increased susceptibility to COPD.
| 1 |
Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.,This was a multicenter, double-blind, randomized, placebo-controlled study.,Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year.,The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization.,Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively).,Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events.,Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively).,Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study.,Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003).,Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different.,Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively).,Significant improvements in quality of life (overall St.,George’s Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05).,Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo.,Arformoterol was well-tolerated and improved lung function vs placebo.,ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov
|
Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β2 agonists have been shown to improve COPD outcomes.,Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures.,We investigated this using record linkage in a Dundee COPD population.,A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number.,A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders.,A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias.,4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study.,There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions.,The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively.,The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation.,There was however an association with increased cataracts and pneumonia hospitalisations.
| 1 |
This paper presents detailed analysis of the global and regional burden of chronic respiratory disease arising from occupational airborne exposures, as estimated in the Global Burden of Disease 2016 study.,The burden of chronic obstructive pulmonary disease (COPD) due to occupational exposure to particulate matter, gases and fumes, and secondhand smoke, and the burden of asthma resulting from occupational exposure to asthmagens, was estimated using the population attributable fraction (PAF), calculated using exposure prevalence and relative risks from the literature.,PAFs were applied to the number of deaths and disability-adjusted life years (DALYs) for COPD and asthma.,Pneumoconioses were estimated directly from cause of death data.,Age-standardised rates were based only on persons aged 15 years and above.,The estimated PAFs (based on DALYs) were 17% (95% uncertainty interval (UI) 14%-20%) for COPD and 10% (95% UI 9%-11%) for asthma.,There were estimated to be 519 000 (95% UI 441,000-609,000) deaths from chronic respiratory disease in 2016 due to occupational airborne risk factors (COPD: 460,100 [95% UI 382,000-551,000]; asthma: 37,600 [95% UI 28,400-47,900]; pneumoconioses: 21,500 [95% UI 17,900-25,400].,The equivalent overall burden estimate was 13.6 million (95% UI 11.9-15.5 million); DALYs (COPD: 10.7 [95% UI 9.0-12.5] million; asthma: 2.3 [95% UI 1.9-2.9] million; pneumoconioses: 0.58 [95% UI 0.46-0.67] million).,Rates were highest in males; older persons and mainly in Oceania, Asia and sub-Saharan Africa; and decreased from 1990 to 2016.,Workplace exposures resulting in COPD, asthma and pneumoconiosis continue to be important contributors to the burden of disease in all regions of the world.,This should be reducible through improved prevention and control of relevant exposures.
|
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 |
Respiratory viruses are major human pathogens that cause approximately 200 million pneumonia cases annually and induce various comorbidities with chronic obstructive pulmonary disease (COPD), resulting in significant health concerns and economic burdens.,Clinical manifestations in respiratory viral infections and inflammations vary from asymptomatic, mild, to severe, depending on host immune cell responses to pathogens and interactions with airway epithelia.,We critically review the activation, effector, and regulation of T cells in respiratory virus infections and chronic inflammations associated with COPD.,Crosstalk among T cells, innate immune cells, and airway epithelial cells is discussed as essential parts of pathogenesis and protection in viral infections and COPD.,We emphasize the specificity of peptide antigens and the functional heterogeneity of conventional CD4+ and CD8+ T cells to shed some light on potential cellular and molecular candidates for the future development of therapeutics and intervention against respiratory viral infections and inflammations.
|
Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem.,Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment.,This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action.,Several dietary options can be considered in terms of COPD prevention and/or progression.,Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD.,Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health.
| 1 |
Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities.,We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks.,Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52.,Adverse events were also assessed.,In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years).,Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02-0.15) were small for all treatments.,Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score).,The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups.,Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%).,There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24.,In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints.,Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful.,All treatments were well tolerated with no new or unexpected safety findings.,ClinicalTrials.gov NCT02536508.,Registered 27 August 2015.,The online version of this article (10.1186/s12931-019-1126-7) contains supplementary material, which is available to authorized users.
|
AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677).,In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 µg, AB 400 µg, or FF 12 µg, or once-daily TIO 18 µg.,Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF).,Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective.,Normalized area under the curve (AUC)0-3/3 h FEV1 and nighttime and early morning symptoms were also assessed.,A subgroup participated in a 24-hour serial spirometry sub-study.,A total of 1,594 patients were randomized; 566 entered the sub-study.,At week 24, 1-hour post-dose FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P<0.0001).,AB/FF significantly improved trough FEV1 vs FF (55 mL, P<0.001) and AB was non-inferior to TIO.,AB/FF significantly improved AUC0-3/3 h FEV1 vs all comparators (P<0.0001) and provided significant improvements in early morning symptoms vs TIO.,The 24-hour spirometry demonstrated significantly greater improvements with AB/FF in AUC12-24/12 h vs all comparators, and in AUC0-24/24 h vs FF or TIO at week 24.,In patients with moderate-to-very severe symptomatic COPD, twice-daily AB/FF significantly improved lung function vs monocomponents and TIO, and early morning symptom control vs TIO.
| 1 |
We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD.,We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function) were reduced in the airways but not circulation of COPD patients.,We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances.,We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages.,Oligomeric structure of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2′-azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue native PAGE.,Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi) and expression of macrophage scavenger receptors.,Oxidation disrupted higher order MBL oligomers.,This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively).,Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels.,Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1) in the presence of pdMBL that was abrogated in the presence of oxMBL.,We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease.
|
Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive.,However, the molecular mechanism of this glucocorticoid insensitivity remains uncertain.,We show that a defect of glucocorticoid receptor (GR) deacetylation caused by impaired histone deacetylase (HDAC) 2 induces glucocorticoid insensitivity toward nuclear factor (NF)-κB-mediated gene expression.,Specific knockdown of HDAC2 by RNA interference resulted in reduced sensitivity to dexamethasone suppression of interleukin 1β-induced granulocyte/macrophage colony-stimulating factor production.,Loss of HDAC2 did not reduce GR nuclear translocation, GR binding to glucocorticoid response element (GRE) on DNA, or GR-induced DNA or gene induction but inhibited the association between GR and NF-κB.,GR becomes acetylated after ligand binding, and HDAC2-mediated GR deacetylation enables GR binding to the NF-κB complex.,Site-directed mutagenesis of K494 and K495 reduced GR acetylation, and the ability to repress NF-κB-dependent gene expression becomes insensitive to histone deacetylase inhibition.,In conclusion, we show that overexpression of HDAC2 in glucocorticoid-insensitive alveolar macrophages from patients with COPD is able to restore glucocorticoid sensitivity.,Thus, reduction of HDAC2 plays a critical role in glucocorticoid insensitivity in repressing NF-κB-mediated, but not GRE-mediated, gene expression.
| 1 |
We built a decision-analytic model to compare the cost-effectiveness of using portable spirometer and questionnaire to screen chronic obstructive pulmonary diseases (COPD) with no screening (i.e. usual care) among chronic bronchitis patient in China.,A lifetime horizon and a payer perspective were adopted.,Cost data of health services including spirometry screening and treatment costs covered both maintenance and exacerbation.,The result indicated that portable spirometer screening was cost-saving compared with questionnaire screening and no screening, with an incremental cost-effectiveness ratio (ICER) of −5026 and −1766 per QALY, respectively.,Sensitivity analyses confirmed the robustness of the results.,In summary, portable spirometer screening is likely the optimal option for COPD screening among chronic bronchitis patients China.
|
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.
| 1 |
Monitoring of regional lung function in interventional COPD trials requires alternative endpoints beyond global parameters such as FEV1.,T1 relaxation times of the lung might allow to draw conclusions on tissue composition, blood volume and oxygen fraction.,The aim of this study was to evaluate the potential value of lung Magnetic resonance imaging (MRI) with native and oxygen-enhanced T1 mapping for the assessment of COPD patients in comparison with contrast enhanced perfusion MRI.,20 COPD patients (GOLD I-IV) underwent a coronal 2-dimensional inversion recovery snapshot flash sequence (8 slices/lung) at room air and during inhalation of pure oxygen, as well as dynamic contrast-enhanced first-pass perfusion imaging.,Regional distribution of T1 at room air (T1), oxygen-induced T1 shortening (ΔT1) and peak enhancement were rated by 2 chest radiologists in consensus using a semi-quantitative 3-point scale in a zone-based approach.,Abnormal T1 and ΔT1 were highly prevalent in the patient cohort.,T1 and ΔT1 correlated positively with perfusion abnormalities (r = 0.81 and r = 0.80; p&0.001), and with each other (r = 0.80; p<0.001).,In GOLD stages I and II ΔT1 was normal in 16/29 lung zones with mildly abnormal perfusion (15/16 with abnormal T1).,The extent of T1 (r = 0.45; p<0.05), ΔT1 (r = 0.52; p<0.05) and perfusion abnormalities (r = 0.52; p<0.05) showed a moderate correlation with GOLD stage.,Native and oxygen-enhanced T1 mapping correlated with lung perfusion deficits and severity of COPD.,Under the assumption that T1 at room air correlates with the regional pulmonary blood pool and that oxygen-enhanced T1 reflects lung ventilation, both techniques in combination are principally suitable to characterize ventilation-perfusion imbalance.,This appears valuable for the assessment of regional lung characteristics in COPD trials without administration of i.v. contrast.
|
Ventilation/perfusion (V/P) single-photon emission computed tomography (SPECT) is recognized as a diagnostic method with potential beyond the diagnosis of pulmonary embolism.,V/P SPECT identifies functional impairment in diseases such as heart failure (HF), pneumonia, and chronic obstructive pulmonary disease (COPD).,The development of hybrid SPECT/computed tomography (CT) systems, combining functional with morphological imaging through the addition of low-dose CT (LDCT), may be useful in COPD, as these patients are prone to lung cancer and other comorbidities.,The aim of this study was to investigate the added value of LDCT among healthy smokers and patients with stable COPD, when examined with V/P SPECT/CT hybrid imaging.,Sixty-nine subjects, 55 with COPD (GOLD I-IV) and 14 apparently healthy smokers, were examined with V/P SPECT and LDCT hybrid imaging.,Spirometry was used to verify COPD grade.,Only one apparently healthy smoker and three COPD patients had a normal or nearly normal V/P SPECT.,All other patients showed various degrees of airway obstruction, even when spirometry was normal.,The same interpretation was reached on both modalities in 39% of the patients.,LDCT made V/P SPECT interpretation more certain in 9% of the patients and, in 52%, LDCT provided additional diagnoses.,LDCT better characterized the type of emphysema in 12 patients.,In 19 cases, tumor-suspected changes were reported.,Three of these 19 patients (ie, 4.3% of all subjects) were in the end confirmed to have lung cancer.,The majority of LDCT findings were not regarded as clinically significant.,V/P SPECT identified perfusion patterns consistent with decompensated left ventricular HF in 14 COPD patients.,In 16 patients (23%), perfusion defects were observed.,HF and perfusion defects were not recognized with LDCT.,In COPD patients and long-time smokers, hybrid imaging had added value compared to V/P SPECT alone, by identifying patients with lung malignancy and more clearly identifying emphysema.,V/P SPECT visualizes comorbidities to COPD not seen with LDCT, such as pulmonary embolism and left ventricular HF.
| 1 |
Beta-blockers are commonly prescribed for patients with cardiovascular disease.,Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial.,However, these benefits may reflect symptom improvements due to the cardiac effects of the medication.,The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts.,We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial.,Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use.,Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment.,We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities.,In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers.,In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year.,Patients without beta-blockers had an exacerbation rate of 1.34/person-year.,We found no detrimental effect of beta blockers with respect to change in lung function over time.,We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.
|
The aim of our study is to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for ischemic heart disease and whether this association is related with a greater prevalence of classical cardiovascular risk factors.,Ours is a case-control cross-sectional study design.,Cases were hospital patients with ischemic heart disease in stable phase, compared with control hospital patients.,All patients underwent post-bronchodilator (PBD) spirometry, a standardized questionnaire, and blood analysis.,COPD was defined as per GOLD PBD forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) < 0.70.,In our series of patient cases (n = 204) and controls (n = 100), there were 169 men in the case group (83%) and 84 in the control group (84%).,Ages were 67 and 64 years, respectively (P < 0.05).,There were no significant differences by weight, body mass index (BMI), packyears, leukocytes, or homocysteine.,The abdominal perimeter was significantly greater in cases (mean 101 cm ± standard deviation [SD] 10 versus 96 cm ± 11; P < 0.000).,Both groups also had significant differences by C-reactive protein (CRP), fibrinogen, and hemoglobin values.,In univariate analysis, increased risks for cases to show with individual classical cardiovascular risk factors were seen, with odds ratio (OR) 1.86 and 95% confidence interval (CI) (1.04-3.33) for diabetes mellitus, dyslipidemia (OR 2.10, 95% CI: 1.29-3.42), arterial hypertension (OR 2.47, 95% CI: 1.51-4.05), and increased abdominal perimeter (OR 1.71, 95% CI: 1.06-2.78).,Percent predicted PBD FEV1 was 97.6% ± 23% in the patient group and 104% ± 19% in the control group (P = 0.01), but the prevalence of COPD was 24.1% in cases and 21% in controls.,Therefore, COPD was not associated with ischemic heart disease: at the crude level (OR 1.19, 95% CI: 0.67-2.13) or after adjustment (OR 1.14, 95% CI:0.57-2.29).,In conclusion, COPD was not associated with ischemic heart disease.,The greater prevalence of classical cardiovascular risk factors in COPD patients could explain the higher occurrence of ischemic heart disease in these patients.
| 1 |
We built a decision-analytic model to compare the cost-effectiveness of using portable spirometer and questionnaire to screen chronic obstructive pulmonary diseases (COPD) with no screening (i.e. usual care) among chronic bronchitis patient in China.,A lifetime horizon and a payer perspective were adopted.,Cost data of health services including spirometry screening and treatment costs covered both maintenance and exacerbation.,The result indicated that portable spirometer screening was cost-saving compared with questionnaire screening and no screening, with an incremental cost-effectiveness ratio (ICER) of −5026 and −1766 per QALY, respectively.,Sensitivity analyses confirmed the robustness of the results.,In summary, portable spirometer screening is likely the optimal option for COPD screening among chronic bronchitis patients China.
|
Supplemental Digital Content is available in the text,The early detection and diagnosis of chronic obstructive pulmonary disease (COPD) is critical to providing appropriate and timely treatment.,We explored a new active case-finding strategy for COPD using handheld spirometry.,We recruited subjects over 40 years of age with a smoking history of more than 10 pack-years who visited a primary clinic complaining of respiratory symptoms.,A total of 190 of subjects were enrolled.,Medical information was obtained from historical records and physical examination by general practitioners.,All subjects had their pulmonary function evaluated using handheld spirometry with a COPD-6 device.,Because forced expiratory volume in 6 seconds (FEV6) has been suggested as an alternative to FVC, we measured forced expiratory volume in 1 second (FEV1)/FEV6 for diagnosis of airflow limitation.,All subjects were then referred to tertiary referral hospitals to complete a “Could it be COPD?”,questionnaire, handheld spiromtery, and conventional spirometry.,The results of each instrument were compared to evaluate the efficacy of both handheld spirometry and the questionnaire.,COPD was newly diagnosed in 45 (23.7%) patients.,According to our receiver-operating characteristic (ROC) curve analysis, sensitivity and specificity were maximal when the FEV1/FEV6 ratio was less than 77%.,The area under the ROC curve was 0.759.,The sensitivity, specificity, positive predictive value, and negative predictive value were 72.7%, 77.1%, 50%, and 90%, respectively.,The area under the ROC curve of respiratory symptoms listed on the questionnaire ranged from 0.5 to 0.65, which indicates that there is almost no difference compared with the results of handheld spirometry.,The present study demonstrated the efficacy of handheld spirometry as an active case-finding tool for COPD in a primary clinical setting.,This study suggested that physicians should recommend handheld spirometry for people over the age of 40, who have a smoking history of more than 10 pack-years, regardless of respiratory symptoms.,Furthermore, people who have abnormal results, determined using the FEV1/FEV6 ≤0.77 cut-off, should be referred for further conventional spirometry to confirm the diagnosis of COPD.,However, further studies within the general population are necessary to establish efficacy in the public.
| 1 |
Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder.,COPD is characterized by an increase in CD8+ T cells within the central and peripheral airways.,We hypothesized that the CD8+ T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways.,Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects.,TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood.,CD8+ T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors.,PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology.,No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects.,However, COPD patients had increased TLR4 and TLR9 expression on lung CD8+ T cells.,Exposure of CD8+ T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression.,CSC exposure also caused the activation of CD8+ T cells, resulting in the production of IL-1β, IL-6, IL-10, IL-12p70, TNFα and IFNγ.,Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFα and IL-10.,Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8+ T cells in COPD.,CD8+ T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production.,These results provide a new perspective on the role of CD8+ T cells in COPD.
|
The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium.,Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations.,We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged.,Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression.,We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease.,Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts.,Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein.,The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS.,Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect.,The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression.,Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens.
| 1 |
Outcomes in early trials of bronchoscopic lung volume reduction using endobronchial valves for the treatment of patients with advanced emphysema were inconsistent.,However improvements in patient selection with focus on excluding those with interlobar collateral ventilation and homogeneous emphysema resulted in significant benefits in the BeLieVeR-HIFi study compared with sham treated controls.,In this manuscript we present data from the control patients in the BeLieVeR-HIFi study who went on to have open label endobronchial valve treatment after completion of the clinical trial (n=12), combined with data from those in the treatment arm who did not have collateral ventilation (n=19).,Three months after treatment FEV1 increased by 27.3 (36.4)%, residual volume reduced by 0.49 (0.76) L, the 6 min walk distance increased by 32.6 (68.7) m and the St George Respiratory Questionnaire for COPD score improved by 8.2 (20.2) points.,These data extend the evidence for endobronchial valve placement in appropriately selected patients with COPD.,ISRCTN04761234; Results.
|
No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD).,Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.,Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors.,Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.,236 COPD patients from five European centres were included.,Results indicated the concept of physical activity in COPD had two domains, labelled “amount” and “difficulty”.,After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14.,Both demonstrated good model fit (person separation index >0.7).,Confirmatory factor analysis supported the bidimensional structure.,Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.,Daily and clinical visit “PROactive physical activity in COPD” instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.,Both PROactive hybrid tools are simple, valid, and reliable measures of physical activity in COPD patientshttp://ow.ly/LJqP8
| 1 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.