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It’s currently well known that smoking and increasing age constitute the most important risk factors for chronic obstructive pulmonary disease (COPD).,However, little is known about COPD among nonsmokers.,The present study aimed to investigate prevalence, risk factors and the profiles of COPD among nonsmokers based on the Tunisian Burden of Obstructive Lung Disease (BOLD) study.,807 adults aged 40 years+ were randomly selected from the general population.,We collected information about history of respiratory disease, risk factors for COPD and quality of life.,Post-bronchodilator spirometry was performed for assessment of COPD.,COPD diagnostic was based on the post-bronchodilator FEV1/FVC ratio, according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines.,The lower limit of normal (LLN) was determined as an alternative threshold for the FEV1/FVC ratio.,Among 485 nonsmokers, 4.7% met the criteria for GOLD grade I and higher COPD.,These proportions were similar even when the LLN was used as a threshold.,None of the nonsmokers with COPD reported a previous doctor diagnosis of COPD compared to 7.1% of smokers.,Nonsmokers accounted for 45.1% of the subjects fulfilling the GOLD spirometric criteria of COPD.,Nonsmokers were predominately men and reported more asthma problems than obstructed smokers.,Among nonsmokers significantly more symptoms and higher co-morbidity were found among those with COPD.,Increasing age, male gender, occupational exposure, lower body mass index and a previous diagnosis of asthma are associated with increased risk for COPD in nonsmokers.,This study confirms previous evidence that nonsmokers comprise a substantial proportion of individuals with COPD.,Nonsmokers with COPD have a specific profile and should, thus, receive far greater attention to prevent and treat chronic airway obstruction. | The aim of this study is to quantify the burden of chronic obstructive pulmonary disease (COPD) - incidence, prevalence, and mortality - and identify trends in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, the United Kingdom, and the United States of America.,A structured literature search was performed (January 2000 to September 2010) of PubMed and EMBASE, identifying English-language articles reporting COPD prevalence, incidence, or mortality.,Of 2838 articles identified, 299 full-text articles were reviewed, and data were extracted from 133 publications.,Prevalence data were extracted from 80 articles, incidence data from 15 articles, and mortality data from 58 articles.,Prevalence ranged from 0.2%-37%, but varied widely across countries and populations, and by COPD diagnosis and classification methods.,Prevalence and incidence were greatest in men and those aged 75 years and older.,Mortality ranged from 3-111 deaths per 100,000 population.,Mortality increased in the last 30-40 years; more recently, mortality decreased in men in several countries, while increasing or stabilizing in women.,Although COPD mortality increased over time, rates declined more recently, likely indicating improvements in COPD management.,In many countries, COPD mortality has increased in women but decreased in men.,This may be explained by differences in smoking patterns and a greater vulnerability in women to the adverse effects of smoking.,Point your SmartPhone at the code above.,If you have a QR code reader the video abstract will appear.,Or use: http://dvpr.es/Nl3LKT | 1 |
Use of inhaled corticosteroids (ICS) increases the risk of pneumonia in chronic obstructive pulmonary disease (COPD), but the magnitude of risk with different ICS remains unclear.,A post hoc analysis of the 4-year UPLIFT® trial to assess whether pneumonia risk differed by type of ICS (fluticasone propionate [FP], other ICS, or no ICS) in permanent users (defined by use until end of study) or in users at baseline (sensitivity analysis).,For the permanent-users analysis, 825 patients receiving FP throughout the trial, 825 patients receiving other ICS and 825 patients not receiving ICS were matched on relevant baseline features 1:1:1.,A significantly greater risk of pneumonia was observed for FP versus no ICS: the hazard ratio (HR) for risk of pneumonia was 1.33 (95% confidence interval [CI] 1.00, 1.75; p = 0.046) and the rate ratio (RR) was 1.58 (95% CI 1.05, 2.37; p = 0.028).,A greater risk was also found for FP versus other ICS: HR 1.28 (95% CI 0.97, 1.68; p = 0.078) and RR 1.48 (95% CI 1.00, 2.19; p = 0.049).,A higher proportion of patients on FP were hospitalized with pneumonia (7.9%) versus other ICS (6.7%) or no ICS (5.9%).,Whilst other ICS use was associated with the highest number of fatal pneumonia events, the total number of fatal pneumonia incidents was low.,A similar pattern was observed in the sensitivity analyses, which included 4002 patients on different treatments at baseline (FP, other ICS, and no ICS) and considered potential switches during the study.,The results support existing evidence of an increased pneumonia risk with FP use compared with other ICS and no ICS use in patients with COPD.,Healthcare professionals should evaluate the risk-benefit ratio of using ICS when making treatment decisions with their patients.,Post hoc analysis of UPLIFT®.,ClinicalTrials.gov number: NCT00144339.,Retrospectively registered September 2, 2005.,The online version of this article (10.1186/s12931-018-0874-0) contains supplementary material, which is available to authorized users. | The use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.,Using claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.,This was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006-2010).,Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest.,A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics.,Daily ICS use was classified into low, medium, and high doses (1 μg-499 μg, 500 μg-999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.,Among 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year).,ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27-1.49) for low-dose users, 1.69 (1.52-1.88) for medium-dose users, and 2.57 (1.98-3.33) for high-dose users (P < 0.01 versus no use and between doses).,The use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia. | 1 |
Pulmonary rehabilitation (PR) is an effective intervention for the management of people with chronic obstructive pulmonary disease (COPD).,However, available resources are often limited, and many patients bear with poor availability of programmes.,Sustaining PR benefits and regular exercise over the long term is difficult without any exercise maintenance strategy.,In contrast to traditional centre-based PR programmes, telerehabilitation may promote more effective integration of exercise routines into daily life over the longer term and broaden its applicability and availability.,A few studies showed promising results for telerehabilitation, but mostly with short-term interventions.,The aim of this study is to compare long-term telerehabilitation with unsupervised exercise training at home and with standard care.,An international multicentre randomised controlled trial conducted across sites in three countries will recruit 120 patients with COPD.,Participants will be randomly assigned to telerehabilitation, treadmill and control, and followed up for 2 years.,The telerehabilitation intervention consists of individualised exercise training at home on a treadmill, telemonitoring by a physiotherapist via videoconferencing using a tablet computer, and self-management via a customised website.,Patients in the treadmill arm are provided with a treadmill only to perform unsupervised exercise training at home.,Patients in the control arm are offered standard care.,The primary outcome is the combined number of hospitalisations and emergency department presentations.,Secondary outcomes include changes in health status, quality of life, anxiety and depression, self-efficacy, subjective impression of change, physical performance, level of physical activity, and personal experiences in telerehabilitation.,This trial will provide evidence on whether long-term telerehabilitation represents a cost-effective strategy for the follow-up of patients with COPD.,The delivery of telerehabilitation services will also broaden the availability of PR and maintenance strategies, especially to those living in remote areas and with no access to centre-based exercise programmes.,ClinicalTrials.gov: NCT02258646.,The online version of this article (doi:10.1186/s12890-016-0288-z) contains supplementary material, which is available to authorized users. | Comprehensive multidisciplinary pulmonary rehabilitation is vital in the management of chronic obstructive pulmonary disease (COPD) and is considered for any stage of the disease.,Rehabilitation programmes are often centre-based and organised in groups.,However, the distance from the patient’s home to the centre and lack of transportation may hinder participation.,Rehabilitation at home can improve access to care for patients regardless of disease severity.,We had previously studied the technology usability and acceptability of a comprehensive home rehabilitation programme designed for patients with very severe COPD receiving long-term oxygen therapy.,The acceptability of such comprehensive home programmes for those with less severe COPD, who may be less homebound, is not known.,The aims of this feasibility study were to assess patient acceptability of the delivery mode and components of a comprehensive pulmonary rehabilitation programme for any stage of COPD, as well as the technology usability, patient outcomes and economic aspects.,Ten participants with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade I-IV were enrolled in a 9-week home programme and divided into two rehabilitation groups, with five patients in each group.,The programme included exercise training and self-management education in online groups of patients, and individual online consultations.,The patients also kept a digital health diary.,To assess the acceptability of the programme, the patients were interviewed after the intervention using a semi-structured interview guide.,In addition the number of sessions attended was observed.,The usability of the technology was assessed using interviews and the System Usability Scale questionnaire.,The St George’s Respiratory Questionnaire (SGRQ) was used to measure health-related quality of life.,The mode of delivery and the components of the programme were well accepted by the patients.,The programme provided an environment for learning from both healthcare professionals and peers, for asking questions and discussing disease-related issues and for group exercising.,The patients considered that it facilitated health-enhancing behaviours and social interactions with a social group formed among the participants.,Even participants who were potentially less homebound appreciated the home group and social aspects of the programme.,The participants found the technology easy to learn and use.,The acceptability and usability results were consistent with those in our previous study of patients with very severe COPD.,Only the mean change in the SGRQ total score of −6.53 (CI 95 % −0.38 to −12.68, p = 0.04) indicates a probable clinically significant effect.,Economic calculations indicated that the cost of the programme was feasible.,The results of this study indicate that comprehensive pulmonary rehabilitation delivered in home-based online groups may be feasible in COPD.,The mode of delivery and components of the programme appeared to be acceptable across patients with different disease severity.,The results in terms of patient outcomes are inconclusive, and further assessment is needed. | 1 |
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. | Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.,Design Cluster randomised controlled parallel group trial.,Setting Ambulance service in Hobart, Tasmania, Australia.,Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.,Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.,Main outcome measure Prehospital or in-hospital mortality.,Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97).,Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm.,Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04).,Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.,Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease.,These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.,Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health.,Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures.,This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations.,It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. | COPD is prevalent in Western society and its incidence is rising in the developing world.,Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden.,Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease.,COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality.,Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use.,Erythromycin has been shown to decrease the rate of COPD exacerbations.,Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life.,Noninvasive ventilation is associated with improved quality of life.,Long-term oxygen therapy improves mortality but only in hypoxic COPD patients.,The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of.,Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates.,Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. | 1 |
The rate of obesity is increasing in Asia, but the clinical impact of body mass index (BMI) on the outcome of chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to assess this impact while focusing on the risk of exacerbation, health-care utilization, and medical costs.,We examined 43,864 subjects registered in the Korean National Health and Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to National Health Insurance (NHI) data.,COPD was confirmed by spirometry.,BMI was used to stratify patients into four categories: underweight (BMI <18.5 kg/m2), normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (≥25 kg/m2).,Of the 1,320 patients with COPD with mild to moderate airflow obstruction, 27.8% had a BMI ≥25 kg/m2.,Compared with normal-weight patients, obese patients tended to experience fewer exacerbations (incidence rate ratio [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not significant in a multivariable analysis.,COPD-related health-care utilization and medical expenses were higher among underweight patients than the other groups.,After adjustment, the risk of COPD-related hospitalization was highest among underweight and higher among overweight patients vs normal-weight patients (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight, and obese groups, respectively; P = 0.01).,Decreased weight tends to negatively influence prognosis of COPD with mild to moderate airflow obstruction, whereas higher BMI was not significantly related to worse outcomes. | Roflumilast is a phosphodiesterase-4 inhibitor, which can decrease exacerbation in patients with chronic obstructive pulmonary disease (COPD).,However, adverse effects are a major barrier to medication use, and little is known regarding the risk factors for discontinuation of roflumilast in COPD patients.,A search of the clinical databases identified all patients who were prescribed roflumilast between December 2012 and April 2015 in the four hospitals of The Catholic University of Korea, Korea.,The study subjects were limited to patients who had taken 500 μg of roflumilast.,We studied the factors associated with drug discontinuation and drug adverse events by univariate and multivariate analyses.,Among 154 eligible patients, 54 (35.1%) discontinued their roflumilast prescription.,Most patients were elderly, male, current or former smokers, and had moderate-to-severe airflow limitation.,Low-body mass index (BMI) patients were more likely to undergo drug discontinuation (1-unit decrease in BMI: odds ratio [OR] =1.165, p=0.006; BMI <23 kg/m2: OR =2.960, p=0.004).,Fifty-five patients (35.7%) had adverse events.,Loss of appetite, diarrhea, nausea, headache, and weight loss were the most frequent adverse events.,Low-BMI patients were more likely to experience adverse events (1-unit decrease in BMI: OR =1.151, p=0.010; BMI <23 kg/m2: OR =2.644, p=0.009).,The patient discontinuation and adverse events rates in this study were higher than in previous randomized controlled studies.,Discontinuation of roflumilast in ethnic Koreans is more likely to occur in low-BMI patients.,In a clinical setting, low-BMI patients can more easily discontinue roflumilast; clinicians should, therefore, provide greater care for these patients. | 1 |
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report provides a framework for classifying COPD reflecting the impacts of disease on patients and for targeting treatment recommendations.,The GOLD 2017 introduced a new classification with 16 subgroups based on a composite of spirometry and symptoms/exacerbations.,Data from the population-based PLATINO study, collected at baseline and at follow-up, in three sites in Latin America were analyzed to compare the following: 1) the distribution of COPD patients according to GOLD 2007, 2013, and 2017; 2) the stability of the 2007 and 2013 classifications; and 3) the mortality rate over time stratified by GOLD 2007, 2013, and 2017.,Of the 524 COPD patients evaluated, most of them were classified as Grade I or II (GOLD 2007) and Group A or B (GOLD 2013), with ≈70% of those classified as Group A in GOLD 2013 also classified as Grade I in GOLD 2007 and the highest percentage (41%) in Group D (2013) classified as Grade III (2007).,According to GOLD 2017, among patients with Grade I airflow limitation, 69% of them were categorized into Group A, whereas Grade IV patients were more evenly distributed among Groups A-D.,Most of the patients classified by GOLD 2007 remained in the same airflow limitation group at the follow-up; a greater temporal variability was observed with GOLD 2013 classification.,Incidence-mortality rate in patients classified by GOLD 2007 was positively associated with increasing severity of airflow obstruction; for GOLD 2013 and GOLD 2017 (Groups A-D), highest mortality rates were observed in Groups C and D.,No clear pattern was observed for mortality across the GOLD 2017 subgroups.,The PLATINO study data suggest that GOLD 2007 classification shows more stability over time compared with GOLD 2013.,No clear patterns with respect to the distribution of patients or incidence-mortality rates were observed according to GOLD 2013/2017 classification. | The BODE index was recently validated as a multidimensional tool for the evaluation of patients with COPD.,The influence of gender on the BODE index has not been studied.,The contribution of each component of the disease to the BODE index may differ according to gender.,We evaluated age, forced expiratory volume in one second (FEV1), Modified Medical Research Council (MMRC) score, 6-min walk distance (6MWD), and body mass index (BMI) in 52 men and 52 women with COPD and the same BODE index.,We compared the studied parameters between men and women and then performed a multiple regression analysis by gender.,We found statistically significant differences between men and women in all parameters: FEV1 % (55 ± 17 vs 63 ± 18, p < 0.001), MMRC [1 (0-2) vs 1 (1-2) p = 0.03], BMI [28 (26-30) vs 25 (22-30), p = 0.05], and 6MWD [546 (451-592) vs 462 (419-520), p = 0.001].,Multiple regression analysis revealed that each component of the BODE index had different weight (β standardized coefficient) in men and women respectively: FEV1% (0.74 vs 0.62), MMRC (0.31 vs 0.48), BMI (−0.09 vs −0.17), and 6MWD (0.13 vs 0.10).,The contribution of each component to the BODE index differs by gender in subjects with similar BODE scores.,Long term longitudinal studies will help determine the significance of our findings. | 1 |
This study examines the effects of the COPD-specific health promoting self-management intervention “Better living with COPD” on different self-management-related domains, self-efficacy, and sense of coherence (SOC).,In a randomized controlled design, 182 people with COPD were allocated to either an intervention group (offered Better living with COPD in addition to usual care) or a control group (usual care).,Self-management-related domains were measured by the Health Education Impact Questionnaire (heiQ) before and after intervention.,Self-efficacy was measured by the General Self-Efficacy Scale (GSE) and SOC was measured by the 13-item Sense of Coherence Scale (SOC-13).,Effects were assessed by ANCOVA, using intention-to-treat (ITT) analysis and per-protocol analysis (PPA).,The PPA and the ITT analysis showed significant positive changes on Constructive attitudes and approaches (heiQ) (ITT: P=0.0069; PPA: P=0.0021) and Skill and technique acquisition (heiQ) (ITT: P=0.0405; PPA: P=0.0356).,Self-monitoring and insight (heiQ) showed significant positive change in the PPA (P=0.0494).,No significant changes were found on the other self-management domains (heiQ), self-efficacy (GSE), or SOC (SOC-13).,Better living with COPD had a significant positive short-term effect on some self-management-related domains, and could be an intervention contributing to the support of self-management in people with COPD.,However, further work is needed to establish the clinical relevance of the findings and to evaluate the long-term effects. | Chronic obstructive pulmonary disease is a leading cause of mortality, and associated with increased healthcare utilization and healthcare expenditure.,In several countries, morbidity-based systems have changed the way resources are allocated in general practice.,In primary care, fee-for-services tariffs are often based on political negotiation rather than costing systems.,The potential for comprehensive measures of patient morbidity to explain variation in negotiated expenditures for patients with chronic obstructive pulmonary disease has not previously been examined.,The aim of this study is to analyze fee-for-service expenditure of patients diagnosed with chronic obstructive pulmonary disease visiting Danish general practice clinics and further to assess what proportion of fee-for-service expenditure variation was explained by patient morbidity and general practice clinic characteristics, respectively.,We used patient morbidity characteristics such as diagnostic markers and multi-morbidity adjustment based on adjusted clinical groups (ACGs) and fee-for-service expenditure for a sample of primary care patients for the year 2010.,Our sample included 3,973 patients in 59 general practices.,We used a multi-level approach.,The average annual fee-for-service expenditure of caring for patients diagnosed with chronic obstructive pulmonary disease in general practice was about EUR 400 per patient.,Variation in the expenditures was driven by multimorbidity characteristics up to 28 % where as characteristics such as age and gender only explained 5 %.,Expenditures increased progressively with the degree of multimorbidity.,In addition, expenditures were higher for patients who had diagnostic markers based on ICPC-2 (body systems and/or components such as infections and symptoms).,Nevertheless, 9.8-15.4 % of the variation in expenditure was related to the clinic in which the patient was cared for.,Patient morbidity and general practice clinic characteristics are significant patient-related fee-for-service expenditure drivers in chronic obstructive pulmonary disease care. | 1 |
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease involving a wide variety of cells and inflammatory mediators.,The most important etiological factor in the development of this disease is cigarette smoking.,Much of the research into the mechanisms of COPD has been concerned with the induction of inflammation and the role of neutrophils and macrophages in the pathophysiology of the disease.,The possible contribution of the epithelium to the development of COPD has only recently become apparent and remains unclear.,In this article we review research into the effect of cigarette smoke on the pulmonary epithelium with particular emphasis on oxidative stress, proteolytic load, pro-inflammatory cytokine and chemokine profile and epithelial secretions.,In addition, we have also reviewed how cigarette smoke may affect epithelial damage and repair processes. | Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia.,These features are partially attributed to activation of the epidermal growth factor receptor (EGFR).,Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists.,We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.,114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted.,Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.,Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression.,Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.,Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs.,14.4%, p = 0.005; 7.9% vs.,13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs.,18.6%, p < 0.001).,Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).,NCT00158847 | 1 |
The Visual Simplified Respiratory Questionnaire (VSRQ) was designed to assess health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD).,It contains eight items: dyspnea, anxiety, depressed mood, sleep, energy, daily activities, social activities and sexual life.,Psychometric properties were assessed during a clinical trial that evaluated the impact of tiotropium on HRQoL of COPD patients.,These included the determination of structure, internal consistency reliability, concurrent validity with the St George’s Respiratory Questionnaire (SGRQ), test - retest reliability, clinical validity and responsiveness to change over two weeks.,Minimal important difference (MID) was calculated; cumulative response curves (CRC) were based on the dyspnea item.,Psychometric analyses showed that VSRQ structure was unidimensional.,The questionnaire demonstrated good internal consistency reliability (Cronbach’s alpha = 0.84), good concurrent validity with SGRQ (Spearman = −0.70) and clinical validity, good test-retest reproducibility (ICC = 0.77), and satisfactory responsiveness (standardized response mean = 0.57; Guyatt’s statistic = 0.63).,MID was 3.4; CRC median value of the ‘minimally improved’ patients was 3.5.,In conclusion, VSRQ brevity and satisfactory psychometric properties make it a good candidate for large studies to assess HRQoL in COPD patients.,Further validation is needed to extend its use in clinical practice. | Patient centred outcomes, such as health status, are important in Chronic Obstructive Pulmonary Disease (COPD).,Extensive questionnaires on health status have good measurement properties, but are not suitable for use in primary care.,The newly developed, short Clinical COPD Questionnaire, CCQ, was therefore validated against the St George's Respiratory Questionnaire (SGRQ).,111 patients diagnosed by general practitioners as having COPD completed the questionnaires twice, 2-3 months apart, without systematic changes in treatment.,Within this sample of patients with "clinical COPD" a subgroup of patients with spirometry verified COPD was identified.,All analyses was performed on both groups.,The mean FEV1 (% predicted) was 58.1% for all patients with clinical COPD and 52.4% in the group with verified COPD (n = 83).,Overall correlations between SGRQ and CCQ were strong for all patients with clinical COPD (0.84) and the verified COPD subgroup (0.82).,The concordance intra-class correlation between SGRQ and CCQ was 0.91 (p < 0.05).,Correlations between CCQ and SGRQ were moderate to good, regardless of COPD severity.,The CCQ is a valid and reliable instrument for assessments of health status on the group level in patients treated for COPD in primary care but its reliability may not be sufficient for the monitoring of individual patients. | 1 |
The gold standard for the diagnosis of chronic obstructive pulmonary disease (COPD) is spirometry, but there are barriers to its use in primary care.,To externally validate the COPD Diagnostic Questionnaire (CDQ) as a diagnostic tool in patients at increased risk in Australian general practice and to compare its performance with other CDQ validation studies.,Patients were recruited from 36 general practices in Sydney, Australia.,Former or current smokers aged 40-85 years with no prior COPD diagnosis were invited to a case-finding appointment with the practice nurse.,The CDQ was collected and pre- and postbronchodilator spirometry was performed.,Cases for whom complete CDQ data were present and the spirometry met quality standards were analysed.,Of 1,631 patients who attended case-finding recruitment, 1,054 (65%) could be analysed.,Spirometry showed 13% had COPD.,The ability of the CDQ to discriminate between patients with and without COPD was fair, represented by the area under the receiver operating characteristic curve of 0.713.,With a CDQ cut-off point value of 16.5 the sensitivity was 80% and specificity 47% and, at a cut-off point value of 19.5, the sensitivity was 63% and specificity 70%.,The CDQ did not discriminate between patients with and without COPD accurately enough to use as a diagnostic tool in patients at increased risk of COPD in Australian general practice.,Further research is needed on the value of the CDQ as a tool for selecting patients for spirometry. | Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies.,To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).,Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years.,We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation.,Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs.,0.9 (1.1) per year, p<0.001) compared to non-inflamed ones.,As a descriptive study our results show associations but do not prove causality.,Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.,Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment. | 1 |
To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility).,Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations.,Global.,3255 patients with COPD (intent-to-treat populations) with a history of exacerbations in the past year.,FF/VI 50/25 µg, 100/25 µg or 200/25 µg, or VI 25 µg; all one time per day.,Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy.,Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils ≤2.4% and smoking history ≤46 pack-years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils ≤2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58).,Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility.,In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations.,In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation.,NCT01009463; NCT01017952; Post-results. | Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation.,Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood.,This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation.,Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation.,Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand.,MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P < 0.01).,TIMP-1 levels decreased from 3.5 μg/g [0.6 to 7.8] to 1.5 μg/g [0.3 to 4.9] (P = 0.16).,MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05).,Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05).,Macrophage numbers remained level.,MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01).,During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1.,This may suggest a pathway connecting frequent exacerbations with lung function decline. | 1 |
► 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. | There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD).,The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1-2% of individuals with COPD.,We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study.,The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population.,Logistic regression models with adjustments of covariates were used to analyze the case-control populations.,Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations.,Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study.,They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730).,Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations.,The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%.,The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels.,Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429).,The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD.,CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer. | 1 |
Maintenance treatment with macrolide antibiotics has shown to be effective in reducing exacerbations in COPD patients.,A major concern with prolonged treatment with antibiotics is the development of bacterial resistance.,In this study we determined the effect of azithromycin on the development and acquisition of resistance to macrolides in the nasopharyngeal flora in COPD patients.,This study was part of the COLUMBUS trial, a randomised, double-blind, placebo-controlled trial to measure the effect of maintenance treatment with azithromycin in 92 COPD patients on the exacerbation rates during a 12-month period.,In order to determine resistance to macrolides, we used a targeted metagenomic approach to measure the presence and relative abundance of specific macrolide resistance genes ermB, ermF and mefA in throat samples collected at different time-points during this 12-month period.,There was no increased risk for acquisition of macrolide resistance genes in the azithromycin group compared to the placebo group in COPD patients.,However, loss of the macrolide resistance gene ermB was increased overtime in the placebo treated group compared to the azithromycin group (n = 5 for the placebo group versus n = 0 for the azithromycin group at 12 months; p = 0.012).,The change in relative abundance of the three macrolide-resistance genes showed that all but one (ermF) increased during treatment with azithromycin.,The acquisition rate of macrolide resistance genes in COPD patients treated with azithromycin maintenance therapy was limited, but the relative abundance of macrolide resistance genes increased significantly over time compared to placebo.,This study was part of the COLUMBUS trial (Clinicaltrials.gov, NCT00985244). | Chronic inflammation plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,However, there are no effective anti-inflammatory pharmacologic therapies available for COPD so far.,Recent evidence suggests that an immunologic mechanism has a role in the pathogenesis of COPD.,Macrolides possess anti-inflammatory and immune-modulating effects may be helpful in the treatment of COPD.,Several clinical studies have shown that long-term use of macrolides reduces the frequency of COPD exacerbations.,However, the subgroups that most effectively respond to long-term treatment of macrolides still need to be determined.,The potential adverse events to individuals and the microbial resistance in community populations raises great concern on the long-term use of macrolides.,Thus, novel macrolides have anti-inflammatory and immuno-modulating effects, but without antibiotic effects, and are promising as an anti-inflammatory agent for the treatment of COPD.,In addition, the combination of macrolides and other anti-inflammatory pharmacologic agents may be a new strategy for the treatment of COPD. | 1 |
Patients with COPD present a major recruitment of the inspiratory muscles, predisposing to chest incoordination, increasing the degree of dyspnea and impairing their exercise capacity.,Stretching techniques could decrease the respiratory muscle activity and improve their contractile capacity; however, the systemic effects of stretching remain unknown.,The aim of this study was to evaluate the effects of aerobic training combined with respiratory muscle stretching on functional exercise capacity and thoracoabdominal kinematics in patients with COPD.,This study was a randomized and controlled trial.,A total of 30 patients were allocated to a treatment group (TG) or a control group (CG; n=15, each group).,The TG was engaged in respiratory muscle stretching and the CG in upper and lower limb muscle stretching.,Both groups performed 24 sessions (twice a week, 12 weeks) of aerobic training.,Functional exercise capacity (6-minute walk test), thoracoabdominal kinematics (optoelectronic plethysmography), and respiratory muscle activity (surface electromyography) were evaluated during exercise.,Analysis of covariance was used to compare the groups at a significance level of 5%.,After the intervention, the TG showed improved abdominal (ABD) contribution, compartmental volume, mobility, and functional exercise capacity with decreased dyspnea when compared with the CG (P<0.01).,The TG also showed a decreased respiratory muscle effort required to obtain the same pulmonary volume compared to the CG (P<0.001).,Our results suggest that aerobic training combined with respiratory muscle stretching increases the functional exercise capacity with decreased dyspnea in patients with COPD.,These effects are associated with an increased efficacy of the respiratory muscles and participation of the ABD compartment. | Skeletal muscle dysfunction is common in chronic obstructive pulmonary disease (COPD), a disease mainly caused by chronic cigarette use.,An important proportion of patients with COPD have decreased muscle mass, suggesting that chronic cigarette smoke exposure may interfere with skeletal muscle cellular equilibrium.,Therefore, the main objective of this study was to investigate the kinetic of the effects that cigarette smoke exposure has on skeletal muscle cell signaling involved in protein homeostasis and to assess the reversibility of these effects.,A mouse model of cigarette smoke exposure was used to assess skeletal muscle changes.,BALB/c mice were exposed to cigarette smoke or room air for 8 weeks, 24 weeks or 24 weeks followed by 60 days of cessation.,The gastrocnemius and soleus muscles were collected and the activation state of key mediators involved in protein synthesis and degradation was assessed.,Gastrocnemius and soleus were smaller in mice exposed to cigarette smoke for 8 and 24 weeks compared to room air exposed animals.,Pro-degradation proteins were induced at the mRNA level after 8 and 24 weeks.,Twenty-four weeks of cigarette smoke exposure induced pro-degradation proteins and reduced Akt phosphorylation and glycogen synthase kinase-3β quantity.,A 60-day smoking cessation period reversed the cell signaling alterations induced by cigarette smoke exposure.,Repeated cigarette smoke exposure induces reversible muscle signaling alterations that are dependent on the duration of the cigarette smoke exposure.,These results highlights a beneficial aspect associated with smoking cessation. | 1 |
Background: COPD is a common cause of morbidity and mortality.,The aim of this study was to explore patients’ experiences, self-reported needs, and needs-driven strategies to cope with self-management of COPD.,Patients and methods: In this phenomenological study, 10 participants with mild to severe COPD were interviewed 1-2 times, until data saturation was reached.,In total, 15 in-depth interviews were conducted, recorded, transcribed, and analyzed.,Results: COPD negatively affected participants’ physical and psychosocial well-being, their family relationships, and social life.,They described their experiences of COPD like fighting a war without weapons in an ever-shrinking world with a loss of freedom at most levels, always fearing possible breathlessness.,Fourteen needs were identified and eight clusters of needs-driven strategies that participants used to cope with self-management of COPD.,Coping with the reality of COPD, a life-threatening disease, meant coping with dyspnea, feelings of suffocation, indescribable smoking addiction, anxiety, and lack of knowledge about the disease.,Reduced participation in family and social life meant loss of ability to perform usual and treasured activities.,Having a positive mindset, accepting help and assuming healthy lifestyle was important, as well as receiving continuous professional health care services.,The participants’ needs-driven strategies comprised conducting financial arrangements, maintaining hope, and fighting their smoking addiction, seeking knowledge about COPD, thinking differently, facing the broken chain of health care, and struggling with accepting support.,Procrastination and avoidance were also evident.,Finally, the study also found that participants experienced a perpetuating cycle of dyspnea, anxiety, and fear of breathlessness due to COPD which could lead to more severe dyspnea and even panic attacks.,Conclusion: COPD negatively affects patients’ physical and psychosocial well-being, family relationships and, social life.,Identifying patients’ self-reported needs and needs-driven strategies can enable clinicians to empower patients by educating them to improve their self-management. | To illuminate patients’ lived experiences of going through the process of being diagnosed with chronic obstructive pulmonary disease (COPD).,A phenomenological-hermeneutic analysis was applied in the interpretation of interviews with eight persons diagnosed with mild or moderate COPD.,One main theme ‘living in negotiation’, and three themes ‘living with a body out of step with the diagnosis’, ‘dealing with the past’, and ‘being challenged by the future’ reflected the process participants were living through in their quest for acceptance and a new balance in life.,Participants found that the diagnostic processes were confusing, and that the diagnosis itself was ‘a slap in the face’.,Unclear messages gave rise to fluctuating between an understanding of the condition as ‘not too severe’, insecurity, and fear.,Shame and guilt related to the diagnosis had origins in the past, and in combination with the idea of ‘chronic’ the COPD diagnosis interfered with the present moment and gave rise to uncertainty for the future.,The understanding of the present is related to negotiations not only with the past, but also with the future.,Thus temporal aspects of the diagnosis are of great significance for the process of finding acceptance.,Regardless of disease severity, the diagnosis seems to be a breakdown of life, which puts life itself at stake.,Medical professionals should be aware that the way the diagnosis is disclosed and communicated has considerable significance for how individuals understand and deal with their illness.,The diagnosis should be communicated face-to-face, clearly and with empathy, and followed by information about COPD.,Physicians should allow time and listen to the patients’ stories, and thus develop a shared understanding of the temporal aspect of the illness and patients’ needs and concerns.,Thus, good communication is essential in determining whether the patient remains in negotiation, or enters a process toward acceptance and new understanding. | 1 |
Glycopyrronium bromide (NVA237) is an inhaled long-acting muscarinic antagonist in development for treatment of COPD.,This study compared the efficacy and safety of once-daily (OD) and twice-daily (BID) glycopyrronium bromide regimens, using a novel model-based approach, in patients with moderate-to-severe COPD.,Double-blind, randomized, dose-finding trial with an eight-treatment, two-period, balanced incomplete block design.,Patients (smoking history ≥10 pack-years, post-bronchodilator FEV1 ≥30% and <80% predicted, FEV1/FVC <0.7) were randomized to one of 16 independent sequences for 28 days.,Primary endpoint: mean trough FEV1 at Day 28.,385 patients (mean age 61.2 years; mean post-bronchodilator FEV1 53% predicted) were randomized; 88.6% completed.,All OD and BID dosing regimens produced dose-dependent bronchodilation; at Day 28, increases in mean trough FEV1 versus placebo were statistically significant for all regimens, ranging from 51 mL (glycopyrronium bromide 12.5 μg OD) to 160 mL (glycopyrronium bromide 50 μg BID).,Pharmacodynamic steady-state was reached by Day 7.,There was a small separation (≤37 mL) between BID and OD dose-response curves for mean trough FEV1 at steady-state in favour of BID dosing.,Over 24 hours, separation between OD and BID regimens was even smaller (FEV1 AUC0-24h maximum difference for equivalent daily dose regimens: 8 mL).,Dose-response results for FEV1 at 12 hours, FEV1 AUC0-12h and FEV1 AUC0-4h at steady-state showed OD regimens provided greater improvement over placebo than BID regimens for total daily doses of 25 μg, 50 μg and 100 μg, while the reverse was true for OD versus BID regimens from 12-24 hours.,The 12.5 μg BID dose produced a marginally higher improvement in trough FEV1 versus placebo than 50 μg OD, however, the response at 12 hours over placebo was suboptimal (74 mL).,Glycopyrronium bromide was safe and well tolerated at all doses.,Glycopyrronium bromide 50 μg OD provides significant bronchodilation over a 24 hour period, and in terms of FEV1 AUC0-24h is not significantly different than the same total daily dose administered BID.,Importantly, OD dosing may confer better patient adherence.,The results are consistent with previous glycopyrronium bromide studies and support once-daily dosing of glycopyrronium bromide 50 μg in patients with moderate-to-severe COPD.,ClinicalTrials.gov: NCT01119950 | Patients with respiratory disease experience disturbed sleep, but there is no widely accepted measure of sleep impairment due to respiratory disease.,We developed and evaluated the psychometric performance of a patient-reported measure to assess the impact on sleep due to respiratory disease, the COPD and Asthma Sleep Impact Scale (CASIS).,Identification of the items forming the CASIS was guided by patient interviews and focus groups.,An observational study involving patients from the US and UK was then conducted to assess the psychometric characteristics of the measure.,Qualitative data from 162 patients were used to develop the CASIS (n = 78 COPD; n = 84 asthma).,The observational study included 311 patients with COPD and 324 patients with asthma.,The final seven items used in the CASIS were identified based on factor and item response theory analyses.,Internal consistency was 0.90 (COPD) and 0.92 (asthma), and test-retest reliability was 0.84 (both groups).,In the COPD sample, CASIS scores were significantly correlated with the Saint George's Respiratory Questionnaire scores (all p < 0.0001) and differed significantly by patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.005).,In the asthma sample, CASIS scores were significantly correlated with the Asthma Quality of Life Questionnaire scores (all p < 0.0001) and differed significantly by clinician and patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.0005).,The CASIS shows good internal consistency, test-retest reliability, and construct validity and may be useful in helping to understand the impact that COPD and asthma have on sleep outcomes. | 1 |
N-Acetylcysteine (NAC) demonstrates applications in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD).,COPD is often characterized by fibrosis of the small airways.,This study aims at investigating the physiological mechanisms by which NAC might mediate the pulmonary fibrosis in COPD.,A total of 10 non-smokers without COPD and 10 smokers with COPD were recruited in this study, and COPD rat models were established.,Cigarette smoke extract (CSE) cell models were constructed.,The gain- or loss-of-function experiments were adopted to determine the expression of VWF and the extent of p38 MAPK phosphorylation, levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and immunoglobulins (IgG, IgM and IgA) in the serum of COPD rats and supernatant of alveolar epithelial cells and to detect cell invasion and migration and the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes.,Expression of VWF and the extent of p38 MAPK phosphorylation were increased in COPD.,NAC inhibited p38 MAPK phosphorylation by reducing the VWF expression.,NAC could inhibit cell migration and invasion, elevate E-cadherin expression, the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes, and levels of IgG, IgA, and IgM, and reduce N-cadherin expression and levels of IL-6 and TNF-α in CSE cells and serum of COPD rats.,NAC promoted immune response and suppressed epithelial-mesenchymal transformation (EMT) to relieve COPD-induced pulmonary fibrosis in vitro and in vivo by inhibiting the VWF/p38 MAPK axis.,Collectively, NAC could ameliorate COPD-induced pulmonary fibrosis by promoting immune response and inhibiting EMT process via the VWF/p38 MAPK axis, therefore providing us with a potential therapeutic target for treating COPD.,The online version contains supplementary material available at 10.1186/s10020-021-00342-y. | We recently reported that epithelial-mesenchymal transition (EMT) is active in the airways in chronic obstructive pulmonary disease (COPD), suggesting presence of an active profibrotic and promalignant stroma.,With no data available on potential treatment effects, we undertook a blinded analysis of inhaled corticosteroids (ICS) effects versus placebo on EMT markers in previously obtained endobronchial biopsies in COPD patients, as a “proof of concept” study.,Assessment of the effects of inhaled fluticasone propionate (FP; 500 μg twice daily for 6 months) versus placebo in 34 COPD patients (23 on fluticasone propionate and eleven on placebo).,The end points were epidermal growth factor receptor (EGFR; marker of epithelial activation) and the biomarkers of EMT: reticular basement membrane (Rbm) fragmentation (“hallmark” structural marker), matrix metalloproteinase-9 (MMP-9) cell expression, and S100A4 expression in basal epithelial and Rbm cells (mesenchymal transition markers).,Epithelial activation, “clefts/fragmentation” in the Rbm, and changes in the other biomarkers all regressed on ICS, at or close to conventional levels of statistical significance.,From these data, we have been able to nominate primary and secondary end points and develop power calculations that would be applicable to a definitive prospective study.,Although only a pilot “proof of concept” study, this trial provided strong suggestive support for an anti-EMT effect of ICS in COPD airways.,A larger and fully powered prospective study is now indicated as this issue is likely to be extremely important.,Such studies may clarify the links between ICS use and better clinical outcomes and protection against lung cancer in COPD. | 1 |
The distance of 6-minute walk test (D6MWT) has been widely used in the assessment of functional status in patients with COPD, while very little attention has been paid to the role of steps of 6-minute walk test (S6MWT).,The purpose of this study was to investigate the relationship between S6MWT and other physiologic parameters of COPD.,Seventy patients with stable COPD were enrolled consecutively in this cross-sectional study.,Pulmonary function tests, including spirometry, impulse oscillometry (IOS) and the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), were carried out at rest.,Quality of life was assessed by health-related quality of life (HRQoL) questionnaires, including modified Medical Research Council dyspnea scale (mMRC), St George’s Respiratory Questionnaire, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) and Clinical Chronic Obstructive Pulmonary Questionnaire.,Both steps and distance were measured in the following 6-minute walk test (6MWT).,Both S6MWT and D6MWT showed significant correlation with spirometry, IOS, DLCO parameters and HRQoL questionnaires score.,Both pre- and post-6MWT inspiratory capacity showed significant correlation with S6MWT (ρ=0.338, P=0.004; ρ=0.359, P=0.002, respectively), whereas did not correlate with D6MWT (ρ=0.145, P=0.230; ρ=0.160, P=0.189, respectively).,In stepwise multiple regression analysis, mMRC grade, age and CAT score remained as significant predictors in the final model for D6MWT (adjusted R2=0.445, P<0.01).,DLCO and CAT score remained as significant predictors in the final model for S6MWT (adjusted R2=0.417, P<0.01).,S6MWT is efficient in the evaluation of functional status and quality of life in COPD and has significant correlation with various parameters indicating disease severity.,Additionally, S6MWT might be better in predicting lung hyperinflation in COPD compared with D6MWT. | Physical activity limitation is common in chronic obstructive pulmonary disease (COPD), and is associated with worse health status, and increased hospitalisation and mortality.,Long-acting bronchodilators, either alone or in combination, have been shown to improve exercise intolerance.,However, none of these studies were designed with physical activity as primary outcome.,This study assessed the effect of indacaterol/glycopyrronium fixed dose combination (IND/GLY) 110/50 μg once daily (OD) versus placebo on lung hyperinflation (inspiratory capacity [IC]) and physical activity in patients with moderate-to-severe COPD.,In this multicentre, randomised, double-blind, placebo-controlled crossover study, patients received IND/GLY or placebo OD in two 21-day treatment periods (14-day washout between periods).,Eligible patients were ≥40 years of age, current or ex-smokers (smoking history ≥10 pack-years), with post-salbutamol forced expiratory volume in 1 s (FEV1) 40-80 % predicted, and FEV1:forced vital capacity <0.70.,The co-primary endpoints were peak IC after 21 days and average daily activity-related energy expenditure.,Key secondary endpoints were average number of steps per day and the duration of at least moderate activity per day.,Peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days were other secondary endpoints.,A total of 194 patients were randomised (65.5 % male, mean age 62.8 years, mean FEV1 61.6 % predicted), with 183 (94.3 %) completing the study.,Compared with placebo, IND/GLY significantly increased peak IC after 21 days (difference 202 mL, p < 0.0001), activity-related energy expenditure (difference 36.7 kcal/day, p = 0.040), and the average number of steps per day (difference 358, p = 0.029), with a trend towards an improvement in the duration of at least moderate activity (difference 4.4 min, p = 0.264).,IND/GLY was associated with statistically significant improvements versus placebo in peak IC and FEV1 on Day 1, and trough IC and FEV1 after 21 days.,The incidence of treatment-emergent adverse events was 22.8 % with IND/GLY and 22.9 % with placebo.,In this study, compared with placebo, IND/GLY reduced hyperinflation, and, despite no patient education or lifestyle advice, improved daily physical activity levels.,This suggests that IND/GLY has the potential to impact two of the main clinical concerns in the care of patients with COPD.,ClinicalTrials.gov number: NCT01996319.,The online version of this article (doi:10.1186/s12890-016-0256-7) contains supplementary material, which is available to authorized users. | 1 |
The effects of Zataria multiflora (Z. multiflora) on systemic inflammation in guinea pigs model of COPD were examined.,Control animals, COPD (induced by exposing animals to cigarette smoke), COPD + drinking water containing three concentrations of the extract of Z. multiflora, and COPD + dexamethasone were studied (n = 6 for each group).,Serum levels of IL-8 and malondialdehyde (MDA), total blood WBC (P < 0.01 for all cases), and eosinophil counts (P < 0.05) were higher and weight changes (P < 0.05) were lower in the COPD group compared to controls.,IL-8 level (P < 0.001) and weight changes (P < 0.01 to P < 0.001) in all treated groups with Z. multiflora and total WBC number and MDA level in treated groups with two higher concentrations of the extract and lymphocytes percentage (P < 0.05) in the highest concentration of Z. multiflora and dexamethasone (P < 0.05 to P < 0.001) were significantly improved compared to the COPD group.,Results showed a preventive effect of hydroethanolic extract from Z. multiflora on all measured parameters in animals model of COPD which was comparable or even higher (in the highest concentration) compared to the effect of dexamethasone at the concentration used. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
A single administration of mesenchymal stromal cells (MSCs) has been shown to reduce lung inflammation in experimental elastase-induced emphysema; however, effects were limited in terms of lung-tissue repair and cardiac function improvement.,We hypothesized that two doses of MSCs could induce further lung and cardiovascular repair by mitigating inflammation and remodeling in a model of emphysema induced by multiple elastase instillations.,We aimed to comparatively investigate the effects of one versus two doses of MSCs, administered 1 week apart, in a murine model of elastase-induced emphysema.,C57BL/6 mice were randomly divided into control (CTRL) and emphysema (E) groups.,Mice in the E group received porcine pancreatic elastase (0.2 IU, 50 μL) intratracheally once weekly for four consecutive weeks; the CTRL animals received sterile saline (50 μL) using the same protocol.,Three hours after the last instillation, the E group was further randomized to receive either saline (SAL) or murine MSCs (105 cells) intratracheally, in one or two doses (1 week apart).,Fourteen days later, mice were euthanized, and all data analyzed.,Both one and two doses of MSCs improved lung mechanics, reducing keratinocyte-derived chemokine and transforming growth factor-β levels in lung homogenates, total cell and macrophage counts in bronchoalveolar lavage fluid (BALF), and collagen fiber content in airways and blood vessels, as well as increasing vascular endothelial growth factor in lung homogenates and elastic fiber content in lung parenchyma.,However, only the two-dose group exhibited reductions in tumor necrosis factor-α in lung tissue, BALF neutrophil and lymphocyte count, thymus weight, and total cellularity, as well as CD8+ cell counts and cervical lymph node CD4+ and CD8+ T cell counts, as well as further increased elastic fiber content in the lung parenchyma and reduced severity of pulmonary arterial hypertension.,Two doses of MSCs enhanced lung repair and improvement in cardiac function, while inducing T cell immunosuppression, mainly of CD8+ cells, in elastase-induced emphysema. | Nuclear factor-κB (NF-κB) signaling plays essential roles in inflammatory responses.,However, whether the expression levels of NF-κB family genes affect inflammatory responses is unclear.,Moreover, little is known regarding the association between NF-κB family genes expression and the pathogenesis of chronic obstructive pulmonary disease (COPD).,The present study was undertaken to assess the relationship between the expression levels of NF-κB family genes mRNA and of inflammatory markers relevant to COPD pathogenesis.,A total of 186 unrelated patients with acute exacerbations of COPD and 180 healthy controls were recruited.,Total RNA was extracted from the peripheral fasting blood of each subject using trizol reagent.,The mRNA levels of NF-κB family genes (NF-κB1, NF-κB2 and c-REL) were measured by real-time quantitative polymerase chain reaction.,The serum levels of cyclooxygenase-2 (COX-2), C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, IL-12 and tumor necrosis factor-α were measured with enzyme-linked immunosorbent assay kits.,The relative mRNA levels of the NF-κB family genes and the levels of inflammatory molecules were significantly higher in the COPD group than in the control group after adjustment for smoking.,The IL-1β, IL-8 and COX-2 levels were significantly lower in the NF-κB2 under-expression subgroup as compared to the NF-κB2 over-expression subgroup.,The COX-2 level was significantly lower (P < 0.05) in the c-REL under-expression subgroup as compared to the c-REL over-expression subgroup.,NF-κB2 over-expression was associated with IL-1β, IL-8 and COX-2 levels, whereas c-REL overexpression was associated with COX-2 level.,Over-expression of both NF-κB2 and c-REL was found to be related to COPD. | 1 |
Little is known of how to organize non-malign palliative care, and existing knowledge show that patients with COPD live with unmet palliative needs and low quality of life.,With the intent to improve palliative care for patients with COPD, we changed the structure of our outpatient clinic from routine visits by a pulmonary specialist to a structure where each patient was assigned a nurse, offered annual advance care planning dialogues, and ad hoc pulmonary specialist visits.,The aim of this study was to explore COPD patients’ experiences with a new and altered palliative organization.,The design was interpretive description as described by Thorne.,We conducted ten semi-structured interviews with patients with severe COPD from January 2017 to December 2017.,Patients described how the professional relationship and the availability of their nurse was considered as the most important and positive change.,It made the patients feel safe, in control, and subsequently influenced their ability to self-manage their life and prevent being hospitalized.,The patients did not emphasize the advanced care planning dialogues as something special or troublesome.,We showed that it is relevant and meaningful to establish a structure that supports professional relationships between patient, nurse and physician based on patients needs.,The new way of structuring the outpatient care was highly appreciated by COPD patients and made them feel safe which brought confidence in self-management abilities.,The online version of this article (10.1186/s12904-019-0410-0) contains supplementary material, which is available to authorized users. | Psychological morbidity is common in chronic respiratory diseases.,The diagnostic accuracy of the Hospital Anxiety and Depression Scale (HADS) and risk factors for comorbid depression in chronic obstructive pulmonary disease (COPD) are addressed.,Consecutive COPD patients (GOLD stage I-IV, 40-75 years old) were enrolled in a multicentre, cross-sectional cohort study.,Diagnosis of depression was ascertained through clinical records.,Lung function, HADS score, 6-minute walking test (6-MWT), MRC dyspnoea score, and COPD Assessment Test (CAT) were evaluated.,Two hundred fifty-nine COPD patients (mean age 62.5 years; 32% female; mean FEV1 48% predicted) were included.,Patients diagnosed with depression (29/259; 11.2%) had significantly higher HADS-D and HADS-Total scores than nondepressed patients (median (quartiles) HADS-D 6 [4; 9] versus 4 [2; 7], median HADS-Total 14 [10; 20] versus 8 [5; 14]).,Receiver-operating characteristic plots showed moderate accuracy for HADS-D, AUC 0.662 (95%CI 0.601-0.719), and HADS-Total, AUC 0.681 (95%CI 0.620-0.737), with optimal cut-off scores of >5 and >9, respectively.,Sensitivity and specificity were 62.1% and 62.6% for HADS-D compared to 75.9% and 55.2% for HADS-Total.,Age, comorbidities, sex, and lower airflow limitation predicted depression.,The HADS exhibits low diagnostic accuracy for depression in COPD patients.,Younger men with comorbidities are at increased risk for depression. | 1 |
Disease control is an important objective of COPD management.,The SINCON study evaluated the level of control in terms of respiratory symptoms and exacerbations in Spanish patients with COPD for ≥2 years.,SINCON was a descriptive, cross-sectional, multicenter study that assessed degree of control using a combined index comprising COPD assessment test (CAT), modified Medical Research Council dyspnea scale (mMRC), and number of moderate/severe exacerbations in the last year.,Based on this score, patients were categorized as “well controlled” or “poorly controlled”.,Degree of control was also assessed relative to patient phenotype, setting (primary care [PC] vs respiratory care [RC]), and impact of treatment on morning symptoms.,Of the 481 patients (PC: 307, RC: 174) analyzed, COPD was poorly controlled in 63.2%.,Some differences were found between clinical settings: PC patients were more poorly controlled (PC: 66.4% vs RC: 57.5%; P = 0.06) and had higher CAT score (PC: 17.9 vs RC: 15.5; P < 0.05), and higher rate of moderate/severe exacerbations during previous year (PC: 1.5 vs RC: 1.1; P < 0.05), while dyspnea degree was similar in both settings.,Regarding phenotypes, non-exacerbators demonstrated better control vs exacerbators.,Morning symptoms score improved between waking and 3 h after bronchodilator treatment (P < 0.05), with greater improvements in PC patients (PC: − 6.5 vs RC: − 5.0 points; P < 0.05).,Most COPD patients were poorly controlled with some differences observed between PC and RC settings and between patient phenotypes.,Our index may be easily used in PC settings to optimize COPD treatment. | It has recently been proposed that the concept of clinical control in COPD may be useful for deciding treatment in COPD, but the original control criteria (OCC) were considered too restrictive.,Define and subsequently validate “modified” control criteria (MCC) of COPD.,Prospective observational study in COPD patients with a 1-year follow-up.,Control was defined as the presence of low clinical impact and clinical stability.,To evaluate clinical impact, the following clinical parameters were assessed: the degree of dyspnea, use of rescue medication, physical activity, and sputum color.,Stability was assessed by clinical changes and exacerbations in the last 3 months.,The COPD assessment test score and their changes were also evaluated as alternative control criteria.,To define the MCC, adjustment for disease severity using BODEx index (MCC-B) or FEV1 (MCC-F) was evaluated, and the best cutoff point was established.,Time to first combined event (emergency visit, hospitalization, or death) was analyzed to evaluate the predictive capacity of risk of the OCC, MCC-B, and MCC-F.,We included 265 patients, 224 (83.9%) men, with a mean age (±SD) of 68±9 years and FEV1 of 58%±17%.,The proportion of controlled patients was higher using clinical MCC-B or MCC-F (61.5% and 59.6%) than OCC (27.5%).,Similar percentages were found using COPD assessment test scores.,The time to the first combined event was significantly greater in controlled patients using MCC criteria (P<0.001, all cases).,The predictive capacity of risk was similar in MCC-B (c-statistic [C]=0.639) and MCC-F (C=0.637) and higher than OCC (C=0.589).,The new MCC identified a higher number of controlled COPD patients.,These patients have a better quality of life and lower risk of poor outcomes.,The concept of control and the new MCC could be a useful tool to optimize therapy. | 1 |
Pulmonary rehabilitation is a cornerstone of care for COPD but uptake of traditional centre-based programmes is poor.,We assessed whether home-based pulmonary rehabilitation, delivered using minimal resources, had equivalent outcomes to centre-based pulmonary rehabilitation.,A randomised controlled equivalence trial with 12 months follow-up.,Participants with stable COPD were randomly assigned to receive 8 weeks of pulmonary rehabilitation by either the standard outpatient centre-based model, or a new home-based model including one home visit and seven once-weekly telephone calls from a physiotherapist.,The primary outcome was change in 6 min walk distance (6MWD).,We enrolled 166 participants to receive centre-based rehabilitation (n=86) or home-based rehabilitation (n=80).,Intention-to-treat analysis confirmed non-inferiority of home-based rehabilitation for 6MWD at end-rehabilitation and the confidence interval (CI) did not rule out superiority (mean difference favouring home group 18.6 m, 95% CI −3.3 to 40.7).,At 12 months the CI did not exclude inferiority (−5.1 m, −29.2 to 18.9).,Between-group differences for dyspnoea-related quality of life did not rule out superiority of home-based rehabilitation at programme completion (1.6 points, −0.3 to 3.5) and groups were equivalent at 12 months (0.05 points, −2.0 to 2.1).,The per-protocol analysis showed the same pattern of findings.,Neither group maintained postrehabilitation gains at 12 months.,This home-based pulmonary rehabilitation model, delivered with minimal resources, produced short-term clinical outcomes that were equivalent to centre-based pulmonary rehabilitation.,Neither model was effective in maintaining gains at 12 months.,Home-based pulmonary rehabilitation could be considered for people with COPD who cannot access centre-based pulmonary rehabilitation.,NCT01423227, clinicaltrials.gov. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia.,The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD.,We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017.,ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry.,Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa.,Propensity score matched models were used as sensitivity analyses.,A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up.,ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use).,A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001).,Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa.,Caution should be taken when administering high doses of ICS in severely ill patients with COPD.,These results should be confirmed in comparable cohorts and other settings. | There is evidence that bacterial colonisation in chronic obstructive pulmonary disease (COPD) is associated with increased neutrophilic airway inflammation.,This study tested the hypothesis that different bacterial phyla and species cause different inflammatory profiles in COPD patients.,Sputum was analysed by quantitative polymerase chain reaction (qPCR) to quantify bacterial load and 16S rRNA gene sequencing to identify taxonomic composition.,Sputum differential cell counts (DCC) and blood DCC were obtained at baseline and 6 months.,Patients were categorised into five groups based on bacterial load defined by genome copies/ml of ≥ 1 × 104, no colonisation and colonisation by Haemophilus influenzae (H. influenzae), Moraxella catarrhalis (M. catarrhalis), Streptococcus pneumoniae (S. pneumoniae), or > 1 potentially pathogenic microorganism (PPM).,We observed an increase in sputum neutrophil (%), blood neutrophil (%) and neutrophil-lymphocyte ratio (NLR) in patients colonised with H. influenzae (82.6, 67.1, and 3.29 respectively) compared to those without PPM colonisation at baseline (69.5, 63.51 and 2.56 respectively) (p < 0.05 for all analyses), with similar findings at 6 months.,The bacterial load of H. influenzae and Haemophilus determined by qPCR and 16s rRNA gene sequencing respectively, and sputum neutrophil % were positively correlated between baseline and 6 months visits (p < 0.0001, 0.0150 and 0.0002 with r = 0.53, 0.33 and 0.44 respectively).,These results demonstrate a subgroup of COPD patients with persistent H. influenzae colonisation that is associated with increased airway and systemic neutrophilic airway inflammation, and less eosinophilic airway inflammation. | 1 |
Outcomes for patients with chronic respiratory diseases remain poor despite the development of novel therapies.,In part, this reflects the fact that adherence to therapy is low and clinicians lack accurate methods to assess this issue.,Digital technologies hold promise to overcome these barriers to care.,For example, algorithmic analysis of large amounts of information collected on health status and treatment use, along with other disease relevant information such as environmental data, can be used to help guide personalised interventions that may have a positive health impact, such as establishing habitual and correct inhaler use.,Novel approaches to data analysis also offer the possibility of statistical algorithms that are better able to predict exacerbations, thereby creating opportunities for preventive interventions that may adapt therapy as disease activity changes.,To realise these possibilities, digital approaches to disease management should be supported by strong evidence, have a solid infrastructure, be designed collaboratively as clinically effective and cost-effective systems, and reflect the needs of patients and healthcare providers.,Regulatory standards for digital interventions and strategies to handle the large amounts of data generated are also needed.,This review highlights the opportunities provided by digital technologies for managing patients with respiratory diseases.,Digital technologies hold promise to improve adherence and personalise care in patients with respiratory diseaseshttp://ow.ly/WjTz30m71ZW | The 1-min sit-to-stand (1-min STS) test and handgrip strength test have been proposed as simple tests of functional exercise performance in chronic obstructive pulmonary disease (COPD) patients.,We assessed the long-term (5-year) predictive performance of the 1-min sit-to-stand and handgrip strength tests for mortality, health-related quality of life (HRQoL) and exacerbations in COPD patients.,In 409 primary care patients, we found the 1-min STS test to be strongly associated with long-term morality (hazard ratio per 3 more repetitions: 0.81, 95% CI 0.65 to 0.86) and moderately associated with long-term HRQoL.,Neither test was associated with exacerbations.,Our results suggest that the 1-min STS test may be useful for assessing the health status and long-term prognosis of COPD patients.,This study was registered at http://www.clinicaltrials.gov/ (NCT00706602, 25 June 2008). | 1 |
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. | Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend limiting the use of inhaled corticosteroids (ICS) to patients with more severe disease and/or increased exacerbation risk.,However, there are discrepancies between guidelines and real-life practice, as ICS are being overprescribed.,In light of the increasing concerns about the clinical benefit and long-term risks associated with ICS use, therapy needs to be carefully weighed on a case-by-case basis, including in patients already on ICS.,Several studies sought out to determine the effects of withdrawing ICS in patients with COPD.,Early studies have deterred clinicians from reducing ICS in patients with COPD as they reported that an abrupt withdrawal of ICS precipitates exacerbations, and results in a deterioration in lung function and symptoms.,However, these studies were fraught with numerous methodological limitations.,Recently, two randomized controlled trials and a real-life prospective study revealed that ICS can be safely withdrawn in certain patients.,Of these, the WISDOM (Withdrawal of Inhaled Steroids During Optimized Bronchodilator Management) trial was the largest and first to examine stepwise withdrawal of ICS in patients with COPD receiving maintenance therapy of long-acting bronchodilators (ie, tiotropium and salmeterol).,Even with therapy being in line with the current guidelines, the findings of the WISDOM trial indicate that not all patients benefit from including ICS in their treatment regimen.,Indeed, only certain COPD phenotypes seem to benefit from ICS therapy, and validated markers that predict ICS response are urgently warranted in clinical practice.,Furthermore, we are now better equipped with a larger armamentarium of novel and more effective long-acting β2-agonist/long-acting muscarinic antagonist combinations that can be considered by clinicians to optimize bronchodilation and allow for safer ICS withdrawal.,In addition to providing a review of the aforementioned, this perspective article proposes an algorithm for the stepwise withdrawal of ICS in real-life clinical practice. | 1 |
Serious inhaler technique errors can impair drug delivery to the lungs.,This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers.,Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order.,Patients inhaled through empty devices after reading the patient information leaflet.,If serious errors potentially affecting dose delivery were recorded, they repeated the inhalations after watching a training video.,Inhaler technique was assessed by a trained nurse observer and an electronic inhalation profile recorder.,Baseline patient characteristics were similar between randomisation arms for the Pulmojet-Diskus (n = 277) and Pulmojet-Turbohaler (n = 144) comparisons.,Non-inferiority in the proportions of patients recording no nurse-observed serious errors was demonstrated for both Pulmojet versus Diskus, and Pulmojet versus Turbohaler; therefore, superiority was tested.,Patients were significantly less likely to make ≥1 nurse-observed serious errors using Pulmojet compared with Diskus (odds ratio, 0.31; 95 % CI, 0.19-0.51) or Pulmojet compared with Turbohaler (0.23; 0.12-0.44) after reading the patient information leaflet with additional video instruction, if required.,These results suggest Pulmojet is easier to learn to use correctly than the Turbohaler or Diskus for current inhaler users switching to a new dry powder inhaler.,ClinicalTrials.gov Identifier: NCT01794390 (February 14, 2013),The online version of this article (doi:10.1186/s12890-016-0169-5) contains supplementary material, which is available to authorized users. | Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | 1 |
Forced expiratory volume in 1s/forced expiratory volume in 6 s ( FEV1/FEV6) assessment with a microspirometer may be useful in the diagnostic work up of subjects who are suspected of having COPD in primary care.,To determine the diagnostic accuracy of a negative pre-bronchodilator (BD) microspirometry test relative to a full diagnostic spirometry test in subjects in whom general practitioners (GPs) suspect airflow obstruction.,Cross-sectional study in which the order of microspirometry and diagnostic spirometry tests was randomised.,Study subjects were (ex-)smokers aged ⩾50 years referred for diagnostic spirometry to a primary care diagnostic centre by their GPs.,A pre-BD FEV1/FEV6 value <0.73 as measured with the PiKo-6 microspirometer was compared with a post-BD FEV1/FVC (forced vital capacity) <0.70 and FEV1/FVC<lower limit of normal (LLN) from diagnostic spirometry.,One hundred and four subjects were analysed (59.6% males, 42.3% current smokers).,Negative predictive values from microspirometry for airflow obstruction based on the fixed and LLN cut-off points were 94.4% (95% confidence interval (CI), 86.4-98.5) and 96.3% (95% CI, 88.2-99.3), respectively.,In all, 18% of positive microspirometry results were not confirmed by a post-BD FEV1/FVC <0.70 and 44% of tests were false positive compared with the LLN criterion for airflow obstruction.,Pre-bronchodilator microspirometry seems to be able to reliably preselect patients for further assessment of airflow obstruction by means of regular diagnostic spirometry.,However, use of microspirometry alone would result in overestimation of airflow obstruction and should not replace regular spirometry when diagnosing COPD in primary care. | Early diagnosis of chronic obstructive pulmonary disease (COPD) in primary care settings is difficult to achieve chiefly due to lack of availability of spirometry.,This study estimated the prevalence of airflow limitation among chronic smokers using a handheld spirometer in this setting.,This is a cross-sectional study performed on consecutive patients who were ≥40 years old with ≥10 pack-years smoking history.,Face-to-face interviews were carried out to obtain demographic data and relevant information.,Handheld spirometry was performed according to a standard protocol using the COPd-6 device (Model 4000, Vitalograph, Ennis, Ireland) in addition to standard spirometry.,Airflow limitation was defined as ratio of forced expiratory volume in 1 s (FEV1)/forced expiratory volume in 6 s <0.75 (COPd-6) or FEV1/forced vital capacity <0.7.,Multiple logistic regression analyses were used to determine predictors of airflow limitation.,A total of 416 patients were recruited with mean age of 53 years old.,The prevalence of airflow limitation was 10.6% (n = 44) with COPd-6 versus 6% as gauged using standard spirometry.,Risk factors for airflow limitation were age >65 years (odds ratio (OR) 3.732 95% confidence interval (CI): 1.100-1.280), a history of ‘bad health’ (OR 2.524, 95% CI: 1.037-6.142) and low to normal body mass index (OR 2.914, 95% CI: 1.191-7.190).,In a primary care setting, handheld spirometry (COPd-6) found a prevalence of airflow limitation of ∼10% in smokers.,Patients were older, not overweight and had an ill-defined history of health problems.,Prevalence of COPD is unknown in Malaysia.,The prevalence of COPD using a handheld spirometer (COPd-6TM) was 10.6% versus 6% as gauged using standard spirometry.,Predictors of COPD were older age, lower BMI and a history of ‘bad health’.,Case-finding for COPD should be targeted in this special population. | 1 |
The role of anxiety and depression in the physical activity (PA) of patients with COPD is controversial.,We prospectively assessed the effect of symptoms of anxiety and depression on PA in COPD patients.,We evaluated anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), PA (Dynaport® accelerometer), and other relevant characteristics in 220 COPD patients from five European countries at baseline and at 6 and 12 months of follow-up.,HADS score was categorized as: no symptoms (score 0-7), suggested (8-10), and probable (>11) anxiety or depression.,We estimated the association between anxiety and depression at t (baseline and 6 months) and PA at t+1 (6 and 12 months) using regression models with a repeated measures approach.,Patients had a mean (standard deviation) age of 67 (8) years, forced expiratory volume in 1 second 57 (20)% predicted.,At baseline, the prevalence of probable anxiety and depression was 10% and 5%, respectively.,In multivariable models adjusted by confounders and previous PA, patients performed 81 fewer steps/day (95% confidence interval, −149 to −12, P=0.02) per extra point in HADS-depression score.,HADS-anxiety symptoms were not associated with PA.,In COPD patients, symptoms of depression are prospectively associated with a measurable reduction in PA 6 months later. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
The purpose of this study was to assess the prevalence of COPD phenotypes at a national level and to determine their geographic distribution among different autonomous communities in Spain.,A total of 1,610 patients (82% men, median age 67 years) recruited in primary care centers and pneumology services participated in an observational, cross-sectional, and multicenter study.,Phenotypes evaluated were the non-exacerbator phenotype, the asthma-COPD overlap syndrome (ACOS), the exacerbator phenotype with emphysema, and the exacerbator phenotype with chronic bronchitis.,The non-exacerbator phenotype was the most common (46.7%) followed by exacerbator with chronic bronchitis (22.4%) and exacerbator with emphysema (16.4%).,The ACOS phenotype accounted for the lowest rate (14.5%).,For each phenotype, the highest prevalence rates were concentrated in two or three autonomous communities, with relatively similar rates for the remaining regions.,Overall prevalence rates were higher for the non-exacerbator and the exacerbator with chronic bronchitis phenotypes than for ACOS and the exacerbator with chronic bronchitis phenotypes.,Differences in the distribution of COPD phenotypes according to gender, age, physician specialty, smoking habit, number of comorbidities, quality of life assessed with the COPD Assessment Test, and BODEx index (body mass index, airflow obstruction, dyspnea, and exacerbations) were all statistically significant.,Differences in the prevalence rates of COPD phenotypes among the Spanish autonomous communities have been documented.,Mapping the distribution of COPD phenotypes is useful to highlight regional differences as starting point for comparisons across time.,This geographic analysis provides health-care planners a valuable platform to assess changes in COPD burden at nationwide and regional levels. | Smoking and subsequent development of COPD is an ever-increasing epidemic in Arabian Gulf and Middle East countries, with no signs of decline.,The important fact to be highlighted is that this COPD epidemic of increasing incidence and prevalence is mostly unrecognized by patients, due to the common attribution of symptoms to “smoker’s cough”, and the underdiagnosis and undertreatment by physicians because the common signs and symptoms masquerade as asthma.,Consequently, there are long-term adverse effects of missing the diagnosis.,The purpose of this review article is to focus upon the status of COPD in Arabian Gulf and Middle East countries, stressing the increasing burden of smoking and COPD, to emphasize the specific factors leading to rise in prevalence of COPD, to bring to light the underdiagnosis and undermanagement of COPD, and to treat COPD in conformity with standard guidelines with local and regional modifications.,This review ends with suggestions and recommendations to the health department to formulate policies and to generate awareness among the general public about the side effects of smoking and consequences of COPD. | 1 |
The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology.,This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD.,Serum levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls.,The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden.,COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group.,Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m2, with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis.,The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year.,Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype.,No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers. | Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution.,The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.,This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age).,Subjects with any other condition associated with an inflammatory process were excluded.,COPD was defined as a post-bronchodilator FEV1/FVC < 0.70.,The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication.,Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests.,Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.,We compared 324 COPD patients and 110 reference subjects.,After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 ± 0.023 vs.,0.376 ± 0.041 log mg/L, p = 0.049), TNF-α (13.12 ± 0.59 vs.,10.47 ± 1.06 pg/mL, p = 0.033), IL-8 (7.56 ± 0.63 vs.,3.57 ± 1.13 pg/ml; p = 0.033) and NOx (1.42 ± 0.01 vs.,1.36 ± 0.02 log nmol/l; p = 0.048) than controls.,In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.,Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. | 1 |
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. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
In some patients with COPD, the disease is characterized by exacerbations.,Severe exacerbations warrant a hospitalization, with prolonged detrimental effects on physical activity.,Interventions after an exacerbation may improve physical activity, with longstanding health benefits.,Physical activity counseling and real-time feedback were effective in stable COPD.,No evidence is available on the use of this therapeutic modality in patients after a COPD exacerbation.,Thirty patients were randomly assigned to usual care or physical activity counseling, by telephone contacts at a frequency of 3 times a week and real-time feedback.,Lung function, peripheral muscle strength, functional exercise capacity, symptom experience and COPD-related health status were assessed during hospital stay and 1 month later.,Both groups significantly recovered in physical activity (PAsteps: control group: 1013 ± 1275 steps vs intervention group: 984 ± 1208 steps (p = 0.0005); PAwalk: control group: 13 ± 14 min vs intervention group: 13 ± 16 min (p = 0.0002)), functional exercise capacity (control group: 64 ± 59 m (p = 0.002) vs intervention group: 67 ± 84 m (p = 0.02)) and COPD-related health status (CAT: control group: −5 [−7 to 1] (p = 0.02) vs intervention group: −3 [−10 to 1] points (p = 0.03)).,No differences between groups were observed.,From our pilot study, we concluded that telephone based physical activity counseling with pedometer feedback after an exacerbation did not result in better improvements in physical activity and clinical outcomes compared to usual care.,Because of the difficult recruitment and the negative intermediate analyses, this study was not continued.,Clinicaltrials.gov NCT02223962.,Registered 4 September 2013. | Most guidelines recommend pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) and modified Medical Research Council dyspnea scale (mMRC) levels ≥2, but the effectiveness of PR in patients with less advanced disease is not well established.,Our aim was to investigate the effects of PR in patients with COPD and mMRC ≤1.,The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.,We identified randomized controlled trials (RCTs) through a systematic, multidatabase literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC ≤1.,Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and dropouts were important outcomes.,Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence.,Meta-analyses were performed when deemed feasible.,Four RCTs (489 participants) were included.,On the basis of moderate-quality evidence, we found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [−4.51 to −3.89]) on St George’s Respiratory Questionnaire, but not at the longest follow-up.,We also found a statistically significant improvement of 25.71 m (95% CI: [15.76-35.65]) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant.,No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity.,No adverse effects were reported.,We found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically nonsignificant improvement in walking distance following PR in patients with COPD and mild symptoms.,This resulted in a weak recommendation of routine PR in these patients using the GRADE approach. | 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 | The aim of this study was to determine if an interactive web-based pulmonary rehabilitation (PR) programme is a feasible alternative to conventional PR.,Randomised controlled feasibility trial.,Participants with a diagnosis of chronic obstructive pulmonary disease were recruited from PR assessments, primary care and community rehabilitation programmes.,Patients randomised to conventional rehabilitation started the programme according to the standard care at their referred site on the next available date.,103 patients were recruited to the study and randomised: 52 to conventional rehabilitation (mean (±SD) age 66 (±8) years, Medical Research Council (MRC) 3 (IQR2-4)); 51 to the web arm (mean (±SD) age 66 (±10) years, MRC 3 (IQR2-4)).,Participants had to be willing to participate in either arm of the trial, have internet access and be web literate.,Patients randomised to the web-based programme worked through the website, exercising and recording their progress as well as reading educational material.,Conventional PR consisted of twice weekly, 2 hourly sessions (an hour for exercise training and an hour for education).,Recruitment rates, eligibility, patient preference and dropout and completion rates for both programmes were collected.,Standard outcomes for a PR assessment including measures of exercise capacity and quality of life questionnaires were also evaluated.,A statistically significant improvement (p≤0.01) was observed within each group in the endurance shuttle walk test (WEB: mean change 189±211.1; PR classes: mean change 184.5±247.4 s) and Chronic Respiratory disease Questionnaire-Dyspnoea (CRQ-D; WEB: mean change 0.7±1.2; PR classes: mean change 0.8±1.0).,However, there were no significant differences between the groups in any outcome.,Dropout rates were higher in the web-based programme (57% vs 23%).,An interactive web-based PR programme is feasible and acceptable when compared with conventional PR.,Future trials maybe around choice-based PR programmes for select patients enabling stratification of patient care.,ISRCTN03142263; Results. | 1 |
Chronic obstructive pulmonary disease (COPD) related to wood smoke exposure is characterized by important inflammation of the central and peripheral airways without significant emphysema.,The objective of this study is to describe the bronchial hyperresponsiveness (BHR) level in women with COPD related to wood smoke exposure and to compare it with the BHR in women with COPD related to tobacco smoking.,Two groups of women with stable COPD were studied: (1) wood smoke exposed (WS-COPD); and (2) tobacco smoke exposed (TS-COPD).,A methacholine challenge test (MCT) was performed in all patients according to American Thoracic Society criteria.,BHR levels were compared using the methacholine concentration, which caused a 20% fall in the FEV1 (PC20).,Thirty-one patients, 19 with WS-COPD and 12 with TS-COPD, were included.,There were no significant differences between the groups in baseline FVC, FEV1, IC, FEF25-75, and FEF25-75/FVC.,All 31 patients had a positive MCT (PC20 < 16 mg/mL) and the fall in the FEV1 and IC was similar in both groups.,The severity of BHR was significantly higher in the WS-COPD patients (PC20: 0.39 mg/mL) than in the TS-COPD patients (PC20: 1.24 mg/mL) (P = 0.028).,The presence of cough, phlegm, and dyspnea during the test were similar in both groups.,We found moderate to severe BHR in women with WS-COPD, which was more severe than in the TS-COPD women with similar age and airflow obstruction.,This paper suggests that the structural and inflammatory changes induced by the chronic exposure to wood smoke, described in other studies, can explain the differences with TS-COPD patients.,Future studies may clarify our understanding of the impact of BHR on COPD physiopathology, phenotypes, and treatment strategies. | Cigarette smoking cannot fully explain the epidemiologic characteristics of chronic obstructive pulmonary disease (COPD) in women, particularly for those who rarely smoke, but COPD risk is not less than men.,The aim of our study is to investigate the relationship between second-hand smoke (SHS) exposure and chronic bronchitis in Taiwanese women.,We used Taiwan's National Health Insurance Bureau claims data in 1999, and cross-checked using criteria set by the American Thoracic Society; there were 33 women with chronic bronchitis, 182 with probable chronic bronchitis, and 205 with no chronic bronchitis during our interview time between 2000 and 2005.,We measured second-hand smoke (SHS) exposure by self-reported measures (household users and duration of exposure), and validated this by measuring urinary cotinine levels of a subset subjects.,Classification of chronic bronchitis was also based on spirometry defined according to the GOLD guidelines to get the severity of COPD.,Women who smoked and women who had been exposed to a lifetime of SHS were 24.81-fold (95% CI: 5.78-106.38) and 3.65-fold (95% CI: 1.19-11.26) more likely to have chronic bronchitis, respectively, than those who had not been exposed to SHS.,In addition, there was a significant increasing trend between the severity of COPD and exposure years of SHS (p < 0.01).,The population attributable risk percentages of chronic bronchitis for smokers and those exposed to SHS were 23.2 and 47.3% respectively.,These findings indicate that, besides cigarette smoking, exposure to SHS is a major risk factor for chronic bronchitis in Taiwanese women. | 1 |
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. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,The prevalence of COPD among cigarette smokers in the Middle East is not well studied.,A prospective descriptive study was performed in the north of Jordan.,Male cigarette smokers (≥10 pack-year) aged 35 years and older were recruited from the community.,They completed a questionnaire and a postbronchodilator spirometry.,Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (postbronchodilator forced expiratory volume in 1 second <70%) was used to define COPD.,A total of 512 subjects completed the study protocol.,According to the GOLD criteria, 42 subjects (8.2%) had COPD.,Of those, 27 subjects (64.3%) had symptomatic COPD.,Using the GOLD criteria, eight subjects (19%) with COPD had mild disease, 24 (57.1%) had moderate disease, eight (19%) had severe disease, and two (4.8%) had very severe disease.,Only 10.6% were aware of COPD as a smoking-related respiratory illness, and 6.4% had received counseling about risk for COPD by a physician.,Chronic bronchitis (cough for 3 months in 2 consecutive years) was reported by 15% of the subjects, wheezes by 44.1%, and dyspnea by 65.2%.,Subjects with COPD reported having more chronic bronchitis 18/42 (42.9%) and wheezing 28/42 (66.7%) than subjects without COPD.,The prevalence of COPD increased with increased number of pack-years smoked.,In conclusion, COPD prevalence among cigarette-smoking men in Jordan is lower than in the developed world.,COPD was largely underdiagnosed, despite the majority of participants being symptomatic and having moderate to severe disease. | 1 |
Many studies have reported the prevalence of chronic obstructive pulmonary disease (COPD) and its effects and prognosis in patients with lung cancer, but few have considered quality of life and survival of patients with lung cancer according to severity of airway obstruction.,This study investigated the presence of COPD and the severity of airway obstruction in patients with non-small cell lung cancer (NSCLC), and analyzed how these factors affected symptoms, quality of life, and prognosis.,We retrospectively reviewed the prospective lung cancer database of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017.,We enrolled patients with advanced NSCLC and evaluated quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30.,We also estimated pulmonary function and analyzed survival data.,Of the 337 patients with advanced NSCLC, 170 (50.5%) had COPD and 167 (49.5%) did not.,Significant differences were observed in symptoms between the two groups.,The COPD group complained of more symptoms, such as cough, sputum, and dyspnea, than those in the non-COPD group.,The distribution according to the severity of obstruction in the COPD group was as follows: Grade 1 (FEV1 ≥ 80%) 35 patients (20.6%), Grade 2 (50% ≤ FEV1 < 80%) 103 patients (60.6%), Grade 3 (30% ≤ FEV1 < 50%) 24 patients (14.1%), and Grade 4 (FEV1 < 30%) 8 patients (4.7%).,The presence of COPD did not affect overall quality of life in patients with NSCLC, but as the airway obstruction increased, physical function decreased, and fatigue and dyspnea were more frequent.,The overall median survival of the COPD group was shorter than that of the non-COPD group (median survival, 224 vs. 339 days, p = 0.035).,In this study, a high prevalence of COPD was found among patients with advanced NSCLC, and COPD patients complained about various symptoms and had diminished quality of life in several sectors.,Therefore, it is necessary to actively evaluate quality of life, lung function, and symptoms in patients with lung cancer and reflect them in the treatment and management plans of these patients. | The aim of this study was to determine the relationship between lobar severity of emphysema and lung cancer using automated lobe segmentation and emphysema quantification methods.,This study included 78 patients (74 males and 4 females; mean age of 72 years) with the following conditions: pathologically proven lung cancer, available chest computed tomographic (CT) scans for lobe segmentation, and quantitative scoring of emphysema.,The relationship between emphysema and lung cancer was analyzed using quantitative emphysema scoring of each pulmonary lobe.,The most common location of cancer was the left upper lobe (LUL) (n = 28), followed by the right upper lobe (RUL) (n = 27), left lower lobe (LLL) (n = 13), right lower lobe (RLL) (n = 9), and right middle lobe (RML) (n = 1).,Emphysema ratio was the highest in LUL, followed by that in RUL, LLL, RML, and RLL.,Multivariate logistic regression analysis revealed that upper lobes (odds ratio: 1.77; 95% confidence interval: 1.01-3.11, P = 0.048) and lobes with emphysema ratio ranked the 1st or the 2nd (odds ratio: 2.48; 95% confidence interval: 1.48-4.15, P < 0.001) were significantly and independently associated with lung cancer development.,In emphysema patients, lung cancer has a tendency to develop in lobes with more severe emphysema. | 1 |
Umeclidinium (UMEC; long-acting muscarinic antagonist) plus vilanterol (VI; long-acting beta2 agonist [LABA]) and the LABA/inhaled corticosteroid fluticasone propionate/salmeterol (FP/SAL) are approved maintenance treatments for chronic obstructive pulmonary disease (COPD).,This 12-week, multicentre, double-blind, parallel-group, double-dummy study compared the efficacy and safety of these treatments in symptomatic patients with moderate-to-severe COPD with no exacerbations in the year prior to enrolment.,Patients (n = 717) were randomised 1:1 to once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 500/50 mcg.,Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, symptoms, quality of life (QoL) and safety.,Improvements with UMEC/VI versus FP/SAL were 0.080 L (95 % confidence interval: 0.046-0.113; wmFEV1) and 0.090 L (0.055-0.125; trough FEV1) (both p < 0.001).,UMEC/VI statistically significantly improved all other lung function measures versus FP/SAL.,Both treatments demonstrated a clinically meaningful improvement in symptoms (Transition Dyspnoea Index ≥1 unit) and QoL (St George’s Respiratory Questionnaire Total score ≥4 unit decrease from baseline) over 12 weeks.,The incidence of adverse events was 28 % (UMEC/VI) and 29 % (FP/SAL); nasopharyngitis and headache were most common.,Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in significant and sustained improvements in lung function versus twice-daily FP/SAL 500/50 mcg in patients with moderate-to-severe COPD and with no exacerbations in the year prior to enrolment.,NCT01822899 Registration date: March 28, 2013,The online version of this article (doi:10.1186/s12890-015-0092-1) contains supplementary material, which is available to authorized users. | Despite the availability of national and international guidelines, evidence suggests that chronic obstructive pulmonary disease (COPD) treatment is not always prescribed according to recommendations.,This study evaluated the current management of patients with COPD using a large UK primary-care database.,This analysis used electronic patient records and patient-completed questionnaires from the Optimum Patient Care Research Database.,Data on current management were analyzed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) group and presence or absence of a concomitant asthma diagnosis, in patients with a COPD diagnosis at ≥35 years of age and with spirometry results supportive of the COPD diagnosis.,A total of 24,957 patients were analyzed, of whom 13,557 (54.3%) had moderate airflow limitation (GOLD Stage 2 COPD).,The proportion of patients not receiving pharmacologic treatment for COPD was 17.0% in the total COPD population and 17.7% in the GOLD Stage 2 subset.,Approximately 50% of patients in both cohorts were receiving inhaled corticosteroids (ICS), either in combination with a long-acting β2-agonist (LABA; 26.7% for both cohorts) or a LABA and a long-acting muscarinic antagonist (LAMA; 23.2% and 19.9%, respectively).,ICS + LABA and ICS + LABA + LAMA were the most frequently used treatments in GOLD Groups A and B.,Of patients without concomitant asthma, 53.7% of the total COPD population and 50.2% of the GOLD Stage 2 subset were receiving ICS.,Of patients with GOLD Stage 2 COPD and no exacerbations in the previous year, 49% were prescribed ICS.,A high proportion of GOLD Stage 2 COPD patients were symptomatic on their current management (36.6% with modified Medical Research Council score ≥2; 76.4% with COPD Assessment Test score ≥10).,COPD is not treated according to GOLD and National Institute for Health and Care Excellence recommendations in the UK primary-care setting.,Some patients receive no treatment despite experiencing symptoms.,Among those on treatment, most receive ICS irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history.,Many patients on treatment continue to have symptoms. | 1 |
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. | Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood.,Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease.,Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2.,A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility.,We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls.,Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene.,Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated.,The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre.,Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053.,No significant associations were identified for TGFbeta1.,These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis. | 1 |
Mesenchymal cells are an essential cell type because of their role in tissue support, their multilineage differentiation capacities and their potential clinical applications.,They play a crucial role during lung development by interacting with airway epithelium, and also during lung regeneration and remodeling after injury.,However, much less is known about their function in lung disease.,In this review, we discuss the origins of mesenchymal cells during lung development, their crosstalk with the epithelium, and their role in lung diseases, particularly in chronic obstructive pulmonary disease. | Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer.,A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins.,This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients.,We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA).,We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose).,To assess residual confounding, a negative control exposure was used to test the validity of our results.,All exposure variables were time-dependent.,The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female.,There were 12,469 patients who received at least one statin prescription.,Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant.,Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99).,Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10).,The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer.,While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy. | 1 |
Purpose.,This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD.,Patients and Methods.,We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR).,In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA.,Data were analyzed using simple and logistic regression and receiver operating characteristic analyses.,Results.,Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01).,Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001).,Conclusion.,Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD. | We have previously shown that the defective ability of alveolar macrophages (AM) to phagocytose apoptotic cells (‘efferocytosis’) in chronic obstructive pulmonary disease/emphysema (COPD) could be therapeutically improved using the C-type lectin, mannose binding lectin (MBL), although the exact mechanisms underlying this effect are unknown.,An S-type lectin, galectin-3, is also known to regulate macrophage phenotype and function, via interaction with its receptor CD98.,We hypothesized that defective expression of galectin/CD98 would be associated with defective efferocytosis in COPD and that mechanisms would include effects on cytoskeletal remodeling and macrophage phenotype and glutathione (GSH) availability.,Galectin-3 was measured by ELISA in BAL from controls, smokers and current/ex-smokers with COPD.,CD98 was measured on AM using flow cytometry.,We assessed the effects of galectin-3 on efferocytosis, CD98, GSH, actin polymerisation, rac activation, and the involvement of PI3K (using β-actin probing and wortmannin inhibition) in vitro using human AM and/or MH-S macrophage cell line.,Significant decreases in BAL galectin-3 and AM CD98 were observed in BAL from both current- and ex-smoker COPD subjects vs controls.,Galectin 3 increased efferocytosis via an increase in active GTP bound Rac1.,This was confirmed with β-actin probing and the role of PI3K was confirmed using wortmannin inhibition.,The increased efferocytosis was associated with increases in available glutathione and expression of CD98.,We provide evidence for a role of airway lectins in the failed efferocytosis in COPD, supporting their further investigation as potential macrophage-targeted therapies. | 1 |
Overlap syndrome shares features of both asthma and chronic obstructive pulmonary disease (COPD).,The aim of this study was to investigate characteristics of overlap syndrome and their effect on self-rated health (SRH).,We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey of 2007-2009.,Subjects with acceptable spirometry and available wheezing history were included.,Subjects were classified into four groups based on forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) results and the presence or absence of self-reported wheezing for the previous 12 months: 1) COPD group, defined as having FEV1/FVC <0.7 without self-reported wheezing history; 2) asthma group, defined as having self-reported wheezing history without FEV1/FVC <0.7; 3) overlap syndrome group, having both FEV1/FVC <0.7 and wheezing history; and 4) non-obstructive disease (NOD) group, having neither FEV1/FVC <0.7 nor self-reported wheezing.,SRH was categorized as better or lower based on responses to a questionnaire.,From a total 9,104 subjects, 700 were assigned to the COPD group, 560 to the asthma group, 210 to the overlap syndrome group, and 7,634 to the NOD group.,Compared to the other groups, subjects in the overlap syndrome group were more likely to have low lung function, a high proportion of smokers, low socioeconomic status, short education duration, lower SRH, and past diagnosis of pulmonary tuberculosis or bronchiectasis.,Multiple logistic regression analysis revealed that both overlap syndrome and asthma groups were independently associated with lower SRH after adjustment for age, sex, socioeconomic status, education level, smoking status, comorbidities, and lung function.,Female, old age, low education level, low economic status, smoker and other comorbidities were also associated with lower SRH.,Overlap syndrome was accompanied by high morbidity and was associated with lower SRH, which needs more appropriate care. | 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. | 1 |
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease commonly encountered in primary care.,This study aimed to audit COPD care at primary care clinics of Hong Kong and to work out improvement strategies.,All COPD patients aged 40 or above who had been followed up at 13 public primary care clinics of Kowloon Central Cluster (KCC) under the Hospital Authority of Hong Kong (HAHK) were included in this clinic audit.,Evidence-based audit criteria and performance standards were established after thorough literature review.,Phase 1 was from 1st April 2016 to 31st March 2017, with deficiencies of care identified.,It was followed by a one-year implementation phase through which a series of improvement strategies were executed.,Outcome of the enhancement was reviewed during Phase 2 from 1st April 2018 to 31st March 2019.,Chi-square test and student’s t test were used to detect statistically significant changes between Phase 1 and Phase 2.,A total of 2358 COPD cases were identified in Phase 1 where 658 of them were smokers.,Of those smokers, 332 (50.5%) had been referred to Smoking Counselling and Cessation Service (SCCS) and 289 (43.9%) actually attended it. 991 cases (42%) received Seasonal Influenza Vaccine (SIV) and 938 cases (39.8%) received Pneumococcal Vaccine (PCV). 698 patients (29.6%) had spirometry done before and 423 patients (17.9%) had been admitted to hospital due to acute exacerbation of COPD (AECOPD).,With the concerted effort taken during the implementation phase, Phase 2 data showed significant improvement in nearly all criteria.,There was a marked increase in the SIV and PCV uptake rate, spirometry performance rate and most importantly, a significant reduction in AECOPD rate leading to hospital admission (13.5%, P = 0.000043).,However, the referral rate and attendance rate of SCCS among smokers remained stagnant (P > 0.05).,Via a systematic team approach, COPD care at primary care clinics of KCC under HAHK had been significantly improved for most of the audit criteria, which in turn reduced the burden of the healthcare system. | Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | 1 |
Pulmonary epithelial cells are widely considered to be the first line of defence in the lung and are responsible for coordinating the innate immune response to injury and subsequent repair.,Consequently, epithelial cells communicate with multiple cell types including immune cells and fibroblasts to promote acute inflammation and normal wound healing in response to damage.,However, aberrant epithelial cell death and damage are hallmarks of pulmonary disease, with necrotic cell death and cellular senescence contributing to disease pathogenesis in numerous respiratory diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and coronavirus disease (COVID)-19.,In this review, we summarise the literature that demonstrates that epithelial damage plays a pivotal role in the dysregulation of the immune response leading to tissue destruction and abnormal remodelling in several chronic diseases.,Specifically, we highlight the role of epithelial-derived damage-associated molecular patterns (DAMPs) and senescence in shaping the immune response and assess their contribution to inflammatory and fibrotic signalling pathways in the lung. | Acute exacerbations of chronic obstructive pulmonary disease (COPD) are associated with a significant mortality, health and economic burden.,Their diagnosis, assessment and management remain suboptimal and unchanged for decades.,Recent clinical and translational studies revealed that the significant heterogeneity in mechanisms and outcomes of exacerbations could be resolved by grouping them etiologically.,This is anticipated to lead to a better understanding of the biological processes that underlie each type of exacerbation and to allow the introduction of precision medicine interventions that could improve outcomes.,This review summarises novel data on the diagnosis, phenotyping, targeted treatment and prevention of COPD exacerbations. | 1 |
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
Desde un punto de vista microbiológico, tanto en el tratamiento antimicrobiano empírico como el dirigido en la infección respiratoria se fundamenta en el perfil de sensibilidad de los microrganismos aislados y los posibles mecanismos de resistencia que puedan presentar.,Estos últimos puedan variar en diferentes áreas geográficas según los perfiles de prescripción y los programas de vacunación.,Los antibióticos betalactámicos, las fluoroquinolonas y los macrólidos son los antimicrobianos más empleados en la exacerbación de la enfermedad pulmonar obstructiva crónica y la neumonía adquirida en la comunidad.,En su prescripción se deben tener en cuenta aspectos como la actividad intrínseca, el efecto bactericida y su capacidad para evitar el desarrollo de resistencias.,Este último está relacionado con los parámetros PK/PD, la concentración preventiva de mutantes y la denominada ventana de selección.,Mas reciente ha crecido en importancia el potencial impacto ecológico, no solo sobre la microbiota intestinal, sino también sobre la respiratoria.,El mantenimiento del estado de eubiosis requiere el uso de antimicrobianos con bajo perfil de actuación sobre los microorganismos anaerobios.,Con ellos se facilita la resiliencia de las poblaciones bacterianas que integran la microbiota, el estado de resistencia de colonización y se limita el daño colateral relacionado con la emergencia de resistencia a los anti-microbianos en los patógenos que producen las infecciones y las poblaciones bacterianas que integran la microbiota. | There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course.,Previous studies on this topic did not generate causally-interpretable estimates.,Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients.,Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes.,We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events.,Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics.,35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up.,The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations.,This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event.,The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality.,There was substantial heterogeneity in the individual-specific rate of severe exacerbations.,Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile.,Using robust statistical methodology that controlled for heterogeneity in exacerbation rates among individuals, we demonstrated potential causal associations among past and future severe exacerbations, albeit the magnitude of association was noticeably lower than previously reported.,The prevention of severe exacerbations has the potential to modify the disease trajectory. | 1 |
Recent studies that assessed the relevance of the blood eosinophil count as a biomarker in patients with COPD may have overestimated it because they included patients with asthma-COPD overlap syndrome (ACOS).,We investigated the clinical implications of the blood eosinophil count in patients with non-ACOS COPD.,From a Korean COPD Subtype Study (KOCOSS) cohort, we selected patients with non-ACOS COPD after excluding ACOS patients according to Spanish criteria.,Clinical characteristics and the incidence of moderate-to-severe exacerbation were compared among the four groups stratified according to the quartiles of blood eosinophil percent and count.,Of the KOCOSS cohort of 1,132 patients with COPD, 467 non-ACOS COPD patients (41.2%) with data of blood eosinophil count remained after excluding those with ACOS based on the Spanish definition.,There was no difference in clinical characteristics among groups classified according to the quartiles of eosinophil percent and count.,On multivariate logistic regression, eosinophil quartiles in percent and absolute count were not associated with the incidence of moderate-to-severe acute exacerbations of COPD (AECOPD).,The eosinophil count did not affect the risk of AECOPD or forced expiratory volume in 1 second (FEV1) changes according to exposure to inhaled corticosteroid (ICS).,However, by increasing the cutoff value for the eosinophil count from 200/μL to 600/μL, the odds ratio for risk of exacerbation increased serially from 0.82 to 2.96 on trend analysis.,In patients with non-ACOS COPD, the blood eosinophil count and percent were not associated with FEV1 changes, quality of life (QoL), AECOPD frequency, or response to ICS.,The clinical implication of the blood eosinophil count should not be overestimated in patients with non-ACOS COPD. | Patients with COPD might not report mild exacerbation.,The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown.,The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD.,An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities.,This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311).,Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year.,Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year.,Findings of the COPD assessment test and the symptom component of the St George’s Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them.,Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to ≥2 per year.,The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD. | 1 |
There is increasing interest in the earlier detection of, and intervention in, patients at highest risk of developing chronic obstructive pulmonary disease (COPD).,The objective of this research was to develop and validate a risk prediction model for general practitioner (GP)-recorded diagnosis of COPD.,We used data from 239 Scottish GP practices; two-thirds were randomly allocated to a derivation cohort and the other third to a validation cohort.,We included patients aged 35-74 years at the cohort entry date, and excluded patients with a recorded diagnosis of COPD prior to the entry date and with missing data on smoking status.,There were 480,903 patients in the derivation cohort and 247,755 in the validation cohort.,The incidence of COPD in the total cohort was 5.53/1,000 patient-years of follow-up (95% confidence interval (CI), 5.46-5.60).,In the derivation cohort, the COPD risk for ever- versus never-smokers was substantially higher in women (hazard ratio (HR)=9.61, 95% CI, 8.92-10.34) than in men (HR=6.72, 95% CI, 6.19-7.30).,Other risk factors for both sexes were level of deprivation and a previously recorded asthma diagnosis.,In the validation cohort, the model discriminated well between patients who did and those who did not develop COPD: area under the receiver operating characteristics curve=0.845 (95% CI, 0.840-0.850) for females and 0.832 (95% CI, 0.827-0.837) for males.,We have developed and validated the first risk prediction model for COPD, which has the major advantage of being populated entirely by routinely collected data and consequently may be used for clinical practice. | Estimation suggests that at least 4 million people die, annually, as a result of chronic respiratory disease (CRD).,The Global Alliance against Chronic Respiratory Diseases (GARD) was formed following a mandate from the World Health Assembly to address this serious and growing health problem.,To investigate the prevalence of CRD in Russian symptomatic patients and to evaluate the frequency of major risk factors for CRD in Russia.,A cross-sectional, population-based epidemiological study using the GARD questionnaire on adults from 12 regions of the Russian Federation.,Common respiratory symptoms and risk factors were recorded.,Spirometry was performed in respondents with suspected CRD.,Allergic rhinitis (AR) and chronic bronchitis (CB) were defined by the presence of related symptoms according to the Allergic Rhinitis and its Impact on Asthma and the Global Initiative for Obstructive Lung Disease guidelines; asthma was defined based on disease symptoms; chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume per 1 second/forced vital capacity ratio <0.7 in symptomatic patients, following the Global Initiative for Obstructive Lung Disease guidelines.,The number of questionnaires completed was 7,164 (mean age 43.4 years; 57.2% female).,The prevalence of asthma symptoms was 25.7%, AR 18.2%, and CB 8.6%.,Based on patient self-reported diagnosis, 6.9% had asthma, 6.5% AR, and 22.2% CB.,The prevalence of COPD based on spirometry in patients with respiratory symptoms was estimated as 21.8%.,The prevalence of respiratory diseases and risk factors was high in Russia when compared to available data.,For bronchial asthma and AR, the prevalence for related symptoms was higher than self-reported previous diagnosis. | 1 |
Asthma and COPD are complex, heterogeneous conditions comprising a wide range of phenotypes, some of which are refractory to currently available treatments.,Elucidation of these phenotypes and identification of biomarkers with which to recognize them and guide appropriate treat-ment remain a priority.,This review describes the utility of blood eosinophils as a surrogate biomarker of eosinophilic airway inflammation, a common feature of specific asthma and COPD phenotypes.,The role of blood eosinophils in airway disease is described, as is their relevance in reflecting airway eosinophilia.,Each disease is discussed separately as the manner in which blood eosinophils might be used as biomarkers differs.,Focusing on patients with severe disease (persistent eosinophilic asthma and exacerbating COPD), we evaluate evidence examining eosinophils as biomarkers.,In asthma, the rationale for using blood eosinophils to guide treatment is clearly defined, backed by prospective, well-controlled studies.,Higher eosinophil counts identify patients with more se-vere disease and poorer outcomes, patients for whom biologic therapies targeting allergic and/or eosino-philic pathways are recommended.,In COPD, the evidence is less robust.,High blood eosinophil counts are a modest predictor of future exacerbations, and may predict a favourable response to ICS on top of LABA/LAMA, especially in patients with a history of frequent exacerbations.,Before extensive application in clinical practice, further evaluation of these findings in pro-spective clinical studies, and standardization of the appropriate thresholds of clinically relevant eosino-philia are needed, together with establishing whether single or multiple measurements are required in dif-ferent clinical settings | Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society.,The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options.,Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system.,This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital.,Risk factors that are amenable to change have been highlighted.,A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.,Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD.,Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. | 1 |
Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU) and cigarette smoke, induces premature cell senescence.,Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients.,However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown.,The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells) impairs repair processes and exacerbates inflammation after airway injury.,C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA) on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce.,The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose.,Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation.,NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312.,Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation.,BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure.,However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell) senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration.,The epithelial senescence was accompanied by p38 MAPK-dependent airway inflammation.,Senescent NCI-H441 cells impaired epithelial wound repair and secreted increased amounts of pro-inflammatory cytokines in a p38 MAPK-dependent manner.,Clara cell senescence in COPD patients was accelerated and accompanied by p38 MAPK activation.,Senescence of airway epithelial cells impairs repair processes and exacerbates p38 MAPK-dependent inflammation after airway injury, and it may contribute to the pathogenesis of COPD. | 1 |
We conducted a randomized controlled trial of a digital health system supporting clinical care through monitoring and self-management support in community-based patients with moderate to very severe chronic obstructive pulmonary disease (COPD).,The aim of this study was to determine the efficacy of a fully automated Internet-linked, tablet computer-based system of monitoring and self-management support (EDGE‚ sElf-management anD support proGrammE) in improving quality of life and clinical outcomes.,We compared daily use of EDGE with usual care for 12 months.,The primary outcome was COPD-specific health status measured with the St George’s Respiratory Questionnaire for COPD (SGRQ-C).,A total of 166 patients were randomized (110 EDGE, 56 usual care).,All patients were included in an intention to treat analysis.,The estimated difference in SGRQ-C at 12 months (EDGE−usual care) was −1.7 with a 95% CI of −6.6 to 3.2 (P=.49).,The relative risk of hospital admission for EDGE was 0.83 (0.56-1.24, P=.37) compared with usual care.,Generic health status (EQ-5D, EuroQol 5-Dimension Questionnaire) between the groups differed significantly with better health status for the EDGE group (0.076, 95% CI 0.008-0.14, P=.03).,The median number of visits to general practitioners for EDGE versus usual care were 4 versus 5.5 (P=.06) and to practice nurses were 1.5 versus 2.5 (P=.03), respectively.,The EDGE clinical trial does not provide evidence for an effect on COPD-specific health status in comparison with usual care, despite uptake of the intervention.,However, there appears to be an overall benefit in generic health status; and the effect sizes for improved depression score, reductions in hospital admissions, and general practice visits warrants further evaluation and could make an important contribution to supporting people with COPD.,International Standard Randomized Controlled Trial Number (ISRCTN): 40367841; http://www.isrctn.com/ISRCTN40367841 (Archived by WebCite at http://www.webcitation.org/6pmfIJ9KK) | Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs.,No systematic review has examined the effectiveness of interventions designed to improve medication adherence.,Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords.,Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English.,Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria.,Of the 1,186 papers identified, seven studies met inclusion criteria.,Methodological quality of the studies was variable.,Five studies identified effective interventions.,Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams.,Further research is needed to establish the most effective and cost effective interventions.,Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations.,Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. | 1 |
Management of acute exacerbations of chronic obstructive pulmonary disease (COPD) is sometimes inadequate leading to either prolonged duration and/or an increased risk of recurrent exacerbations in the period following the initial event.,To evaluate the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ inhibitor, in patients experiencing an acute exacerbation of COPD.,In this double-blind, placebo-controlled study, COPD patients (40-80 years, ≥10 pack-year smoking history, current moderate/severe acute exacerbation of COPD requiring standard-of-care treatment) were randomized to placebo or nemiralisib 12.5 µg, 50 µg, 100 µg, 250 µg, 500 µg, or 750 µg (ratio of 3:1:1:1:1:1:3; N=938) for 12 weeks with an exploratory 12-week follow-up period.,The primary endpoint was change from baseline in post-bronchodilator FEV1 at week 12.,Key secondary endpoints were rate of re-exacerbations, patient-reported outcomes (Exacerbations of Chronic Pulmonary Disease Tool, COPD Assessment Test, St George's Respiratory Questionnaire-COPD), plasma pharmacokinetics (PK) and safety/tolerability.,There was no difference in change from baseline FEV1 at week 12 between the nemiralisib and placebo treatment groups (posterior adjusted median difference, nemiralisib 750 µg and placebo: −0.004L (95% CrI: −0.051L to 0.042L)).,Overall, there were also no differences between nemiralisib and placebo in secondary endpoints, including re-exacerbations.,Plasma PK increased in a dose proportional manner.,The most common adverse event for nemiralisib was post-inhalation cough which appeared to be dose-related.,The addition of nemiralisib to standard-of-care treatment for 12 weeks did not improve lung function or re-exacerbations in patients with, and following an acute exacerbation of COPD.,However, this study demonstrated that large clinical trials recruiting acutely exacerbating patients can successfully be conducted. | Clinical outcomes are worse in patients with COPD and chronic bronchitis.,N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits.,We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis.,The aim of this study was to determine whether very high-dose NAC would improve respiratory health status in patients with COPD and chronic bronchitis.,Patients with COPD and chronic bronchitis were enrolled in a randomized, controlled, double-blinded trial.,Patients received oral NAC (1,800 mg) or matching placebo twice daily for 8 weeks in addition to their usual respiratory medications.,The primary outcome, respiratory health status, was assessed by changes in the St George’s Respiratory Questionnaire.,The effects of NAC on lung function and circulating markers of oxidative stress and inflammation were also evaluated.,We terminated the study prematurely because new external information suggested the possibility of a safety issue.,Of the planned 130 patients, 51 were randomized and 45 (22 in the placebo arm and 23 in the NAC arm) completed the study.,There was no statistically significant difference between changes in the St George’s Respiratory Questionnaire total score, comparing NAC to placebo (adjusted mean difference, 0.1 U; 95% CI, −7.8 to 8.18 U; P=0.97).,There were also no significant NAC-related improvements in any of the secondary outcomes.,In this 8-week trial, we were unable to show any clinical benefit from a very high dose of NAC in patients with COPD and chronic bronchitis. | 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. | Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future.,Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes.,We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease (COPD) and clinically relevant disease phenotypes.,Breath samples from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry.,Subjects with COPD also underwent sputum induction.,Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis: 1. principal component analysis; 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis.,Comparing COPD versus healthy controls, principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71% of the variance.,Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69%.,The model had 85% sensitivity, 50% specificity and ROC area under the curve of 0.74.,Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy.,Models were constructed which classified subjects with ≥2% sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95.,Potential biomarkers correlated to clinical variables were identified in each subgroup.,The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinically relevant COPD subgroups.,If these findings are validated in prospective cohorts, they may have diagnostic and management value in this disease. | 1 |
Natriuretic peptides (NPs) are a family of prognostic biomarkers in patients with heart failure (HF).,HF is one of the most frequent comorbidities in patients with chronic obstructive pulmonary disease (COPD).,However, the prognostic role of NP in COPD patients remains unclear.,The aim of this meta-analysis was to evaluate the relation between NP and all-cause mortality in COPD patients.,We performed a systematic review and meta-analysis of observational studies assessing prognostic implications of elevated NP levels on all-cause mortality in COPD patients.,Nine studies were considered for qualitative analysis for a total of 2788 patients.,Only two studies focused on Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and brain natriuretic peptide (BNP), respectively, but seven studies focused on pro-BNP (NT-proBNP) and were included in the quantitative analysis.,Elevated NT-proBNP values were related to increased risk of all-cause mortality in COPD patients both with and without exacerbation (hazard ratio (HR): 2.87, p < 0.0001 and HR: 3.34, p = 0.04, respectively).,The results were confirmed also after meta-regression analysis for confounding factors (previous cardiovascular history, hypertension, HF, forced expiratory volume at 1 second and mean age).,NT-proBNP may be considered a reliable predictive biomarker of poor prognosis in patients with COPD. | Exacerbations of chronic obstructive pulmonary disease (COPD) are the third largest cause of emergency hospital admissions in the UK.,This systematic literature review explored the relationship between the hospitalization rates and the COPD comorbidities, anxiety, and depression.,The Centre for Research Dissemination’s framework for systematic reviews was followed using search terms relating to COPD, anxiety, depression, and hospital admission.,Papers identified were assessed for relevance and quality, using a suitable Critical Appraisal Skills Programme tool and Mixed Methods Assessment Tool.,Twenty quantitative studies indicated that anxiety and depression led to a statistically significant increase in the likelihood of COPD patients being hospitalized.,These comorbidities also led to an increased length of stay and a greater risk of mortality postdischarge.,Other significant factors included lower Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise scores, female gender, lower socioeconomic status, poorer patient perceived quality of life, increased severity of lung function, and less improvement in dyspnea from admission to discharge.,It was also highlighted that only 27%-33% of those with depression were being treated for it.,Four qualitative studies revealed that patients saw anxiety and depression as a major factor that affected their ability to cope with and self-manage their condition.,Findings from the systematic review have highlighted a need for better recognition and treatment of anxiety and depression amongst individuals with COPD.,Ongoing research will develop and test strategies for promoting better management and self-management as a means of reducing hospital admissions. | 1 |
The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | Chronic obstructive pulmonary disease (COPD) patients may suffer from poor sleep and health-related quality of life.,We hypothesized that disturbed sleep in COPD is correlated with quality of life.,In 180 patients with COPD (forced expired volume in 1 second [FEV1] 47.6 ± 15.2% predicted, 77.8% male, aged 65.9 ± 11.7 years), we administered general (Health Utilities Index 3) and disease-specific (St George’s Respiratory) questionnaires and an index of disturbed sleep (Pittsburgh Sleep Quality Index).,Overall scores indicated poor general (Health Utilities Index 3: 0.52 ± 0.38), disease- specific (St George’s: 57.0 ± 21.3) quality of life and poor sleep quality (Pittsburgh 11.0 ± 5.4).,Sleep time correlated with the number of respiratory and anxiety symptoms reported at night.,Seventy-seven percent of the patients had Pittsburg scores >5, and the median Pittsburgh score was 12.,On multivariate regression, the Pittsburgh Sleep Quality Index was an independent predictor of both the Health Utilities Index 3 and the St George’s scores, accounting for 3% and 5%, respectively, of the scores.,Only approximately 25% of the patients demonstrated excessive sleepiness (Epworth Sleepiness Scale >9).,Most patients with COPD suffer disturbed sleep.,Sleep quality was correlated with general and disease-specific quality of life.,Only a minority of COPD patients complain of being sleepy. | 1 |
The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression.,To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100™).,105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects.,The reliability coefficient and the coefficient of variation (CV) were calculated.,The performance of each analyte and mean analyte levels were evaluated across sample types.,20% of analytes were not consistently detectable in any sample type.,Higher reliability and/or smaller CV were determined for 12 analytes in EDTA plasma compared to serum, and for 11 analytes in serum compared to EDTA plasma.,While reliability measures were similar for EDTA plasma and P100 plasma for a majority of analytes, CV was modestly increased in P100 plasma for eight analytes.,Each analyte within a multiplex produced independent measurement characteristics, complicating selection of sample type for individual multiplexes.,There were notable detectability and measurability differences between serum and plasma.,Multiplexing may not be ideal if large reliability differences exist across analytes measured within the multiplex, especially if values differ based on sample type.,For some analytes, the large CV should be considered during experimental design, and the use of duplicate and/or triplicate samples may be necessary.,These results should prove useful for studies evaluating selection of samples for evaluation of potential blood biomarkers. | 1 |
Using a mobile health (mHealth) intervention, consisting of a smartphone and compatible medical device, has the potential to enhance chronic obstructive pulmonary disease (COPD) treatment outcomes while mitigating health care costs.,The aim of this study was to explore the potential facilitators and barriers among health care providers (HCPs) regarding the use of mHealth interventions for COPD management.,This was a qualitative study.,Semistructured individual interviews were conducted with HCPs, including nurses, pharmacists, and physicians who work directly with patients with COPD.,A flexible prompts guide was used to facilitate discussions.,Interview topics included the following: demographics, mHealth usage, perceptions toward challenges of mHealth adoption, factors facilitating mHealth adoption, and preferences regarding features of the mHealth intervention for COPD management.,Interviews were conversational in nature, and items were not asked verbatim or in the order presented.,The interviews were transcribed verbatim and compared against the digital recordings to ensure the accuracy of the content.,After creating a codebook for analysis, 2 researchers independently coded the remaining interview data using pattern coding.,They discussed commonalities and differences in coding until a consensus was reached.,A total of 30 nurses, physicians, and pharmacists participated.,The main facilitators to mHealth adoption are possible health benefits for patients, ease of use, educating patients and their HCPs, credibility, and reducing cost to the health care system.,Alternatively, the barriers to adoption are technical issues, privacy and confidentiality issues, lack of awareness, potential limited uptake from the elderly, potential limited connection between patients and HCPs, and finances.,It is important to understand the perceptions of HCPs regarding the adoption of innovative mHealth interventions for COPD management.,This study identifies some potential facilitators and barriers that may inform the successful development and implementation of mHealth interventions for COPD management. | Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients.,To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines.,Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months.,Patients in the control group had no improvement.,Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline.,IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group.,The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group.,A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients.,Decreased systemic inflammation may contribute to these clinical benefits.,(Clinical trial registration No.: NCT01631019) | 1 |
Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity.,Potential biomarkers need to be readily available in real-life clinical practice.,Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).,In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up.,Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.,178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods.,Median BNC was 5200cells/μL (IQR 4000-7000cells/μL).,Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL).,People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs.,5%, P < 0.001) in the following year.,Eosinophil counts were much less predictive of these outcomes.,In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.,High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients. | Blood eosinophil counts have been documented as a good biomarker for patients with chronic obstructive pulmonary disease (COPD) using inhaled corticosteroid (ICS) therapy.,However, the effectiveness and safety of prescribing high or medium dose of ICS for patients with different eosinophil counts are unknown.,A post hoc analysis of a previous prospective randomized study was performed for COPD patients using higher dose (HD: Fluticasone 1,000 μg/day) or medium dose (MD: Fluticasone 500 μg/day) of ICS combined with Salmeterol (100 μg/day).,Patients were classified into two groups: those with high eosinophil counts (HE ≥3%) and those with low eosinophil counts (LE <3%).,Lung function was evaluated with forced expiratory volume in 1 second, forced vital capacity, and COPD assessment test.,Frequencies of acute exacerbation and pneumonia were also measured.,Two hundred and forty-eight patients were studied and classified into higher eosinophil (HE) (n=85, 34.3%) and lower eosinophil (LE) groups (n=163, 65.7%).,The levels of forced expiratory volume in 1 second were significantly increased in patients of HE group treated with HD therapy, compared with the other groups (HE/HD: 125.9±27.2 mL vs HE/MD: 94.3±23.7 mL, vs LE/HD: 70.4±20.5 mL, vs LE/MD: 49.8±16.7 mL; P<0.05) at the end of the study.,Quality of life (COPD assessment test) markedly improved in HE/HD group than in MD/LE group (HE/HD: 9±5 vs LE/MD: 16±7, P=0.02).,The frequency of acute exacerbation was more decreased in HE/HD group patients, compared with that in LE/MD group (HE/HD: 13.5% vs LE/MD: 28.7%, P<0.01).,Pneumonia incidence was similar in the treatment groups (HE/HD: 3.2%, HE/MD: 2.6%, LE/HD: 3.5%, LE/MD 2.8%; P=0.38).,The study results support using blood eosinophil counts as a biomarker of ICS response and show the benefits of greater improvement of lung function, quality of life, and decreased exacerbation frequency in COPD patients with blood eosinophil counts higher than 3%, especially treated with higher dose of ICS. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations can negatively impact disease severity, progression, mortality and lead to hospitalizations.,We aimed to develop a model that predicts a patient’s risk of hospitalization due to severe exacerbations (defined as COPD-related hospitalizations) of COPD, using Swedish patient level data.,Patient level data for 7823 Swedish patients with COPD was collected from electronic medical records (EMRs) and national registries covering healthcare contacts, diagnoses, prescriptions, lab tests, hospitalizations and socioeconomic factors between 2000 and 2013.,Models were created using machine-learning methods to predict risk of imminent exacerbation causing patient hospitalization due to COPD within the next 10 days.,Exacerbations occurring within this period were considered as one event.,Model performance was assessed using the Area under the Precision-Recall Curve (AUPRC).,To compare performance with previous similar studies, the Area Under Receiver Operating Curve (AUROC) was also reported.,The model with the highest mean cross validation AUPRC was selected as the final model and was in a final step trained on the entire training dataset.,The most important factors for predicting severe exacerbations were exacerbations in the previous six months and in whole history, number of COPD-related healthcare contacts and comorbidity burden.,Validation on test data yielded an AUROC of 0.86 and AUPRC of 0.08, which was high in comparison to previously published attempts to predict COPD exacerbation.,Our work suggests that clinically available information on patient history collected via automated retrieval from EMRs and national registries or directly during patient consultation can form the basis for future clinical tools to predict risk of severe COPD exacerbations. | There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | 1 |
Diseases of accelerated aging often occur together (multimorbidity), and their prevalence is increasing, with high societal and health care costs.,Chronic obstructive pulmonary disease (COPD) is one such condition, in which one half of patients exhibit ≥4 age-related diseases.,Diseases of accelerated aging share common molecular pathways, which lead to the detrimental accumulation of senescent cells.,These senescent cells no longer divide but release multiple inflammatory proteins, known as the senescence-associated secretory phenotype, which may perpetuate and speed disease.,Here, we show that inhibiting miR-570-3p, which is increased in COPD cells, reverses cellular senescence by restoring the antiaging molecule sirtuin-1.,MiR-570-3p is induced by oxidative stress in airway epithelial cells through p38 MAP kinase-c-Jun signaling and drives senescence by inhibiting sirtuin-1.,Inhibition of elevated miR-570-3p in COPD small airway epithelial cells, using an antagomir, restores sirtuin-1 and suppresses markers of cellular senescence (p16INK4a, p21Waf1, and p27Kip1), thereby restoring cellular growth by allowing progression through the cell cycle.,MiR-570-3p inhibition also suppresses the senescence-associated secretory phenotype (matrix metalloproteinases-2/9, C-X-C motif chemokine ligand 8, IL-1β, and IL-6).,Collectively, these data suggest that inhibiting miR-570-3p rejuvenates cells via restoration of sirtuin-1, reducing many of the abnormalities associated with cellular senescence.-Baker, J.,R., Vuppusetty, C., Colley, T., Hassibi, S., Fenwick, P.,S., Donnelly, L.,E., Ito, K., Barnes, P.,J.,MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. | Exposure to biomass smoke (BMS) has been implicated in chronic obstructive pulmonary disease (COPD).,About 3 billion people worldwide use biomass fuel for cooking and heating.,Women in rural communities of low- and lower-middle-income countries are disproportionately exposed to massive amounts of BMS during active cooking hours (4-6 h/day).,Therefore, BMS exposure is considered as a risk factor for COPD in the same order of magnitude as tobacco smoke.,In rural India, due to cultural reasons, women are the primary cook of the family and are mostly nonsmokers.,Thus, BMS-induced COPD is predominant among rural Indian women.,However, BMS-COPD remains a relatively unexplored health problem globally.,Therefore, we investigated the serum chemokine and cytokine signatures of BMS-COPD and tobacco smoke-induced COPD (TS-COPD) patients compared to their control in a rural South Indian population for this field study.,Concentrations of 40 serum chemokines and cytokines were measured using a multiplexed immunoassay.,The study cohort consisted of BMS-COPD (female; n = 29) and BMS-exposed subjects without COPD (BMS-CONTROL; female; n = 24).,For comparison, data from TS-COPD patients (male, n = 23) and tobacco smokers without COPD (TS-CONTROL; male, n = 22) were investigated.,Subjects were matched for age, sex, and biomass exposure.,Tobacco consumption was slightly higher in TS-COPD subjects compared to TS-CONTROL.,BMS-exposed and TS-exposed subjects (currently exposed) were from the same locality with similar dwelling habits and socioeconomic status.,A validated structured questionnaire-based survey and spirometry was performed.,An additional control group with no tobacco and BMS exposure (TS-BMS-CONTROL; n = 15) was included.,Statistical significance was set at p ≤ 0.01.,Serum median concentrations (pg/ml) of CCL15 [8799.35; 5977.22], CCL27 [1409.14; 1024.99], and CXCL13 [37.14; 26.03] were significantly higher in BMS-CONTROL compared to BMS-COPD subjects.,Nine analytes exhibited higher concentrations in TS-CONTROL compared to TS-COPD subjects.,Comparison of chemokine and cytokine concentrations among BMS-COPD versus TS-COPD and BMS-CONTROL versus TS-CONTROL subjects also revealed distinct molecular signatures.,Our data identifies CCL27 and CXCL13 as putative, plausibly homeostatic/protective biomarkers for BMS-COPD within the investigated population that warrants validation in larger and multiple cohorts.,The findings further indicate exposure-specific systemic response of chemokines and cytokines. | 1 |
Rescue medication use is common in chronic obstructive pulmonary disease (COPD) patients and tends to increase with symptoms and disease severity.,An analysis of baseline rescue medication use was conducted to inform on patient phenotypes and subsequent effects on lung function, symptoms, and safety following 12 weeks of nebulized glycopyrrolate (GLY) 25 µg twice daily or placebo in patients with moderate-to-very-severe COPD.,Pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies (n=781) were used to assign patients into quarters based on baseline rescue medication use (ie, average puffs-per-day) during the run-in period.,Placebo-adjusted trough forced expiratory volume in 1 second (FEV1), St.,George’s Respiratory Questionnaire (SGRQ) total score and EXAcerbations of COPD Tool-Respiratory Symptoms (EXACT-RS) total score data were reported; safety was evaluated by reviewing the incidence of adverse events (AEs) and serious AEs (SAEs).,Baseline rescue medication use was a proxy for disease severity, evidenced by decreased lung function, increased health status scores, symptom scores and use of background long-acting β2-agonists and inhaled corticosteroids across quarters and treatment groups.,Treatment with GLY led to greater improvements from baseline in trough FEV1, SGRQ and EXACT-RS scores compared with placebo in all rescue medication use quarters.,Additionally, the SGRQ and EXACT-RS exhibited greater improvement with increased baseline rescue medication use with GLY treatment.,In the Q4 patients, SGRQ (≥4-unit reduction) or EXACT-RS (≥2-unit reduction) responders were significantly greater with GLY compared with placebo.,AE and SAE incidences were similar across quartiles.,These results suggest that baseline rescue medication use assessments may be useful in the management of COPD.,Treatment with nebulized GLY improved lung function and symptom scores, regardless of baseline rescue medication use.,These results support the use of nebulized GLY for the treatment of COPD, independent of baseline rescue medication use. | This study was conducted to determine COPD severity at the time of diagnosis as confirmed by spirometry in patients treated in a US managed care setting.,All patients with one or more inpatient stays, one or more emergency department visits, or two or more outpatient visits with diagnosis codes for COPD during 1994-2006 were identified from the Lovelace Patient Database.,From this group, a subset of continuously enrolled patients with evidence in claims of a first available pulmonary function test or pulmonary clinic visit and a confirmatory claim for a COPD diagnosis was selected.,Medical chart abstraction was undertaken for this subset to gather information for diagnosis and severity staging of each patient based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD.,Of the 12,491 patients with a primary or secondary COPD diagnosis between 1994 and 2006, there were 1520 continuously enrolled patients who comprised the study cohort.,Among the 648 eligible records from patients with evidence of a pulmonary function test, 366 were identified by spirometry as having COPD of GOLD stage I or higher (average percentage of predicted forced expiratory volume in 1 second: 60%): 19% were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III or IV, respectively).,The majority of patients in these groups were not receiving maintenance treatment.,The results demonstrate a very low incidence of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a large US sample and support calls for increased screening for COPD and treatment upon diagnosis. | 1 |
Smoke exposure is known to decrease total pulmonary surfactant and alter its composition, but the role of surfactant in chronic obstructive pulmonary disease (COPD) remains unknown.,We aimed to analyze the compositional changes in the surfactant lipidome in COPD and identify specific lipids associated with pulmonary function decline.,Bronchoalveolar lavage (BAL) fluid was obtained from 12 former smokers with COPD and 5 non-smoking, non-asthmatic healthy control volunteers.,Lipids were extracted and analyzed by liquid chromatography and mass spectrometry.,Pulmonary function data were obtained by spirometry, and correlations of lung function with lipid species were determined.,Wild-type C57BL/6 mice were exposed to 6 months of second-hand smoke in a full-body chamber.,Surfactant lipids were decreased by 60% in subjects with COPD.,All phospholipid classes were dramatically decreased, including ether phospholipids, which have not been studied in pulmonary surfactant.,Availability of phospholipid, cholesterol, and sphingomyelin in BAL strongly correlated with pulmonary function and this was attributable to specific lipid species of phosphatidylcholine with surface tension reducing properties, and of phosphatidylglycerol with antimicrobial roles, as well as to other less studied lipid species.,Mice exposed to smoke for six months recapitulated surfactant lipidomic changes observed in human subjects with COPD.,In summary, we show that the surfactant lipidome is substantially altered in subjects with COPD, and decreased availability of phospholipids correlated with decreased pulmonary function.,Further investigation of surfactant alterations in COPD would improve our understanding of its physiopathology and reveal new potential therapeutic targets. | Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism.,We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects.,PBMCs were isolated from healthy non-smokers (HNS), healthy smokers (HS) and COPD subjects, cultured and the mitochondrial respiration while utilizing glucose (glycolysis), fatty acids (β-oxidation) or pyruvate (direct Krebs’ cycle substrate) was measured using the XFp Extracellular Flux Analyzer.,Plasma levels of inflammatory cytokines IFN-γ, IL-17, TNF-α, IL-5, IL-9 and IFN-α were measured using flow cytometry.,RAW264.7 cells were exposed to cigarette smoke condensate (CSC) for 1 h and its effect on cell viability, cellular metabolism and phagocytosis ability were also studied.,Patient’s data was analyzed using the Mann Whitney U test, whereas Student’s t test was performed to analyze the in-vitro data.,PBMCs from COPD subjects showed a significant decrease in extracellular acidification rate (ECAR) while utilizing glucose as compared to HNS (151.9 Vs 215%).,Mitochondrial oxygen consumption rate (OCR) on palmitate or pyruvate was also found to be significantly lower in COPD subjects as compared to HS and a strong positive correlation between palmitate OCR in PBMCs and FEV1 (r = 0.74, p < 0.05) and FVC (r = 0.79, p < 0.05) values in HS was observed.,The metabolic shift towards fatty acid metabolism in healthy smokers promoted an inflammatory cytokine response with a greater increase in the levels of IL-5, IL-9 and IFN-α as compared to IFN-γ, IL-17 and TNF-α.,In-vitro experiments with RAW 264.7 cells showed similar metabolic alterations and a reduced ability to phagocytose Streptococcus pneumonia and Haemophilus influenza after cigarette smoke exposure in the presence of glucose or palmitate.,These findings indicate a metabolic basis for the inflammatory response in COPD and could suggest a new therapeutic target for controlling the immune response and delaying the onset of disease.,This observational study was retrospectively registered in the Clinical Trails Registry - India (ICMR - NIMS) on 19th January 2018 with the registration number CTRI/2018/01/011441.,The online version of this article (10.1186/s12931-019-1139-2) contains supplementary material, which is available to authorized users. | 1 |
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most common reason for the hospitalization and death of pulmonary patients.,The use of antibiotics as adjuvant therapy for AECOPD, however, is still a matter of debate.,In this study, we searched the PubMed, EmBase, and Cochrane databases for randomized controlled trials published until September 2016 that evaluated the use of antibiotics for AECOPD treatment.,The major outcome variables were clinical cure rate and adverse effects.,The microbiological response rate, relapse of exacerbation, and mortality were also analysed.,A random-effect network was used to assess the effectiveness and tolerance of each antibiotic used for AECOPD treatment.,In this meta-analysis, we included 19 articles that assessed 17 types of antibiotics used in 5906 AECOPD patients.,The cluster ranking showed that dirithromycin had a high clinical cure rate with a low rate of adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole had high clinical cure rates with median rates of adverse effects.,In terms of the microbiological response rate, only doxycycline was significantly better than placebo (odds ratio (OR), 3.84; 95% confidence interval (CI), 1.96-7.54; p < 0.001).,There were no other significant results with respect to the frequency of recurrence or mortality.,Our study indicated that dirithromycin is adequate for improving the clinical cure rate of patients with AECOPD with few adverse effects.,Ofloxacin, ciprofloxacin, and trimethoprim-sulfamethoxazole are also recommended for disease treatment.,However, caution should still be exercised when using antibiotics to treat AECOPD.,Trial Registration Not applicable.,The online version of this article (doi: 10.1186/s12890-017-0541-0) contains supplementary material, which is available to authorized users. | Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD.,Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations.,We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD.,This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals.,All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included.,The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters.,The main outcome was death or readmission during a 5-year follow-up.,The secondary outcome was death.,Survival analysis was performed (log-rank and Cox).,We identified a total of 359 patients (195 men and 164 women, average age 72 years).,During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD.,In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02-1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42-15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003-2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68-4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004-1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003-1.05; P=0.028) on admission were significantly associated with the primary outcome.,Age, cancer, and procalcitonin were significantly associated with the secondary outcome.,COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization.,Baseline pulmonary function remains the strongest predictor of mortality and new admission.,Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient.,Respiratory rate at admission appears to be the most prognostic clinical parameter.,A prospective validation is, however, still required to enable the identification of patients at higher risk of death or readmission. | 1 |
Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend limiting the use of inhaled corticosteroids (ICS) to patients with more severe disease and/or increased exacerbation risk.,However, there are discrepancies between guidelines and real-life practice, as ICS are being overprescribed.,In light of the increasing concerns about the clinical benefit and long-term risks associated with ICS use, therapy needs to be carefully weighed on a case-by-case basis, including in patients already on ICS.,Several studies sought out to determine the effects of withdrawing ICS in patients with COPD.,Early studies have deterred clinicians from reducing ICS in patients with COPD as they reported that an abrupt withdrawal of ICS precipitates exacerbations, and results in a deterioration in lung function and symptoms.,However, these studies were fraught with numerous methodological limitations.,Recently, two randomized controlled trials and a real-life prospective study revealed that ICS can be safely withdrawn in certain patients.,Of these, the WISDOM (Withdrawal of Inhaled Steroids During Optimized Bronchodilator Management) trial was the largest and first to examine stepwise withdrawal of ICS in patients with COPD receiving maintenance therapy of long-acting bronchodilators (ie, tiotropium and salmeterol).,Even with therapy being in line with the current guidelines, the findings of the WISDOM trial indicate that not all patients benefit from including ICS in their treatment regimen.,Indeed, only certain COPD phenotypes seem to benefit from ICS therapy, and validated markers that predict ICS response are urgently warranted in clinical practice.,Furthermore, we are now better equipped with a larger armamentarium of novel and more effective long-acting β2-agonist/long-acting muscarinic antagonist combinations that can be considered by clinicians to optimize bronchodilation and allow for safer ICS withdrawal.,In addition to providing a review of the aforementioned, this perspective article proposes an algorithm for the stepwise withdrawal of ICS in real-life clinical practice. | Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact.,Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations.,The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events.,Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy.,GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β2-agonists (LABAs), such as formoterol and salmeterol.,Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present.,Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components.,This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease. | 1 |
The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).,This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension.,Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo.,The trial’s co-primary endpoints were mean changes from baseline, as area under the curve (AUC), in forced expiratory volume (FEV1) over 0-12 hours (AUC0-12 h FEV1) with MF/F versus MF, and in morning (AM) pre-dose (trough) FEV1 with MF/F versus F after 13 weeks of treatment.,Key secondary endpoints were the effects of MF/F on respiratory health status using the Saint George’s Respiratory Questionnaire (SGRQ), symptom-free nights, partly stable COPD at 26 weeks, and time to first COPD exacerbation.,The largest improvements in AUC0-12 h FEV1 were observed with MF/F 400/10 μg and MF/F 200/10 μg.,Serial spirometry results demonstrated that bronchodilator effects with MF/F occurred rapidly (within 5 minutes), persisted for 12 hours after dosing, and were sustained over the 26-week treatment period.,Similar findings were observed for AM pre-dose FEV1, for which effects were further investigated, excluding subjects whose AM FEV1 data were incorrectly collected after 2 days from the last dose of study treatment.,Improvements in SGRQ scores surpassed the minimum clinically important difference of more than four units with both MF/F treatments.,At 26 weeks, no notable between-treatment differences in the occurrence and nature of adverse events (AEs) were reported.,No unexpected AEs were observed.,Overall, 90 subjects reported AEs considered to be treatment-related, the most common of which were lenticular opacities, dysphonia, and oral candidiasis.,In conclusion, MF/F treatments improved lung function and respiratory health status, reduced exacerbations, and were well tolerated in subjects with moderate-to-very severe COPD. | Objectives To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.,Design Cluster randomised controlled parallel group trial.,Setting Ambulance service in Hobart, Tasmania, Australia.,Participants 405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.,Interventions High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.,Main outcome measure Prehospital or in-hospital mortality.,Results In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97).,Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm.,Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04).,Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure −33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.,Conclusions Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease.,These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.,Trial registration Australian New Zealand Clinical Trials Register ACTRN12609000236291. | 1 |
Reducing the severity of respiratory symptoms is a key goal in the treatment of chronic obstructive pulmonary disease (COPD).,We evaluated the effect of aclidinium bromide 400 μg twice daily (BID) on respiratory symptoms, assessed using the Evaluating Respiratory Symptoms in COPD (E-RS™: COPD) scale (formerly EXACT-RS).,Data were pooled from the aclidinium 400 μg BID and placebo arms of two 24-week, double-blind, randomized Phase III studies evaluating aclidinium monotherapy (ATTAIN) or combination therapy (AUGMENT COPD I) in patients with moderate to severe airflow obstruction.,Patients were stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) Groups A-D.,Change from baseline in E-RS scores, proportion of responders (patients achieving pre-defined improvements in E-RS scores), and net benefit (patients who improved minus patients who worsened) were analyzed.,Of 1210 patients, 1167 had data available for GOLD classification.,Mean (standard deviation) age was 63.2 (8.6) years, 60.7 % were male, and mean post-bronchodilator forced expiratory volume in 1 s was 54.4 % predicted.,Compared with placebo, aclidinium 400 μg BID significantly improved RS-Total (2.38 units vs 0.79 units, p < 0.001) and domain scores (all p < 0.001) at Week 24, and doubled the likelihood of being an RS-Total score responder (p < 0.05), irrespective of GOLD group.,The net benefit for RS-Total (Overall: 56.9 % vs 19.4 %; A + C: 65.7 % vs 6.3 %; B + D: 56.0 % vs 20.8 %, for aclidinium 400 μg BID and placebo respectively; all p < 0.05) and domain scores (all p < 0.05) was significantly greater with aclidinium compared with placebo, in both GOLD Groups A + C and B + D.,Aclidinium 400 μg BID significantly improved respiratory symptoms regardless of the patients’ level of symptoms at baseline.,Net treatment benefit was similar in patients with low or high levels of symptoms.,ATTAIN (ClinicalTrials.gov identifier: NCT01001494) and AUGMENT COPD I (ClinicalTrials.gov identifier: NCT01437397).,The online version of this article (doi:10.1186/s12931-016-0372-1) contains supplementary material, which is available to authorized users. | Patients with respiratory disease experience disturbed sleep, but there is no widely accepted measure of sleep impairment due to respiratory disease.,We developed and evaluated the psychometric performance of a patient-reported measure to assess the impact on sleep due to respiratory disease, the COPD and Asthma Sleep Impact Scale (CASIS).,Identification of the items forming the CASIS was guided by patient interviews and focus groups.,An observational study involving patients from the US and UK was then conducted to assess the psychometric characteristics of the measure.,Qualitative data from 162 patients were used to develop the CASIS (n = 78 COPD; n = 84 asthma).,The observational study included 311 patients with COPD and 324 patients with asthma.,The final seven items used in the CASIS were identified based on factor and item response theory analyses.,Internal consistency was 0.90 (COPD) and 0.92 (asthma), and test-retest reliability was 0.84 (both groups).,In the COPD sample, CASIS scores were significantly correlated with the Saint George's Respiratory Questionnaire scores (all p < 0.0001) and differed significantly by patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.005).,In the asthma sample, CASIS scores were significantly correlated with the Asthma Quality of Life Questionnaire scores (all p < 0.0001) and differed significantly by clinician and patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.0005).,The CASIS shows good internal consistency, test-retest reliability, and construct validity and may be useful in helping to understand the impact that COPD and asthma have on sleep outcomes. | 1 |
COPD is characterized by persistent airflow limitation, progressive breathlessness, cough, and sputum production.,Long-acting muscarinic antagonists (LAMAs) are one of the recommended first-choice therapeutic options for patients with COPD, and several new agents have been developed in recent years.,A literature search identified 14 published randomized, placebo-controlled studies of the efficacy and safety of LAMAs in patients with COPD, with improvements seen in lung function, exacerbations, breathlessness, and health status.,A greater weight of evidence currently exists for glycopyrronium (GLY) and tiotropium than for umeclidinium and aclidinium, especially in terms of exacerbation reductions.,To date, there have been few head-to-head clinical studies of the different LAMAs.,Available data indicate that GLY and aclidinium have similar efficacy to tiotropium in terms of improving lung function, dyspnea, exacerbations, and health status.,Overall, evidence demonstrates that currently available LAMAs provide effective and generally well-tolerated therapy for patients with COPD.,Delivery devices for the different LAMAs vary, which may affect individual patient’s adherence to and preference for treatment.,Subtle differences between individual therapeutic options may be important to individual patients and the final treatment choice should involve physician’s and patient’s experiences and preferences. | Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD).,To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes.,A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015.,Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint.,Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group).,Each association was assessed at 6 months and study end.,Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation.,Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George’s Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end.,Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028).,CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001).,The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively.,A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations.,This analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes.,The online version of this article (doi:10.1186/s12931-017-0566-1) contains supplementary material, which is available to authorized users. | 1 |
Pulmonary rehabilitation (PR) is recommended in the management of people with chronic obstructive pulmonary disease (COPD), but referral to this service is low.,To identify barriers to, and facilitators for, referral to PR programmes from the perspective of Australian general practitioners.,Semi-structured interviews were conducted with general practitioners involved in the care of people with COPD.,Interview questions were informed by a validated behavioural framework and asked about participants’ experience of referring people with COPD for PR, and barriers to, or facilitators of, this behaviour.,Interviews were audiotaped, transcribed verbatim, and analysed using content analysis.,Twelve general practitioners participated in this study, 10 of whom had never referred a patient to a PR programme.,Four major categories relating to barriers to referral were identified: low knowledge of PR for COPD; low knowledge of how to refer; actual or anticipated access difficulties for patients; and questioning the need to do more to promote exercise behaviour change.,Awareness of benefit was the only current facilitator.,Three major categories of potential facilitators were identified: making PR part of standard COPD care through financial incentive; improving information flow with regard to referrals and services; and informing patients and public.,Significant barriers to referral exist, but opportunities to change the organisation of practice and information management were identified.,Behaviour change strategies which directly target these barriers and incorporate facilitators should make up the key components of interventions to improve referral to PR by general practitioners who care for people with COPD. | Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy.,It is unknown whether socioeconomic deprivation associates with rates of completion of PR or the magnitude of clinical benefits bequeathed by PR.,PR services across England and Wales enrolled patients to the National PR audit in 2015.,Deprivation was assessed using Index of Multiple Deprivation (IMD) derived from postcodes.,Study outcomes were completion of therapy and change in measures of exercise performance and health status.,Univariate and multivariate analyses investigated associations between IMD and these outcomes.,210 PR programmes enrolled 7413 patients.,Compared with the general population, the PR sample lived in relatively deprived neighbourhoods.,There was a statistically significant association between rates of completion of PR and quintile of deprivation (70% in the least and 50% in the most deprived quintiles).,After baseline adjustments, the risk ratio (95% CI) for patients in the most deprived relative to the least deprived quintile was 0.79 (0.73 to 0.85), p<0.001.,After baseline adjustments, IMD was not significantly associated with improvements in exercise performance and health status.,In a large national dataset, we have shown that patients living in more deprived areas are less likely to complete PR.,However, deprivation was not associated with clinical outcomes in patients who complete therapy.,Interventions targeted at enhancing referral, uptake and completion of PR among patients living in deprived areas could reduce morbidity and healthcare costs in such hard-to-reach populations. | 1 |
Admission to hospital with chronic obstructive pulmonary disease (COPD) is associated with deprivation and season.,However, it is not known whether deprivation and seasonality act synergistically to influence the risk of hospital admission with COPD.,To investigate whether the relationship between season/temperature and admission to hospital with COPD differs with deprivation.,All COPD admissions (ICD10 codes J40-J44 and J47) were obtained for the decade 2001-2010 for all Scottish residents by month of admission and 2009 Scottish Index of Multiple Deprivation (SIMD) quintile.,Confidence intervals for rates and absolute differences in rates were calculated and the proportion of risk during winter attributable to main effects and interactions were estimated.,Monthly rates of admission by average daily minimum temperatures were plotted for each quintile of SIMD.,Absolute differences in admission rates between winter and summer increased with greater deprivation.,In the most deprived quintile, in winter 19.4% (95% CI 17.3% to 21.4%) of admissions were attributable to season/deprivation interaction, 61.2% (95% CI 59.5% to 63.0%) to deprivation alone, and 5.2% (95% CI 4.3% to 6.0%) to winter alone.,Lower average daily minimum temperatures over a month were associated with higher admission rates, with stronger associations evident in the more deprived quintiles.,Winter and socioeconomic deprivation-related factors appear to act synergistically, increasing the rate of COPD admissions to hospital more among deprived people than among affluent people in winter than in the summer months.,Similar associations were observed for admission rates and temperatures.,Interventions effective at reducing winter admissions for COPD may have potential for greater benefit if delivered to more deprived groups. | 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 |
Respiratory symptoms are increasingly recognized as an important consideration in COPD management.,Understanding the links between the time(s) of day symptoms are experienced and overall symptom burden could support personalized management strategies.,This real-world study aimed to establish the association between the time of day of symptoms and the burden on patients using validated patient-reported outcomes, health care resource utilization, and physician-perceived impact of COPD on patients’ lives.,Analyses used data from four waves (2012, 2013, 2014, and 2016) of the Respiratory Disease Specific Programme: cross-sectional surveys of patients with COPD in Germany, Italy, Spain, and the UK.,Patients were classified by their physicians as having symptoms in the morning (M), daytime (D), and/or nighttime (N) in the 4 weeks before entering the Disease Specific Programme.,Outcomes included health care resource utilization, work productivity and activity impairment, COPD Assessment Test, EuroQol 5-dimension 3-level questionnaire with visual analog scale, and Jenkins Sleep Evaluation Questionnaire.,In total, 8,844 patients were included, and 8,185 had evaluable time-of-day symptom data.,Physicians reported that in the previous 4 weeks, 25% of patients experienced no symptoms, 16% D only, 17% M/D only, 6% D/N only, 4% M, N, or M/N only, and 32% M/D/N.,In general, patients with M/D/N symptoms utilized more health care resources in the previous 12 months, had more prior exacerbations, and reported worse activity impairment, health status, and sleep than other symptom groups, whereas patients with symptoms at any time of the day utilized more resources, experienced more exacerbations, and reported worse health status than patients with no symptoms during the 4 weeks before entering the survey.,Patients experiencing morning, daytime, and nighttime symptoms experience a greater disease burden than those in other groups.,An individualized approach to COPD treatment based on the timing and persistence of symptoms may improve outcomes for these patients. | 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 |
Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions.,We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020.,The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days.,Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days.,Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease.,In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients. | Objective To test the effectiveness of telemonitoring integrated into existing clinical services such that intervention and control groups have access to the same clinical care.,Design Researcher blind, multicentre, randomised controlled trial.,Setting UK primary care (Lothian, Scotland).,Participants Adults with at least one admission for chronic obstructive pulmonary disease (COPD) in the year before randomisation.,We excluded people who had other significant lung disease, who were unable to provide informed consent or complete the study, or who had other significant social or clinical problems.,Interventions Participants were recruited between 21 May 2009 and 28 March 2011, and centrally randomised to receive telemonitoring or conventional self monitoring.,Using a touch screen, telemonitoring participants recorded a daily questionnaire about symptoms and treatment use, and monitored oxygen saturation using linked instruments.,Algorithms, based on the symptom score, generated alerts if readings were omitted or breached thresholds.,Both groups received similar care from existing clinical services.,Main outcome measures The primary outcome was time to hospital admission due to COPD exacerbation up to one year after randomisation.,Other outcomes included number and duration of admissions, and validated questionnaire assessments of health related quality of life (using St George’s respiratory questionnaire (SGRQ)), anxiety or depression (or both), self efficacy, knowledge, and adherence to treatment.,Analysis was intention to treat.,Results Of 256 patients completing the study, 128 patients were randomised to telemonitoring and 128 to usual care; baseline characteristics of each group were similar.,The number of days to admission did not differ significantly between groups (adjusted hazard ratio 0.98, 95% confidence interval 0.66 to 1.44).,Over one year, the mean number of COPD admissions was similar in both groups (telemonitoring 1.2 admissions per person (standard deviation 1.9) v control 1.1 (1.6); P=0.59).,Mean duration of COPD admissions over one year was also similar between groups (9.5 days per person (standard deviation 19.1) v 8.8 days (15.9); P=0.88).,The intervention had no significant effect on SGRQ scores between groups (68.2 (standard deviation 16.3) v 67.3 (17.3); adjusted mean difference 1.39 (95% confidence interval −1.57 to 4.35)), or on other questionnaire outcomes.,Conclusions In participants with a history of admission for exacerbations of COPD, telemonitoring was not effective in postponing admissions and did not improve quality of life.,The positive effect of telemonitoring seen in previous trials could be due to enhancement of the underpinning clinical service rather than the telemonitoring communication.,Trial registration ISRCTN96634935.,Funding: The trial was funded by an NHS applied research programme grant from the Chief Scientist Office of the Scottish government (ARPG/07/03).,The funder had no role in study design and the collection, analysis, and interpretation of data and the writing of the article and the decision to submit it for publication.,NHS Lothian supported the telemonitoring service and the clinical services. | 1 |
Although chronic obstructive pulmonary disease (COPD) is regarded as a chronic inflammatory lung disease, the disease mechanism is still not known.,Intriguingly, aging lungs are quite similar to COPD-affected lungs in many ways, and COPD has been viewed as a disease of accelerated premature aging of the lungs.,In this paper, based on a literature review, we would like to propose immunosenescence, age-associated decline in immunity, as a critical mechanism for the development of COPD.,Immunosenescence can cause a low-grade, systemic inflammation described as inflammaging.,This inflammaging may be directly involved in the COPD pathogenesis.,The potential contributors to the development of inflammaging in the lungs possibly leading to COPD are discussed in the review paper.,A notable fact about COPD is that only 15% to 20% of smokers develop clinically significant COPD.,Given that there is a substantial inter-individual variation in inflammaging susceptibility, which is genetically determined and significantly affected by the history of the individual's exposure to pathogens, immunosenescence and inflammaging may also provide the answer for this unexpectedly low susceptibility of smokers to clinically significant COPD. | Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the accelerated ageing of the lung and associated with increased oxidative stress.,Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD.,Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins.,Induction of miR-34a expression with H2O2 was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction.,Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible.,Other sirtuin isoforms were not affected by miR-34a.,Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases. | 1 |
Asthma and COPD are complex, heterogeneous conditions comprising a wide range of phenotypes, some of which are refractory to currently available treatments.,Elucidation of these phenotypes and identification of biomarkers with which to recognize them and guide appropriate treat-ment remain a priority.,This review describes the utility of blood eosinophils as a surrogate biomarker of eosinophilic airway inflammation, a common feature of specific asthma and COPD phenotypes.,The role of blood eosinophils in airway disease is described, as is their relevance in reflecting airway eosinophilia.,Each disease is discussed separately as the manner in which blood eosinophils might be used as biomarkers differs.,Focusing on patients with severe disease (persistent eosinophilic asthma and exacerbating COPD), we evaluate evidence examining eosinophils as biomarkers.,In asthma, the rationale for using blood eosinophils to guide treatment is clearly defined, backed by prospective, well-controlled studies.,Higher eosinophil counts identify patients with more se-vere disease and poorer outcomes, patients for whom biologic therapies targeting allergic and/or eosino-philic pathways are recommended.,In COPD, the evidence is less robust.,High blood eosinophil counts are a modest predictor of future exacerbations, and may predict a favourable response to ICS on top of LABA/LAMA, especially in patients with a history of frequent exacerbations.,Before extensive application in clinical practice, further evaluation of these findings in pro-spective clinical studies, and standardization of the appropriate thresholds of clinically relevant eosino-philia are needed, together with establishing whether single or multiple measurements are required in dif-ferent clinical settings | Chronic obstructive pulmonary disease(COPD) is characterized by enhanced chronic inflammation in the airways, lung parenchyma, and circulation.,We investigated whether SUV39H1, a histone methyltransferase, is causatively implicated in the abnormal inflammation observed in COPD.,The SUV39H1 and H3K9me3 levels were reduced in peripheral blood mononuclear cells(PBMCs), primary human small airway epithelial cells(HSAEpCs) and lung tissues from COPD patients, which were correlated with poor lung function and the serum IL-8 and IL-6 levels.,A specific SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory cytokines in normal PBMCs.,Mechanistically, chaetocin reduced the SUV39H1 and H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked unstimulated COPD HSAEpCs and led to decreased HP-1α levels and increased RNA polymerase II levels.,SUV39H1 knockdown reproduced the pattern of COPD inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3 levels and suppressed inflammation.,In COPD mice, chaetocin further repressed the SUV39H1/H3K9me3 levels and enhanced inflammation.,SUV39H1 epigenetically controls a distinct panel of pro-inflammatory cytokines.,Its reduction in COPD leads to a loss of the repressive chromatin mark H3K9me3 and confers an abnormal inflammatory response to stimulators.,SUV39H1 and its regulatory pathways are potential therapeutic targets for COPD. | 1 |
To evaluate the association among chronic obstructive pulmonary disease (COPD) with asthma, steroid use, and pneumonia in the general population.,Using Taiwan’s National Health Insurance Research Database to identify patients with incident pneumonia, we established a COPD with asthma cohort of 12,538 patients and a COPD cohort of 25,069 patients.,In both cohorts, the risk of incident pneumonia was assessed using multivariable Cox proportional hazards models.,The adjusted hazard ratio (aHR) with 95% confidence interval (CI) for incident pneumonia was 2.38 (2.14, 2.66) in the COPD with asthma cohort, regardless of age, sex, comorbidities, and drug use.,COPD cohort without inhaled corticosteroids (ICSs) use served as a reference.,The aHR (95% CI) for COPD cohort with ICSs use was 1.34 (0.98, 1.83); that for COPD with asthma cohort without ICSs use was 2.46 (2.20, 2.76); and that for COPD with asthma cohort with ICSs use was 2.32 (1.99, 2.72).,COPD cohort without oral steroids (OSs) use served as a reference; the aHR (95% CI) for COPD with asthma cohort without OSs use and with OSs use was 3.25 (2.72, 3.89) and 2.38 (2.07, 2.74), respectively.,The COPD with asthma cohort had a higher risk of incident pneumonia, regardless of age, sex, comorbidities, and ICSs or OSs use.,COPD cohort with ICSs use did not have a notable risk of incident pneumonia.,The COPD with asthma cohort had a higher risk of incident pneumonia, even without ICSs/OSs use. | The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.,From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort).,Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables.,Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort).,The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.,A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively.,In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02-1.11] for per 80 mg of budesonide).,Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline.,In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).,This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE.,ICS should be judiciously used in indicated COPD patients. | 1 |
To assess the treatment progression during the 24 months following a formal diagnosis of chronic obstructive pulmonary disease (COPD) in the UK primary care setting.,A retrospective cohort of newly diagnosed COPD patients was identified in the Clinical Practice Research Datalink (CPRD) from 1/1/2008 until 31/12/2009.,Maintenance therapy prescribed within the first 3 months of diagnosis and in the subsequent 3-month intervals for 24 months were analyzed.,Treatment classes included long-acting β2-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), inhaled corticosteroids (ICSs), and respective combinations.,At each 3-month interval, discontinuation, switching, addition, and stepping down patterns were analyzed cumulatively for the first 12 months and over the 24-month of follow-up.,A total of 3199 patients with at least one prescription of a maintenance therapy at baseline and during 4th-6th month interval were included in the analysis.,At diagnosis (0-3 months), the most frequently prescribed maintenance therapy was LABA+ICS (43%), followed by LAMA (24%) and LABA+LAMA+ICS (23%).,Nearly half the patients (LABA-50%, LAMA-43%) starting on a monobronchodilator had additions to their treatment in 24 months.,Compared to other medications, patients starting on a LAMA were most likely to escalate to triple therapy in 24 months.,Nearly one-fourth of the patients prescribed triple therapy at baseline stepped down to LABA+ICS (25%) or LAMA (31%) within 24 months.,Disease progression is evident over the 24 months after COPD diagnosis, as more patients were prescribed additional maintenance therapy in the 24-month period compared to baseline.,The changes in therapy suggest that it is difficult to achieve a consistently improved COPD disease state. | Inhaled corticosteroids (ICS) reduce exacerbation rates and improve health status but can increase the risk of pneumonia in COPD.,The GLUCOLD study, investigating patients with mild-to-moderate COPD, has shown that long-term (2.5-year) ICS therapy induces anti-inflammatory effects.,The literature suggests that cigarette smoking causes ICS insensitivity.,The aim of this study is to compare anti-inflammatory effects of ICS in persistent smokers and persistent ex-smokers in a post-hoc analysis of the GLUCOLD study.,Persistent smokers (n = 41) and persistent ex-smokers (n = 31) from the GLUCOLD cohort were investigated.,Effects of ICS treatment compared with placebo were estimated by analysing changes in lung function, hyperresponsiveness, and inflammatory cells in sputum and bronchial biopsies during short-term (0-6 months) and long-term (6-30 months) treatment using multiple regression analyses.,Bronchial mast cells were reduced by short-term and long-term ICS treatment in both smokers and ex-smokers.,In contrast, CD3+, CD4+, and CD8+ cells were reduced by short-term ICS treatment in smokers only.,In addition, sputum neutrophils and lymphocytes, and bronchial CD8+ cells were reduced after long-term treatment in ex-smokers only.,No significant interactions existed between smoking and ICS treatment.,Even in the presence of smoking, long-term ICS treatment may lead to anti-inflammatory effects in the lung.,Some anti-inflammatory ICS effects are comparable in smokers and ex-smokers with COPD, other effects are cell-specific.,The clinical relevance of these findings, however, are uncertain. | 1 |
Early palliative care is not a common practice for patients with COPD.,Important barriers are the identification of patients for palliative care and the organization of such care in this patient group.,Pulmonologists have a central role in providing good quality palliative care for patients with COPD.,To guide future research and develop services, their view on palliative care for these patients was explored.,A survey study was performed by the members of the Netherlands Association of Physicians for Lung Diseases and Tuberculosis.,The 256 respondents (31.8%) covered 85.9% of the hospital organizations in the Netherlands.,Most pulmonologists (92.2%) indicated to distinguish a palliative phase in the COPD trajectory, but there was no consensus about the different criteria used for its identification.,Aspects of palliative care in COPD considered important were advance care planning conversation (82%), communication between pulmonologist and general practitioner (77%), and identification of the palliative phase (75.8%), while the latter was considered the most important aspect for improvement (67.6%).,Pulmonologists indicated to prefer organizing palliative care for hospitalized patients with COPD themselves (55.5%), while 30.9% indicated to prefer cooperation with a specialized palliative care team (SPCT).,In the ambulatory setting, a multidisciplinary cooperation between pulmonologist, general practitioner, and a respiratory nurse specialist was preferred (71.1%).,To encourage pulmonologists to timely initiate palliative care in COPD, we recommend to conduct further research into more specific identification criteria.,Furthermore, pulmonologists should improve their skills of palliative care, and the members of the SPCT should be better informed about the management of COPD to improve care during hospitalization.,Communication between pulmonologist and general practitioner should be emphasized in training to improve palliative care in the ambulatory setting. | FEV1 is universally used as a measure of severity in COPD.,Current thresholds are based on expert opinion and not on evidence.,We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients.,We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS).,Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival.,A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%).,Overall 975 (28.1%) patients died at 5 years.,The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%.,Survival at 5 years was 0.89 for patients with FEV1≥70 vs.,0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74).,The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001).,Prognostic reliability is maintained at 1, 3, 5, and 10 years.,In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear.,The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%.,These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs. | 1 |
Aging is an important risk factor for most chronic diseases.,Patients with COPD develop more comorbidities than non-COPD subjects.,We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD.,We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain).,We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups.,Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups.,We divided the groups into 5 incremental age categories and compared their comorbidity networks.,We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups.,In addition, we replicated the analysis in the smokers’ subgroup to correct for the confounding effect of cigarette smoking.,Subjects with COPD had more comorbidities and died at a younger age compared to controls.,Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network’s density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older.,The findings persisted after adjusting for smoking.,Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age. | The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions.,Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs.,Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety.,Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease.,This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age.,The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy.,The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions.,The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy.,Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams. | 1 |
The potential of whole-body vibration (WBV) as a mode of dyspnoea free physical activity for people with chronic obstructive pulmonary disease (COPD) is unknown among community-based settings.,Furthermore, the acute effects of WBV on people with COPD have not been profiled in community-based settings.,The aim of this community-based proof-of-concept trial was to describe acute effects of WBV by profiling subjective and objective responses to physical activity.,Seventeen community-dwelling older adults with COPD were recruited to participate in two sessions; WBV and sham WBV (SWBV).,Each session consisted of five one-minute bouts interspersed with five one-minute passive rest periods.,The gravitational force was ~2.5 g for WBV and ~0.0 g for SWBV.,Reliability of baseline dyspnoea, heart rate, and oxygen saturation was first established and then profiled for both sessions.,Acute responses to both WBV and SWBV were compared with repeated measures analysis of variance and repeated contrasts.,Small changes in dyspnoea and oxygen saturation lacked subjective and clinical meaningfulness.,One session of WBV and SWBV significantly increased heart rate (p ≤ 0.02), although there was no difference among WBV and SWBV (p = 0.67).,This community-based proof-of-concept trial showed that a session of WBV can be completed with the absence of dyspnoea for people with COPD.,Furthermore, there were no meaningful differences among WBV and SWBV for heart rate and oxygen saturation.,There is scope for long-term community-based intervention research using WBV given the known effects of WBV on peripheral muscle function and functional independence. | Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterised by dyspnoea, excessive sputum production, chronic cough, bronchitis and emphysema.,Functionally, exercise tolerance is poor for people with COPD and is linked to difficulty in performing daily tasks.,More specifically, exercise difficulties are due partly to dyspnoea and lower limb skeletal muscle dysfunction.,The benefit of exercise that does not exacerbate the disease while improving exercise tolerance is salient.,Whole-body vibration (WBV) is a mode of physical activity known to improve muscular function of the lower limbs, yet efficacy has not been investigated for a WBV intervention conducted in a home-based setting for people with COPD.,This clinically registered trial is a non-randomised placebo cross-over intervention based in the home of each participant (ACTRN12612000508875).,Participants diagnosed with COPD will complete a six-week WBV intervention and then after a two-week washout period, will complete a six-week placebo training intervention.,Participants will complete sessions twice a week.,The duration of the trial is 14 weeks.,Community-dwelling older adults with COPD will provide informed voluntary consent to participate.,Outcome measures will include immediate, acute, and long-term responses to exercise.,Quantifying responses to WBV among people with COPD will allow discussion of efficacy of WBV as a mode of physical activity.,The skill required by the participant to perform physical activity with WBV is not demanding and may enhance habitual sustainability.,The results of this trial could be used to support further research in both clinical and community settings.,Australian New Zealand Clinical Trials Registry (ANZCTR12612000508875) | 1 |
To investigate the gene-expression profile of chronic obstructive pulmonary disease (COPD) patients and explore the possible therapeutic targets.,The microarray raw dataset GSE29133, including three COPD samples and three normal samples, was obtained from Gene Expression Omnibus.,After data preprocessing with the Affy package, Student’s t-test was employed to identify the differentially expressed genes (DEGs).,The up- and downregulated DEGs were then pooled for gene-ontology and pathway-enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID).,The upstream regulatory elements of these DEGs were also explored by using Whole-Genome rVISTA.,Furthermore, we constructed a protein-protein interaction (PPI) network for DEGs.,The surfactant protein D (SP-D) serum level and HLA-A gene frequency in COPD patients and healthy controls were also measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction, respectively.,A total of 39 up- and 15 downregulated DEGs were screened.,Most of the upregulated genes were involved in the immune response process, while the downregulated genes were involved in the steroid metabolic process.,Moreover, we also found that HLA-A has the highest degree in the PPI network.,The SP-D serum level and HLA-A gene frequency in COPD patients were significantly higher than those in healthy controls (13.62±2.09 ng/mL vs 10.28±2.86 ng/mL; 62.5% vs 12.5%; P<0.05).,Our results may help further the understanding of the mechanisms of COPD.,The identified DEGs, especially HLA-A, may serve as diagnosis markers for COPD. | Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a serious event that is responsible for the progress of the disease, increases in medical costs and high mortality.,The aim of the present study was to identify AECOPD-specific biomarkers by evaluating the dynamic gene expression profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD on days 1, 3 and 10 after hospital admission and to compare the derived data with data from healthy controls or patients with stable COPD.,We found that 14 genes were co-differentially upregulated and 2 downregulated greater than 10-fold in patients with COPD or AECOPD compared with the healthy individuals.,Eight co-differentially upregulated genes and six downregulated genes were identified as a panel of AECOPD-specific genes.,Downregulation of TCF7 in PBMCs was found to be associated with the severity of COPD.,Dynamic changes of Aminolevulinate-delta-synthase 2 and carbonic anhydrase I had similar patterns of Digital Evaluation Score System scores and may serve as potential genes of interest during the course of AECOPD.,Thus, our findings indicate a panel of altered gene expression patterns in PBMCs that can be used as AECOPD-specific dynamic biomarkers to monitor the course of AECOPD.,The online version of this article (doi:10.1186/s13054-014-0508-y) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.,The major risk factor of COPD, which has been proven in many studies, is the exposure to cigarette smoke.,However, it is 15-20% of all smokers who develop COPD.,This is why we should recognize the pathobiology of COPD as involving a complex interaction between several factors, including genetic vulnerability.,Oxidant-antioxidant imbalance is recognized as one of the significant factors in COPD pathogenesis.,Numerous exogenous and endogenous sources of ROS are present in pathobiology of COPD.,One of endogenous sources of ROS is mitochondria.,Although leakage of electrons from electron transport chain and forming of ROS are the effect of physiological functioning of mitochondria, there are various intra- and extracellular factors which may increase this amount and significantly contribute to oxidative-antioxidative imbalance.,With the coexistence with impaired antioxidant defence, all these issues lead to oxidative and carbonyl stress.,Both of these states play a significant role in pathobiology of COPD and may account for development of major comorbidities of this disease. | Familial clustering of chronic obstructive pulmonary disease (COPD) is well established, but the familial risk of COPD has not been determined among adoptees.,The aim was to determine whether the familial transmission of COPD is related to disease in biological and/or adoptive parents.,Historic cohort study.,80 214 (50% females).,The Swedish Multi-Generation Register was used to follow all Swedish-born adoptees born in 1932-2004 (n=80 214) between 1 January 1964 and 31 December 2010 for COPD (n=1978).,The risk of COPD was estimated in adoptees with at least one biological parent with COPD but no adoptive parent with COPD (n=162) compared with adoptees without a biological or adoptive parent with COPD.,The risk of COPD was also determined in adoptees with at least one adoptive parent but no biological parent with COPD (n=110), and in adoptees with both affected biological and adoptive parents (n=162).,COPD in adoptees.,Adoptees with COPD in at least one biological parent but no adoptive parent were more likely to have COPD than adoptees without a biological or adoptive parent with COPD (standardised incidence ratio, SIR=1.98 (95% CI 1.69 to 2.31)).,The familial SIR for adoptees with both a biological parent and an adoptive parent with COPD was 1.68 (95% CI 1.39 to 2.00).,Adoptees with at least one adoptive parent with COPD but no biological parent with COPD were not at an increased risk of COPD (SIR=1.12 (95% CI 0.92 to 1.35)).,The findings of the study show that the familial transmission of COPD is associated with COPD in biological but not adoptive parents, suggesting that genetic or early life factors are important in the familial transmission of COPD. | 1 |
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses a serious threat to healthcare systems worldwide.,Binding of the virus to angiotensin‐converting enzyme 2 (ACE2) is an important step in the infection mechanism.,However, it is unknown if ACE2 expression in patients with chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary arterial hypertension (IPAH), or pulmonary fibrosis (PF), is changed as compared to controls.,We used lung samples from patients with COPD (n = 28), IPAH (n = 10), and PF (n = 10) as well as healthy control donor (n = 10) tissue samples to investigate the expression of ACE2 and related cofactors that might influence the course of SARS‐CoV‐2 infection.,Expression levels of the ACE2 receptor, the putative receptor CD147/BSG, and the viral entry cofactors TMPRSS2 (transmembrane serine protease 2), EZR, and FURIN were determined by quantitative PCR and in open‐access RNA sequencing datasets.,Immunohistochemical and single‐cell RNA sequencing (scRNAseq) analyses were used for localization and coexpression, respectively.,Soluble ACE2 (sACE2) plasma levels were analyzed by enzyme‐linked immunosorbent assay.,In COPD as compared to donor, IPAH, and PF lung tissue, gene expression of ACE2, TMPRSS2, and EZR was significantly elevated, but circulating sACE2 levels were significantly reduced in COPD and PF plasma compared to healthy control and IPAH plasma samples.,Lung tissue expressions of FURIN and CD147/BSG were downregulated in COPD.,None of these changes were associated with changes in pulmonary hemodynamics.,Histological analysis revealed coexpression of ACE2, TMPRSS2, and Ezrin in bronchial regions and epithelial cells.,This was confirmed by scRNAseq analysis.,There were no significant expression changes of the analyzed molecules in the lung tissue of IPAH and idiopathic PF as compared to control.,In conclusion, we reveal increased ACE2 and TMPRSS2 expression in lung tissue with a concomitant decrease of protective sACE2 in COPD patients.,These changes represent the possible risk factors for an increased susceptibility of COPD patients to SARS‐CoV‐2 infection. | 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 | 1 |
COPD is a major cause of mortality, and the unpredictable trajectory of the disease can bring challenges to end-of-life care.,We aimed to investigate known prognostic variables and scores that predict prognosis in COPD in a systematic literature review, specifically including variables that contribute to risk assessment of patients for death within 12 months.,We conducted a systematic review on prognostic variables, multivariate score or models for COPD.,Ovid MEDLINE, EMBASE, the Cochrane database, Cochrane CENTRAL, DARE and CINAHL were searched up to May 1, 2016.,A total of 5,276 abstracts were screened, leading to 516 full-text reviews, and 10 met the inclusion criteria.,No multivariable indices were developed with the specific aim of predicting all-cause mortality in stable COPD within 12 months.,Only nine indices were identified from four studies, which had been validated for this time period.,Tools developed using expert knowledge were also identified, including the Gold Standards Framework Prognostic Indicator Guidance, the RADboud Indicators of Palliative Care Needs, the Supportive and Palliative Care Indicators Tool and the Necesidades Paliativas program tool.,A number of variables contributing to the prediction of all-cause mortality in COPD were identified.,However, there are very few studies that are designed to assess, or report, the prediction of mortality at or less than 12 months.,The quality of evidence remains low, such that no single variable or multivariable score can currently be recommended. | Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis.,However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial.,We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable.,We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation.,From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality.,The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL.,The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%.,In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7.,We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised. | 1 |
Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD.,In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.,Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC).,Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD.,Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1 second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation.,In Definition 2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.,Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001).,With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).,These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD.,Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting β2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population. | 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. | 1 |
Targeted lung denervation (TLD) is a bronchoscopically delivered ablation therapy that selectively interrupts pulmonary parasympathetic nerve signaling.,The procedure has the potential to alter airway smooth muscle tone and reactivity, decrease mucous secretion, and reduce airway inflammation and reflex airway hyperresponsiveness.,Secondary outcome analysis of a previous randomized, sham-controlled trial showed a reduction in moderate-to-severe exacerbations in patients with COPD after TLD treatment.,A pivotal trial, AIRFLOW-3 has been designed to evaluate the safety and efficacy of TLD combined with optimal medical therapy to reduce moderate or severe exacerbations throughout 1 year, compared with optimal medical therapy alone.,The study design is a multicenter, randomized, full sham bronchoscopy controlled, double-blind trial that will enroll 400 patients (1:1 randomization).,Key inclusion criteria are FEV1/FVC < 0.7, FEV1 30 to 60% of predicted, post-bronchodilator, ≥ 2 moderate or 1 severe COPD exacerbations in the prior year, and COPD assessment test (CAT) ≥ 10.,Primary objective will be the comparison of moderate or severe COPD exacerbations through 12 months of TLD therapy with optimal medical therapy versus optimal medical therapy alone.,The sham group will be allowed to cross over at 1 year.,Patients will be followed for up to 5 years.,The multicenter, randomized, full sham bronchoscopy controlled, double-blind AIRFLOW-3 trial will evaluate the efficacy of TLD to reduce moderate or severe COPD exacerbations beyond optimal medical therapy alone.,The target population are patients with COPD, who suffer persistent symptoms and exacerbations despite optimal treatment, defining an unmet medical need requiring novel therapeutic solutions.,This trial is registered at clinicaltrials.gov: NCT03639051. | Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation.,The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure.,This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%-60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators.,The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year.,Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life.,Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up.,A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min.,Primary safety end point of freedom from worsening of COPD was 100%.,There were no procedural complications reported.,Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD.,Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy.,TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years. | 1 |
Asthma-COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach.,We investigated the urinary levels of l-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.,We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm.,Urinary l-histidine levels were measured using liquid chromatography-mass spectrometry.,High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.,Urinary l-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly.,High urinary l-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount.,Among patients with airflow obstruction, the urinary l-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm−3; and frequent exacerbations (P < 0.05).,Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used. | Chronic obstructive pulmonary disease (COPD) has seriously impacted the health of individuals and populations.,In this study, proton nuclear magnetic resonance (1H NMR)-based metabonomics combined with multivariate pattern recognition analysis was applied to investigate the metabolic signatures of patients with COPD.,Serum and urine samples were collected from COPD patients (n = 32) and healthy controls (n = 21), respectively.,Samples were analyzed by high resolution 1H NMR (600 MHz), and the obtained spectral profiles were then subjected to multivariate data analysis.,Consistent metabolic differences have been found in serum as well as in urine samples from COPD patients and healthy controls.,Compared to healthy controls, COPD patients displayed decreased lipoprotein and amino acids, including branched-chain amino acids (BCAAs), and increased glycerolphosphocholine in serum.,Moreover, metabolic differences in urine were more significant than in serum.,Decreased urinary 1-methylnicotinamide, creatinine and lactate have been discovered in COPD patients in comparison with healthy controls.,Conversely, acetate, ketone bodies, carnosine, m-hydroxyphenylacetate, phenylacetyglycine, pyruvate and α-ketoglutarate exhibited enhanced expression levels in COPD patients relative to healthy subjects.,Our results illustrate the potential application of NMR-based metabonomics in early diagnosis and understanding the mechanisms of COPD. | 1 |
There is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations.,We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.,Predictive variables were selected using Cox regression for time to first severe COPD exacerbation.,We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment.,The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months.,Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.,The best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex.,Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX).,Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).,SCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk. | The economic burden of chronic obstructive pulmonary disease (COPD) exacerbations is significant, but the impact of other sources on the overall cost of COPD management is largely unknown.,We aimed to estimate overall costs for patients experiencing none, one, or two or more exacerbations per year in the UK.,A retrospective cohort of prevalent COPD patients was identified in the Clinical Practice Research Datalink UK database.,Patients with information recorded for at least 12 months before and after cohort entry date were included (first prevalent COPD diagnosis confirmed by spirometry on/after April 1, 2009).,Patients were categorized as having none, one, or two or more moderate-to-severe COPD exacerbations in the 12 months after cohort entry and further classified by the Global initiative for chronic Obstructive Lung Disease (GOLD) category of airflow obstruction and the Medical Research Council dyspnea scale.,Study outcomes included counts of general practitioner interactions, moderate-severe COPD exacerbations, and non-COPD hospitalizations.,Estimated resource use costs were calculated using National Health Service reference costs for 2010-2011.,The cohort comprised 58,589 patients (mean age 69.5 years, mean dyspnea grade 2.5, females 46.6%, current smokers 33.1%).,The average total annual per patient cost of COPD management, excluding medications, was £2,108 for all patients and £1,523, £2,405, and £3,396 for patients experiencing no, one, or two or more moderate-to-severe exacerbations, respectively.,General practitioner interactions contributed most to these annual costs, accounting for £1,062 (69.7%), £1,313 (54.6%), and £1,592 (46.9%) in patients with no, one, or two or more moderate-to-severe exacerbations, respectively.,Disease management strategies focused on reducing costs in primary care may help reduce total COPD costs significantly. | 1 |
Pulmonary surfactant D (SP-D) has important regulatory functions for innate immunity and has been implicated as a biomarker for chronic obstructive pulmonary disease (COPD).,We hypothesized that COPD patients would have reduced bronchoalveolar lavage (BAL) fluid SP-D levels compared to healthy smoking and non-smoking controls.,BAL SP-D and phospholipids were quantified and corrected for dilution in 110 subjects (65 healthy never smokers, 23 smokers with normal spirometry, and 22 smokers with COPD).,BAL SP-D was highest in never smokers (mean 51.9 μg/mL ± 7.1 μg/mL standard error) compared to both smokers with normal spirometry (16.0 μg/mL ± 11.8 μg/mL) and subjects with COPD (19.1 μg/mL ± 12.9 μg/mL; P < 0.0001).,Among smokers with COPD, BAL SP-D correlated significantly with FEV1% predicted (R = 0.43; P < 0.05); however, the strongest predictor of BAL SP-D was smoking status.,BAL SP-D levels were lowest in current smokers (12.8 μg/mL ± 11.0 μg/mL), intermediate in former smokers (25.2 μg/mL ± 14.2 μg/mL; P < 0.008), and highest in never smokers.,BAL phospholipids were also lowest in current smokers (6.5 nmol ± 1.5 nmol), intermediate in former smokers (13.1 nmol ± 2.1 nmol), and highest in never smokers (14.8 nmol ± 1.1 nmol; P < 0.0001).,These data suggest that smokers, and especially current smokers, exhibit significantly reduced BAL SP-D and phospholipids compared to nonsmokers.,Our findings may help better explain the mechanism that leads to the rapid progression of disease and increased incidence of infection in smokers. | There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD).,The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.,We studied 23 patients with advanced COPD.,Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.,At baseline, FEV1 was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549).,Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status.,The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018).,Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.,Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD.,These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients. | 1 |
Influenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD).,Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs.,Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.,We conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD.,The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria.,The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.,Seventeen articles describing 13 different studies were found to be pertinent to this review.,Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD.,Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation.,Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo.,Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.,Additional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination.,Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.,The online version of this article (doi:10.1186/s12890-017-0420-8) contains supplementary material, which is available to authorized users. | Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria.,The optimum antibiotic choice remains unknown.,We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo.,This was a single-centre, single-blind, randomised placebo-controlled trial.,Patients aged ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400 mg daily for 5 days every 4 weeks, doxycycline 100 mg/day, azithromycin 250 mg 3 times a week or one placebo tablet daily for 13 weeks.,The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S quantitative PCR (qPCR), sputum inflammation and antibiotic resistance.,99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed.,After adjustment, there was a non-significant reduction in bacterial load of 0.42 log10 cfu/mL (95% CI −0.08 to 0.91, p=0.10) with moxifloxacin, 0.11 (−0.33 to 0.55, p=0.62) with doxycycline and 0.08 (−0.38 to 0.54, p=0.73) with azithromycin from placebo, respectively.,There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation.,More treatment-related adverse events occurred with moxifloxacin.,Of note, mean inhibitory concentrations of cultured isolates increased by at least three times over placebo in all treatment arms.,Total airway bacterial load did not decrease significantly after 3 months of antibiotic therapy.,Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.,clinicaltrials.gov (NCT01398072). | 1 |
Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow obstruction, is a major cause of morbidity and mortality worldwide.,However, geographic differences in the clinical characteristics of severe COPD patients have not been widely studied.,We recruited a total of 828 severe COPD cases from three continents.,Subjects in Poland were enrolled by the Institute of Tuberculosis and Lung Diseases in Warsaw; subjects in Korea participated at several university hospitals in Korea; and subjects in USA were enrolled at two clinics affiliated with academic medical centers.,All subjects were over the age of 30 with at least 10 pack-years of cigarette smoking history.,Cases manifested severe to very severe airflow obstruction with post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and FEV1/forced vital capacity <0.7.,All subjects completed a detailed questionnaire and underwent standardized pre-bronchodilator and post-bronchodilator spirometry.,Subjects with known tuberculosis (TB)-associated lung parenchymal destruction were excluded.,Univariate and multivariate assessments of the impact of the country of origin on respiratory symptoms and respiratory illness were performed.,In both univariate and multivariate analyses, a history of TB (38.7%) and physician-diagnosed asthma (43.9%) were significantly more common in subjects with severe COPD from Korea than USA or Poland, while attacks of bronchitis (64.2%) were more common in subjects with severe COPD from Poland.,COPD subjects from Poland had more severe dyspnea (modified Medical Research Council 3.3±1.0) and more frequently reported symptoms of chronic bronchitis (52.2%).,A history of TB was also more common in Poland (10.8%) than in USA (0.3%) severe COPD patients.,Respiratory symptoms and other respiratory illnesses associated with severe COPD differed widely among three continents. | Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide.,We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients.,This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia.,The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life.,Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea.,These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons).,Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George’s Respiratory Questionnaire [SGRQ] total score, P = 0.001).,Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006).,In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life. | 1 |
We aim to assess if air pollution levels and climatological factors are associated with hospital admissions for exacerbation of chronic obstructive pulmonary disease (COPD) in Spain from 2004 to 2013.,We conducted a retrospective study.,Information on pollution level and climatological factors were obtained from the Spanish Meteorological Agency and hospitalizations from the Spanish hospital discharge database.,A case-crossover design was used to identify factors associated with hospitalizations and in hospital mortality.,Postal codes were used to assign climatic and pollutant factors to each patient.,We detected 162,338 hospital admissions for COPD exacerbation.,When seasonal effects were evaluated we observed that hospital admissions and mortality were more frequent in autumn and winter.,In addition, we found significant associations of temperature, humidity, ozone (O3), carbon monoxide (CO), particulate matter up to 10 μm in size (PM10) and nitrogen dioxide (NO2) with hospital admissions.,Lower temperatures at admission with COPD exacerbation versus 1, 1.5, 2 and 3 weeks prior to hospital admission for COPD exacerbation, were associated with a higher probability of dying in the hospital.,Other environmental factors that were related to in-hospital mortality were NO2, O3, PM10 and CO.,Epidemiology of hospital admissions by COPD exacerbation was negatively affected by colder climatological factors (seasonality and absolute temperature) and short-term exposure to major air pollution (NO2, O3, CO and PM10). | The objective of the study is to develop a scoring system for predicting a 90-day re-exacerbation in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,A total of 176 consecutive hospitalized patients with AECOPD were included.,The sociodemographic characteristics, status before acute exacerbation (AE), presentations of and treatment for the current AE, and the re-exacerbation in 90 days after discharge from hospital were collected.,The re-exacerbation rate in 90 days was 48.9% (86 out of 176).,It was associated with the degree of lung function impairment (Global initiative for chronic Obstructive Lung Disease [GOLD] grades), frequency of AE in the previous year, and parameters of the current AE, including pleural effusion, use of accessory respiratory muscles, inhaled long-acting β-2-agonists, inhaled corticosteroids, controlled oxygen therapy, noninvasive mechanical ventilation, and length of hospital stay, but was not associated with body mass index, modified Medical Research Council scale, or chronic obstructive pulmonary disease assessment test.,A subgroup of ten variables was selected and developed into the re-exacerbation index scoring system (age grades, GOLD grades, AE times in the previous year, pleural effusion, use of accessory respiratory muscles, noninvasive mechanical ventilation, controlled oxygen therapy, inhaled long-acting β-2-agonists and inhaled corticosteroids, and length of hospital stay).,The re-exacerbation index showed good discrimination for re-exacerbation, with a C-statistic of 0.750 (P<0.001).,A comprehensive assessment integrating parameters of stable chronic obstructive pulmonary disease, clinical presentations at exacerbation, and treatment showed a strong predictive capacity for short-term outcome in patients with AECOPD.,Further studies are required to verify these findings. | 1 |
Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema.,No cohorts have examined the association between sRAGE and progressive decline of lung function.,There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population.,This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction.,A meta-analysis is used to quantify sRAGE associations with clinical phenotypes.,sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399).,We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity).,Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV1 (P < 0.001), and emphysema severity (P < 0.001).,In an inverse-variance weighted meta-analysis, one SD lower log10-transformed sRAGE was associated with 105 ± 22 mL lower FEV1 and 4.14 ± 0.55 g/L lower adjusted lung density.,After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 decline and emphysema progression only in the ECLIPSE cohort.,Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar.,Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed.,In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling.,Thus, genotype should be included in sRAGE evaluations.,The online version contains supplementary material available at 10.1186/s12931-021-01686-z. | Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD).,From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB.,We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects.,We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.,We divided 2703 GOLD 1-4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%).,Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com).,Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).,There were no differences in % emphysema (11.4 ± 12.0 vs.,12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs.,36.3 ± 20.6%, p = 0.272) between groups.,Mean segmental WA% (63.0 ± 3.2 vs.,62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs.,3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs.,5.17 ± 0.20, p < 0.0001) were greater in the CB + group.,Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group.,In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.,Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB.,These data provide clinical and radiologic correlations to the clinical phenotype of CB. | 1 |
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. | The GOLD guidelines suggest that the presence of a post-bronchodilator forced expiratory volume in one second (FEV1) < 80% of the predicted value in combination with a FEV1/forced vital capacity (FVC) < 70% confirms the diagnosis of COPD.,Limited data exist regarding the accuracy of these criteria to distinguish between COPD and asthma.,The aim of this study therefore was to investigate the diagnostic value of post-bronchodilator lung function parameters in obstructive lung disease.,The pulmonary function tests of 43 (22 = COPD, 21 = asthma) patients with similar baseline characteristics were evaluated (baseline FEV1 were 55.7% ± 7.6%, and 59.3% ± 8.4% predicted for COPD and asthma, respectively).,Bronchodilator responsiveness (BDR) was calculated according to three recognized pulmonary function test criteria.,The first criteria, post-bronchodilator FEV1 < 80% of the predicted value in combination with a post-bronchodilator FEV1/FVC ratio of <70%, had an accuracy of 70% to diagnose COPD.,This combination was very sensitive (100%) in diagnosing COPD, but it was not specific (38%).,The second BDR criteria, defined as an increase of <12% and 200 mL of initial FEV1 and criterion number 3, an increase of < 9% of predicted FEV1, were less sensitive (55% and 59%, respectively), but more specific (81% and 76% respectively) to diagnose COPD.,Our findings suggest that the current recommended spirometric indices are not optimal in differentiating between COPD and asthma. | 1 |
The combination of aclidinium bromide, a long-acting anticholinergic, and formoterol fumarate, a long-acting beta2-agonist (400/12 μg twice daily) achieves improvements in lung function greater than either monotherapy in patients with chronic obstructive pulmonary disease (COPD), and is approved in the European Union as a maintenance treatment.,The effect of this combination on symptoms of COPD and exacerbations is less well established.,We examined these outcomes in a pre-specified analysis of pooled data from two 24-week, double-blind, parallel-group, active- and placebo-controlled, multicentre, randomised Phase III studies (ACLIFORM and AUGMENT).,Patients ≥40 years with moderate to severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <70 % and FEV1 ≥30 % but <80 % predicted normal) were randomised (ACLIFORM: 2:2:2:2:1; AUGMENT: 1:1:1:1:1) to twice-daily aclidinium/formoterol 400/12 μg or 400/6 μg, aclidinium 400 μg, formoterol 12 μg or placebo via Genuair™/Pressair®.,Dyspnoea (Transition Dyspnoea Index; TDI), daily symptoms (EXAcerbations of Chronic pulmonary disease Tool [EXACT]-Respiratory Symptoms [E-RS] questionnaire), night-time and early-morning symptoms, exacerbations (Healthcare Resource Utilisation [HCRU] and EXACT definitions) and relief-medication use were assessed.,The pooled intent-to-treat population included 3394 patients.,Aclidinium/formoterol 400/12 μg significantly improved TDI focal score versus placebo and both monotherapies at Week 24 (all p < 0.05).,Over 24 weeks, significant improvements in E-RS total score, overall night-time and early-morning symptom severity and limitation of early-morning activities were observed with aclidinium/formoterol 400/12 μg versus placebo and both monotherapies (all p < 0.05).,The rate of moderate or severe HCRU exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg compared with placebo (p < 0.05) but not monotherapies; the rate of EXACT-defined exacerbations was significantly reduced with aclidinium/formoterol 400/12 μg versus placebo (p < 0.01) and aclidinium (p < 0.05).,Time to first HCRU or EXACT exacerbation was longer with aclidinium/formoterol 400/12 μg compared with placebo (all p < 0.05) but not the monotherapies.,Relief-medication use was reduced with aclidinium/formoterol 400/12 μg versus placebo and aclidinium (p < 0.01).,Aclidinium/formoterol 400/12 μg significantly improves 24-hour symptom control compared with placebo, aclidinium and formoterol in patients with moderate to severe COPD.,Furthermore, aclidinium/formoterol 400/12 μg reduces the frequency of exacerbations compared with placebo.,NCT01462942 and NCT01437397 (ClinicalTrials.gov),The online version of this article (doi:10.1186/s12931-015-0250-2) contains supplementary material, which is available to authorized users. | The 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 |
The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.,From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort).,Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables.,Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort).,The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.,A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively.,In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02-1.11] for per 80 mg of budesonide).,Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline.,In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).,This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE.,ICS should be judiciously used in indicated COPD patients. | To estimate the incidence of pneumonia by COPD status and the excess cost of inpatient primary pneumonia in elders with COPD.,A retrospective, longitudinal study using claims linked to eligibility/demographic data for a 5% sample of fee-for-service Medicare beneficiaries from 2005 through 2007.,Incidence rates of pneumonia were calculated for elders with and without COPD and for elders with COPD and coexistent congestive heart failure (CHF).,Propensity-score matching with multivariate generalized linear regression was used to estimate the excess direct medical cost of inpatient primary pneumonia in elders with COPD as compared with elders with COPD but without a pneumonia hospitalization.,Elders with COPD had nearly six-times the incidence of pneumonia compared with elders without COPD (167.6/1000 person-years versus 29.5/1000 person-years; RR=5.7, p <0 .01); RR increased to 8.1 for elders with COPD and CHF compared with elders without COPD.,The incidence of inpatient primary pneumonia among elders with COPD was 54.2/1000 person-years compared with 7/1000 person-years for elders without COPD; RR=7.7, p<0.01); RR increased to 11.0 for elders with COPD and CHF compared with elders without COPD.,The one-year excess direct medical cost of inpatient pneumonia in COPD patients was $ 22,697 ($45,456 in cases vs. $ 22,759 in controls (p <0.01)); 70.2% of this cost was accrued during the quarter of the index hospitalization.,During months 13 through 24 following the index hospitalization, the excess direct medical cost was $ 5,941 ($23,215 in cases vs. $ 17,274 in controls, p<0.01).,Pneumonia occurs more frequently in elders with COPD than without COPD.,The excess direct medical cost in elders with inpatient pneumonia extends up to 24 months following the index hospitalization and represents $28,638 in 2010 dollars. | 1 |
The extent of the survival benefit of augmentation therapy for alpha-1 antitrypsin deficiency (AATD) in individuals with advanced COPD is difficult to define.,We performed a retrospective analysis using all available data from the observational registry of individuals with severe deficiency of alpha-1 antitrypsin (AAT) conducted by the NHLBI investigators.,Individuals (N=1129) with severe deficiency of AAT were evaluated for mortality using all data sources and stratified by 10% increments of baseline forced expiratory volume in 1 second (FEV1) percent predicted and by augmentation therapy status (ever receiving versus never receiving).,Kaplan-Meier survival curves were constructed for each of the deciles comparing survival in treated vs non-treated groups.,A multivariable model was performed to define the correlates of survival in individuals with FEV1 <30% predicted.,Amongst all subjects, augmentation was associated with improved survival (p<0.0001).,Among the individuals ever receiving augmentation therapy, survival was better than for those not receiving augmentation at all 10% increments of FEV1% predicted from 10% to 60% (P values <0.05 in all deciles).,In subgroups of participants with hyperinflation defined as residual volume (RV)>120% predicted and in subgroups of participants with reduced diffusing capacity for carbon monoxide (DLCO) <70% predicted, there was significantly better survival for those ever receiving augmentation therapy than for those who never received augmentation (p<0.001).,A multivariable analysis showed that mortality benefit is influenced by age, DLCO % predicted, and augmentation therapy.,There is a survival benefit from augmentation therapy in AATD between FEV1 values in the 10-60% predicted range.,Screening and treatment of AATD patients should therefore not be limited by the severity of illness as defined by FEV1. | Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide.,It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases.,Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea.,The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections.,Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria.,This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations.,Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response.,Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system.,These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.”,Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status.,In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients. | 1 |
Adequate peak inspiratory flow rate (PIFR) is required for drug dispersion with dry powder inhalers (DPIs).,Prevalence of PIFR discordance (suboptimal PIFR with prescribed inhalers) and factors influencing device-specific PIFR are unclear in COPD.,The objective of this study was to determine the prevalence of PIFR discordance and associated clinical factors in a stable COPD population.,An observational, single-center, cohort study was conducted including 66 outpatients with COPD.,PIFR was measured using the In-Check™ Dial with applied resistance of prescribed inhalers.,Participants were defined as discordant if measured PIFR was <30 L/min and <60 L/min for high and low-medium resistance devices, respectively, using an inspiratory effort the participant normally used with their prescribed DPI.,The median age of the COPD participants was 69.4 years, 92% were white and 47% were female.,A total of 48% were using low-medium resistance DPIs (Diskus®/Ellipta®) and 76% used high-resistance DPI (Handihaler®).,A total of 40% of COPD participants were discordant to prescribed inhalers.,Female gender was the only factor consistently associated with lower PIFR.,Shorter height was associated with reduced PIFR for low-medium resistance (r=0.44; P=0.01), but not high resistance (r=0.20; P=0.16).,There was no correlation between PIFR by In-Check™ dial and PIFR measured by standard spirometer.,PIFR is reduced in stable COPD patients, with female gender being the only factor consistently associated with reduced PIFR.,Discordance with prescribed inhalers was seen in 40% of COPD patients, suggesting that many COPD patients do not generate adequate inspiratory force to overcome prescribed DPIs resistance in the course of normal use. | Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required. | 1 |
In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD.,The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD.,Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014.,Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography.,One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis.,Six observational studies with 881 patients were included in the meta-analysis.,The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%.,Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history.,Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation.,In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value. | Bacterial colonisation in chronic obstructive pulmonary disease (COPD) contributes to airway inflammation and modulates exacerbations.,We assessed risk factors for bacterial colonisation in COPD.,Patients with stable COPD consecutively recruited over 1 year gave consent to provide a sputum sample for microbiologic analysis.,Bronchial colonisation by potentially pathogenic microorganisms (PPMs) was defined as the isolation of PPMs at concentrations of ≥102 colony-forming units (CFU)/mL on quantitative bacterial culture.,Colonised patients were divided into high (>105 CFU/mL) or low (<105 CFU/mL) bacterial load.,A total of 119 patients (92.5% men, mean age 68 years, mean forced expiratory volume in one second [FEV1] [% predicted] 46.4%) were evaluated.,Bacterial colonisation was demonstrated in 58 (48.7%) patients.,Patients with and without bacterial colonisation showed significant differences in smoking history, cough, dyspnoea, COPD exacerbations and hospitalisations in the previous year, and sputum colour.,Thirty-six patients (62% of those colonised) had a high bacterial load.,More than 80% of the sputum samples with a dark yellow or greenish colour yielded PPMs in culture.,In contrast, only 5.9% of white and 44.7% of light yellow sputum samples were positive (P < 0.001).,Multivariate analysis showed an increased degree of dyspnoea (odds ratio [OR] = 2.63, 95% confidence interval [CI] 1.53-5.09, P = 0.004) and a darker sputum colour (OR = 4.11, 95% CI 2.30-7.29, P < 0.001) as factors associated with the presence of PPMs in sputum.,Almost half of our population of ambulatory moderate to very severe COPD patients were colonised with PPMs.,Patients colonised present more severe dyspnoea, and a darker colour of sputum allows identification of individuals more likely to be colonised. | 1 |
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
The response to treatment and progression of Chronic Obstructive Pulmonary Disease (COPD) varies significantly.,Small airways disease (SAD) is being increasingly recognized as a key pathological feature of COPD.,Studies have brought forward pathological evidence of small airway damage preceding the development of emphysema and the detection of obstruction using traditional spirometry.,In recent years, there has been a renewed interest in the early detection of SAD and this has brought along an increased demand for physiological tests able to identify and quantify SAD.,Early detection of SAD allows early targeted therapy and this suggests the potential for altering the course of disease.,The aim of this article is to review the evidence available on the physiological testing of small airways.,The first half will focus on the role of lung function tests such as maximum mid-expiratory flow, impulse oscillometry and lung clearance index in detecting and quantifying SAD.,The role of Computed Tomography (CT) as a radiological biomarker will be discussed as well as the potential of recent CT analysis software to differentiate normal aging of the lungs to pathology.,The evidence behind SAD biomarkers sourced from blood as well as biomarkers sourced from sputum and broncho-alveolar lavage (BAL) will be reviewed.,This paper focuses on CC-16, sRAGE, PAI-1, MMP-9 and MMP-12. | Early detection of the effects of smoking is of the utmost importance in the prevention of chronic obstructive pulmonary disease (COPD).,The forced oscillation technique (FOT) is easy to perform since it requires only tidal breathing and offers a detailed approach to investigate the mechanical properties of the respiratory system.,The FOT was recently suggested as an attractive alternative for diagnosing initial obstruction in COPD, which may be helpful in detecting COPD in its initial phases.,Thus, the purpose of this study was twofold: (1) to evaluate the ability of FOT to detect early smoking-induced respiratory alterations; and (2) to compare the sensitivity of FOT with spirometry in a sample of low tobacco-dose subjects.,Results from a group of 28 smokers with a tobacco consumption of 11.2 ± 7.3 pack-years were compared with a control group formed by 28 healthy subjects using receiver operating characteristic (ROC) curves and a questionnaire as a gold standard.,The early adverse effects of smoking were adequately detected by the absolute value of the respiratory impedance (Z4Hz), the intercept resistance (R0), and the respiratory system dynamic compliance (Crs, dyn).,Z4Hz was the most accurate parameter (Se = 75%, Sp = 75%), followed by R0 and Crs, dyn.,The performances of the FOT parameters in the detection of the early effects of smoking were higher than that of spirometry (p < 0.05).,This study shows that FOT can be used to detect early smoking-induced respiratory changes while these pathologic changes are still potentially reversible.,These findings support the use of FOT as a versatile clinical diagnostic tool in aiding COPD prevention and treatment. | 1 |
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