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Pulmonary rehabilitation increases functional capacity and quality of life and decrease exacerbations in patients with chronic obstructive pulmonary disease (COPD), but there is little knowledge of how it influences their next of kin.,To describe the experience of a multidisciplinary programme of pulmonary rehabilitation in primary health care from the perspective of the next of kin.,A descriptive qualitative study was undertaken as part of a longitudinal study comprising a multidisciplinary programme for patients with COPD where the next of kin were invited to one session.,Semi-structured interviews were conducted with 20 next of kin and analysed by qualitative content analysis.,One main theme emerged - Life still remains overshadowed by illness.,There were three sub-themes: a sense of deepened understanding; a sense of personal vulerability; and a sense of relief of burden.,The next of kin's life was still overshadowed by illness, despite the multidisciplinary programme.,Although experiencing positive outcomes two years after the programme, the next of kin expressed a need for more support.,This study has shown that next of kin could benefit from their own participation and/or that of the patient in a multidisciplinary programme of pulmonary rehabilitation.,We believe that next of kin should be offered primary health care support for the sake of their own health, but also in order to manage their informal caregiver role.,The experiences described here could form a basis for further development of interventions for next of kin of patients with COPD. | International and national bodies promote interdisciplinary care in the management of people with chronic conditions.,We examine one facilitative factor in this team-based approach - the co-location of non-physician disciplines within the primary care practice.,We used survey data from 330 General Practices in Ontario, Canada and New Zealand, as a part of a multinational study using The Quality and Costs of Primary Care in Europe (QUALICOPC) surveys.,Logistic and linear multivariable regression models were employed to examine the association between the number of disciplines working within the practice, and the capacity of the practice to offer specialized and preventive care for patients with chronic conditions.,We found that as the number of non-physicians increased, so did the availability of special sessions/clinics for patients with diabetes (odds ratio 1.43, 1.25-1.65), hypertension (1.20, 1.03-1.39), and the elderly (1.22, 1.05-1.42).,Co-location was also associated with the provision of disease management programs for chronic obstructive pulmonary disease, diabetes, and asthma; the equipment available in the centre; and the extent of nursing services.,The care of people with chronic disease is the ‘challenge of the century’.,Co-location of practitioners may improve access to services and equipment that aid chronic disease management.,The online version of this article (doi:10.1186/1471-2296-15-149) contains supplementary material, which is available to authorized users. | 1 |
The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity. | Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5) has been associated with respiratory risk.,However, evidence on the risk of chronic obstructive pulmonary disease (COPD) exacerbations is still limited.,The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations.,After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model.,In addition, the population-attributable fractions (PAFs) were also calculated, and a subgroup analysis was conducted.,Heterogeneity was assessed by I2.,In total, 59 studies were included.,In the single-pollutant model, the risks of COPD were calculated by each 10 μg/m3 increase in pollutant concentrations, with the exception of CO (100 μg/m3).,There was a significant association between short-term exposure and COPD exacerbation risk for all the gaseous and particulate pollutants.,The associations were strongest at lag0 and lag3 for gaseous and particulate air pollutants, respectively.,The subgroup analysis not only further confirmed the overall adverse effects but also reduced the heterogeneities obviously.,When 100% exposure was assumed, PAFs ranged from 0.60% to 4.31%, depending on the pollutants.,The adverse health effects of SO2 and NO2 exposure were more significant in low-/middle-income countries than in high-income countries: SO2, relative risk: 1.012 (95% confidence interval: 1.001, 1.023); and NO2, relative risk: 1.019 (95% confidence interval: 1.014, 1.024).,Short-term exposure to air pollutants increases the burden of risk of COPD acute exacerbations significantly.,Controlling ambient air pollution would provide benefits to COPD patients. | 1 |
Telerehabilitation (TR) aimed at patients with COPD has shown promising effects on symptoms, physical function, and quality of life, but little research has been conducted to understand the impact of implementation on frontline health professionals.,Therefore, the aim of this study was to examine the barriers and enablers of health professionals to online exercise-based TR in patients with COPD, to support a successful implementation process.,Semistructured individual and focus group interviews were conducted with 25 health professionals working with conventional COPD rehabilitation or TR.,Interviews were audio-taped and transcribed verbatim.,Investigator triangulation was applied during data generation.,The Theoretical Domains Framework directed the interview guide and was used as a coding framework in the analysis.,We identified six predominant domains essential in understanding the enablers and barriers of TR from a staff perspective: 1) skills, 2) professional role and identity, 3) beliefs about capabilities, 4) beliefs about consequences, 5) environmental context and resources, and 6) social influences.,We found that health professionals held both enablers and barriers important for the implementation process of TR.,TR introduces new work tasks and new ways for the health professionals to communicate and exercise with the patients, which influence their professional role and self-perceived capability.,Specific attention toward involvement of the health professionals in the decision process combined with sufficient education and skill training is highly essential to support a successful implementation of TR in clinical practice. | Clinical care components for people with COPD are recommended in guidelines if high-level evidence exists.,However, there are gaps in their implementation, and factors which act as barriers or facilitators to their uptake are not well described.,The aim of this pilot study was to explore implementation of key high-evidence COPD guideline recommendations in patients admitted to hospital with a disease exacerbation, to inform the development of a larger observational study.,This study recruited consecutive COPD patients admitted to a tertiary hospital.,Patient demographic, disease and admission characteristics were recorded.,Information about implementation of target guideline recommendations (smoking cessation, pulmonary rehabilitation referral, influenza vaccination, medication use and long-term oxygen use if hypoxaemic) was gained from medical records and patient interviews.,Interviews with hospital-based doctors examined their perspectives on recommendation implementation.,Fifteen patients (aged 76(9) years, FEV1%pred 58(15), mean(SD)) and nine doctors participated.,Referral to pulmonary rehabilitation (5/15 patients) was underutilised by comparison with other high-evidence recommendations.,Low awareness of pulmonary rehabilitation was a key barrier for patients and doctors.,Other barriers for patients were access difficulties, low perceived health benefits, and co-morbidities.,Doctors reported they tended to refer patients with severe disease and frequent hospital attendance, a finding supported by the quantitative data.,This study provides justification for a larger observational study to test the hypothesis that pulmonary rehabilitation referral is low in suitable COPD patients, and closer investigation of the reasons for this evidence-practice gap. | 1 |
Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations.,However, the magnitude of this reduction varies between studies.,Electronic databases were searched from January 2020 to May 2021.,Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria.,A modified version of the Newcastle-Ottawa Scale was used to assess study quality.,A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions.,Exacerbation reduction was compared against the COVID-19 Containment and Health Index.,A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries.,Nine studies could be included in the meta-analysis.,The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57).,Findings on the rate of community-treated exacerbations were inconclusive.,Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period.,There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).,There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations.,Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period. | Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking.,The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.,The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT.,A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only.,The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events.,Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter.,Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year.,Outcome data are obtained from medical history and record review during study visits, as well as from national registries.,BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD.,The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.,ClinicalTrials.gov, ID: NCT03566667.,Registered on 25 June 2018. | 1 |
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.,The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada.,Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified.,The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.,The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively.,The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th.,The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first.,Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.,The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation.,Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | Dyspnea is a distressing, debilitating, and near-ubiquitous symptom affecting patients with COPD.,In addition to the functional consequences of dyspnea, which include activity limitation and reduced exercise tolerance, it is important to consider its psychological impact on patients with COPD, such as onset of depression or anxiety.,Moreover, the anticipation of dyspnea itself can have a significant effect on patients’ emotions and behavior, with patients frequently self-limiting physical activity to avoid what has become the hallmark symptom of COPD.,Dyspnea is, therefore, a key target for COPD treatments.,Pharmacologic treatments can optimize respiratory mechanics, provide symptom relief, and reduce patients’ increased inspiratory neural drive to breathe.,However, it is important to acknowledge the value of non-pharmacologic interventions, such as pulmonary rehabilitation and patient self-management education, which have proven to be invaluable tools for targeting the affective components of dyspnea.,Furthermore, it is important to encourage maintenance of physical activity to optimize long-term patient outcomes.,Here, we review the physiological and psychological consequences of activity-related dyspnea in COPD, assess the efficacy of modern management strategies in improving this common respiratory symptom, and discuss key unmet clinical and research needs that warrant further immediate attention. | 1 |
Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis.,Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD.,COPD-associated osteoporosis is however extremely undertreated.,Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients.,Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described.,It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks.,Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms that significantly impair health-related quality of life.,Despite this, COPD treatment and its management are mainly based on lung function assessments.,There is increasing evidence that conventional lung function measures alone do not correlate well with COPD symptoms and their associated impact on patients’ everyday lives.,Instead, symptoms should be assessed routinely, preferably by using patient-centered questionnaires that provide a more accurate guide to the actual burden of COPD.,Numerous questionnaires have been developed in an attempt to find a simple and reliable tool to use in everyday clinical practice.,In this paper, we review three such patient-reported questionnaires recommended by the latest Global Initiative for Chronic Obstructive Lung Disease guidelines, ie, the modified Medical Research Council questionnaire, the clinical COPD questionnaire, and the COPD Assessment Test, as well as other symptom-specific questionnaires that are currently being developed. | Improvement in quality of life (QOL) has become a focus for the management of incurable chronic diseases, including chronic obstructive pulmonary disease (COPD).,This study investigates factors influencing the QOL of patients with COPD in India.,Seventy-three consecutive COPD patients visiting an outpatient pulmonary clinic underwent health-related QOL (HRQOL) assessment using the World Health Organization’s QOL abbreviated questionnaire and St George’s Respiratory Questionnaire (SGRQ).,Symptom severity and grade of dyspnea were estimated by the Chronic Lung Disease Severity Index (CLD) and Medical Research Council assessments, and patient demographic data were collected.,Spirometry and 6-minute walk tests were performed to assess lung function and functional status.,Patients with COPD showed significantly reduced HRQOL when measured by the World Health Organization’s QOL abbreviated questionnaire and the SGRQ.,CLD estimate for severity of lung disease (P < 0.001), Medical Research Council assessment for dyspnea (P < 0.01), and duration of illness (P < 0.05) showed close correlation with HRQOL.,Worsening forced expiratory volume in 1 second and 6-minute walk test results closely correlated with poorer HRQOL (P < 0.01).,No association between QOL and age, quantum of smoking, education, comorbid illnesses, or occupational exposure was found.,This study showed that Indian patients with COPD had reduced HRQOL.,Longer disease duration, patient perception of disease severity, and worsening dyspnea impacted negatively on HRQOL. | 1 |
Symptomatic relief is an important treatment goal for patients with COPD.,To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines.,The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need.,The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation.,The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.,This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international).,Subjects completed the E-RS as part of a daily eDiary.,Tests of reliability, validity, and responsiveness were conducted in each dataset.,In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74).,RS-Total scores correlated significantly with the following criterion variables (Spearman’s rho; p < 0.01, all comparisons listed here): FEV1% predicted (−0.19, −0.14, −0.15); St.,George’s Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (−0.30, −0.14) and incremental shuttle walk (ISWT) (−0.18) tests.,Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity.,RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001).,RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001).,Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.,Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.,MPEX: NCT00739648; AZ1: NCT00949975; AZ 2: NCT01023516,The online version of this article (doi:10.1186/s12931-014-0124-z) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) has traditionally been considered an inexorably progressive disease, associated with a constant increase of symptoms that occur as the forced expiratory volume in 1 second (FEV1) worsens, only intermittently interrupted by exacerbations.,However, this paradigm has been challenged in recent decades by the available evidence.,Recent studies have pointed out that COPD-related symptoms are not consistently perceived by patients in the same way, showing not only seasonal variation, but also changes in symptom perception during a week or even within a single day.,According to the available data, patients experience the biggest increase in respiratory symptoms during the first hours of the early morning, followed by the nighttime.,This variation over time is of considerable importance, since it impacts on daily life activities and health-related quality of life, as measured by a recently developed ad hoc questionnaire.,Additionally, recent clinical trials have suggested that the use of rapid-onset long-acting bronchodilators may have an impact on morning symptoms, despite their current use as maintenance treatment for a determined period.,Although this hypothesis is to be validated in future long-term clinical trials comparing fast-onset versus slow-onset inhaled drugs in COPD, it may bring forward a new concept of long-term bronchodilator therapy.,At the present time, the two available long-acting, fast-onset bronchodilators used in the treatment of COPD are formoterol and the recently marketed indacaterol.,Newer drugs have also been shown to have a rapid onset of action in preclinical studies.,Health care professionals caring for COPD patients should consider this variation in the perception of symptoms during their clinical interview as a potential new target in the long-term treatment plan. | 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 | Challenges associated with COPD increase patients’ risk of physical immobility and emotional distress, perpetuating a cycle of symptomatic living that hinders patients’ self-management and adherence to a treatment regimen.,There is limited evidence available on how discrete behavioral and health risk factors contribute to the physical and mental distress experienced by people living with COPD.,This secondary data analysis of 2016 Behavioral Risk Factor Surveillance System (BRFSS) sought to identify subgroups of people with COPD who were at the highest risk for physical and mental distress.,We selected 16 relevant risk indicators in four health-related domains - 1) health risk behaviors, 2) lack of preventive vaccinations, 3) limited health care access, and 4) comorbidities - as predictors of physical and mental health-related quality of life (HRQoL) in the COPD population.,Latent class modeling (LCM) was applied to understand how various health-related indicators in these four health domains influenced reports of physical and/or mental distress.,The majority of BRFSS respondents who reported a COPD diagnosis experienced physical (53.76%) and/or mental (58.23%) distress in the past 14 days.,Frequent physical and mental distress were more common in females with COPD in the 45-64 years age group, who were also identified as white and in the lower socioeconomic group.,Respondents with intermediate- to high-risk behaviors, intermediate to multiple comorbidities, limited access to health care, and intermediate to low use of preventive vaccinations were more likely to report frequent physical distress compared to the low-risk respondents.,Similarly, respondents with high-risk behaviors, intermediate to multiple comorbidities, and low use of preventive vaccinations were more likely to report frequent mental distress than the low-risk group.,This analysis of updated 2016 BRFSS data identified high-risk Americans with COPD who could benefit from disease management and secondary/tertiary health promotion interventions that may improve HRQoL.,Future research should address noted disparities in risk factors, particularly among low socioeconomic populations living with COPD. | 1 |
To determine the underdiagnosis rate in new COPD cases at the end of a nine-year follow-up period-in the study designated "Projeto Latino-Americano de Investigação em Obstrução Pulmonar" (PLATINO, Latin-American Pulmonary Obstruction Investigation Project)-and compare that with the underdiagnosis rate during the initial phase of the study, as well as to identify the clinical features exhibited by the subjects who were not diagnosed until the end of the follow-up phase.,The study population comprised the 1,000 residents of the city of São Paulo, Brazil, who took part in the PLATINO study.,Of those, 613 participated in the follow-up phase, during which the subjects were assessed with the same instruments and equipment employed in the initial phase of the study.,We used the chi-square test or the independent sample t-test to analyze the underdiagnosis rate and to identify the characteristics of the subjects who were not diagnosed until the end of the follow-up phase.,The underdiagnosis rate for new COPD cases at the end of the nine-year follow-up period was 70.0%.,The underdiagnosis rate during the follow-up phase was 17.5% lower than that reported for the initial phase of the study.,The subjects who were not diagnosed until the end of the follow-up phase presented with fewer respiratory symptoms, better pulmonary function, and less severe disease than did those previously diagnosed with COPD.,The underdiagnosis rate for new COPD cases was lower in the follow-up phase of the study than in the initial phase.,The subjects who were not diagnosed until the end of the follow-up phase of the PLATINO study presented with the same clinical profile as did those who were not diagnosed in the initial phase.,These findings underscore the need for spirometry in order to confirm the diagnosis of COPD and provide early intervention.,Determinar a taxa de subdiagnóstico em novos casos de DPOC em uma amostra de pacientes após nove anos de seguimento do estudo "Projeto Latino-Americano de Investigação em Obstrução Pulmonar" (PLATINO) e compará-la à taxa de subdiagnóstico obtida na fase inicial do estudo, assim como identificar as características clínicas dos indivíduos subdiagnosticados na fase de seguimento.,A população desse estudo foi composta por 1.000 residentes na cidade de São Paulo que fizeram parte do estudo PLATINO.,Desses, 613 indivíduos participaram da fase de seguimento.,Os indivíduos foram avaliados utilizando-se os mesmos instrumentos e equipamentos na fase inicial do estudo.,O teste do qui-quadrado ou o teste t para amostras independentes foi utilizado para analisar a taxa de subdiagnóstico e identificar as características dos indivíduos subdiagnosticados durante a fase de seguimento.,A taxa de subdiagnóstico para novos casos da DPOC após nove anos de acompanhamento foi de 70,0%.,A taxa de subdiagnóstico na fase de seguimento foi 17,5% menor que a da fase inicial do estudo.,Os indivíduos subdiagnosticados na fase de seguimento apresentavam poucos sintomas respiratórios, função pulmonar mais preservada e menor gravidade da doença do que aqueles previamente diagnosticados com DPOC.,A taxa de subdiagnóstico na fase de seguimento foi menor que a da fase inicial do estudo.,Os indivíduos subdiagnosticados na fase de seguimento do estudo PLATINO apresentavam o mesmo perfil clínico daqueles subdiagnosticados na fase inicial.,Esses achados reforçam a necessidade da utilização da espirometria para o diagnóstico de DPOC e possibilitar a intervenção precoce. | During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data.,Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer.,Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators.,The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted.,They recorded pedometer data on a median 198 days (IQR 134-353).,At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min.,Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045).,Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001).,Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001).,Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).,Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002).,COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. | 1 |
Most interventions aimed at reducing hospitalizations and emergency department (ED) visits in patients with chronic obstructive pulmonary disease (COPD) have employed resource-intense programs in high-risk individuals.,Although COPD is a progressive disease, little is known about the effectiveness of proactive interventions aimed at preventing hospitalizations and ED visits in the much larger population of low-risk (no known COPD-related hospitalizations or ED visits in the prior year) patients, some of whom will eventually become high-risk.,We tested the effect of a simple educational and self-efficacy intervention (n = 2243) versus usual care (n = 2182) on COPD/breathing-related ED visits and hospitalizations in a randomized study of low-risk patients at three Veterans Affairs (VA) medical centers in the upper Midwest.,Administrative data was used to track VA admissions and ED visits.,A patient survey was used to determine health-related events outside the VA.,Rates of COPD-related VA hospitalizations in the education and usual care group were not significantly different (3.4 versus 3.6 admissions per 100 person-years, respectively; 95% CI of difference −1.3 to 1.0, P = 0.77).,The much higher patient-reported rates of non-VA hospitalizations for breathing-related problems were lower in the education group (14.0 versus 19.0 per 100 person-years; 95% CI −8.6 to −1.4, P = 0.006).,Rates of COPD-related VA ED visits were not significantly different (6.8 versus 5.3; 95% CI −0.1 to 3.0, P = 0.07), nor were non-VA ED visits (32.4 versus 36.5; 95% CI −9.3 to 1.1, P = 0.12).,All-cause VA admission and ED rates did not differ.,Mortality rates (6.9 versus 8.3 per 100 person-years, respectively; 95% CI −3.0 to 0.4, P = 0.13) did not differ.,An educational intervention that is practical for large numbers of low-risk patients with COPD may reduce the rate of breathing-related hospitalizations.,Further research that more closely tracks hospitalizations to non-VA facilities is needed to confirm this finding. | The COPD Assessment Test (CAT™) is a new short health status measure for routine use.,New questionnaires require reference points so that users can understand the scores; descriptive scenarios are one way of doing this.,A novel method of creating scenarios is described.,A Bland and Altman plot showed a consistent relationship between CAT scores and scores obtained with the St George's Respiratory Questionnaire for COPD (SGRQ-C) permitting a direct mapping process between CAT and SGRQ items.,The severity associated with each CAT item was calculated using a probabilistic model and expressed in logits (log odds of a patient of given severity affirming that item 50% of the time).,Severity estimates for SGRQ-C items in logits were also available, allowing direct comparisons with CAT items.,CAT scores were categorised into Low, Medium, High and Very High Impact.,SGRQ items of corresponding severity were used to create scenarios associated with each category.,Each CAT category was associated with a scenario comprising 12 to 16 SGRQ-C items.,A severity 'ladder' associating CAT scores with exemplar health status effects was also created.,Items associated with 'Low' and 'Medium' Impact appeared to be subjectively quite severe in terms of their effect on daily life.,These scenarios provide users of the CAT with a good sense of the health impact associated with different scores.,More generally they provide a surprising insight into the severity of the effects of COPD, even in patients with apparently mild-moderate health status impact. | 1 |
The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses.,Also, miRNAs are dysregulated in smoking-associated diseases.,We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks.,After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant.,Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA.,In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD.,Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c.,Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD. | Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available.,Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease.,Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice.,We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects.,Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both.,C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both.,Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar and vascular morphometry) as well as the heart ratio were determined after 6 months of tobacco smoke exposure.,In addition, the number of alveolar macrophages in the respective lungs was counted.,Preventive treatment with Tadalafil, Piclamilast or a combination of both almost completely prevented the development of emphysema, the increase in lung compliance, tidal volume, structural remodeling of the lung vasculature, right ventricular systolic pressure, and right ventricular hypertrophy induced by cigarette smoke exposure.,Single, but not combination treatment prevented or reduced smoke-induced increase in alveolar macrophages.,Cigarette smoke-induced emphysema and PH could be prevented by inhibition of the phosphodiesterases 4 and 5 in mice. | 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) | This study aims to (1) examine the variation in implementation of a 2-year chronic obstructive pulmonary disease (COPD) management programme called RECODE, (2) analyse the facilitators and barriers to implementation and (3) investigate the influence of this variation on health outcomes.,Implementation variation among the 20 primary-care teams was measured directly using a self-developed scale and indirectly through the level of care integration as measured with the Patient Assessment of Chronic Illness Care (PACIC) and the Assessment of Chronic Illness Care (ACIC).,Interviews were held to obtain detailed information regarding the facilitators and barriers to implementation.,Multilevel models were used to investigate the association between variation in implementation and change in outcomes.,The teams implemented, on average, eight of the 19 interventions, and the specific package of interventions varied widely.,Important barriers and facilitators of implementation were (in)sufficient motivation of healthcare provider and patient, the high starting level of COPD care, the small size of the COPD population per team, the mild COPD population, practicalities of the information and communication technology (ICT) system, and hurdles in reimbursement.,Level of implementation as measured with our own scale and the ACIC was not associated with health outcomes.,A higher level of implementation measured with the PACIC was positively associated with improved self-management capabilities, but this association was not found for other outcomes.,There was a wide variety in the implementation of RECODE, associated with barriers at individual, social, organisational and societal level.,There was little association between extent of implementation and health outcomes. | 1 |
COPD is characterized by a pulmonary and systemic inflammatory process.,Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations.,The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count.,We performed a systematic literature review using the PRISMA statement.,Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls.,Compared with controls, COPD patients had significantly higher NLR values.,We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients.,Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively).,Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity.,The NLR is an independent predictor of in-hospital and late mortality after exacerbation.,In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR. | COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function.,Inflammation is central for the development of COPD.,Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways.,The contribution of resident airway structural cells to the inflammatory process is also important in COPD.,Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia.,Persistent airway inflammation might contribute to airway remodeling and small airway obstruction.,However, the underlying mechanisms remain unclear.,In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling. | 1 |
Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression.,We aimed to assess this in a prospective observational study.,The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD).,Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline.,Effect modification by blood eosinophils was studied through interaction terms.,Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS.,In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001).,This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.,Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS.,More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function. | COPD is associated with a large disease burden.,The use of dual (two maintenance treatments) and triple (combination of any three treatments) therapy has shown efficacy for symptom relief; however, some patients with COPD remain symptomatic despite these therapies.,This study assessed the scope and magnitude of the symptomatic burden for patients with COPD receiving dual or triple therapy.,Cross-sectional data from three Adelphi COPD surveys (2013-2016) conducted in the USA, Europe, Japan, and China were analyzed for patients with COPD and forced expiratory volume in 1 second ≤65% receiving dual or triple therapy for ≥3 months.,Physicians completed clinical and disease characteristic forms for identified patients.,Corresponding patients completed questionnaires that included validated survey instruments to assess adherence and symptom impact.,Descriptive statistics are reported.,Our analysis included 690 patients (mean age 68.2 years; 73.3% male); 41.4% and 58.6% were receiving dual and triple therapy, respectively.,Most patients had dyspnea with substantial disability (modified Medical Research Council dyspnea scale rating ≥2, 56.3%; large health status impairment from symptoms, COPD Assessment Test score >20, 64.4%).,A large symptom burden was observed, even for patients highly adherent to treatment (Morisky Medication Adherence Scale 8, 30.3% [185/612]), of whom 62.1% still had a COPD Assessment Test score >20.,Sensitivity analyses of patients regardless of their forced expiratory volume in 1 second status and of those receiving treatment for >6 months both reported similar results.,Although patients who consult their physicians more frequently than average may be overrepresented because of the observational design of this study, we report that unmet needs remain for patients with COPD, despite the use of dual or triple therapy.,A percentage of patients with COPD reported major symptom burden affecting their daily living and causing a large impairment in the health status, regardless of treatment adherence. | 1 |
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. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD).,COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments.,The differential effects of TS, BS or their combined exposure have not been well characterized yet.,This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination.,Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS.,Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups.,TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01).,Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients.,CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01).,Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05).,There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures.,The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant. | Pixin Ran, Nanshan Zhong, and colleagues report that cleaner cooking fuels and improved ventilation were associated with better lung function and reduced COPD among a cohort of villagers in Southern China.,Please see later in the article for the Editors' Summary,Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning.,The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.,A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China.,Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011.,That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes.,Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions.,Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders.,The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y).,The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05).,The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.,Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD.,Chinese Clinical Trial Register ChiCTR-OCH-12002398,Please see later in the article for the Editors' Summary,Nearly 3 billion people in developing countries heat their homes and cook by burning biomass-wood, crop waste, and animal dung-in open fires and leaky stoves.,Burning biomass this way releases pollutants into the home that impair lung function and that are responsible for more than a million deaths from chronic obstructive pulmonary disease (COPD) every year.,COPD is a group of diseases that interfere with breathing.,Normally, air is breathed in through the nose or mouth and travels down the windpipe into two bronchial tubes (airways) in the lungs.,These tubes branch into smaller tubes (bronchioles) that end in bunches of tiny air sacs (alveoli).,Oxygen in the air passes through the thin walls of these sacs into small blood vessels and is taken to the heart for circulation round the body.,The two main types of COPD-chronic bronchitis (long-term irritation and swelling of the bronchial tubes) and emphysema (damage to the walls of the alveoli)-make it hard for people to breathe.,Most people with COPD have both chronic bronchitis and emphysema, both of which are caused by long-term exposure to cigarette smoke, indoor air pollution, and other lung irritants.,Symptoms of COPD include breathlessness during exercise and a persistent cough that produces large amounts of phlegm (mucus).,There is no cure for COPD, but drugs and oxygen therapy can relieve its symptoms, and avoiding lung irritants can slow disease progression.,Exposure to indoor air pollution has been associated with impaired lung function and COPD in several studies.,However, few studies have assessed the long-term effects on lung function and on the incidence of COPD (the proportion of a population that develops COPD each year) of replacing biomass with biogas (a clean fuel produced by bacterial digestion of biodegradable materials) for cooking and heating, or of improving kitchen ventilation during cooking.,Here, the researchers undertook a nine-year prospective cohort study in rural southern China to investigate whether these interventions are associated with any effects on lung function and on the incidence of COPD.,A prospective cohort study enrolls a group of people, determines their characteristics at baseline, and follows them over time to see whether specific characteristic are associated with specific outcomes.,The researchers offered nearly 1,000 people living in 12 villages in southern China access to biogas and to improved kitchen ventilation.,All the participants, who adopted these interventions according to personal preferences, completed a questionnaire about their smoking habits and occupational exposure to pollutants and had their lung function measured using a spirometry test at the start and end of the study.,Some participants also completed a questionnaire and had their lung function measured three and six years into the study.,Finally, the researchers measured levels of indoor air pollution in a randomly selected subset of homes at the end of the study to confirm that the interventions had reduced indoor air pollution.,Compared with non-use, the use of clean fuels and of improved ventilation were both associated with a reduction in the decline in lung function over time after adjusting for known characteristics that affect lung function, such as smoking.,The use of both interventions reduced the decline in lung function more markedly than either intervention alone, and the benefits of using the interventions increased with length of use.,Notably, the combined use of both interventions reduced the risk of COPD occurrence among the study participants.,These findings suggest that, among people living in rural southern China, the combined interventions of use of biogas instead of biomass and improved kitchen ventilation were associated with a reduced decline in lung function over time and with a reduced risk of COPD.,Because participants were not randomly allocated to intervention groups, the people who adopted the interventions may have shared other unknown characteristics (confounders) that affected their lung function (for example, having a healthier lifestyle).,Thus, it is not possible to conclude that either intervention actually caused a reduction in the decline in lung function.,Nevertheless, these findings suggest that the use of biogas as a substitute for biomass for cooking and heating and improvements in kitchen ventilation might lead to a reduction in the global burden of COPD associated with biomass smoke.,Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001621.,The US National Heart, Lung, and Blood Institute provides detailed information for the public about COPD,The US Centers for Disease Control and Prevention provides information about COPD and links to other resources (in English and Spanish),The UK National Health Service Choices website provides information for patients and carers about COPD, personal stories, and links to other resources,The British Lung Foundation, a not-for-profit organization, provides information about COPD in several languages,The Global Initiative for Chronic Obstructive Lung Disease works to improve prevention and treatment of COPD around the world,The World Health Organization provides information about all aspects of indoor air pollution and health (in English, French, and Spanish),MedlinePlus provides links to other information about COPD (in English and Spanish) | 1 |
The 2017 GOLD ABCD classification shifts patients from groups C-D to A-B.,Group A was the most widely distributed group in several studies.,It would be useful to understand the characteristics for group A patients, but little has been reported concerning these issues.,This was a multicenter cross-sectional study using the COPD Assessment in Practice study database from 15 primary or secondary care facilities in Japan.,We investigated the clinical characteristics of group A by stratification according to a mMRC grade 0 or 1.,In 1,168 COPD patients, group A patients accounted for approximately half of the patients.,Compared with the groups B-D, group A was younger and had a higher proportion of males, higher pulmonary function, and higher proportion of monotherapy with long-acting muscarinic antagonist or long-acting β-agonist.,The prevalence of mMRC grade 1 patients was about two-thirds of group A.,Compared with the mMRC 0 patients, mMRC 1 patients showed a tendency to have a higher proportion of exacerbations (P=0.054) and had a significantly lower pulmonary function.,Regardless of the mMRC grade, 60% of group A patients were treated with monotherapy of long-acting muscarinic antagonist or long-acting β-agonist.,Group A patients accounted for approximately half of the patients, and they were younger, had higher pulmonary function, and had lower pharmacotherapy intensity compared with groups B-D.,By stratifying according to the mMRC grade 0 or 1 in group A patients, there were differences in the exacerbation risk and airflow limitation. | Chronic obstructive pulmonary disease (COPD) can greatly impact the quality of life by limiting patients’ activities.,However, data on impact of symptomatic burden on the health care resource utilization (HCRU) and employment in COPD are lacking.,We examined the association between COPD Assessment Test (CAT) score and direct/indirect costs associated with HCRU and work productivity.,Data from >2,100 patients with COPD consulting for routine care were derived from respiratory disease-specific programs in Europe, the USA and China.,Questionnaires, including CAT and Work Productivity and Activity Impairment (WPAI), were used to collect the past and current disease status data and HCRU characteristics from physicians (general practitioners/specialists) and patients.,A regression approach was used to quantify the association of CAT with HCRU and WPAI variables.,CAT score was modeled as a continuous independent variable (range: 0-40).,Ninety percent of patients with COPD had a CAT score ≥10.,Short-acting therapy and maintenance bronchodilator monotherapy, respectively, were currently prescribed to patients with CAT scores of 10-19 (5.8% and 27.6%), 20-29 (5.1% and 13.1%) and 30-40 (2.8% and 6.6%).,Prescribing of maintenance bronchodilator dual therapy was low across the CAT score groups (0-9, 7.8%; 10-19, 6.4%; 20-29, 5.9%; 30-40, 4.4%), whereas maintenance triple combination therapy was prescribed more commonly in patients with higher CAT scores (0-9, 16.1%; 10-19, 23.2%; 20-29, 25.9%; 30-40, 35.5%).,Increasing CAT scores were significantly associated with a higher frequency of primary care physician visits (P<0.001), pulmonologist visits (P=0.007), exacerbations requiring hospitalization (P<0.001) and WPAI scores (P<0.001).,Most patients with COPD presented with high symptom levels, despite being treated for COPD.,Increasing symptom burden was associated with increasing HCRU and had a detrimental impact on work productivity. | 1 |
Cigarette smoke is the main risk factor of pulmonary emphysema development, which is characterized by alveolar wall destruction.,Mitochondria are important for alveolar type II (ATII) cell metabolism due to ATP generation.,We isolated ATII cells from control non-smoker and smoker organ donors, and after lung transplant of patients with emphysema to determine mitochondrial function, dynamics and mitochondrial (mt) DNA damage.,We found high mitochondrial superoxide generation and mtDNA damage in ATII cells in emphysema.,This correlated with decreased mtDNA amount.,We also detected high TOP1-cc and low TDP1 levels in mitochondria in ATII cells in emphysema.,This contributed to the decreased resolution of TOP1-cc leading to accumulation of mtDNA damage and mitochondrial dysfunction.,Moreover, we used lung tissue obtained from areas with mild and severe emphysema from the same patients.,We found a correlation between the impaired fusion and fission as indicated by low MFN1, OPA1, FIS1, and p-DRP1 levels and this disease severity.,We detected lower TDP1 expression in severe compared to mild emphysema.,We found high DNA damage and impairment of DNA damage repair in mitochondria in ATII cells isolated from emphysema patients, which contribute to abnormal mitochondrial dynamics.,Our findings provide molecular mechanisms of mitochondrial dysfunction in this disease.,This work was supported by National Institutes of Health (NIH) grant R01 HL118171 (B.K.) and the Catalyst Award from the American Lung Association (K.B.). | Cardiovascular disease (CVD) is a major cause of death in smokers, particularly in those with chronic obstructive pulmonary disease (COPD).,Circulating endothelial progenitor cells (EPC) are required for endothelial homeostasis, and their dysfunction contributes to CVD.,To investigate EPC dysfunction in smokers, we isolated and expanded blood outgrowth endothelial cells (BOEC) from peripheral blood samples from healthy nonsmokers, healthy smokers, and COPD patients.,BOEC from smokers and COPD patients showed increased DNA double-strand breaks and senescence compared to nonsmokers.,Senescence negatively correlated with the expression and activity of sirtuin-1 (SIRT1), a protein deacetylase that protects against DNA damage and cellular senescence.,Inhibition of DNA damage response by silencing of ataxia telangiectasia mutated (ATM) kinase resulted in upregulation of SIRT1 expression and decreased senescence.,Treatment of BOEC from COPD patients with the SIRT1 activator resveratrol or an ATM inhibitor (KU-55933) also rescued the senescent phenotype.,Using an in vivo mouse model of angiogenesis, we demonstrated that senescent BOEC from COPD patients are dysfunctional, displaying impaired angiogenic ability and increased apoptosis compared to cells from healthy nonsmokers.,Therefore, this study identifies epigenetic regulation of DNA damage and senescence as pathogenetic mechanisms linked to endothelial progenitors' dysfunction in smokers and COPD patients.,These defects may contribute to vascular disease and cardiovascular events in smokers and could therefore constitute therapeutic targets for intervention. | 1 |
COPD exacerbations are associated with neutrophilic airway inflammation.,Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways.,We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections.,Blood and sputum were collected from 9 COPD subjects and 10 smoking and age-matched control subjects at baseline, and neutrophil expression of the adhesion molecules and activation markers measured using flow cytometry.,The markers examined were CD62L and CD162 (mediating initial steps of neutrophil rolling and capture), CD11a and CD11b (required for firm neutrophil adhesion), CD31 and CD54 (involved in neutrophil transmigration through the endothelial monolayer) and CD63 and CD66b (neutrophil activation markers).,Subjects were then experimentally infected with rhinovirus-16 and repeat samples collected for neutrophil analysis at post-infection time points.,At baseline there were no differences in adhesion molecule expression between the COPD and non-COPD subjects.,Expression of CD11a, CD31, CD62L and CD162 was reduced on sputum neutrophils compared to blood neutrophils.,Following rhinovirus infection expression of CD11a expression on blood neutrophils was significantly reduced in both subject groups.,CD11b, CD62L and CD162 expression was significantly reduced only in the COPD subjects.,Blood neutrophil CD11b expression correlated inversely with inflammatory markers and symptom scores in COPD subjects.,Following rhinovirus infection neutrophils with higher surface expression of adhesion molecules are likely preferentially recruited to the lungs.,CD11b may be a key molecule involved in neutrophil trafficking in COPD exacerbations. | Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function.,This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers.,We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.,Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33.,COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287).,The control group had an FEV1/FVC ratio ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 20 pack years of smoking.,Logistic and linear regressions were used for the analysis.,Age, sex, and smoking status were considered as potential confounders.,Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007).,Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25-75 (p values 0.001 - 0.02).,S2 was associated with FEV1/FVC ratio (p < 0.05).,The association between S1 and residual volume revealed a trend toward significance (p value < 0.07).,Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.,Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers.,Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life.,Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays.,The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients.,We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations.,78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George’s Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test.,Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time.,Correlations between the CAT and other measurements were examined.,After 7 days’ therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001).,Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001).,The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05).,The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = -0.101, P > 0.05).,No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).,The CAT is associate with the changes of systemic inflammation following COPD exacerbations.,Moreover, the CAT is responsive to the treatments, similar to other measures such as SGRQ, mMRC dyspnea scale and pulmonary function.,Therefore, the CAT is a potentially useful instrument to assess the efficacy of treatments following COPD exacerbations. | The identification of biological markers in order to assess different aspects of COPD is an area of growing interest.,The objective of this study was to investigate whether levels of procalcitonin (PCT), C-reactive protein (CRP), and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis.,We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia.,A serum sample was collected from each patient at the time of being included in the study.,A second sample was also collected 1 month later from 23 patients in the exacerbation group.,We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group.,PCT and CRP were measured using an immunofluorescence assay.,Neopterin levels were measured using a competitive immunoassay.,PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001).,For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased.,Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP.,No significant differences were found when comparing biomarker levels according to the Gram result: PCT (P = 0.191), CRP (P = 0.080), and neopterin (P = 0.109).,However, median values of PCT and CRP were high for Streptococcus pneumoniae, Staphylococcus aureus, and enterobacteria.,All biomarkers were higher in patients who died within 1 month after the sample collection than in patients who died later on.,According to our results, biomarker levels vary depending on the clinical status.,However, the identification of the etiology of infectious exacerbation by means of circulating biomarkers is encouraging, but its main disadvantage is the absence of a microbiological gold standard, to definitively demonstrate their value.,High biomarker levels during an exacerbation episode correlate with the short-term prognosis, and therefore their measurement can be useful for COPD management. | 1 |
Fibrinogen is a marker of systemic inflammation and may be important in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD).,We used baseline data from Atherosclerosis Risk in Communities and Cardiovascular Health Studies to determine the relation between fibrinogen levels and COPD and to examine how fibrinogen levels at baseline affected outcomes of death, development of COPD, lung function decline, and COPD-hospitalizations.,Our study sample included 20,192 subjects, of whom 2995 died during the follow-up period.,The mean fibrinogen level was 307.6 mg/dL and 10% of the sample had levels >393.0 mg/dL.,Subjects with Stage 3 or 4 COPD were more likely to have a fibrinogen level >393.0 mg/dL (odds ratio 2.28, 95% confidence interval [CI]: 1.79-2.95).,In the longitudinal adjusted models, fibrinogen levels >393 mg/dL predicted mortality (hazards ratio 1.54, 95% CI: 1.39-1.70), COPD-related hospitalization (hazards ratio 1.45, 95% CI: 1.27-1.67), and incident Stage 2 COPD (odds ratio 1.36, 95% CI: 1.07-1.74).,Similar findings were seen with continuous fibrinogen levels.,In the Atherosclerosis Risk in Communities/Cardiovascular Health Studies cohort data, higher fibrinogen levels are predictors of mortality, COPD-related hospitalizations, and incident Stage 2 COPD. | Recent studies described association between chronic obstructive pulmonary disease (COPD) and increased risk of cardiovascular diseases (CVD).,In their analysis none of these studies accounted for sociodemographic factors, health behaviors, and patient comorbidities simultaneously.,To study whether COPD diagnosis is an independent risk factor for CVD.,Subjects aged 40 years and older (N = 18,342) from the sample adult file of the 2002 National Health Interview Survey (NHIS) were included in the analysis.,Chi-squared tests and odds ratios (OR) were utilized to compare the data.,Multiple logistic regression was employed to analyze the association between COPD and CVD with simultaneous control for sociodemographic factors (age, gender, race, marital status, education, income), health behaviors (tobacco use, alcohol consumption, physical activity), and patient comorbidities (diabetes, hypertension, high cholesterol, and obesity).,The analysis employed NHIS sampling weights to generate data representative of the entire US population.,The COPD population had increased prevalence of CVD (56.5% vs 25.6%; P < 0.0001).,Adjusted logistic regression showed that COPD patients (N = 958) were at higher risk of having coronary heart disease (OR = 2.0, 95% CI: 1.5-2.5), angina (OR = 2.1, 95% CI: 1.6-2.7), myocardial infarction (OR = 2.2, 95% CI: 1.7-2.8), stroke (OR = 1.5, 95% CI: 1.1-2.1), congestive heart failure (OR = 3.9, 95% CI: 2.8-5.5), poor circulation in lower extremities (OR = 2.5, 95% CI: 2.0-3.0), and arrhythmia (OR = 2.4, 95% CI: 2.0-2.8).,Overall, the presence of COPD increased the odds of having CVD by a factor of 2.7 (95% CI: 2.3-3.2).,These findings support the conclusion that COPD is an independent risk factor for CVD. | 1 |
A genetic contribution to develop chronic obstructive pulmonary disease (COPD) is well established.,However, the specific genes responsible for enhanced risk or host differences in susceptibility to smoke exposure remain poorly understood.,The goal of this review is to provide a comprehensive literature overview on the genetics of COPD, highlight the most promising findings during the last few years, and ultimately provide an updated COPD gene list.,Candidate gene studies on COPD and related phenotypes indexed in PubMed before January 5, 2012 are tabulated.,An exhaustive list of publications for any given gene was looked for.,This well-documented COPD candidate-gene list is expected to serve many purposes for future replication studies and meta-analyses as well as for reanalyzing collected genomic data in the field.,In addition, this review summarizes recent genetic loci identified by genome-wide association studies on COPD, lung function, and related complications.,Assembling resources, integrative genomic approaches, and large sample sizes of well-phenotyped subjects is part of the path forward to elucidate the genetic basis of this debilitating disease. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Diesel exhaust particles (DEPs) lead to elevation of reactive oxygen species, which can activate the nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain 3 (NLRP3)-inf lammasome.,In this study, we elucidated whether NLRP3 -inf lammasome is activated by DEPs and whether antioxidants (N-acetylcysteine [NAC]) could inhibit such activation.,RAW 264.7 cells and ex vivo lung tissues explants obtained from elastase-induced emphysema animal models were stimulated with cigarette smoking extract (CSE), DEPs, and lipopolysaccharide, and levels of interleukin-1β (IL-1β), caspase-1 and nucleotide-binding oligomerization domain-like receptor (NLR) family members containing the pyrin domain (NLRP3)-inflammasome were assessed by Western blotting and immunohistochemistry.,NAC and caspase-1 inhibitor suppressed CSE- and DEP-induced secretion of IL-1β in RAW 264.7 cells.,The expression levels of the NLRP3-inflammasome and caspase-1 were upregulated in RAW 264.7 cells by stimulation with CSE and DEPs and were inhibited by NAC.,CSE and DEPs increased the secretion of IL-1β in lung tissues from both the normal and elastase-induced emphysema groups.,The secretion of IL-1β by CSE and DEPs was increased in the elastin-induced emphysema group more than that in the normal group (CSE: 309 ± 19 pg/mL vs. 151 ± 13 pg/mL, respectively, p < 0.05; DEP: 350 ± 24 pg/mL vs. 281 ± 15 pg/mL, respectively, p < 0.05).,NAC inhibited CSE- and DEP-induced IL-1β secretion in both the normal and elastase-induced emphysema groups.,NLRP3-inflammasome expression as determined by immunohistochemistry was increased by CSE and DEPs in both the normal and elastin-induced emphysema groups, and was suppressed by NAC.,The NLRP3-inf lammasome is activated by DEPs in ex vivo tissue explants from elastase-induced emphysema animal model, and this activation is inhibited by NAC. | Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible.,The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations.,Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD.,Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective.,Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.,This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD. | 1 |
Current guidelines recommend inhaled pharmacologic therapy as the preferred route of administration for treating COPD.,Bronchodilators (β2-agonists and antimuscarinics) are the mainstay of pharmacologic therapy in patients with COPD, with long-acting agents recommended for patients with moderate to severe symptoms or those who are at a higher risk for COPD exacerbations.,Dry powder inhalers and pressurized metered dose inhalers are the most commonly used drug delivery devices, but they may be inadequate in various clinical scenarios (eg, the elderly, the cognitively impaired, and hospitalized patients).,As more drugs become available in solution formulations, patients with COPD and their caregivers are becoming increasingly satisfied with nebulized drug delivery, which provides benefits similar to drugs delivered by handheld inhalers in both symptom relief and improved quality of life.,This article reviews recent innovations in nebulized drug delivery and the important role of nebulized therapy in the treatment of COPD. | 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 | 1 |
Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients.,Bacterial infection causes increased airway neutrophilic inflammation.,The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain.,We tested the hypothesis that bacterial load and eosinophil counts are inversely related.,COPD patients were seen at stable state and exacerbation onset.,Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae.,PPM positive was defined as total load ≥1 × 104copies/ml.,Sputum and whole blood were analysed for differential cell counts.,At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs.,1.25% respectively, p = 0.01).,Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs.,0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.,These findings indicate an inverse relationship between bacterial infection and eosinophil counts.,Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.,The online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users. | Eosinophilic COPD appears to be a distinct patient subgroup with an increased corticosteroid response.,Eosinophilic COPD has been labelled as part of the asthma COPD overlap syndrome (ACOS).,We compared the clinical characteristics of eosinophilic COPD patients (without any clinical history of asthma) and COPD patients with a childhood history of asthma.,COPD patients with asthma were characterised by more allergies and more exacerbations, but less eosinophilic inflammation.,While terms such as “ACOS” are used to “lump” patients together, we report distinct differences between eosinophilic COPD and COPD patients with asthma, and propose that these groups should be split rather than lumped. | 1 |
Respiratory inhalers, which directly deliver medication to the airway, are important for controlling symptoms and preventing exacerbations of chronic obstructive pulmonary disease (COPD).,The inhaler misuse rate of patients with COPD in Taiwan is unclear.,In this study, the inhaler techniques and patient characteristics associated with incorrect inhaler techniques among patients with COPD were evaluated.,This cross-sectional study enrolled 298 patients with COPD (mean age 72.10 years) who used at least one inhaler device.,The following five types of inhalers were included: metered-dose inhaler (MDI) with spacer, Diskus®, Turbuhaler®, Respimat®, and Breezhaler®.,The inhaler technique was evaluated step by step.,Misuse of an individual inhaler was defined as an error in at least one step.,The sociodemographic characteristics, vision, hearing ability, type and number of inhalers, and inhaler-related knowledge of these patients were recorded.,The misuse rates of the five types of inhalers ranged from 65.00% to 87.89%.,The Respimat inhaler was the most likely to be assembled incorrectly.,The steps that were most commonly performed incorrectly were “breathing out fully” and “holding breath”.,In the logistic regression analysis, poor hearing was related to misuse of the MDI with spacer (adjusted odds ratio [aOR] 9.85; 95% CI 1.40-69.30); the number of acute exacerbations was related to misuse of Breezhaler (aOR 4.07; 95% CI 1.50-11.08).,Incorrect inhaler-related knowledge was significantly associated with misuse in handling the MDI with spacer (aOR 9.58; 95% CI 2.14-42.80), Respimat (aOR 5.14; 95% CI 2.07-12.76), and Breezhaler (aOR 6.98; 95% CI 1.95-25.08).,The misuse rates were high for all five types of inhaler.,Poor hearing and the number of acute exacerbations were device-specific factors related to the misuse of inhalers.,Inhaler-related knowledge was significantly associated with misuse, emphasizing the importance of inhaler education. | Different inhalation devices are characterized by different techniques of use.,The untrained switching of device in chronic obstructive pulmonary disease (COPD) and asthma patients may be associated with inadequate inhalation technique and, consequently, could lead to a reduction in adherence to treatment and limit control of the disease.,The aim of this analysis was to estimate the potential economic impact related to errors in inhalation in patients switching device without adequate training.,An Italian real-practice study conducted in patients affected by COPD and asthma has shown an increase in health care resource consumption associated with misuse of inhalers.,Particularly, significantly higher rates of hospitalizations, emergency room visits (ER), and pharmacological treatments (steroids and antimicrobials) were observed.,In this analysis, those differences in resource consumption were monetized considering the Italian National Health Service (INHS) perspective.,Comparing a hypothetical cohort of 100 COPD patients with at least a critical error in inhalation vs 100 COPD patients without errors in inhalation, a yearly excess of 11.5 hospitalizations, 13 ER visits, 19.5 antimicrobial courses, and 47 corticosteroid courses for the first population were revealed.,In the same way, considering 100 asthma patients with at least a critical error in inhalation vs 100 asthma patients without errors in inhalation, the first population is associated with a yearly excess of 19 hospitalizations, 26.5 ER visits, 4.5 antimicrobial courses, and 21.5 corticosteroid courses.,These differences in resource consumption could be associated with an increase in health care expenditure for INHS, due to inhalation errors, of €23,444/yr in COPD and €44,104/yr in asthma for the considered cohorts of 100 patients.,This evaluation highlights that misuse of inhaler devices, due to inadequate training or nonconsented switch of inhaled medications, is associated with a decrease in disease control and an increase in health care resource consumption and costs. | 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. | There are limited data describing patients with moderate COPD exacerbations and evaluating comparative effectiveness of maintenance treatments in this patient population.,The study examined COPD patients with moderate COPD exacerbations.,COPD-related outcomes were compared between patients initiating fluticasone propionate-salmeterol 250/50 mcg (FSC) vs anticholinergics (ACs) following a moderate COPD exacerbation.,This retrospective observational study used a large administrative claims database (study period: 2003-2009) to identify and describe patients with an initial, moderate COPD exacerbation.,A descriptive analysis of patients with moderate COPD exacerbations was done evaluating maintenance treatment rates, subsequent COPD exacerbation rates, and COPD-related costs during a 1-year period.,A cohort analysis compared COPD exacerbation rates and associated costs during a variable-length follow-up period between patients initiating maintenance therapy with FSC or ACs.,COPD exacerbations were reported as rate per 100 patient-years, and monthly costs were reported (standardized to USD 2009).,COPD exacerbation rates between cohorts were evaluated using Cox proportional hazards models, and costs were analyzed using generalized linear models with log-link and gamma distribution.,21,524 patients with a moderate COPD exacerbation were identified.,Only 25% initiated maintenance therapy, and 13% had a subsequent exacerbation.,Annual costs averaged $594 per patient.,A total of 2,849 treated patients (FSC = 925; AC = 1,924) were eligible for the cohort analysis.,The FSC cohort had a significantly lower rate of COPD exacerbations compared to the AC cohort (20.8 vs 32.8; P = 0.04).,After adjusting for differences in baseline covariates, the FSC cohort had a 42% significantly lower risk of a COPD exacerbation (HR = 0.58; 95% CI: 0.38, 0.91).,The FSC cohort incurred significantly higher adjusted pharmacy costs per patient per month by $37 (95% CI: $19, $72) for COPD-related medications vs the AC cohort.,However, this increase was offset by a significant reduction in adjusted monthly medical costs per patient for the FSC vs the AC cohort ($82 vs $112; P < 0.05).,Total monthly COPD-related costs, as a result, did not differ between cohorts.,Only a quarter of patients with a moderate COPD exacerbation were subsequently treated with maintenance therapy.,Initiation of FSC among those treated was associated with better clinical and economic outcomes compared to AC. | 1 |
Smoking cessation in chronic obstructive pulmonary disease (COPD) reduces accelerated forced expiratory volume in 1 s decline, but impact on key health outcomes is less clear.,We studied the relationship of smoking status to mortality and hospitalisation in a UK primary care COPD population.,Using patient-anonymised routine data in the Hampshire Health Record Analytical Database, we identified a prevalent COPD cohort, categorising patients by smoking status (current, ex- or never-smokers).,Three outcomes were measured over 3 years (2011-2013): all-cause mortality, respiratory-cause unplanned hospital admission and respiratory-cause emergency department attendance.,Survival analysis using multivariable Cox regression after multiple imputation was used to estimate hazard ratios for each outcome by smoking status, adjusting for measured confounders (including age, lung function, socioeconomic deprivation, inhaled medication and comorbidities).,We identified 16 479 patients with COPD, mean±sd age 70.1±11.1 years.,Smoking status was known in 91.3%: 35.1% active smokers, 54.3% ex-smokers, 1.9% never-smokers.,Active smokers predominated among younger patients.,Compared with active smokers (n=5787), ex-smokers (n=8941) had significantly reduced risk of death, hazard ratio (95% confidence interval) 0.78 (0.70-0.87), hospitalisation, 0.82 (0.74-0.89) and emergency department attendance, 0.78 (0.70-0.88).,After adjusting for confounders, ex-smokers had significantly better outcomes, emphasising the importance of effective smoking cessation support, regardless of age or lung function.,Many COPD patients smoke: better outcomes in ex-smokers suggest many deaths and admissions avoidable if smokers quithttp://ow.ly/l85u30aizmK | Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year.,Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.,1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly.,Exacerbations were defined by health care utilisation.,Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.,Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE.,More severe disease was associated with changing from IE to FE and less severe disease from FE to IE.,Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.,No parameter clearly predicts an imminent change in exacerbation frequency category.,SCO104960, clinicaltrials.gov identifier NCT00292552 | 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 COPD represent an important medical and health care problem.,Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis.,The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease.,However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients.,In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care.,This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) affects approximately 3 million people in the UK.,An 8-week pulmonary rehabilitation (PR) course is recommended under current guidelines.,However, studies show that initial benefits diminish over time.,We present here an economic evaluation conducted alongside a randomised controlled trial (RCT) of a low-intensity maintenance programme over a time horizon of 1 year delivered in UK primary and secondary care settings.,Patients with COPD who completed at least 60 % of a standard 8-week PR programme were randomised to a 2-h maintenance session at 3, 6 and 9 months (n = 73) or treatment as usual (n = 75).,Outcomes were change in Chronic Respiratory Questionnaire (CRQ) score, EQ-5D-based QALYs, cost (price year 2014) to the UK NHS and social services over the 12 months following initial PR, and incremental cost-effectiveness ratios (ICERs).,At 12 months, incremental cost to the NHS and social services was −£204.04 (95 % CI −£1522 to £1114).,Incremental CRQ and QALY gains were −0.007 (−0.461 to 0.447) and +0.015 (−0.050 to 0.079), respectively.,Based on point estimates, PR maintenance therefore dominates treatment as usual from the perspective of the NHS and social services in terms of cost per QALY gained.,Whether it is cost effective in terms of CRQ depends on whether the £204 per patient could be reinvested elsewhere to a CRQ gain of greater than 0.007.,However, there is much decision uncertainty: 95 % CIs around increments did not exclude zero, and there is a 72.9 % (72.5 %) probability that the ICER is below £20,000 (£30,000) per QALY.,Future research should explore whether more intensive maintenance regimens offer benefit to patients at reasonable cost.,The online version of this article (doi:10.1007/s40258-015-0199-9) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is predicted to become a major cause of death worldwide.,Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies.,In the present study, we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union, focusing on prevalence, severity, frequency of exacerbations and mortality, as well as on differences between the studies' methods.,This systematic review was based on a search for the relevant literature in the Science Citation Index database via the Web of Science and on COPD mortality rates issued from national statistics.,Analysis was finally based on 65 articles and Eurostat COPD mortality data for 21 European countries.,Epidemiological characteristics of COPD varied widely from country to country.,For example, prevalence estimates ranged between 2.1% and 26.1%, depending on the country, the age group and the methods used.,Likewise, COPD mortality rates ranged from 7.2 to 36.1 per 105 inhabitants.,The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD, severity scales, methods of investigation and target populations.,Nevertheless, to a large extent, several recent international guidelines or research initiatives, such as GOLD, BOLD or PLATINO, have boosted a substantial standardization of methodology in data collection and have resulted in the availability of more comparable epidemiological estimates across countries.,On the basis of such standardization, severity estimates as well as prevalence estimates present much less variation across countries.,The contribution of these recent guidelines and initiatives is outlined, as are the problems remaining in arriving at more accurate COPD epidemiological estimates across European countries.,The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures, interventions and patient management in various health care systems.,Therefore, the recent initiatives for standardizing data collection should be enhanced to result in COPD epidemiological estimates of improved quality.,Moreover, establishing international guidelines for reporting research on COPD may also constitute a major contribution. | 1 |
In recent years, the so-called asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has received much attention, not least because elderly individuals may present characteristics suggesting a diagnosis of both asthma and COPD.,At present, ACOS is described clinically as persistent airflow limitation combined with features of both asthma and COPD.,The aim of this paper is, therefore, to review the currently available literature focusing on symptoms and clinical characteristics of patients regarded as having ACOS.,Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic literature review was performed.,A total of 11 studies met the inclusion criteria for the present review.,All studies dealing with dyspnea (self-reported or assessed by the Medical Research Council dyspnea scale) reported more dyspnea among patients classified as having ACOS compared to the COPD and asthma groups.,In line with this, ACOS patients have more concomitant wheezing and seem to have more cough and sputum production.,Compared to COPD-only patients, the ACOS patients were found to have lower FEV1% predicted and FEV1/FVC ratio in spite of lower mean life-time tobacco exposure.,Furthermore, studies have revealed that ACOS patients seem to have not only more frequent but also more severe exacerbations.,Comorbidity, not least diabetes, has also been reported in a few studies, with a higher prevalence among ACOS patients.,However, it should be acknowledged that only a limited number of studies have addressed the various comorbidities in patients with ACOS.,The available studies indicate that ACOS patients may have more symptoms and a higher exacerbation rate than patients with asthma and COPD only, and by that, probably a higher overall respiratory-related morbidity.,Similar to patients with COPD, ACOS patients seem to have a high occurrence of comorbidity, including diabetes.,Further research into the ACOS, not least from well-defined prospective studies, is clearly needed. | Underdiagnosis of chronic obstructive pulmonary disease (COPD) is widespread.,Early detection of COPD may improve the outcome by timely smoking cessation, a change in lifestyle, and treatment with an inhaled bronchodilator (BD).,The objective of this study was to evaluate the diagnostic role of BD reversibility testing in early COPD case finding.,General practitioners (n=241) consecutively recruited subjects aged ≥35 years with relevant exposure (history of smoking, and/or occupational exposure) and at least one respiratory symptom.,Information on age, smoking status, body mass index, dyspnea score (Medical Research Council scale), and spirometry was obtained.,Individuals with airway obstruction (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] <0.70) underwent a BD test with an inhaled β2 agonist, which was considered positive if ΔFEV1 was >0.20 L and >12%.,Asthma and COPD were, respectively, defined as an FEV1 increase >0.50 L and a post-BD FEV1/FVC <0.70.,In total, 4,049 subjects (51% male) were included (mean age 58 years, body mass index 27, 32 pack-years of smoking).,A significant BD response was found in 143 (15%) of the 937 subjects (23%) with airway obstruction at screening spirometry.,In 59% of these subjects, the post-BD FEV1/FVC remained <0.70.,In 24% of the subjects with pre-BD airway obstruction, the post-BD FEV1/FVC ratio was within the reference range.,In subjects with confirmed COPD, the mean increase in FEV1 following BD was 0.11 L±0.10 L.,The subjects with COPD and a significant BD response were characterized by a higher prevalence of dyspnea (72% versus 57%, P=0.02) but less cough (55% versus 75%, P=0.001) when compared with COPD subjects without BD reversibility.,Administration of a BD in COPD case finding is important in order to determine the post-BD FEV1/FVC ratio.,Exclusion of subjects with a significant BD response may result in underdiagnosis of COPD, and we question the need for the BD reversibility test in the diagnostic screening algorithm in early COPD case finding. | 1 |
Early treatment response markers, for example, improvement in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total score, may help clinicians to better manage patients with chronic obstructive pulmonary disease (COPD).,We investigated the prevalence of clinically important improvements in FEV1 and SGRQ scores after 2-month budesonide/formoterol or formoterol treatment and whether such improvements predict subsequent improvements and exacerbation rates.,This post hoc analysis is based on data from three double-blind, randomized studies in patients with moderate-to-very-severe COPD receiving twice-daily budesonide/formoterol or formoterol alone for 6 or 12 months.,Prebronchodilator FEV1 and SGRQ total score were measured before treatment and at 2 and 12 months; COPD exacerbation rates were measured during months 2-12.,Responders were defined by ≥100 mL improvement in prebronchodilator FEV1 and ≥4-point decrease in SGRQ total score.,Overall, 2,331 and 1,799 patients were included in the 0-2- and 0-12-month responder analyses, respectively, and 2,360 patients in the 2-12-month exacerbation rate analysis.,At 2 months, 35.1% of patients were FEV1 responders and 44.3% were SGRQ responders.,The probability of response was significantly greater with budesonide/formoterol than with formoterol or placebo for both parameters.,Two-month responders had a greater chance of 12-month response than 2-month nonresponders for both FEV1 (odds ratio, 5.57; 95% confidence interval, 4.14-7.50) and SGRQ (odds ratio, 3.87; 95% confidence interval, 2.83-5.31).,Two-month response in FEV1 (P<0.001), but not SGRQ (P=0.11), was associated with greater reductions in exacerbation risk.,Early FEV1 and SGRQ treatment responses relate to their changes at 12 months.,FEV1 response, but not SGRQ response, at 2 months predicts the risk of a future COPD exacerbation in some, but not all patients.,This is potentially useful in clinical practice, although more sensitive and specific markers of favorable treatment response are required. | Real-world prescription pathways leading to triple therapy (TT) (inhaled corticosteroid [ICS] plus long-acting β2-agonist bronchodilator [LABA] plus long-acting muscarinic antagonist) differ from Global initiative for chronic Obstructive Lung Disease [GOLD] and National Institute for Health and Care Excellence treatment recommendations.,This study sets out to identify COPD patients without asthma receiving TT, and determine the pathways taken from diagnosis to the first prescription of TT.,This was a historical analysis of COPD patients without asthma from the Optimum Patient Care Research Database (387 primary-care practices across the UK) from 2002 to 2010.,Patient disease severity was classified using GOLD 2013 criteria.,Data were analyzed to determine prescribing of TT before, at, and after COPD diagnosis; the average time taken to receive TT; and the impact of lung function grade, modified Medical Research Council dyspnea score, and exacerbation history on the pathway to TT.,During the study period, 32% of patients received TT.,Of these, 19%, 28%, 37%, and 46% of patients classified as GOLD A, B, C, and D, respectively, progressed to TT after diagnosis (P<0.001).,Of all patients prescribed TT, 25% were prescribed TT within 1 year of diagnosis, irrespective of GOLD classification (P=0.065).,The most common prescription pathway to TT was LABA plus ICS.,It was observed that exacerbation history did influence the pathway of LABA plus ICS to TT.,Real life UK prescription data demonstrates the inappropriate prescribing of TT and confirms that starting patients on ICS plus LABA results in the inevitable drift to overuse of TT.,This study highlights the need for dissemination and implementation of COPD guidelines to physicians, ensuring that patients receive the recommended therapy. | 1 |
The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described.,This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors.,A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study.,A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively.,Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%).,The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups.,Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01).,Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions.,Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects.,The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
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. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
Patient preference is an important factor when choosing an inhaler device for asthma or chronic obstructive pulmonary disease (COPD).,To identify characteristics of patients with asthma or COPD who prefer a once-daily controller medication regimen.,This retrospective observational study used electronic patient records and linked outcomes from patient-completed questionnaires in a primary care database.,We compared the characteristics of patients indicating a preference for once-daily therapy with those who were unsure or indicating no preference.,Of 3,731 patients with asthma, 2,174 (58%) were women; the mean age was 46 years (range 2-94).,Of 2,138 patients with COPD, 980 (46%) were women; the mean age was 70 years (range 35-98).,Approximately half of the patients in each cohort indicated once-daily preference, one-quarter were unsure, and one-quarter did not prefer once-daily therapy.,In patients with asthma or COPD, the preference for once-daily controller medication was significantly associated with poor adherence and higher concerns about medication.,In asthma, good control and low self-perceived controller medication need were associated with once-daily preference.,By contrast, in COPD, a high self-perceived need for controller medication was associated with once-daily preference.,There was no significant relationship between once-daily preference and age, sex, disease severity, or exacerbation history.,Understanding patient preferences may help prescribers to individualise therapy better for asthma and COPD. | COPD is often associated with cardiovascular comorbidity.,Treatment guidelines recommend therapy with bronchodilators as first choice.,We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.,In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD.,Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score.,Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout.,All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators.,Consensus decisions were taken on every value and parameter.,The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.,Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol.,Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time.,The cardiac frequency was also significantly reduced in indacaterol-treated patients.,Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea.,These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency. | 1 |
Pulmonary rehabilitation (PR) is an important, evidence-based treatment that improves outcomes for people with COPD.,Individualized exercise programmes aim to improve exercise capacity; self-management education and psychological support are also provided.,Translating increased exercise capacity into sustained behavioural change of increased physical activity is difficult.,Other unresolved problems with PR programmes include improving uptake, completion, response and sustaining long-term benefit.,We offer a different perspective drawn from clinical experience of PR, quantitative and qualitative studies of singing groups for people with COPD, and stroke rehabilitation research that gives psychological factors a more central role in determining outcomes after PR.,We discuss Take Charge; a simple but effective psychological intervention promoting self-management--that could be used as part of a PR programme or in situations where PR was declined or unavailable.,This may be particularly relevant now when traditional face-to-face group programmes have been disrupted by COVID-19 precautions. | Baduanjin exercise is a traditional Chinese health Qigong routine created by an ancient physician for health promotion.,Its mild-to-moderate exercise intensity is suitable for individuals with medical conditions.,Recently, a large number of trials have been conducted to investigate the effects of Baduanjin exercise in patients with chronic obstructive pulmonary disease (COPD).,It remains to be determined whether Baduanjin exercise prescription is beneficial for the management of COPD patients.,Thus, we conducted a systematic review to objectively evaluate the existing literature on this topic.,We searched six databases (PubMed, Web of Science, Cochrane Library, Scopus, China National Knowledge Infrastructure, and Wanfang) from inception until early May 2018.,The adapted Physical Therapy Evidence Database (PEDro) scale was used for study quality assessment of all randomized controlled trials (RCTs).,Based on 95% confidence interval (CI), the pooled effect size (Hedge’s g) of exercise capability (6-Minute Walking Test, 6-MWT), lung function parameters (forced expiratory volume in one second, FEV1; forced volume vital capacity, FVC; FEV1/FVC ratio), and quality of life were calculated based on the random-effects model.,Twenty RCTs (n = 1975 COPD patients) were included in this review, with sum scores of the adapted PEDro scale between 5 and 9.,Study results of the meta-analysis indicate that Baduanjin is effective in improving exercise capability (Hedge’s g = 0.69, CI 0.44 to 0.94, p < 0.001, I2 = 66%), FEV1 (Hedge’s g = 0.47, CI 0.22 to 0.73, p < 0.001, I2 = 68.01%), FEV1% (Hedge’s g = 0.38, CI 0.21 to 0.56, p < 0.001, I2 = 54.74%), FVC (Hedge’s g = 0.39, CI 0.22 to 0.56, p < 0.001, I2 = 14.57%), FEV1/FVC (Hedge’s g = 0.5, CI 0.33 to 0.68, p < 0.001, I2 = 53.49%), and the quality of life of COPD patients (Hedge’s g = −0.45, CI −0.77 to −0.12, p < 0.05, I2 = 77.02%), as compared to control groups.,Baduanjin exercise as an adjunctive treatment may potentially improve exercise capability and pulmonary function of COPD patients as well as quality of life.,Baduanjin exercise could be tentatively prescribed for COPD in combination with the conventional rehabilitation program to quicken the process of recovery.,To confirm the positive effects of Baduanjin exercise for COPD patients, future researchers need to consider our suggestions mentioned in this article. | 1 |
Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The aim of this study is to investigate the expression of cytokines in AECOPD.,Patients with AECOPD requiring hospitalization were recruited.,Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited.,Induced sputum and serum were collected.,Induced sputum of participants was processed and tested for thirteen viruses and bacteria.,Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.).,The most common virus detected in virus positive AECOPD (VP) was influenza A (16%).,No virus was found in controls.,Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05).,Additionally, VP patients were less likely to have received influenza vaccination.,VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages.,There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD. | COPD is characterized by a progressive decline in lung function and mental and physical comorbidities.,It is a significant burden worldwide due to its growing prevalence, comorbidities, and mortality.,Complication by bronchial-pulmonary infection causes 50%-90% of acute exacerbations of COPD (AECOPD), which may lead to the aggregation of COPD symptoms and the development of acute respiratory failure.,Non-invasive or invasive ventilation (IV) is usually implemented to treat acute respiratory failure.,However, ventilatory support (mainly IV) should be discarded as soon as possible to prevent the onset of time-dependent complications.,To withdraw IV, an optimum timing has to be selected based on weaning assessment and spontaneous breathing trial or replacement of IV by non-IV at pulmonary infection control window.,The former method is more suitable for patients with AECOPD without significant bronchial-pulmonary infection while the latter method is more suitable for patients with AECOPD with acute significant bronchial-pulmonary infection. | 1 |
Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region.,Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting.,The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria.,Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment.,3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma-COPD overlap.,Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma-COPD cohort.,There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes.,The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes.,Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatmenthttp://ow.ly/oMZI307ndr5 | Chronic obstructive pulmonary disease (COPD) imposes a substantial burden on individuals with the disease, which can include a range of symptoms (breathlessness, cough, sputum production, wheeze, chest tightness) of varying severities.,We present an overview of the biomedical literature describing reported relationships between COPD symptoms and disease burden in terms of quality of life, health status, daily activities, physical activity, sleep, comorbid anxiety, and depression, as well as risk of exacerbations and disease prognosis.,In addition, the substantial variability of COPD symptoms encountered (morning, daytime, and nighttime) is addressed and their implications for disease burden considered.,The findings from this narrative review, which mainly focuses on real-world and observational studies, demonstrate the impact of COPD symptoms on the burden of disease and that improved recognition and understanding of their impact is central to alleviating this burden. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common lung disease during middle age which one of its complications is depression.,Depression is considered one of the major causes of severe disability worldwide.,One of the factors that affect the severity and incidence of this disease is a lifestyle, especially dietary pattern.,On the other hand, some studies showed the relationship between dietary patterns and depression.,The present study aims to investigate the dietary patterns of people with chronic obstructive pulmonary disease and its association with depression.,The present cross-sectional study was performed on 220 patients (mean ± SD age = 54.58 ± 5.08) with chronic obstructive pulmonary disease (56.6% men, 43.4% women) from Tabriz, Iran.,Questionnaires of general information, food frequency, Beck depression and physical activity were completed.,The dominant dietary patterns were determined by factor analysis, and their relationship with depression was discussed by regression analysis.,Three dominant dietary patterns were identified as healthy, unhealthy, and mixed dietary patterns.,An inverse relationship was found between healthy and mixed dietary patterns with depression.,There is no meaningful connection between unhealthy dietary patterns and depression.,Depression had a significant inverse relationship with physical activity.,There was no relationship between dietary patterns and Forced Expiratory Volume for 1 s (FEV1) and Forced Vital Capacity (FVC) criteria.,A positive and significant relationship was observed between mixed dietary patterns with FEV1/FVC.,Inverse relationships exist between healthy dietary patterns and depression in patients with COPD, and improves the function of the lungs.,Further studies are needed to show the exact relationship between diet and COPD depression. | Chronic obstructive pulmonary disease (COPD) is a growing healthcare concern and will represent the third leading cause of death worldwide within the next decade.,COPD is the result of a complex interaction between environmental factors, especially cigarette smoking, air pollution, and genetic preconditions, which result in persistent inflammation of the airways.,There is growing evidence that the chronic inflammatory state, measurable by increased levels of circulating cytokines, chemokines, and acute phase proteins, may not be confined to the lungs.,Cardiovascular disease (CVD) and especially coronary artery disease (CAD) are common comorbidities of COPD, and low-grade systemic inflammation plays a decisive role in its pathogenesis.,Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert multiple functions in humans and are crucially involved in limiting and resolving inflammatory processes. n-3 PUFAs have been intensively studied for their ability to improve morbidity and mortality in patients with CVD and CAD.,This review aims to summarize the current knowledge on the effects of n-3 PUFA on inflammation and its impact on CAD in COPD from a clinical perspective. | 1 |
Viral-bacterial co-infections are associated with severe exacerbations of COPD.,Epithelial antimicrobial peptides, including human β-defensin-2 (HBD-2), are integral to innate host defenses.,In this study, we examined how co-infection of airway epithelial cells with rhinovirus and Pseudomonas aeruginosa modulates HBD-2 expression, and whether these responses are attenuated by cigarette smoke and in epithelial cells obtained by bronchial brushings from smokers with normal lung function or from COPD patients.,When human airway epithelial cells from normal lungs were infected with rhinovirus, Pseudomonas aeruginosa, or the combination, co-infection with rhinovirus and bacteria resulted in synergistic induction of HBD-2 (p<0.05).,The combination of virus and flagellin replicated this synergistic increase (p<0.05), and synergy was not seen using a flagella-deficient mutant Pseudomonas (p<0.05).,The effects of Pseudomonas aeruginosa were mediated via interactions of flagellin with TLR5.,The effects of HRV-16 depended upon viral replication but did not appear to be mediated via the intracellular RNA helicases, retinoic acid-inducible gene-I or melanoma differentiation-associated gene-5.,Cigarette smoke extract significantly decreased HBD-2 production in response to co-infection.,Attenuated production was also observed following co-infection of cells obtained from healthy smokers or COPD patients compared to healthy controls (p<0.05).,We conclude that co-exposure to HRV-16 and Pseudomonas aeruginosa induces synergistic production of HBD-2 from epithelial cells and that this synergistic induction of HBD-2 is reduced in COPD patients.,This may contribute to the more severe exacerbations these patients experience in response to viral-bacterial co-infections. | 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. | 1 |
Several studies have reported an association between chronic obstructive pulmonary disease (COPD) and periodontal diseases.,However, a large-scale population-based cohort study was previously absent from the literature.,Therefore, we evaluated the risk of periodontal diseases in patients with COPD in a nationwide population.,From the National Health Insurance claims data of Taiwan, we identified 22,332 patients with COPD who were newly diagnosed during 2000 to 2010.,For each case, two individuals without COPD were randomly selected and frequency matched by age, sex, and diagnosis year.,Both groups were followed up till the end of 2011.,The overall incidence of periodontal diseases was 1.19-fold greater in the COPD group than in the comparison group (32.2 vs 26.4 per 1000 person-years; 95% confidence interval [CI] 1.15-1.24).,Compared with non-COPD patients, the adjusted hazard ratios of patients with COPD increased with the number of emergency room visits (from 1.14 [95% CI 1.10-1.19] to 5.09 [95% CI 4.53-5.72]) and admissions (from 1.15 [95% CI 1.10-1.20] to 3.17 [95% CI 2.81-3.57]).,In addition, the adjusted hazard ratios of patients with COPD treated with inhaled corticosteroids (1.22, 95% CI 1.11-1.34) and systemic corticosteroids (1.15, 95% CI 1.07-1.23) were significantly higher than those of patients not treated with corticosteroids.,Patient with COPD are at a higher risk of developing periodontal diseases than the general population.,Our results also support that the risk of periodontal diseases is proportional to COPD control.,In addition, patients who receive corticosteroid treatment are at a higher risk of developing periodontal diseases. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
Self-management interventions (SMIs) are recommended for individuals with COPD to help monitor symptoms and optimize health-related quality of life (HRQOL).,However, SMIs vary widely in content, delivery, and intensity, making it unclear which methods and techniques are associated with improved outcomes.,This systematic review aimed to summarize the current evidence base surrounding the effectiveness of SMIs for improving HRQOL in people with COPD.,Systematic reviews that focused upon SMIs were eligible for inclusion.,Intervention descriptions were coded for behavior change techniques (BCTs) that targeted self-management behaviors to address 1) symptoms, 2) physical activity, and 3) mental health.,Meta-analyses and meta-regression were used to explore the association between health behaviors targeted by SMIs, the BCTs used, patient illness severity, and modes of delivery, with the impact on HRQOL and emergency department (ED) visits.,Data related to SMI content were extracted from 26 randomized controlled trials identified from 11 systematic reviews.,Patients receiving SMIs reported improved HRQOL (standardized mean difference =−0.16; 95% confidence interval [CI] =−0.25, −0.07; P=0.001) and made fewer ED visits (standardized mean difference =−0.13; 95% CI =−0.23, −0.03; P=0.02) compared to patients who received usual care.,Patients receiving SMIs targeting mental health alongside symptom management had greater improvement of HRQOL (Q=4.37; P=0.04) and fewer ED visits (Q=5.95; P=0.02) than patients receiving SMIs focused on symptom management alone.,Within-group analyses showed that HRQOL was significantly improved in 1) studies with COPD patients with severe symptoms, 2) single-practitioner based SMIs but not SMIs delivered by a multidisciplinary team, 3) SMIs with multiple sessions but not single session SMIs, and 4) both individual- and group-based SMIs.,SMIs can be effective at improving HRQOL and reducing ED visits, with those targeting mental health being significantly more effective than those targeting symptom management alone. | COPD is a leading cause of morbidity and mortality.,Self-management interventions are considered important in order to limit the progression of the disease.,Computer-tailored interventions could be an effective tool to facilitate self-management.,This randomized controlled trial tested the effectiveness of a web-based, computer-tailored COPD self-management intervention on physical activity and smoking behavior.,Participants were recruited from an online panel and through primary care practices.,Those at risk for or diagnosed with COPD, between 40 and 70 years of age, proficient in Dutch, with access to the Internet, and with basic computer skills (n=1,325), were randomly assigned to either the intervention group (n=662) or control group (n=663).,The intervention group received the web-based self-management application, while the control group received no intervention.,Participants were not blinded to group assignment.,After 6 months, the effect of the intervention was assessed for the primary outcomes, smoking cessation and physical activity, by self-reported 7-day point prevalence abstinence and the International Physical Activity Questionnaire - Short Form.,Of the 1,325 participants, 1,071 (80.8%) completed the 6-month follow-up questionnaire.,No significant treatment effect was found on either outcome.,The application however, was used by only 36% of the participants in the experimental group.,A possible explanation for the nonsignificant effect on the primary outcomes, smoking cessation and physical activity, could be the low exposure to the application as engagement with the program has been shown to be crucial for the effectiveness of computer-tailored interventions.,(Netherlands Trial Registry number: NTR3421.) | 1 |
Psoriasis is considered a systemic inflammatory disorder.,Previous studies have reported conflicting positive or negative correlations between psoriasis and chronic obstructive pulmonary disease.,We performed a meta-analysis to determine whether there is an associated risk between psoriasis and chronic obstructive pulmonary disease.,We performed a complete 30-year literature search of MEDLINE, Embase, and Cochrane Central Register databases on this topic.,Four observational studies with a total of 13,418 subjects were identified.,The odds ratios of chronic obstructive pulmonary disease in subjects with psoriasis/mild-to-moderate psoriasis were analyzed using the random-effects model, while the odds ratios of chronic obstructive pulmonary disease in subjects with severe psoriasis and current smoking in subjects with psoriasis were analyzed using the fixed-effect model.,We found that psoriasis patients were at a greater risk of developing chronic obstructive pulmonary disease than the general population (odds ratio, 1.90; 95% confidence interval, 1.36-2.65) and that the association between of psoriasis and with chronic obstructive pulmonary disease was stronger among patients with severe psoriasis (odds ratio, 2.15; 95% confidence interval, 1.26-3.67).,Psoriasis patients should be advised to cease smoking to reduce their risk of COPD.,Moreover, identification of this potential risk may enable earlier implementation of preventive measures for reduction comorbidity and mortality rates. | Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung and systemic inflammation as well as airway goblet cell hyperplasia (GCH).,Mucin production is activated in part by stimulation of the epidermal growth factor (EGF) receptor pathway through neutrophils and macrophages.,How circulating cytokine levels relate to GCH is not clear.,We performed phlebotomy and bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, and eight COPD subjects FEV1 30-60 %).,Six endobronchial biopsies per subject were performed.,GCH was measured by measuring mucin volume density (MVD) using stereological techniques on periodic acid fast-Schiff stained samples.,We measured the levels of chemokines CXCL8/IL-8, CCL2/MCP-1, CCL7/MCP-3, CCL22/MCD, CCL3/MIP-1α, and CCL4/MIP-1β, and the cytokines IL-1, IL-4, IL-6, IL-9, IL-17, EGF, and vascular endothelial growth factor (VEGF).,Differences between groups were assessed using one-way ANOVA, t test, or Chi squared test.,Post hoc tests after ANOVA were performed using Bonferroni correction.,MVD was highest in healthy smokers (27.78 ± 10.24 μL/mm2) compared to COPD subjects (16.82 ± 16.29 μL/mm2, p = 0.216) and nonsmokers (3.42 ± 3.07 μL/mm2, p <0.0001).,Plasma CXCL8 was highest in healthy smokers (11.05 ± 8.92 pg/mL) compared to nonsmokers (1.20 ± 21.92 pg/mL, p = 0.047) and COPD subjects (6.01 ± 5.90 pg/mL, p = 0.366).,CCL22 and CCL4 followed the same trends.,There were no significant differences in the other cytokines measured.,When the subjects were divided into current smokers (healthy smokers and COPD current smokers) and non/ex-smokers (nonsmokers and COPD ex-smokers), plasma CXCL8, CCL22, CCL4, and MVD were greater in current smokers.,No differences in other cytokines were seen.,Plasma CXCL8 moderately correlated with MVD (r = 0.552, p = 0.003).,In this small cohort, circulating levels of the chemokines CXCL8, CCL4, and CCL22, as well as MVD, attain the highest levels in healthy smokers compared to nonsmokers and COPD subjects.,These findings seem to be driven by current smoking and are independent of airflow obstruction.,These data suggest that smoking upregulates a systemic pattern of neutrophil and macrophage chemoattractant expression, and this correlates significantly with the development of goblet cell hyperplasia. | 1 |
The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes.,FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations.,In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use.,This post-hoc analysis included 2557 men and 805 women.,Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year.,Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73-0.91], 0.89 [0.74-1.07] in men and women, respectively).,Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70-0.89] and 0.76 [0.63-0.91] in men and women, respectively).,Results were similar for all (mild/moderate/severe) exacerbations.,Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women.,The smaller sample size for women may account for some observed discrepancies in treatment responses.,Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC.,Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis.,Post hoc analysis of the FLAME study.,ClinicalTrials.gov number: NCT01782326.,Registered 1 February 2013. | 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 |
Chronic obstructive pulmonary disease (COPD) patients include those who have never smoked.,However, risk factors other than smoking in never-smokers have not been elucidated sufficiently.,This study investigated the risk factors for COPD among never-smokers in Korea using population-based data.,The data were retrieved from the Korean National Health and Nutrition Survey IV conducted from 2007 to 2009.,Among subjects aged 40 years or older who underwent appropriate pulmonary function tests, never-smokers not diagnosed with asthma and not showing a restrictive pattern on pulmonary function tests were enrolled.,Risk factors of COPD in never-smokers were analyzed using logistic regression models.,Among 24,871 participants in the representative Korean cohort, 3,473 never-smokers were enrolled.,COPD patients accounted for 7.6% of the never-smokers.,In the logistic regression analysis, low education status (odds ratio [OR]: 2.0; 95% confidence interval [CI]: 1.2-3.2), occupational exposure (OR: 2.6; 95% CI: 1.3-5.3), a history of tuberculosis (OR: 4.5; 95% CI: 2.3-8.7), bronchiectasis (OR: 6.0; 95% CI: 1.4-25.4), male sex (OR: 4.2; 95% CI: 2.6-6.7), advanced age (60-69 years vs 40-49 years; OR: 3.8; 95% CI: 2.0-7.0), and being underweight (body mass index <18.5 vs 18.0-24.9 kg/m2; OR: 3.1; 95% CI: 1.0-9.4) were associated with the development of COPD.,Low education status, manual labor, a history of tuberculosis and bronchiectasis, as well as male sex, advanced age and being underweight were risk factors for COPD in Korean never-smokers. | Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking.,However, COPD mortality is high in poor countries with low smoking rates.,Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD.,We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI).,National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence.,The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked.,National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men rs=0.73, p=0.0001; women rs=0.90, p<0.0001; 60+ years: men rs=0.63, p=0.0022; women rs=0.37, p=0.1) than obstruction (<60 years: men rs=0.28, p=0.20; women rs=0.17, p<0.46; 60+ years: men rs=0.28, p=0.23; women rs=0.22, p=0.33).,Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$15 000.,Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$15 000.,Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high ‘COPD’ mortality in poor countries. | 1 |
The purpose of this study was to evaluate the frequency of inadequate diagnosis and factors predictive of this in patients with chronic obstructive pulmonary disease (COPD) participating in the On-Sint study.,The On-Sint cohort was recruited for a multicenter observational study in which 356 physicians (71.6% from primary care) included adult patients who had been diagnosed with COPD.,Patients’ clinical and functional information since diagnosis and details for the recruiting physicians were collected from patient files and at the inclusion visit.,We performed a multivariate analysis to evaluate the influence of these variables on diagnostic inadequacy (absence of postbronchodilator forced expiratory volume in one second/forced vital capacity [FEV1/FVC] <0.70 or, if this value was missing, prebronchodilator FEV1/FVC <0.70).,In total, 1,214 patients were included in the study.,The patients had a mean age of 66.4±9.7 years and 78.8% were male.,In total, 51.3% of patients did not have an obstructive spirometry performed, and 21.4% had a normal or non-obstructive spirometry pattern.,Patient-related factors associated with inadequate diagnosis were: years since diagnosis (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05), number of exacerbations in the previous year (OR 1.01, 95% CI 1.01-1.02), comorbidities (OR 1.05, 95% CI 1.01-1.015), and obesity (OR 1.06, 95% CI 1.02-1.10 per kg/m2 of body mass index), while a longer smoking history (OR 0.98, 95% CI 0.97-0.99 for each pack/year) and short-acting or long-acting bronchodilator therapy (OR 0.61, 95% CI 0.44-0.76 and OR 0.46, 95% CI 0.27-0.76, respectively) were inversely related.,With regard to physician-related variables, being followed up by primary care physicians (OR 3.0, 95% CI 2.11-4.34) and in rural centers (OR 1.63, 95% CI 1.12-2.38) were positively associated with an inadequate diagnosis, while having regular follow-ups in the most severe cases (OR 0.66, 95% CI 0.46-0.93) and use of quality of life questionnaires (OR 0.55, 95% CI 0.40-0.76) were negatively associated.,Diagnosis of COPD was inadequate in half of the patients from the On-Sint cohort.,There were multiple factors, both patient-related and physician-related, associated with this misdiagnosis. | This study aimed to characterize and differentiate the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy 2011 cut points through the modified Medical Research Council dyspnea scale (mMRC) and chronic obstructive pulmonary disease (COPD) assessment test (CAT).,Analysis of COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was conducted in Europe and US.,Matched data from physicians and patients included CAT and mMRC scores.,Receiver operating characteristic curves and kappa analysis determined a cut point for CAT and mMRC alignment and thus defined patient movement (“movers”) within GOLD groups A-D, depending on the tool used.,Logistic regression analysis, with a number of physician- and patient-reported covariates, characterized those movers.,Comparing GOLD-defined high-symptom patients using mMRC and CAT cut points (≥2 and ≥10, respectively), there were 890 (53.65%) movers; 887 of them (99.66%) moved from less symptomatic GOLD groups A and C (using mMRC) to more symptomatic groups B and D (using CAT).,For receiver operating characteristic (area under the curve: 0.82, P<0.001) and kappa (maximized: 0.45) recommended CAT cut points of ≥24 and ≥26, movers reduced to 429 and 403 patients, respectively.,Logistic regression analysis showed variables significantly associated with movers were related to impact on normal life, age, cough, and sleep (all P<0.05).,Within movers, direction of movement was significantly associated with the same variables (all P<0.05).,Use of current mMRC or CAT cut points leads to inconsistencies for COPD assessment classification.,It is recommended that cut points are aligned and both tools administered simultaneously for optimal patient care and to allow for closer management of movers.,Our research may suggest an opportunity to investigate a combined score approach to patient management based on the worst result of mMRC and CAT.,The reduced number of remaining movers may then identify patients who have greater impact of disease and may require a more personalized treatment plan. | 1 |
The objective was to assess whether dyspnea, peripheral muscle strength and the level of physical activity are correlated with life-space mobility of older adults with COPD.,Sixty patients over 60 years of age (40 in the COPD group and 20 in the control group) were included.,All patients were evaluated for lung function (spirometry), life-space mobility (University of Alabama at Birmingham Study of Aging Life-Space Assessment), dyspnea severity (Modified Dyspnea Index), peripheral muscle strength (handgrip dynamometer), level of physical activity and number of daily steps (accelerometry).,Groups were compared using unpaired t-test.,Pearson’s correlation was used to test the association between variables.,Life-space mobility (60.41±16.93 vs 71.07±16.28 points), dyspnea (8 [7-9] vs 11 [10-11] points), peripheral muscle strength (75.16±14.89 vs 75.50±15.13 mmHg), number of daily steps (4,865.4±2,193.3 vs 6,146.8±2,376.4 steps), and time spent in moderate to vigorous activity (197.27±146.47 vs 280.05±168.95 minutes) were lower among COPD group compared to control group (p<0.05).,The difference was associated with the lower mobility of COPD group in the neighborhood.,Life-space mobility is decreased in young-old adults with COPD, especially at the neighborhood level.,This impairment is associated to higher dyspnea, peripheral muscle weakness and the reduced level of physical activity. | Persons with Chronic Obstructive Pulmonary Disease (COPD), performing some level of regular physical activity, have a lower risk of both COPD-related hospital admissions and mortality.,COPD patients of all stages seem to benefit from exercise training programs, thereby improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue.,Physical inactivity, which becomes more severe with increasing age, is a point of concern in healthy older adults.,COPD might worsen this scenario, but it is unclear to what degree.,This literature review aims to present the extent of the impact of COPD on objectively-measured daily physical activity (DPA).,The focus is on the extent of the impact that COPD has on duration, intensity, and counts of DPA, as well as whether the severity of the disease has an additional influence on DPA.,A literature review was performed in the databases PubMed [MEDLINE], Picarta, PEDRO, ISI Web of Knowledge and Google scholar.,After screening, 11 studies were identified as being relevant for comparison between COPD patients and healthy controls with respect to duration, intensity, and counts of DPA.,Four more studies were found to be relevant to address the subject of the influence the severity of the disease may have on DPA.,The average percentage of DPA of COPD patients vs. healthy control subjects for duration was 57%, for intensity 75%, and for activity counts 56%.,Correlations of DPA and severity of the disease were low and/or not significant.,From the results of this review, it appears that patients with COPD have a significantly reduced duration, intensity, and counts of DPA when compared to healthy control subjects.,The intensity of DPA seems to be less affected by COPD than duration and counts.,Judging from the results, it seems that severity of COPD is not strongly correlated with level of DPA.,Future research should focus in more detail on the relation between COPD and duration, intensity, and counts of DPA, as well as the effect of disease severity on DPA, so that these relations become more understandable. | 1 |
The interleukin-1 (IL-1) gene polymorphisms have been implicated in chronic obstructive pulmonary disease (COPD) risk, but results are controversial.,We aimed to conduct a meta-analysis to address this issue.,Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association.,The meta-analysis revealed no association between the IL1B (−511), (−31), (+3954) polymorphisms and COPD risk.,However, stratification by ethnicity indicated that the T allele carriers of the IL1B (−511) polymorphism and the C allele carriers of the IL1B (−31) variant were associated with an increased risk for developing COPD in East Asians (OR = 1.61, 95% CI: 1.13-2.31, Pz = 0.009 and OR = 1.55, 95% CI: 1.14-2.11, Pz = 0.006, respectively).,The meta-analysis revealed a significant association between the IL1RN (VNTR) polymorphism and COPD risk in all study subjects and East Asians under homozygote model (22 vs.,LL: OR = 3.16, 95% CI: 1.23-8.13, Pz = 0.017 and OR = 3.20, 95% CI: 1.13-9.12, Pz = 0.029, respectively).,Our meta-analysis suggests that the IL1B (−511), (−31) and IL1RN (VNTR) polymorphisms are associated with COPD risk in East Asians.,There is no association between the IL1B (+3954) polymorphism and COPD risk.,Further studies should be performed in other ethnic groups besides East Asians. | Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD).,In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP).,The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs) 8 and 9 and prolyl endopeptidase (PE).,Here we investigated whether cigarette smoke extract (CSE) stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP.,Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9.,PMNs constitutively expressed PE activity as well as PE protein.,Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation.,Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9.,Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors.,Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors.,Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE.,This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema.,MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD. | 1 |
This paper explores the recent literature surrounding comorbid depression and COPD.,The literature reveals a high prevalence of depression in patients with COPD and some evidence that the depression is a result of the disease.,The literature highlights the negative impact of depression on quality of life and a possible impact on mortality.,Depression also negatively impacts on compliance and smoking cessation.,Treatment of depression in COPD, particularly by cognitive behavioral therapy, has positive impact on quality of life.,Tricyclic antidepressants have a positive impact on mood and COPD, but side effects limit their use.,The advent of the new antidepressants may improve acceptability and outcomes, but the research is yet to be undertaken.,Physical rehabilitation may have a positive impact on mood.,This paper highlights the difficulty in screening for depression in patients with COPD due to the overlap of symptoms between the two diseases.,Despite the difficulties, it is important to recognize and treat depression in patients with COPD because of the significant likelihood of improvement in quality of life. | Guidelines on COPD diagnosis and management encourage primary care physicians to detect the disease at an early stage and to treat patients according to their condition and needs.,Problems in guideline implementation include difficulties in diagnosis, using spirometry and the disputed role of reversibility testing.,These lead to inaccurate diagnostic registers and inadequacy of administered treatments.,This study represents an audit of COPD diagnosis and management in primary care practices in Devon.,Six hundred and thirty two patients on COPD registers in primary care practices were seen by a visiting Respiratory Specialist Nurse.,Diagnoses were made according to the NICE guidelines.,Reversibility testing was carried out either routinely or based on clinical indication in two sub-samples.,Dyspnoea was assessed.,Data were entered into a novel IT-based software which computed guideline-based treatment recommendations.,Current and recommended treatments were compared.,Five hundred and eighty patients had spirometry.,Diagnoses of COPD were confirmed in 422 patients (73%).,Thirty nine patients were identified as asthma only, 94 had normal spirometry, 23 were restrictive and 2 had a cardiac disorder.,Reversibility testing changed diagnosis of 11% of patients with airflow obstruction, and severity grading in 18%.,Three quarters of patients with COPD had been offered practical help with smoking cessation.,Short and long-acting anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15-18% of patients they were indicated but not received.,Inhaled steroids had been over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients with a chronic productive cough were receiving mucolytics.,Pulmonary rehabilitation was not available in some areas and was under-used in other areas.,Diagnostic registers of COPD in primary care contain mistakes leading to inaccurate prevalence estimates and inappropriate treatment decisions.,Use of pre-bronchodilator readings for diagnosis overestimates the prevalence and severity in a significant minority, thus post bronchodilator readings should be used.,Management of stable COPD does often not correspond to guidelines.,The IT system used in this study has the potential to improve diagnosis and management of COPD in primary care. | 1 |
Current COPD management recommendations indicate that pharmacological treatment can be stepped up or down, but there are no recommendations on how to make this adjustment.,We aimed to describe pharmacological prescriptions during a routine clinical visit for COPD and study the determinants of changing therapy.,EPOCONSUL is a Spanish nationwide observational cross-sectional clinical audit with prospective case recruitment including 4,508 COPD patients from outpatient respiratory clinics for a period of 12 months (May 2014-May 2015).,Prescription patterns were examined in 4,448 cases and changes analyzed in stepwise backward, binomial, multivariate, logistic regression models.,Patterns of prescription of inhaled therapy groups were no treatment prescribed, 124 (2.8%) cases; one or two long-acting bronchodilators (LABDs) alone, 1,502 (34.6%) cases; LABD with inhaled corticosteroids (ICSs), 389 (8.6%) cases; and triple therapy cases, 2,428 (53.9%) cases.,Incorrect prescriptions of inhaled therapies were observed in 261 (5.9%) cases.,After the clinical visit was audited, 3,494 (77.5%) cases did not modify their therapeutic prescription, 307 (6.8%) cases had a step up, 238 (5.3%) cases had a change for a similar scheme, 182 (4.1%) cases had a step down, and 227 (5.1%) cases had other nonspecified change.,Stepping-up strategies were associated with clinical presentation (chronic bronchitis, asthma-like symptoms, and exacerbations), a positive bronchodilator test, and specific inhaled medication groups.,Stepping down was associated with lung function impairment, ICS containing regimens, and nonexacerbator phenotype.,The EPOCONSUL study shows a comprehensive evaluation of pharmacological treatments in COPD care, highlighting strengths and weaknesses, to help us understand how physicians use available drugs. | The Spanish Guidelines for COPD (GesEPOC) describe four clinical phenotypes: non-exacerbator (NE), asthma-COPD overlap syndrome (ACO), frequent exacerbator with emphysema (EE), and exacerbator with chronic bronchitis (ECB).,The objective of this study was to determine the frequency of COPD phenotypes, their clinical characteristics, and the availability of diagnostic tools to classify COPD phenotypes in clinical practice.,This study was an epidemiological, cross-sectional, and multi-centered study.,Patients ≥40 years old with a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.7 and who were smokers or former smokers (with at least 10 pack-years) were included.,The availability of diagnostic tools to classify COPD phenotypes was assessed by an ad hoc questionnaire.,A total of 647 patients (294 primary care [PC], 353 pulmonology centers) were included.,Most patients were male (80.8%), with a mean age (SD) of 68.2 (9.2) years, mean post-bronchodilator FEV1 was 53.2% (18.9%) and they suffered a mean of 2.2 (2.1) exacerbations in the last year.,NE was the most frequent phenotype (47.5%) found, followed by ECB (29.1%), EE (17.0%), and ACO (6.5%).,Significant differences between the four phenotypes were found regarding age; sex; body mass index; FEV1; body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE)/body mass index, airflow obstruction, dyspnea and exacerbations (BODEx) index; modified Medical Research Council dyspnea scale; respiratory symptoms; comorbidi-ties; hospitalizations; and exacerbations in the last year.,Physicians considered that >80% of the diagnostic tools needed to classify COPD phenotypes were available, with the exception of computed tomography (26.9%) and carbon monoxide transfer test (13.5%) in PC, and sputum eosinophilia count in PC and pulmonology centers (40.4% and 49.4%, respectively).,In Spanish clinical practice, almost half of the patients with COPD presented with NE phenotype.,The prevalence of ACO according to the Spanish consensus definition was very low.,In general, physicians indicated that they had the necessary tools for diagnosing COPD phenotypes. | 1 |
A 6-second spirometry test is easier than full exhalations.,We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV1/FEV6) to the ratio of the FEV1/Forced vital capacity (FEV1/FVC) for the detection of airway obstruction.,The PLATINO population-based survey in individuals aged 40 years and over designed to estimate the prevalence of post-Bronchodilator airway obstruction repeated for the same study participants after 5-9 years in three Latin-American cities.,Using the FEV1/FVC<Lower limit of normal (LLN) index, COPD prevalence apparently changed from 9.8 to 13.2% in Montevideo, from 9.7 to 6.0% in São Paulo and from 8.5 to 6.6% in Santiago, despite only slight declines in smoking prevalence (from 30.8% to 24.3%).,These changes were associated with differences in Forced expiratory time (FET) between the two surveys.,In contrast, by using the FEV1/FEV6 to define airway obstruction, the changes in prevalence were smaller: 9.7 to 10.6% in Montevideo, 8.6 to 9.0% in São Paulo, and 7.5 to 7.9% in Santiago.,Changes in the prevalence of COPD with criteria based on FEV1/FVC correlated strongly with changes in the FET of the tests (R2 0.92) unlike the prevalence based on a low FEV1/FEV6 (R2 = 0.40).,The FEV1/FEV6 is a more reliable index than FEV1/FVC because FVC varies with the duration of the forced exhalation.,Reporting FET and FEV1/FEV6<LLN helps to understand differences in prevalence of COPD obtained from FEV1/FVC-derived indices. | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
Combining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD).,We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.,Two replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD.,Primary efficacy end points were area under the curve from 0-3 hours of forced expiratory volume in 1 second (FEV1 AUC0-3) and trough FEV1 after 12 weeks (for the individual trials).,A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).,Olodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0-3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points.,These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001).,The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.,These studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD.,In general, both treatments were well tolerated. | The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care.,This study aimed to evaluate its cost-effectiveness.,An economic analysis was performed from the Belgian healthcare payer’s perspective.,A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care.,Three types of costs were calculated: intervention costs, medication costs and exacerbation costs.,Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year.,Follow-up was 1 year in the basecase analysis.,Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty.,In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon.,This reflects cost savings of €227 for the PHARMACOP-intervention.,The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care).,Results showed robust cost-savings in various sensitivity analyses.,Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies. | 1 |
The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo.,In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods.,Primary end points were peak plasma concentration (Cmax,ss), and area under the plasma concentration-time profile (AUC0-6h,ss), both at steady state.,The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity).,Safety was evaluated as adverse events and by electrocardiogram/Holter.,Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices.,The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss, indicating that bioequivalence was not established.,Dose ordering for bronchodilation was observed.,Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation.,All treatments were well tolerated with no apparent relation to dose or device.,Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD. | 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 |
Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients.,However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index.,For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.,In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation.,The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months.,The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index.,Mortality was assessed using Kaplan-Meier survival and Cox Regression.,Performance of models was compared using C-statistics.,Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively.,Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function.,The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.,Cachexia is associated with increased mortality among COPD patients.,Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.,The online version of this article (10.1186/s12931-019-1073-3) contains supplementary material, which is available to authorized users. | To investigate the validity of an eight-contact electrode bioelectrical impedance analysis (BIA) system within a household scale for assessing whole body composition in COPD patients.,Seventeen patients with COPD (mean age = 67 ± 8 years; mean FEV1 = 38.6 ± 16.1% of predicted; and mean body mass index = 24.7 ± 5.4 kg/m2) underwent dual-energy X-ray absorptiometry (DEXA) and an eight-contact electrode BIA system for body composition assessment.,There was a strong inter-method correlation for fat mass (r = 0.95), fat-free mass (r = 0.93), and lean mass (r = 0.93), but the correlation was moderate for bone mineral content (r = 0.73; p < 0.01 for all).,In the agreement analysis, the values between DEXA and the BIA system differed by only 0.15 kg (−6.39 to 6.70 kg), 0.26 kg (−5.96 to 6.49 kg), −0.13 kg (−0.76 to 0.50 kg), and −0.55 kg (−6.71 to 5.61 kg) for fat-free mass, lean mass, bone mineral content, and fat mass, respectively.,The eight-contact electrode BIA system showed to be a valid tool in the assessment of whole body composition in our sample of patients with COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by different phenotypes with either bronchial airways alterations or emphysema prevailing.,As blood biomarkers could be clinically useful for COPD stratification, we aimed at investigating the levels of blood biomarkers in COPD patients differentiated by phenotype: prevalent chronic airway disease versus emphysema.,In 23 COPD patients with prevalent airway disease (COPD-B), 22 COPD patients with prevalent emphysema (COPD-E), 9 control smokers (CSs), and 18 control nonsmokers (CNSs), we analyzed the expression levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, epidermal growth factor (EGF), monocyte chemotactic protein (MCP)-1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay in plasma/serum; glutathione peroxidase and superoxide dismutase (SOD)-1 by immunochemical kits in plasma; and free F2-isoprostanes (F2-IsoPs) by gas chromatography in plasma.,F2-IsoPs level was increased in COPD-B and COPD-E compared with CSs and CNSs; in addition, CS showed higher levels than CNSs; SOD1 level was lower in COPD-B and COPD-E than that in CNSs.,Interestingly, MCP-1 level was higher only in COPD-E versus CSs and CNSs; EGF and IL-8 levels were higher in COPD-B and COPD-E versus CNSs; IL-6 level was increased in all three smoking groups (COPD-B, COPD-E, and CSs) versus CNS; IFN-γ and IL-1α levels were higher in CSs than in CNSs; and IL-1α level was also higher in CSs versus COPD-B and COPD-E.,In all subjects, F2-IsoPs level correlated positively and significantly with MCP-1, IL-2, IL-1β, IFN-γ, and TNF-α and negatively with SOD1.,When correlations were restricted to COPD-E and COPD-B groups, F2-IsoPs maintained the positive associations with IFN-γ, TNF-α, and IL-2.,We did not find any specific blood biomarkers that could differentiate COPD patients with prevalent airway disease from those with prevalent emphysema.,The MCP-1 increase in COPD-E, associated with the imbalance of oxidant/antioxidant markers, may play a role in inducing emphysema. | The high prevalence of COPD in the Russian Federation has been demonstrated in several epidemiological studies.,However, there are still no data on the clinical characteristics of these patients according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups and phenotypes, which could provide additional understanding of the burden of COPD, routine clinical practice, and ways to improve the treatment of patients with COPD in Russia.,SUPPORT was an observational multicenter study designed to obtain data about the distribution of patients with previously diagnosed COPD according to the severity of bronchial obstruction, symptom severity, risk of exacerbation, COPD phenotypes, and treatment of COPD.,We included patients with a previous diagnosis of COPD who visited one of 33 primary-care centers for any reason in 23 cities in Russia.,Among the 1,505 patients with a previous diagnosis of COPD who attended the primary-care centers and were screened for the study, 1,111 had a spirometry-confirmed diagnosis and were included in the analysis.,Up to 53% of the patients had severe or very severe COPD (GOLD stages III-IV), and 74.3% belonged to the GOLD D group.,The majority of patients were frequent exacerbators (exacerbators with chronic bronchitis [37.3%], exacerbators without chronic bronchitis [14%]), while 35.8% were nonexacerbators and 12.9% had asthma-COPD overlap.,Among the GOLD D group patients, >20% were treated with only short-acting bronchodilators.,COPD is still misdiagnosed in primary care in Russia.,COPD patients in primary care are usually GOLD D with frequent exacerbations and are often treated with only short-acting bronchodilators. | 1 |
The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations.,The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations.,However, the clinical characteristics and outcomes in these patients are not well documented.,In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry.,All patients with stable COPD were classified into the four groups defined by GOLD 2017.,The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups.,Four hundred and one patients with stable COPD were identified.,There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D.,Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A.,Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period.,Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B).,Mortality was not different between the high-risk and low-risk groups.,The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality. | Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome).,It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS).,Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] ≤80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography.,The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group).,The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group).,The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group.,The peripheral eosinophil counts and sputum eosinophil counts were significantly higher.,The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher.,A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening.,Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value.,COPD patients with asthmatic symptoms had some clinical features.,ICS should be considered earlier as a potential treatment in such patients.,High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS. | 1 |
To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort.,Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively.,Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).,Cox regression was used for analyses.,Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics curves and Youden's index were calculated.,Main causes of death were cardiovascular, respiratory and cancer.,Baseline COPD was associated with overall mortality (HR = 1.43 for FEV1/FVC<LLN; 2.01 for GOLD 2-4; 1.46 for GOLD 1-4; 1.50 for FEV1/FEV6 <LLN).,For cardiovascular mortality, significant associations were found with GOLD 2-4 (HR = 2.68) and with GOLD 1-4 (HR = 1.78) for both genders together (not among women).,Low FEV1 was risk for overall and respiratory mortality (both genders combined).,FVC was not associated with overall mortality.,For most COPD criteria sensitivity was low and specificity high.,The area under the curve for FEV1 was greater than for FVC for overall and cardiovascular mortality.,COPD and low FEV1 are important predictors for overall and cardiovascular mortality in Latin America. | 1) To estimate the annual cost of patients with stable chronic obstructive pulmonary disease (COPD) followed in primary care in Spain; 2) To analyze the possible cost predictor variables.,A multicenter, epidemiological, observational, descriptive study.,Sociodemographic data, severity of disease, associated comorbidity, treatment followed by patients, quality of life (SF-12 questionnaire), health care resource utilization in the previous 12 months and duration of working disability due to COPD were collected.,A total of 10,711 patients (75.6% men; 24.4% women) with a mean age of 67.1 ± 9.66 years were evaluated.,The mean forced expiratory volume in one second (FEV1) value was 57.4 ± 13.4%.,The total cost per patient per year was €1,922.60 ± 2,306.44.,The largest component of this cost was hospitalization (€788.72 ± 1,766.65), followed by cost of drugs (€492.87 ± 412.15) and visits to emergency rooms (€134.32 ± 195.44).,Linear regression analysis found associated heart disease, FEV1, physical component of quality of life, number of medical visits (primary care physician, pneumologist and emergency room), hospital admissions (frequency and duration of stay) and duration of working disability to be significant predictors of the total annual cost.,The total annual cost of a COPD patient followed in primary care in Spain was considered high in this study.,The presence of associated heart disease, severity of airflow obstruction, physical component of quality of life, health care resource utilization and duration of work disability were found to be predictor of cost. | 1 |
There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care.,This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD.,A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis.,Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO).,Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer.,A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis. | To evaluate the clinical implementation of pharmacotherapy recommendations for chronic obstructive pulmonary disease (COPD) based on the Global Initiative for chronic obstructive lung disease (GOLD) guidelines, in a longitudinal setting.,This is a sub-analysis of a prospective, non-interventional cohort study including patients with confirmed mild-to-very-severe COPD from seven pulmonary outpatient clinics in Switzerland.,Follow-up visits took place annually for up to 7 years, from October 2010 until December 2016.,For each visit, we evaluated the compliance of the prescribed pharmacotherapy with the concurrently valid GOLD guideline.,We investigated whether step-ups or step-downs in GOLD stage or risk-group were accompanied by concordant changes in prescribed medication.,Groups were compared via ANOVA.,Data of 305 patients (62±7 years, 66% men) were analysed.,In 59.1% of visits, the prescribed medication conformed to the respective valid GOLD-guideline.,Patients with very severe COPD were most likely to receive pharmacotherapy in compliance with guidelines.,Step-ups and step-downs in risk group, requiring escalation, or de-escalation of pharmacotherapy, were noticed in 24 and 43 follow-up visits, respectively.,Step-ups were adequately implemented in 4 (16.7%) and step-downs in six cases (14.0%).,The compliance of COPD-pharmacotherapy with GOLD-guidelines is suboptimal, especially in lower risk groups.,The high rates of missed out treatment-adjustments suggest that the familiarity of physicians with guidelines leaves room for improvement. | 1 |
People with COPD have a decline in functional status, but little is known about the rate of decline and factors that contribute.,Of particular concern is the decline in cognitive and functional performance.,Decrease in cognitive and functional performance will finally lead to decreased health status, sedentary life style and premature frailty.,The aim of this study is to compare functional performance and cognitive status in patients with COPD of different ages and to examine the changes in extrapulmonary effects.,This study included 62 patients with COPD risk class D who were divided into two groups (<70 years, N=30 and >70 years, N=32).,Patients first completed the Montreal Cognitive Assessment (MoCA), which is a 30-point test that assesses different cognitive domains, while isometric knee extension (IKE) was measured using a digital handheld dynamometer, and functional exercise level was assessed using the 6-minute walking distance (6MWD) test.,The patients’ older age (age higher than 70 years) was associated with a significantly lower body mass index (BMI, 27.50 vs 24.24 kg/m2; P=0.020), higher vital capacity parameters, forced vital capacity (FVC, 2.74 vs 2.82 L; P=0.799), FVC (%) (73.00 vs 66.50, P=132), forced expiratory volume in the first second (FEV1, 0.93 vs 1.13 L; P=0.001) and FEV1 (%) (28.50 vs 30.50, P=0.605).,In addition, patients at older age presented a significantly reduced physical activity capacity, 6MWD (385.93 vs 320.84 m, P<0.001) and IKE (24.75 vs 22.55 kgf, P=0.005), as well as higher values for inflammatory biomarkers, C-reactive protein (8.77 vs 3.34 mg/L, P=0.022).,Moreover, patients at older age presented significantly lower score at the cognitive assessment, MoCA (23.50 vs 20.00, P<0.001).,Elderly COPD patients have reduced exercise capacity and muscle strength, deteriorated cognitive function and increased inflammatory markers.,Furthermore, inflammation markers were significantly correlated with muscle strength, walking distance and cognitive impairment. | Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | 1 |
There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care.,This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD.,A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis.,Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO).,Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer.,A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity.,Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited.,To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999-2009) with a focus on management, co-morbidity, and mortality.,This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS).,A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females).,The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years.,The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year.,Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting β2-agonist inhalers increased from 0% to 36% and 37%, respectively.,The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes.,Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all-cause mortality was 3.5 times higher.,Management of COPD in Sweden has improved during the 11-year study period.,Despite this, patients with COPD have a substantially reduced life expectancy than the general population. | To estimate patient- and episode-level direct costs of chronic obstructive pulmonary disease (COPD) among commercially insured patients in the US.,In this retrospective claims-based analysis, commercial enrollees with evidence of COPD were grouped into five mutually exclusive cohorts based on the most intensive level of COPD-related care they received in 2006, ie, outpatient, urgent outpatient (outpatient care in addition to a claim for an oral corticosteroid or antibiotic within seven days), emergency department (ED), standard inpatient admission, and intensive care unit (ICU) cohorts.,Patient- level COPD-related annual health care costs, including patient- and payer-paid costs, were compared among the cohorts.,Adjusted episode-level costs were calculated.,Of the 37,089 COPD patients included in the study, 53% were in the outpatient cohort, 37% were in the urgent outpatient cohort, 3% were in the ED cohort, and the standard admission and ICU cohorts together comprised 6%.,Mean (standard deviation, SD) annual COPD-related health care costs (2008 US$) increased across the cohorts (P < 0.001), ranging from $2003 ($3238) to $43,461 ($76,159) per patient.,Medical costs comprised 96% of health care costs for the ICU cohort.,Adjusted mean (SD) episode-level costs were $305 ($310) for an outpatient visit, $274 ($336) for an urgent outpatient visit, $327 ($65) for an ED visit, $9745 ($2968) for a standard admission, and $33,440 for an ICU stay.,Direct costs of COPD-related care for commercially insured patients are driven by hospital stays with or without ICU care.,Exacerbation prevention resulting in reduced need for inpatient care could lower costs. | 1 |
Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | To investigate the association between serpin family E member 1 (SERPINE1) -844 A/G and -675 4G/5G polymorphisms and chronic obstructive pulmonary disease (COPD) in a Chinese Han population.,SERPINE1 -844 A/G and -675 4G/5G polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism sequencing of genomic DNA from patients with COPD and healthy smoking controls.,Out of 140 patients with COPD and 100 controls, all SERPINE1 -844 and -675 polymorphisms were in Hardy-Weinberg equilibrium.,Differences in SERPINE1 -675 4G and 5G allele frequencies were statistically significant between the COPD and control groups (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.00, 2.09), but there was no significant between-group difference in SERPINE1 -844 A and G allele frequencies.,The SERPINE1 -675 4G/4G genotype was associated with COPD (OR 1.87, 95% CI 1.06, 3.32 [binary logistic regression]).,Haplotype analysis showed that COPD was associated with SERPINE1 -844G/4G (OR 2.11, 95% CI 1.32, 3.38) and SERPINE1 -844G/5G (OR 0.66, 95% CI 0.45, 0.95).,The SERPINE1 -675 polymorphism, but not SERPINE1 -844 polymorphism, was associated with susceptibility to COPD in a Chinese Han population. | 1 |
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. | 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. | 1 |
This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD.,This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012.,Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital.,They were randomly allocated to case and placebo group.,The patients received routine treatment for COPD.,Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months.,Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients.,In each group, there were 44 patients.,After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients.,Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly.,Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD.,It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. | Reduced neutrophil apoptosis plays an important role in the pathogenesis of acute exacerbation chronic obstructive pulmonary disease (AECOPD).,The p38 mitogen-activated protein kinase (MAPK) signaling pathway is involved in neutrophil apoptosis. 1α,25-Dihydroxyvitamin D3 (1α,25VitD3) can induce tumor cell apoptosis.,The aim of this study was to assess the effects of 1α,25VitD3 on peripheral blood neutrophil apoptosis in AECOPD and examine the role of the p38 MAPK signaling pathway.,The study enrolled 36 AECOPD patients and 36 healthy volunteers.,Venous blood samples were obtained from both groups.,Serum 25-hydroxyvitamin D (25-(OH) D) levels in peripheral venous blood were assayed using liquid chromatography-tandem mass spectrometry (LC-MS/MS); the neutrophils were separated and cultured with SB203580 (a p38 inhibitor) and 1α,25VitD3.,Neutrophil apoptosis was measured using flow cytometry, and phospho-p38 MAPK protein expression was detected by Western blot.,Statistical analysis was performed using analysis of variance.,Student's t-test and Pearson's correlation coefficient were used for the between-group differences and correlation analysis, respectively.,The 25-(OH) D levels were lower in AECOPD patients than in healthy controls, and the peripheral blood neutrophil apoptosis results were similar. 1α,25VitD3 increased the apoptosis rate and the level of phospho-p38 MAPK in peripheral blood neutrophils of AECOPD patients.,SB203580 partly inhibited 1α,25VitD3-induced peripheral blood neutrophil apoptosis and phospho-p38 MAPK overexpression.,The 25-(OH) D levels were positively correlated with increased peripheral blood neutrophil apoptosis and phospho-p38 MAPK levels.,In addition, expression of the phospho-p38 MAPK protein was also positively correlated with peripheral blood neutrophil apoptosis.,Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients. | 1 |
Chronic obstructive pulmonary disease (COPD) are managed predominantly in primary care.,However, key opportunities to optimize treatment are often not realized due to unrecognized disease and delayed implementation of appropriate interventions for both diagnosed and undiagnosed individuals.,The COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) is the first-of-its-kind, collaborative, interventional COPD registry.,It comprises an integrated quality improvement program focusing on patients (diagnosed and undiagnosed) at a modifiable and higher risk of COPD exacerbations.,The first step in CONQUEST was the development of quality standards (QS).,The QS will be imbedded in routine primary and secondary care, and are designed to drive patient-centered, targeted, risk-based assessment and management optimization.,Our aim is to provide an overview of the CONQUEST QS, including how they were developed, as well as the rationale for, and evidence to support, their inclusion in healthcare systems.,The QS were developed (between November 2019 and December 2020) by the CONQUEST Global Steering Committee, including 11 internationally recognized experts with a specialty and research focus in COPD.,The process included an extensive literature review, generation of QS draft wording, three iterative rounds of review, and consensus.,Four QS were developed: 1) identification of COPD target population, 2) assessment of disease and quantification of future risk, 3) non-pharmacological and pharmacological intervention, and 4) appropriate follow-up.,Each QS is followed by a rationale statement and a summary of current guidelines and research evidence relating to the standard and its components.,The CONQUEST QS represent an important step in our aim to improve care for patients with COPD in primary and secondary care.,They will help to transform the patient journey, by encouraging early intervention to identify, assess, optimally manage and followup COPD patients with modifiable high risk of future exacerbations. | Clinical guidelines for management of patients with chronic obstructive pulmonary disease (COPD) include recommendations based on high levels of evidence, but gaps exist in their implementation.,The aim of this study was to examine the perspectives of medical practitioners regarding implementation of six high-evidence recommendations for the management of people with COPD.,Semi-structured interviews were conducted with medical practitioners involved with care of COPD patients in hospital and general practice.,Interviews sought medical practitioners’ experience regarding implementation of smoking cessation, influenza vaccination, pulmonary rehabilitation, guideline-based medications, long-term oxygen therapy for hypoxemia and plan and advice for future exacerbations.,Interviews were audiotaped, transcribed verbatim and analyzed using content analysis.,Nine hospital-based medical practitioners and seven general practitioners participated.,Four major categories were identified which impacted on implementation of the target recommendations in the care of patients with COPD: (1) role clarity of the medical practitioner; (2) persuasive communication with the patient; (3) complexity of behavioral change required; (4) awareness and support available at multiple levels.,For some recommendations, strength in all four categories provided significant enablers supporting implementation.,However, with regard to pulmonary rehabilitation and plans and advice for future exacerbations, all identified categories that presented barriers to implementation.,This study of medical practitioner perspectives has indicated areas where significant barriers to the implementation of key evidence-based recommendations in COPD management persist.,Developing strategies to target the identified categories provides an opportunity to achieve greater implementation of those high-evidence recommendations in the care of people with COPD. | 1 |
Batefenterol (BAT) is a bi-functional molecule with both muscarinic antagonist and β2-adrenoceptor agonist pharmacology.,This Phase II, randomized, placebo-controlled, double-blind study evaluated the safety and tolerability of BAT 300 μg with fluticasone furoate (FF) 100 μg administered via the ELLIPTA inhaler (BAT/FF 300/100).,Subjects with stable chronic obstructive pulmonary disease were randomized 2:1 to receive BAT/FF 300/100 or placebo once daily for 6 weeks.,The primary endpoint was change from baseline in 0-4-h weighted mean (WM) heart rate (HR, measured by electrocardiogram [ECG]) on Day 42.,Other endpoints included WM and maximum 0-4-h corrected QT interval (ECG on Days 1, 28, and 42), HR measured by Holter monitoring (Day 42), and standard safety assessments.,Study protocol was approved by an Investigational Review Board.,Sixty-two patients were randomized and received ≥1 dose of study medication (BAT/FF 300/100 n = 42; placebo n = 20).,Mean age was 62.5 years (standard deviation [SD] 8.17).,Study completion rates were 83% (BAT/FF 300/100) and 100% (placebo).,Screening mean (SD) post-bronchodilator percentage-predicted forced expiratory volume in 1 s was 57.57 (11.42) in the BAT/FF 300/100 group and 55.68 (14.03) in the placebo group.,BAT/FF 300/100 was non-inferior to placebo for the primary endpoint, treatment difference: − 2.2 beats per minute (bpm), 95% confidence interval [CI]: − 6.2, 1.7).,There were no clinically relevant differences between treatment groups in WM or maximum 0-4-h corrected QT interval, or mean HR based on Holter monitoring on Day 42 (BAT/FF 300/100: 76.3 bpm [SD 11.38]; placebo: 84.8 bpm [SD 9.87]).,Adverse events (AEs) occurred in 38% (BAT/FF 300/100) and 35% (placebo) of patients.,AEs in ≥2 subjects with BAT/FF 300/100 were dysgeusia (10%), diarrhea (7%), nasopharyngitis (7%), and cough (5%).,AEs leading to discontinuation occurred in two subjects who received BAT/FF 300/100: post-treatment severe pneumonia (serious AE) and non-serious AEs of moderate vomiting and severe gastroenteritis; both were not considered drug-related.,No deaths occurred.,Six weeks of BAT/FF 300/100 treatment was non-inferior to placebo for change from baseline in HR, with no new clinically relevant general or cardiovascular safety signals.,Clinicaltrials.gov: NCT02573870 (submitted October 12, 2015). | Patients with COPD most frequently complain of breathlessness and cough and these are both increased during exacerbations.,Studies have generally focused on quality of life during end-stage disease, where breathlessness becomes dominant and cough less important.,There are very little data on the frequency and severity of cough in COPD or its impact on quality of life at different stages of disease.,Little is known about the factors that influence objective cough counts in COPD.,Cough may be a marker for progressive disease in milder COPD patients who continue to smoke, and it may be useful in case-finding for milder disease in the community.,The cough reflex sensitivity is heightened in COPD compared with healthy volunteers and similar to that in subjects with asthma.,The degree of airflow obstruction does not predict cough reflex sensitivity or objective cough counts, implying an independent process.,Effective treatments for cough in COPD have not yet been identified.,Improved outcome measures of cough, a better understanding of cough in the natural history of COPD, and its importance to patients are needed. | 1 |
Dual bronchodilation combining a long-acting β2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials.,The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year.,Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments.,The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population).,The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; [Δ = 1.09 units]), and to LABA or LAMA on trough FEV1 (Δ = +101 mL) and a TDI (Δ = 1.26 units).,Improvements in health status and lower rescue medication use were also observed with IND/GLY.,The safety profile of the study medication was similar to that observed in previous studies.,IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments.,ClinicalTrials.gov number: NCT01985334.,The online version of this article (doi:10.1186/s12931-017-0622-x) contains supplementary material, which is available to authorized users. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
There is good evidence to suggest that chronic obstructive pulmonary disease (COPD) increases the risk of ischaemic heart disease, in particular myocardial infarction (MI).,The relationship between stroke and COPD, however, is not as well established, and studies conducted to date have generated conflicting results.,MEDLINE and Embase will be searched for relevant articles using a prespecified search strategy.,We will target observational studies conducted in the general population that employ either a longitudinal cohort or case-control study design to estimate ORs, HRs or incident rate ratios for the association between COPD and a subsequent first stroke.,Both stages of screening, title and abstract followed by full-text screening, will be conducted independently by two reviewers.,The Population, Exposure, Comparator, Outcomes, Study characteristics (PECOS) framework will be used to systematise the process of extracting data from those studies meeting our selection criteria.,Study quality will be assessed using an adapted version of the Newcastle-Ottawa risk of bias tool.,The data extraction and the risk of bias assessment will also be conducted in duplicate.,A meta-analysis will be considered if there is sufficient homogeneity across selected studies or groups of studies.,If a meta-analysis is not justified, a narrative synthesis will be conducted.,Selected Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria will be used to assess the quality of the cumulative evidence.,Currently ranking second and fourth in the list of global causes of mortality, respectively, stroke and COPD are important non-communicable diseases.,With this review, we hope to clarify some of the current uncertainty that surrounds the COPD-stroke relationship and in turn improve understanding of the nature of the role of COPD in comorbid stroke.,CRD42016035932. | Low adherence to Global initiative for chronic Obstructive Lung Disease (GOLD) guideline recommendations has been reported worldwide.,There has been no study on the adherence to GOLD guidelines for COPD treatment in Turkey.,To investigate the rates of adherence to GOLD 2010 guidelines for COPD treatment among pulmonologists.,A multi-center, cross-sectional, observational study was carried out in eleven pulmonary outpatient clinics across Turkey.,Adherence to GOLD was evaluated through hospital records.,Demographic and clinical data were recorded.,Study included 719 patients (mean age: 62.9±9.7 years; males 85.4%) of whom 16 was classified as GOLD Stage I, 238 as II, 346 as III, and 119 as IV, and only 59.5% received appropriate treatment.,Rates of guideline adherence varied across GOLD stages (I, 6.3%; II, 14.7%; III, 84.4%; and IV, 84%).,Causes of inappropriate therapies were overtreatment (Stage I, 100% and Stage II, 91.1%), undertreatment (Stage III, 3.3% and Stage IV, 10.9%) and lack of treatment (Stage II, 3.8%; Stage III, 2.3%; and Stage IV, 5.9%).,The most preferred regimen (43.4%) was long-acting β2-agonist-inhaled corticosteroid-long-acting muscarinic antagonist.,Overall, 614 patients (89%) received treatment containing inhaled corticosteroid.,Pulmonologists in Turkey have low rates of adherence to GOLD guidelines in COPD treatment.,Inappropriateness of therapies was due to overtreatment in early stages and excessive use of inhaled corticosteroid (ICS) in all disease stages. | 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. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear.,This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo.,Backward elimination via Cox’s proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation.,Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216.,Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk.,BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2.,The modelled probability of pneumonia varied between 3 and 12% during the first year.,Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment.,The influence of the other exacerbation risk factors was not modified by ICS treatment.,Modelled probabilities of an exacerbation varied between 31 and 82% during the first year.,The probability of an exacerbation was considerably higher than for pneumonia.,ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex.,The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2.,Analyses of this type may help the development of COPD risk equations. | The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease.,The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality.,The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number.,The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure.,The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions.,Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels.,The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally.,Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments.,MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis.,Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC.,These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF).,Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD.,Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease.,Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion. | The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear.,We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in COPD patients.,Precision-cut lung slices (PCLS) were prepared from guinea pigs challenged with lipopolysaccharide or saline two times weekly for 12 wk.,Peripheral PCLS were obtained from patients with mild to moderate COPD and non-COPD controls.,AHR to methacholine was measured in large and small airways using video-assisted microscopy.,Airway smooth muscle mass and alveolar airspace size were determined in the same slices.,A mathematical model was used to identify potential changes in biomechanical properties underlying AHR.,In guinea pigs, lipopolysaccharide increased the sensitivity of large (>150 μm) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (<150 μm) by 1.5-fold.,Similarly increased small airway responsiveness was found in COPD patients.,In both lipopolysaccharide-challenged guinea pigs and patients, airway smooth muscle mass was unaltered, whereas increased alveolar airspace correlated with small airway hyperresponsiveness in guinea pigs.,Fitting the parameters of the model indicated that COPD weakens matrix mechanical properties and enhances stiffness differences between the airway and the parenchyma, in both species.,In conclusion, this study demonstrates small airway hyperresponsiveness in PCLS from COPD patients.,These changes may be related to reduced parenchymal retraction forces and biomechanical changes in the airway wall.,PCLS from lipopolysaccharide-exposed guinea pigs may be useful to study mechanisms of small airway hyperresponsiveness in COPD. | 1 |
Background.,Innate immune antimicrobial peptides, including β-defensin-1, promote the chemotaxis and activation of several immune cells.,The role of β-defensin-1 in asthma and chronic obstructive pulmonary disease (COPD) remains unclear.,Methods.,Induced sputum was collected from healthy controls and individuals with asthma or COPD. β-defensin-1 protein in sputum supernatant was quantified by ELISA.,Biomarker potential was examined using receiver operating characteristic curves. β-defensin-1 release from primary bronchial epithelial cells (pBECs) was investigated in culture with and without cigarette smoke extract (CSE).,Results.,Airway β-defensin-1 protein was elevated in COPD participants compared to asthma participants and healthy controls.,Inflammatory phenotype had no effect on β-defensin-1 levels in asthma or COPD. β-defensin-1 protein was significantly higher in severe asthma compared to controlled and uncontrolled asthma. β-defensin-1 protein could predict the presence of COPD from both healthy controls and asthma patients.,Exposure of pBECs to CSE decreased β-defensin-1 production in healthy controls; however in pBECs from COPD participants the level of β-defensin-1 remanied unchanged.,Conclusions.,Elevated β-defensin-1 protein is a feature of COPD and severe asthma regardless of inflammatory phenotype. β-defensin-1 production is dysregulated in the epithelium of patients with COPD and may be an effective biomarker and potential therapeutic target. | 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. | 1 |
In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity.,Intercostal muscle ultrasound offers a repeatable and radiation-free alternative, however requires validation.,We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters.,Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2nd and 3rd parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT.,Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91.,Inter-rater ICC was fair to excellent.,Ultrasound intercostal thickness moderately correlated with FEV1% predicted (r = 0.33) and quadriceps thickness (r = 0.31).,Echogenicity correlated negatively with FEV1% predicted (r = −0.32).,CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness.,These data confirm ultrasound of parasternal intercostal musculature is reproducible.,Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity.,This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics.,The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall. | Limited mobility is a risk factor for developing chronic obstructive pulmonary disease (COPD)-related disabilities.,Little is known about the validity of the Short Physical Performance Battery (SPPB) for identifying mobility limitations in patients with COPD.,To determine the clinical validity of the SPPB summary score and its three components (standing balance, 4-meter gait speed, and five-repetition sit-to-stand) for identifying mobility limitations in patients with COPD.,This cross-sectional study included 137 patients with COPD, recruited from a hospital in Spain.,Muscle strength tests and SPPB were measured; then, patients were surveyed for self-reported mobility limitations.,The validity of SPPB scores was analyzed by developing receiver operating characteristic curves to analyze the sensitivity and specificity for identifying patients with mobility limitations; by examining group differences in SPPB scores across categories of mobility activities; and by correlating SPPB scores to strength tests.,Only the SPPB summary score and the five-repetition sit-to-stand components showed good discriminative capabilities; both showed areas under the receiver operating characteristic curves greater than 0.7.,Patients with limitations had significantly lower SPPB scores than patients without limitations in nine different mobility activities.,SPPB scores were moderately correlated with the quadriceps test (r>0.40), and less correlated with the handgrip test (r<0.30), which reinforced convergent and divergent validities.,A SPPB summary score cutoff of 10 provided the best accuracy for identifying mobility limitations.,This study provided evidence for the validity of the SPPB summary score and the five-repetition sit-to-stand test for assessing mobility in patients with COPD.,These tests also showed potential as a screening test for identifying patients with COPD that have mobility limitations. | 1 |
COPD is one of the leading causes of morbidity and mortality in the world; however, the most varied amounts of clinical and laboratory characteristics acts in different ways in the mortality among over time.,Therefore, this study aimed to evaluate the predictors of mortality in patients with COPD after 9 years.,One hundred and thirty-three patients with COPD were assessed at baseline by spirometry, pulse oximetry (SpO2), body composition, intensity of dyspnea, distance walked in the 6-minute walk test (6MWT), and Charlson Comorbidity Index (CCI).,After 9 years, it was not possible to identify the lifetime of 4 patients who died and of 19 patients who stopped follow-up; thus, 110 patients were included in the analysis of predictors of mortality (67% male, 65±9 years old, and FEV1: 52.5 [40%-73%]).,Male sex, age, SpO2, Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index, and frequency of exacerbations in the first 3 years of follow-up were considered in the model.,Patients classified at baseline with BODE class 2 (HR: 2.62, 95% CI: 1.36-5.04; P=0.004), BODE class 3 (HR: 2.54, 95% CI: 1.15-5.61; P=0.02), and BODE class 4 (HR: 15.35, 95% CI: 3.11-75.75; P=0.001) showed increased risk of death compared to those with BODE class 1.,The CCI (HR: 1.29, 95% CI: 1.00-1.68; P=0.04) and the number of exacerbations in the first 3 years (HR: 1.32, 95% CI: 1.00-1.76; P=0.04) also showed increased risk of death.,By replacing the BODE index for the variables that compose it, those with body mass index ≤21 kg/m2 showed increased risk of death compared to those with body mass index (BMI)>21 kg/m2 (HR: 2.70, 95% CI: 1.38-5.25; P=0.003).,After 9 years, we identified that those with high BODE index, greater CCI, greater frequency of exacerbations in the first 3 years, and BMI ≤21 kg/m2 showed increased risk of death. | Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD).,Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs.,We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders.,We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients.,We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index.,Elixhauser comorbidity counts were clustered from 0 to 7 or more.,We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence.,Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased.,ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black).,Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders.,Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD.,Female sex was associated with COPD-related and non-COPD-related ED visits.,Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD.,Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team. | 1 |
We aimed to investigate the efficacy of four severity-of-disease scoring systems in predicting the 28-day survival rate among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring emergency care.,Clinical data of patients with AECOPD who required emergency care were recorded over 2 years.,APACHE II, SAPS II, SOFA, and MEDS scores were calculated from severity-of-disease indicators recorded at admission and compared between patients who died within 28 days of admission (death group; 46 patients) and those who did not (survival group; 336 patients).,Compared to the survival group, the death group had a significantly higher GCS score, frequency of comorbidities including hypertension and heart failure, and age (P < 0.05 for all).,With all four systems, scores of age, gender, renal inadequacy, hypertension, coronary heart disease, heart failure, arrhythmia, anemia, fracture leading to bedridden status, tumor, and the GCS were significantly higher in the death group than the survival group.,The prediction efficacy of the APACHE II and SAPS II scores was 88.4%.,The survival rates did not differ significantly between APACHE II and SAPS II (P = 1.519).,Our results may guide triage for early identification of critically ill patients with AECOPD in the emergency department. | Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high.,The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care.,We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools.,The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014.,Consecutive admissions were identified by screening admissions and searching coding records.,Admission clinical data, including DECAF indices, and mortality were recorded.,The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve.,In the internal and external validation cohorts, 880 and 845 patients were recruited.,Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted.,Overall mortality was 7.7%.,The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality.,DECAF is a robust predictor of mortality, using indices routinely available on admission.,Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation.,UKCRN ID 14214. | 1 |
Self-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms.,However, many factors impede engagement for patients and practitioners.,Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors.,Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted.,Following a systematic search and screening, 31 studies were appraised and data extracted for analysis.,This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process.,Emotional needs are considerable; frustration, depression, and anxiety are common.,In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction.,Over time, COPD can consume their existence, reducing motivation.,Support from family can prove vital, yet tinged with ambivalence and burden.,Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs.,This can compound patients’ capability to engage in self-management.,For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management.,In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease.,Patients with COPD are not a homogenous group and no one intervention will prove effective for all.,Finally, practitioners require greater education, training, and support to successfully assist patients. | In this narrative review, we put self-management in the context of a 50-year history of research about how patients with COPD respond to their illness.,We review a definition of self-management, and emphasize that self-management should be combined with disease management and the chronic care model in order to be effective.,Reviewing the empirical status of self-management in COPD, we conclude that self-management is part and parcel of modern, patient-oriented biopsychosocial care.,In pulmonary rehabilitation programs, self-management is instrumental in improving patients’ functional status and quality of life.,We conclude by emphasizing how studying the way persons with COPD make sense of their illness helps in refining self-management, and thereby patient-reported outcomes in COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers.,The utility of these clinical subtypes is unclear.,However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant.,The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.,Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis.,Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%.,Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%).,Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized.,Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St.,George’s Respiratory Questionnaire score 43 vs 31, p < 0.0001).,Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use.,The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study.,Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes.,COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa.,Clinicaltrials.gov identifiers: COPDGene NCT00608764, ECLIPSE NCT00292552.,The online version of this article (doi:10.1186/1471-2466-14-164) contains supplementary material, which is available to authorized users. | The ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) is a measure used to diagnose airflow obstruction and is highly heritable.,We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated with the FEV1/FVC ratio, analyzed as a percent of the predicted value.,Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction.,Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09).,One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham) was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV1/FVC (p-value = 2.0e-04).,The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G) associated with higher FEV1/FVC ratio levels.,Results from the Family Heart Study demonstrated that the association extended to FEV1 and dichotomous airflow obstruction phenotypes, particularly among smokers.,The SNP rs13147758 was associated with the percent predicted FEV1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript.,The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP) gene and several expressed sequence tags cloned from fetal lung.,Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation. | 1 |
COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease.,Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).,This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers.,Patients who met GOLD criteria for COPD and were able to tolerate bronchoscopies were randomly assigned (1:1:1) to receive placebo, 25 μmoles, or 150 μmoles sulforaphane daily by mouth for four weeks.,The primary outcomes were changes in Nrf2 target gene expression (NQ01, HO1, AKR1C1 and AKR1C3) in alveolar macrophages and bronchial epithelial cells.,Secondary outcomes included measures of oxidative stress and airway inflammation, and pulmonary function tests.,Between July 2011 and May 2013, 89 patients were enrolled and randomized.,Sulforaphane was absorbed in the patients as evident from their plasma metabolite levels.,Changes in Nrf2 target gene expression relative to baseline ranged from 0.79 to 1.45 and there was no consistent pattern among the three groups; the changes were not statistically significantly different from baseline.,Changes in measures of inflammation and pulmonary function tests were not different among the groups.,Sulforaphane was well tolerated at both dose levels.,Sulforaphane administered for four weeks at doses of 25 μmoles and 150 μmoles to patients with COPD did not stimulate the expression of Nrf2 target genes or have an effect on levels of other anti-oxidants or markers of inflammation.,Clinicaltrials.gov: NCT01335971. | ► Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited.,► HDAC inhibition decreases Nrf2 protein stability.,► HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples.,► HDAC inhibition increases Nrf2 acetylation.,Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes.,However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain.,Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress.,Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H2O2) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA).,TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo.,HDAC2 knock-down by RNA interference resulted in reduced H2O2-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect.,Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001).,Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences. | 1 |
We investigated the effect of the long-acting muscarinic antagonist aclidinium bromide on chronic obstructive pulmonary disease (COPD) exacerbations by pooling data from five randomized, placebo-controlled, parallel-group Phase III studies of 3-6 months’ duration.,Data were pooled from the aclidinium 400 μg twice-daily (BID) and placebo arms (N = 2,521) and stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) group (A, B, C and D).,Results showed that fewer patients experienced ≥1 exacerbation with aclidinium (any severity: 12.5%; moderate to severe: 10.9%) compared with placebo (any severity: 15.7%; moderate to severe: 13.3%) and the odds of experiencing ≥1 exacerbation of any severity were reduced in patients receiving aclidinium (odds ratio = 0.78, p = 0.039).,Furthermore, aclidinium reduced the rate of exacerbations compared with placebo (any severity: rate ratio = 0.79, p = 0.026; moderate to severe: 0.80, p = 0.044).,The time to first exacerbation of any severity was delayed with aclidinium compared with placebo (hazard ratio = 0.79, p = 0.026) and there was a numerical delay in time to first moderate-to-severe exacerbation.,Finally, the effects of aclidinium on exacerbations versus placebo were greater in patients in GOLD Groups B and D; however, it is of note that only 10.7% of patients were classified in Group A or C.,In summary, the results indicate that aclidinium 400 μg BID reduces the frequency of COPD exacerbations compared with placebo and that these effects are greater in symptomatic patients. | The specific attributes of inhaler devices can influence patient use, satisfaction and treatment compliance, and may ultimately impact on clinical outcomes in patients with chronic obstructive pulmonary disease (COPD).,To assess patient preference, satisfaction and critical inhaler technique errors with Genuair (a multidose inhaler) and Breezhaler (a single-dose inhaler) after 2 weeks of daily use.,Patients with COPD and moderate to severe airflow obstruction were randomised in a cross-over, open-label, multicentre study to consecutive once-daily inhalations of placebo via Genuair and Breezhaler, in addition to current COPD medication.,The primary end point was the proportion of patients who preferred Genuair versus Breezhaler after 2 weeks (Patient Satisfaction and Preference Questionnaire).,Other end points included overall satisfaction and correct use of the inhalers after 2 weeks, and willingness to continue with each device.,Of the 128 patients enrolled, 127 were included in the safety population (male n=91; mean age 67.6 years).,Of the 110 of the 123 patients in the intent-to-treat population who indicated an inhaler preference, statistically significantly more patients preferred Genuair than Breezhaler (72.7 vs.,27.3%; P<0.001).,Mean overall satisfaction scores were also greater for Genuair than for Breezhaler (5.9 vs.,5.3, respectively; P<0.001).,After 2 weeks, there was no statistically significant difference in the number of patients who made ⩾1 critical inhaler technique error with Breezhaler than with Genuair (7.3 vs.,3.3%, respectively).,Patient overall preference and satisfaction was significantly higher with Genuair compared with Breezhaler.,The proportion of patients making critical inhaler technique errors was low with Genuair and Breezhaler. | 1 |
To investigate the prevalence of smoking and the reasons for continuing to smoke among adults in Brazil.,This was a cross-sectional, population-based study including 1,054 individuals ≥ 40 years of age, residents of the city of Florianopolis, Brazil, of whom 183 were smokers.,All of the smokers completed the University of São Paulo Reasons for Smoking Scale (USP-RSS).,Depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale, and spirometry was performed to screen for COPD.,Of the 183 smokers, 105 (57.4%) were female, 138 (75.4%) were White, and 125 (63.8%) were in a low economic class.,The mean level of education among the smokers was 9.6 ± 6.1 years.,The mean smoking history was 29 ± 15 pack-years, 59% of the men having a ≥ 30 pack-year smoking history.,Approximately 20% of the smokers had COPD, and 29% had depressive symptoms, which were more common in the women.,The USP-RSS scores were highest for the pleasure of smoking (PS), tension reduction (TR), and physical dependence (PD) domains (3.9 ± 1.1, 3.6 ± 1.2, and 3.5 ± 1.3, respectively).,Scores for the PS, TR, and weight control (WC) domains were significantly higher in women.,Smokers with a > 20 pack-year smoking history scored significantly higher on the PD, PS, automatism, and close association (CA) domains.,Smoking history was associated with the PD, PS, TR, and CA domains.,Depressive symptoms were associated with the PD, social smoking, and CA domains (p = 0.001; p = 0.01; p = 0.09, respectively).,Female gender and a low level of education were associated with the PS domain (p = 0.04) and TR domain (p < 0.001).,The prevalence of smoking in our sample was relatively high (17.4%).,The USP-RSS domains PS, TR, and WC explain why individuals continue smoking, as do depressive symptoms. | Biomass smoke exposure (BSE) is a recognized cause of COPD particularly in rural areas.,However, little research has been focused on BSE in suburban areas.,The aim of this study was to determine the prevalence of COPD, respiratory symptoms (RS) and BSE in women living in a suburban area of Mexico City exposed to BSE.,A cross-sectional epidemiological survey of a female population aged >35 years was performed using a multistage cluster sampling strategy.,The participants completed questionnaires on RS and COPD risk factors.,The COPD prevalence was based on the postbronchodilator forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio.,Of the 1,333 women who completed the respiratory questionnaires, spirometry data were obtained from 1,190, and 969 of these were scored as A-C.,The prevalence of BSE was 47%, and the estimated prevalence of COPD was 2.5% for the total population (n=969) and 3.1% for those with BSE only.,The spirometry and oximetry values were significantly lower in women with greater exposure levels.,The prevalence of RS (cough, phlegm, wheezing and dyspnea) was significantly higher in the women with BSE compared to those without exposure.,We concluded that the association of COPD with biomass exposure is not only a rural phenomenon but also may be observed in the suburban areas of the big cities. | 1 |
Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.,Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.,Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups.,The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function.,In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs.,These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen).,The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.,An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.,The online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users. | Goblet cell hyperplasia is a classic but variable pathologic finding in COPD.,Current literature shows that smoking is a risk factor for chronic bronchitis but the relationship of these clinical features to the presence and magnitude of large airway goblet cell hyperplasia has not been well described.,We hypothesized that current smokers and chronic bronchitics would have more goblet cells than nonsmokers or those without chronic bronchitis (CB), independent of airflow obstruction.,We recruited 15 subjects with moderate to severe COPD, 12 healthy smokers, and 11 healthy nonsmokers.,Six endobronchial mucosal biopsies per subject were obtained by bronchoscopy and stained with periodic acid Schiff-Alcian Blue.,Goblet cell density (GCD) was quantified as goblet cell number per millimeter of basement membrane.,Mucin volume density (MVD) was quantified as volume of mucin per unit area of basement membrane.,Healthy smokers had a greater GCD and MVD than nonsmokers and COPD subjects.,COPD subjects had a greater GCD than nonsmokers.,When current smokers (healthy smokers and COPD current smokers, n = 19) were compared with all nonsmokers (nonsmoking controls and COPD ex-smokers, n = 19), current smokers had a greater GCD and MVD.,When those with CB (n = 12) were compared to those without CB (n = 26), the CB group had greater GCD.,This finding was also seen in those with CB in the COPD group alone.,In multivariate analysis, current smoking and CB were significant predictors of GCD using demographics, lung function, and smoking pack years as covariates.,All other covariates were not significant predictors of GCD or MVD.,Current smoking is associated with a more goblet cell hyperplasia and number, and CB is associated with more goblet cells, independent of the presence of airflow obstruction.,This provides clinical and pathologic correlation for smokers with and without COPD. | 1 |
B-type natriuretic peptide (BNP) and the N-terminal fragment of pro-BNP (NT-pro-BNP) are established biomarkers of heart failure.,Increased levels of natriuretic peptide (NP) have been associated with poor outcomes in acute exacerbation of COPD (AECOPD); however, most studies did not address the conditions that can also increase NT-pro-BNP levels.,We aimed to determine if NT-pro-BNP levels correlate with outcomes of AECOPD in patients without heart failure and other conditions that can affect NT-pro-BNP levels.,We conducted a retrospective study in patients hospitalized for AECOPD with available NT-pro-BNP levels and normal left ventricular ejection fraction.,We compared patients with normal and elevated NT-pro-BNP levels and analyzed the clinical and outcome data.,A total of 167 of 1,420 (11.7%) patients met the study criteria.,A total of 77% of male patients and 53% of female patients had elevated NT-pro-BNP levels (P=0.0031).,NT-pro-BNP levels were not associated with COPD severity and comorbid illnesses.,Log-transformed NT-pro-BNP levels were positively associated with echocardiographically estimated right ventricular systolic pressure (r=0.3658; 95% confidence interval [CI]: 0.2060-0.5067; P<0.0001).,Patients with elevated NT-pro-BNP levels were more likely to require intensive care (63% vs 43%; P=0.0207) and had a longer hospital length of stay (P=0.0052).,There were no differences in the need for noninvasive positive pressure ventilation (P=0.1245) or mechanical ventilation (P=0.9824) or in regard to in-hospital mortality (P=0.5273).,Patients with AECOPD and elevated NT-pro-BNP levels had increased hospital length of stay and need for intensive care.,Based on our study, serum NT-pro-BNP levels cannot be used as a biomarker for increased mortality or requirement for invasive or noninvasive ventilation in this group of patients. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
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. | 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 |
This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).,Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks.,The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6.,Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.,Results: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]).,Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (Δ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (Δ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6.,Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo.,Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05).,Adverse-event (AE) incidence (28%) was similar between treatments.,Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.,Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks.,Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium.,Aclidinium was generally well tolerated. | 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: Indonesia ranks 7th highest in the world for the number of deaths caused by tobacco use including those caused by Chronic Obstructive Pulmonary Disease (COPD).,The purpose of this study was to determine the influence of initial smoking age and habit on the incidence of COPD.,Methods: This research was a case-control study.,The sampling in this research took a systematic random sampling method.,The samples of this study were 56 respondents of a case group and 56 respondents of a control group.,This study was conducted at Ngudi Waluyo Hospital, Wlingi, Blitar from October to November 2017.,Results: The factors that influenced the incidence of COPD were being male (p = 0.00; OR = 6.333; 95%CI = 2.776-14.450), a smoker (p = 0.00050; OR = 5.1318; 95%CI = 1.9004-13.8958), initially smoking at <15 years old (p = 0.00; OR = 11,769; 95%CI = 4.086-33.903), initially getting into a smoking habit at the age of <15 years old (OR = 12; CI = 1346-106,950), initially getting into a smoking habit at the age of ≥15 years old (OR = 3647; CI = 1625-8183) and having smoked for ≥30 years (OR = 8857; CI = 3298-23,787).,Conclusion: There are three factors of smoking behavior that influence COPD: smoking habit, initial smoking age and smoking duration.,Of all factors, forming a smoking habit at the age of <15 years old has the biggest risk (OR = 12; CI = 1346-106,950). | 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. | 1 |
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD).,In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new.,In combination, these variants strongly predict COPD in independent patient populations.,Furthermore, the combined effect of these variants showed generalizability across smokers and never-smokers, and across ancestral groups.,We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function associated variants.,This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD. | To determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers.,Of the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival.,Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system.,Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of −950 HU or less) (LAA-950).,Median duration of follow-up was 7.4 years.,Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1).,Observer agreement in visual scoring was good (weighted κ values, 0.71-0.80).,There were 519 deaths in the study cohort.,Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001).,This increased mortality generally persisted after adjusting for LAA-950.,The visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema.,Online supplemental material is available for this article. | 1 |
Dyspnea, fatigue, and decline in sleep quality are symptoms of chronic obstructive pulmonary disease (COPD).,Pulmonary rehabilitation programs have been shown to ameliorate dyspnea and fatigue.,However, only a few studies have investigated the effects of pulmonary rehabilitation on the sleep quality of COPD patients.,In this study, we analyzed the benefits of a pulmonary rehabilitation program to sleep quality and daytime somnolence in COPD patients.,This study was a study of 30 moderate-severe COPD patients.,All patients were evaluated by a pulmonologist and underwent polysomnography before participating in the study.,For this study, we selected only ex-smokers and patients with sleep apnea were referred to the sleep clinic.,These participants were prospectively recruited and not selected based on program completion.,Before the start of the program, sleep quality and daytime somnolence of the participants were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), respectively.,Rehabilitation program consisted of muscular training sessions conducted at the gym 3 times per week for 12 weeks.,After rehabilitation program, the patients were reassessed and their sleep quality and daytime somnolence were reevaluated using the PSQI and the ESS, respectively.,Before rehabilitation, PSQI evaluation revealed that 73% of the participants had poor sleep quality, and ESS evaluation showed that 86.7% of the participants experienced daytime somnolence.,After pulmonary rehabilitation, the PSQI specifically improved in terms of subjective sleep quality and sleep duration (< 0.001), habitual sleep efficiency (0.001), and sleep latency and sleep alterations (0.002) and there was also improvement in the ESS (< 0.001).,Pulmonary rehabilitation program of gradually increasing intensity has the potential to provide sleep-related benefits to patients with COPD who have poor sleep quality and daytime somnolence.,Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR62b4z2. | 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. | 1 |
Informal carers play a key supportive role for patients with chronic obstructive pulmonary disease.,However, caring can have a considerable impact on health and wellbeing.,Carers may have unidentified support needs that could be a target for intervention.,Literature on the support needs of informal carers has not been fully synthesised, and our knowledge of the comprehensiveness of the Carer Support Needs Assessment Tool for these individuals is limited.,To explore whether the Carer Support Needs Assessment Tool covers the support needs of carers of patients with chronic obstructive pulmonary disease identified in published literature.,English language studies were identified against predetermined inclusion/exclusion criteria through database searching.,Further studies were identified through searching reference lists and citations of included papers.,Papers were critically appraised and data extracted and synthesised by two reviewers.,Identified needs were mapped to Carer Support Needs Assessment Tool questions.,MEDLINE, CINAHL, EMBASE, CDSR, ASSIA, PsycINFO and Scopus databases (Jan 1997-Dec 2017).,Twenty-four studies were included.,Results suggest that carers have support needs in a range of domains including physical, social, psychological and spiritual.,Many of these needs are unmet.,Particular areas of concern relate to prolonged social isolation, accessing services, emotional support and information needs.,Findings also suggest amendment of the Carer Support Needs Assessment Tool may be required relating to difficulties within relationship management.,Evidence suggests that carers of patients with chronic obstructive pulmonary disease would benefit from identification and response to their support needs by healthcare professionals but to enable this, the Carer Support Needs Assessment Tool requires an additional question.,Future planned work will explore this with carers of patients with chronic obstructive pulmonary disease. | The aim of this study was to evaluate the predictive ability of multiple social, and clinical factors for readmission after a severe acute exacerbation of COPD (AECOPD) during various time periods.,We performed a prospective cohort study in which recruited patients with AECOPD.,We systematically collected numerous clinical (symptoms, pulmonary function, comorbidities, and treatment) and social (financial situation, housing situation, family support, caregiver overload, ability to perform activities, and risk of social exclusion) variables using several questionnaires and indices.,The patients were followed closely for one year and readmissions at 30, 60, and 365 days were analysed.,253 patients were included, aged 68.9±9.8years, FEV1 = 42.1%±14.2%, and a Charlson’s index = 1.8±0.9.,Of these patients, 20.2%, 39.6%, and 63.7% were readmitted within the first 30, 90, and 365 days after discharge, respectively.,In the multivariate model applied, the variables that were independently associated with readmission over all three periods of the analysis were dependence to perform basic activities of daily living (BADLs) (odds ratio [OR] = 2.10-4.10) and a history of two or more admissions within the previous year (OR = 2.78-3.78).,At 90 days, a history of bacterial isolates in a previous sputum culture (OR = 2.39) and at 365 days, a high grade of dyspnoea (OR = 2.51) and obesity (OR = 2.38) were also identified as predictors of hospital readmission.,The patients’ limitation to perform BADLs and their history of admissions for AECOPD were the best predictive variables for the likelihood of readmission when adjusted for many other social and clinical variables, regardless of the time period considered for such prediction. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 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 |
Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments.,Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results.,Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management.,This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils.,It also examined the repeatability of blood eosinophil counts.,Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts.,Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia.,Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts.,Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001).,Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001).,Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67-0.84; P<0.0001).,At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases.,A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7).,In contrast, ≥0.2×109/L offered a better sensitivity (91.1%) for ruling out sputum eosinophilia.,There was a good agreement between two measurements of blood eosinophil count over a median of 28 days (intraclass correlation coefficient =0.8; 95% CI =0.66-0.88; P<0.0001).,Peripheral blood eosinophil counts can help identify the presence or absence of sputum eosinophilia in stable COPD patients with a reasonable degree of accuracy. | Chronic obstructive pulmonary disease is a common condition and a major cause of mortality.,COPD is characterized by irreversible airflow obstruction.,The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation.,The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages.,Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%-40% of induced sputum samples from patients with stable COPD.,This airway eosinophilia is increased in exacerbations.,Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD.,Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation.,In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions.,Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation. | 1 |
COPD has complex etiologies involving both genetic and environmental determinants.,Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD).,Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors.,Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD.,Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity.,Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study.,We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms.,We also integrated the miRNA and the differentially expressed putative target mRNA.,For data analyses, we used the R statistical language R Studio (version 3.2.5).,The severe and mild COPD-AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy.,In severe COPD-AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD-AATD disease.,Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients.,Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD-AATD.,Nonetheless, our findings warrant further validation in large studies. | Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality.,The most widely used marker of disease severity and progression is FEV1.,However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD.,Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD.,Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker.,Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality.,There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality.,Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity.,The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear.,Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations.,Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality. | 1 |
Imbalance between antioxidant and oxidative stress is a major risk factor for pathogenesis of some chronic diseases such as chronic obstructive pulmonary disease (COPD).,This study aimed to determine antioxidant and oxidative stress status, and also theirs association with respiratory function of male COPD patients to find the antioxidant predictors’ factors.,A total of 149 subjects were involved in a cross-sectional study.,The study was conducted at two medical centers in Kuala Lumpur, Malaysia.,Results of the study showed that plasma vitamin C was low in most of the subjects (86.6%).,Total antioxidant capacity was the lowest in COPD stage IV compare to other stages (p < 0.05).,Level of plasma vitamin A (p= 0.012) and vitamin C (p= 0.007) were low in malnourished subjects.,The predictors for total antioxidant capacity were forced vital capacity (FVC) % predicted and intake of β-carotene (R2= 0.104, p= 0.002).,Number of cigarette (pack/year) and smoking index (number/year) were not associated with total antioxidant capacity of this COPD population.,Plasma oxidative stress as assessed plasma lipid peroxidation (LPO) was only positively correlated with plasma glutathione (p= 0.002).,It might be a need to evaluate antioxidant status especially in older COPD patients to treat antioxidant deficiency which is leading to prevent COPD progression. | Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the world.,The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking.,Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease.,The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses.,In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD.,The complexity of COPD will necessitate a multi-target therapeutic approach.,It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies. | 1 |
Inherited deficiency of the antiprotease alpha-1 antitrypsin (AAT) is associated with liver failure and early-onset emphysema.,In mice, in vivo lentiviral transduction of alveolar macrophages (AMs) has been described to yield protective pulmonary AAT levels and ameliorate emphysema development.,We here investigated the pulmonary transplantation of macrophages (PMT) transgenic for AAT as a potential therapy for AAT deficiency-associated lung pathology.,Employing third-generation SIN-lentiviral vectors expressing the human AAT cDNA from the CAG or Cbx-EF1α promoter, we obtained high-level AAT secretion in a murine AM cell line as well as murine bone marrow-derived macrophages differentiated in vitro (AAT MΦ).,Secreted AAT demonstrated a physiologic glycosylation pattern as well as elastase-inhibitory and anti-apoptotic properties.,AAT MΦ preserved normal morphology, surface phenotype, and functionality.,Furthermore, in vitro generated murine AAT MΦ successfully engrafted in AM-deficient Csf2rb-/- mice and converted into a CD11c+/Siglec-F+ AM phenotype as detected in bronchoalveolar lavage fluid and homogenized lung tissue 2 months after PMT.,Moreover, human AAT was detected in the lung epithelial lining fluid of transplanted animals.,Efficient AAT expression and secretion were also demonstrated for human AAT MΦ, confirming the applicability of our vectors in human cells. | MicroRNAs (MiRNA) are small non-coding RNAs that regulate gene expression.,The aim of this study was to identify miRNAs differentially expressed between mild and moderately emphysematous lung, as well as their functional target mRNAs.,Resected lung from patients with COPD undergoing lung cancer surgery was profiled using miRNA (Agilent Human miRNA profiler G4470 V1.01) and mRNA (OperonV2.0) microarrays.,Cells of lung origin (BEAS-2B and HFL1) were profiled using mRNA microarrays (Illumina HumanHT-12 V3) after in vitro manipulation.,COPD patients had mean (SD) age 68 (6) years, FEV1 72 (17)% predicted and gas transfer (KCO) 70 (10)% predicted.,Five miRNAs (miR-34c, miR-34b, miR-149, miR-133a and miR-133b) were significantly down-regulated in lung from patients with moderate compared to mild emphysema as defined by gas transfer (p < 0.01).,In vitro upregulation of miR-34c in respiratory cells led to down-regulation of predicted target mRNAs, including SERPINE1, MAP4K4, ZNF3, ALDOA and HNF4A.,The fold change in ex-vivo expression of all five predicted target genes inversely correlated with that of miR-34c in emphysematous lung, but this relationship was strongest for SERPINE1 (p = 0.05).,Differences in miRNA expression are associated with emphysema severity in COPD patients.,MiR-34c modulates expression of its putative target gene, SERPINE1, in vitro in respiratory cell lines and ex vivo in emphysematous lung tissue. | 1 |
Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) - tiotropium and glycopyrronium.,Previous studies have compared glycopyrronium with open-label tiotropium.,In the GLOW5 study, we compare glycopyrronium with blinded tiotropium.,In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily.,The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: -50 mL).,Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment.,657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study.,Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: -32, 31 mL).,Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0-4 h post-dose versus tiotropium (all p < 0.001).,FEV1 area under the curve from 0-4 h (AUC0-4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12.,Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant).,Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035).,Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%).,In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium.,ClinicalTrial.gov, NCT01613326 | NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD).,The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks.,Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks.,Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks.,1,066 patients were randomised, 810 completed the study.,At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6-130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6-121.4; p<0.001).,Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St George's Respiratory Questionnaire at week 52; p<0.001).,NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo.,NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes.,Safety profiles were similar across groups.,NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium.,NVA237 can potentially be an alternative choice of LAMA for COPD patients. | 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. | Mortality rate is high in patients with chronic obstructive pulmonary disease (COPD).,Our aim was to investigate long-term mortality and associated risk factors in COPD patients previously hospitalized for a COPD exacerbation.,A total of 256 patients from the Nordic countries were followed for 8.7 ± 0.4 years after the index hospitalization in 2000-2001.,Prior to discharge, the St George’s Respiratory Questionnaire was administered and data on therapy and comorbidities were obtained.,Information on long-term mortality was obtained from national registries in each of the Nordic countries.,In total, 202 patients (79%) died during the follow up period, whereas 54 (21%) were still alive.,Primary cause of death was respiratory (n = 116), cardiovascular (n = 43), malignancy (n = 28), other (n = 10), or unknown (n = 5).,Mortality was related to older age, with a hazard risk ratio (HRR) of 1.75 per 10 years, lower forced expiratory volume in 1 second (FEV1) (HRR 0.80), body mass index (BMI) <20 kg/m2 (HRR 3.21), and diabetes (HRR 3.02).,Older age, lower BMI, and diabetes were related to both respiratory and cardiovascular mortality.,An association was also found between lower FEV1 and respiratory mortality, whereas mortality was not significantly associated with therapy, anxiety, or depression.,Almost four out of five patients died within 9 years following an admission for COPD exacerbation.,Increased mortality was associated with older age, lower lung function, low BMI, and diabetes, and these factors should be taken into account when making clinical decisions about patients who have been admitted to hospital for a COPD exacerbation. | 1 |
Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma.,Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM).,To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals.,By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM.,The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients. | Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD).,We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals.,We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2.,Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. | 1 |
Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs.,Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet.,We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade.,Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke.,The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied.,However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between.,Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively.,Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. | Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | 1 |
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