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Pixin Ran, Nanshan Zhong, and colleagues report that cleaner cooking fuels and improved ventilation were associated with better lung function and reduced COPD among a cohort of villagers in Southern China.,Please see later in the article for the Editors' Summary,Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning.,The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.,A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China.,Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011.,That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes.,Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions.,Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders.,The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y).,The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05).,The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.,Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD.,Chinese Clinical Trial Register ChiCTR-OCH-12002398,Please see later in the article for the Editors' Summary,Nearly 3 billion people in developing countries heat their homes and cook by burning biomass-wood, crop waste, and animal dung-in open fires and leaky stoves.,Burning biomass this way releases pollutants into the home that impair lung function and that are responsible for more than a million deaths from chronic obstructive pulmonary disease (COPD) every year.,COPD is a group of diseases that interfere with breathing.,Normally, air is breathed in through the nose or mouth and travels down the windpipe into two bronchial tubes (airways) in the lungs.,These tubes branch into smaller tubes (bronchioles) that end in bunches of tiny air sacs (alveoli).,Oxygen in the air passes through the thin walls of these sacs into small blood vessels and is taken to the heart for circulation round the body.,The two main types of COPD-chronic bronchitis (long-term irritation and swelling of the bronchial tubes) and emphysema (damage to the walls of the alveoli)-make it hard for people to breathe.,Most people with COPD have both chronic bronchitis and emphysema, both of which are caused by long-term exposure to cigarette smoke, indoor air pollution, and other lung irritants.,Symptoms of COPD include breathlessness during exercise and a persistent cough that produces large amounts of phlegm (mucus).,There is no cure for COPD, but drugs and oxygen therapy can relieve its symptoms, and avoiding lung irritants can slow disease progression.,Exposure to indoor air pollution has been associated with impaired lung function and COPD in several studies.,However, few studies have assessed the long-term effects on lung function and on the incidence of COPD (the proportion of a population that develops COPD each year) of replacing biomass with biogas (a clean fuel produced by bacterial digestion of biodegradable materials) for cooking and heating, or of improving kitchen ventilation during cooking.,Here, the researchers undertook a nine-year prospective cohort study in rural southern China to investigate whether these interventions are associated with any effects on lung function and on the incidence of COPD.,A prospective cohort study enrolls a group of people, determines their characteristics at baseline, and follows them over time to see whether specific characteristic are associated with specific outcomes.,The researchers offered nearly 1,000 people living in 12 villages in southern China access to biogas and to improved kitchen ventilation.,All the participants, who adopted these interventions according to personal preferences, completed a questionnaire about their smoking habits and occupational exposure to pollutants and had their lung function measured using a spirometry test at the start and end of the study.,Some participants also completed a questionnaire and had their lung function measured three and six years into the study.,Finally, the researchers measured levels of indoor air pollution in a randomly selected subset of homes at the end of the study to confirm that the interventions had reduced indoor air pollution.,Compared with non-use, the use of clean fuels and of improved ventilation were both associated with a reduction in the decline in lung function over time after adjusting for known characteristics that affect lung function, such as smoking.,The use of both interventions reduced the decline in lung function more markedly than either intervention alone, and the benefits of using the interventions increased with length of use.,Notably, the combined use of both interventions reduced the risk of COPD occurrence among the study participants.,These findings suggest that, among people living in rural southern China, the combined interventions of use of biogas instead of biomass and improved kitchen ventilation were associated with a reduced decline in lung function over time and with a reduced risk of COPD.,Because participants were not randomly allocated to intervention groups, the people who adopted the interventions may have shared other unknown characteristics (confounders) that affected their lung function (for example, having a healthier lifestyle).,Thus, it is not possible to conclude that either intervention actually caused a reduction in the decline in lung function.,Nevertheless, these findings suggest that the use of biogas as a substitute for biomass for cooking and heating and improvements in kitchen ventilation might lead to a reduction in the global burden of COPD associated with biomass smoke.,Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001621.,The US National Heart, Lung, and Blood Institute provides detailed information for the public about COPD,The US Centers for Disease Control and Prevention provides information about COPD and links to other resources (in English and Spanish),The UK National Health Service Choices website provides information for patients and carers about COPD, personal stories, and links to other resources,The British Lung Foundation, a not-for-profit organization, provides information about COPD in several languages,The Global Initiative for Chronic Obstructive Lung Disease works to improve prevention and treatment of COPD around the world,The World Health Organization provides information about all aspects of indoor air pollution and health (in English, French, and Spanish),MedlinePlus provides links to other information about COPD (in English and Spanish) | Variation in ADAM33 has been shown to be important in the development of asthma and altered lung function.,This relationship however, has not been investigated in the population susceptible to COPD; long term tobacco smokers.,We evaluated the association between polymorphisms in ADAM33 gene with COPD and lung function in long term tobacco smokers.,Caucasian subjects, at least 50 year old, who smoked ≥ 20 pack-years (n = 880) were genotyped for 25 single nucleotide polymorphisms (SNPs) in ADAM33.,COPD was defined as an FEV1/FVC ratio < 70% and percent-predicted (pp)FEV1 < 75% (n = 287).,The control group had an FEV1/FVC ratio ≥ 70% and ppFEV1 ≥ 80% (n = 311) despite ≥ 20 pack years of smoking.,Logistic and linear regressions were used for the analysis.,Age, sex, and smoking status were considered as potential confounders.,Five SNPs in ADAM33 were associated with COPD (Q-1, intronic: p < 0.003; S1, Ile → Val: p < 0.003; S2, Gly → Gly: p < 0.04; V-1 intronic: p < 0.002; V4, in 3' untranslated region: p < 0.007).,Q-1, S1 and V-1 were also associated with ppFEV1, FEV1/FVC ratio and ppFEF25-75 (p values 0.001 - 0.02).,S2 was associated with FEV1/FVC ratio (p < 0.05).,The association between S1 and residual volume revealed a trend toward significance (p value < 0.07).,Linkage disequilibrium and haplotype analyses suggested that S1 had the strongest degree of association with COPD and pulmonary function abnormalities.,Five SNPs in ADAM33 were associated with COPD and lung function in long-term smokers.,Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD. | 1 |
COPD is often associated with cardiovascular comorbidity.,Treatment guidelines recommend therapy with bronchodilators as first choice.,We investigated the acute effect of single-dose indacaterol on lung hyperinflation in COPD subjects, for the first time evaluating the potential effects on right heart performance.,In this Phase IV, randomized, interventional, double-blind, crossover clinical study, we recruited 40 patients (50-85 years of age) with stable COPD.,Patients were treated with 150 μg indacaterol or placebo and after 60 minutes (T60) and 180 minutes (T180) the following tests were performed: trans-thoracic echocardiography (TTE), plethysmography, diffusing capacity of the lung for carbon monoxide, saturation of peripheral oxygen, and visual analog scale dyspnea score.,Patients underwent a crossover re-challenge after a further 72 hours of pharmacological washout.,All TTE measurements were conducted blindly by the same operator and further interpreted by two different blinded operators.,Consensus decisions were taken on every value and parameter.,The primary outcome was the effect of the reduction of residual volume and functional residual capacity on right heart systolic and diastolic function indexes evaluated by TTE in patients treated with indacaterol, as compared to placebo.,Vital capacity, inspiratory capacity, and forced expiratory volume in 1 second were significantly increased by indacaterol, when compared with placebo, while residual volume, intrathoracic gas volume, and specific airway resistance were significantly reduced in patients treated with indacaterol.,Tricuspid annular plane systolic excursion was significantly increased versus placebo, paralleled by an increase of tricuspid E-wave deceleration time.,The cardiac frequency was also significantly reduced in indacaterol-treated patients.,Indacaterol significantly reduces lung hyperinflation in acute conditions, with a clinically relevant improvement of dyspnea.,These modifications are associated with a significant increase of the right ventricular compliance indexes and may have a role in improving left ventricular preload leading to a reduction in cardiac frequency. | The GOLD classification of COPD severity introduces a stage 0 (at risk) comprising individuals with productive cough and normal lung function.,The aims of this study were to investigate total mortality risks in GOLD stages 0-4 with special focus on stage 0, and furthermore to assess the influence of symptoms of chronic bronchitis on mortality risks in GOLD stages 1-4.,Between 1974 and 1992, a total of 22 044 middle-aged individuals participated in a health screening, which included a spirometry as well as recording of respiratory symptoms and smoking habits.,Individuals with comorbidity at baseline (diabetes, stroke, cancer, angina pectoris, or heart infarction) were excluded from the analyses.,Hazard ratios (HR 95% CI) of total mortality were analyzed in GOLD stages 0-4 with individuals with normal lung function and without symptoms of chronic bronchitis as a reference group.,HR:s in smoking individuals with symptoms of chronic bronchitis within the stages 1-4 were calculated with individuals with the same GOLD stage but without symptoms of chronic bronchitis as reference.,The number of deaths was 3674 for men and 832 for women based on 352 324 and 150 050 person-years respectively.,The proportion of smokers among men was 50% and among women 40%.,Self reported comorbidity was present in 4.6% of the men and 6.6% of the women.,Among smoking men, Stage 0 was associated with an increased mortality risk, HR; 1.65 (1.32-2.08), of similar magnitude as in stage 2, HR; 1.41 (1.31-1.70).,The hazard ratio in stage 0 was significantly higher than in stage 1 HR; 1.13 (0.98-1.29).,Among male smokers with stage 1; HR: 2.04 (1.34-3.11), and among female smokers with stage 2 disease; HR: 3.16 (1.38-7.23), increased HR:s were found in individuals with symptoms of chronic bronchitis as compared to those without symptoms of chronic bronchitis.,Symptoms fulfilling the definition of chronic bronchitis were associated with an increased mortality risk among male smokers with normal pulmonary function (stage 0) and also with an increased risk of death among smoking individuals with mild to moderate COPD (stage 1 and 2). | 1 |
Chronic obstructive pulmonary disease (COPD) ranks among the leading causes of morbidity and mortality worldwide.,COPD rarely occurs in isolation and is often combined with various diseases.,It is considered that systemic inflammation underlies the comorbid course of COPD.,The data obtained in recent years have shown the importance of violations of the cross-links of lipid metabolism and the immune response, which are links in the pathogenesis of both COPD and atherosclerosis.,The role of lipid metabolism disorders in the pathogenesis of the comorbid course of COPD and atherosclerosis and the participation of ATP-binding cassette (ABC) transporters in these processes is discussed in this article.,It is known that about 20 representatives of a large family of ABC transporters provide lipid homeostasis of cells by moving lipids inside the cell and in its plasma membrane, as well as removing lipids from the cell.,It was shown that some representatives of the ABC-transporter family are involved in various links of the pathogenesis of COPD and atherosclerosis, which can determine their comorbid course. | The aim of this study is to summarize the evidence on the dose-response relationship between body mass index (BMI) and mortality in patients with chronic obstructive pulmonary disease (COPD).,We performed a systemic literature search in PubMed, Embase, and Web of Science for relevant studies that were published until June 2015.,A random effects meta-analysis was used to estimate the pooled relative risks (RRs) of all-cause mortality in COPD patients with normal weight compared with those who were underweight, overweight, or obese.,In addition, a dose-response meta-analysis was conducted to explore the dose-response relationship between BMI and all-cause mortality in COPD patients.,A total of 17 observational studies involving 30,182 COPD patients among 285,960 participants were included.,Compared with the reference category, the RRs of underweight, overweight, and obese individuals were 1.40 (95% confidence interval (CI), 1.20-1.63), 0.80 (95% CI, 0.67-0.96), and 0.77 (95% CI, 0.62-0.95), respectively.,A significant nonlinear relationship between BMI and mortality of COPD patients was found by using a random effects model.,COPD patients with BMI of <21.75 kg/m2 had a higher risk of death.,Moreover, an increase in the BMI resulted in a decrease in the risk of death.,The risk of death was lowest when BMI was 30 kg/m2 (RR = 0.69; 95% CI, 0.53-0.89).,The BMI was not associated with all-cause mortality when BMI was >32 kg/m2.,Our findings indicate that overweight is associated with a lower risk of all-cause mortality among patients with COPD whereas underweight is associated with a higher risk of all-cause mortality in these patients.,However, there is limited evidence to support the association between obesity and the risk of all-cause mortality in patients with COPD. | 1 |
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required.,It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms.,The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic.,It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2.,During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery.,Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering.,Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination.,Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management.,Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications.,Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging.,If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered.,Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation.,Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome.,Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols.,Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy. | Chronic Obstructive Pulmonary Disease (COPD) is defined by post-bronchodilator spirometry.,Data on “normal values” come predominantly from pre-bronchodilator spirometry.,The effects of this on diagnosis are unknown.,Lower limits of normal (LLN) were estimated from “normal” participants in the Burden of Obstructive Lung Disease (BOLD) programme.,Values separately derived using pre- and post-bronchodilator spirometry were compared.,Sensitivity and specificity of criteria derived from pre-bronchodilator spirometry and pre-bronchodilator spirometry adjusted by a constant were assessed in the remaining population.,The “gold standard” was the LLN for the post-bronchodilator spirometry in the “normal population”.,For FEV1/FVC, sensitivity and specificity of criteria were also assessed when a fixed value of < 70% was used rather than LLN.,Of 6,600 participants with full data, 1,354 were defined as “normal”.,Mean differences between pre- and post- bronchodilator measurements were small and the Bland-Altman plots showed no association between difference and mean value.,Compared with using the gold standard, however, tests using pre-bronchodilator spirometry had a sensitivity and specificity of detecting a low FEV1 of 78.4% and 100%, a low FVC of 99.8% and 99.1% and a low FEV1/FVC ratio of 65% and 100%.,Adjusting this by a constant improved the sensitivity without substantially altering the specificity for FEV1 (99%, 99.8%), FVC (97.4%, 99.9%) and FEV1/FVC (98.7%, 99.5%).,Using pre-bronchodilator spirometry to derive norms for lung function reduces sensitivity compared to a post-bronchodilator gold standard.,Adjustment of these values by a constant can improve validity of the test. | 1 |
Chronic obstructive pulmonary disease (COPD) management remains challenging due to the high heterogeneity of clinical symptoms and the complex pathophysiological basis of the disease.,Airflow limitation, diagnosed by spirometry, remains the cornerstone of the diagnosis.,However, the calculation of the forced expiratory volume in the first second (FEV1) alone, has limitations in uncovering the underlying complexity of the disease.,Incorporating additional pulmonary function tests (PFTs) in the everyday clinical evaluation of COPD patients, like resting volume, capacity and airway resistance measurements, diffusion capacity measurements, forced oscillation technique, field and cardiopulmonary exercise testing and muscle strength evaluation, may prove essential in tailoring medical management to meet the needs of such a heterogeneous patient population.,We aimed to provide a comprehensive overview of the available PFTs, which can be incorporated into the primary care physician’s practice to enhance the efficiency of COPD management. | COPD self-management is a complex behavior influenced by many factors.,Despite scientific evidence that better disease outcomes can be achieved by enhancing self-management, many COPD patients do not respond to self-management interventions.,To move toward more effective self-management interventions, knowledge of characteristics associated with activation for self-management is needed.,The purpose of this study was to identify key patient and disease characteristics of activation for self-management.,An explorative cross-sectional study was conducted in primary and secondary care in patients with COPD.,Data were collected through questionnaires and chart reviews.,The main outcome was activation for self-management, measured with the 13-item Patient Activation Measure (PAM).,Independent variables were sociodemographic variables, self-reported health status, depression, anxiety, illness perception, social support, disease severity, and comorbidities.,A total of 290 participants (age: 67.2±10.3; forced expiratory volume in 1 second predicted: 63.6±19.2) were eligible for analysis.,While poor activation for self-management (PAM-1) was observed in 23% of the participants, only 15% was activated for self-management (PAM-4).,Multiple linear regression analysis revealed six explanatory determinants of activation for self-management (P<0.2): anxiety (β: −0.35; −0.6 to −0.1), illness perception (β: −0.2; −0.3 to −0.1), body mass index (BMI) (β: −0.4; −0.7 to −0.2), age (β: −0.1; −0.3 to −0.01), Global Initiative for Chronic Obstructive Lung Disease stage (2 vs 1 β: −3.2; −5.8 to −0.5; 3 vs 1 β: −3.4; −7.1 to 0.3), and comorbidities (β: 0.8; −0.2 to 1.8), explaining 17% of the variance.,This study showed that only a minority of COPD patients is activated for self-management.,Although only a limited part of the variance could be explained, anxiety, illness perception, BMI, age, disease severity, and comorbidities were identified as key determinants of activation for self-management.,This knowledge enables health care professionals to identify patients at risk of inadequate self-management, which is essential to move toward targeting and tailoring of self-management interventions.,Future studies are needed to understand the complex causal mechanisms toward change in self-management. | 1 |
Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD).,The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.,A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.,One hundred and seventy-eight stable COPD patients were included (age, 62 [56-69] years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37-72] % predicted) (median [Q1-Q3]).,In univariate analyses, health-related quality of life (Saint George’s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety.,All four domains introduced separately were independently associated with health-related quality of life.,When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60).,With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).,This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients. | COPD is a long-term condition associated with considerable disability with a clinical course characterized by episodes of worsening respiratory signs and symptoms associated with exacerbations.,Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal conditions in the general population and has emerged as a comorbidity of COPD.,GERD may be diagnosed by both symptomatic approaches (including both typical and atypical symptoms) and objective measurements.,Based on a mix of diagnostic approaches, the prevalence of GERD in COPD ranges from 17% to 78%.,Although GERD is usually confined to the lower esophagus in some individuals, it may be associated with pulmonary microaspiration of gastric contents.,Possible mechanisms that may contribute to GERD in COPD originate from gastroesophageal dysfunction, including altered pressure in the lower esophageal sphincter (which normally protect against GERD) and changes in esophageal motility.,Proposed respiratory contributions to the development of GERD include respiratory medications that may alter esophageal sphincter tone and changes in respiratory mechanics, with increased lung hyperinflation compromising the antireflux barrier.,Although the specific cause and effect relationship between GERD and COPD has not been fully elucidated, GERD may influence lung disease severity and has been identified as a significant predictor of acute exacerbations of COPD.,Further clinical effects could include a poorer health-related quality of life and an increased cost in health care, although these factors require further clarification.,There are both medical and surgical options available for the treatment of GERD in COPD and while extensive studies in this population have not been undertaken, this comorbidity may be amenable to treatment. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) are progressively limited in their ability to undertake normal everyday activities by a combination of exertional dyspnoea and peripheral muscle weakness.,COPD is characterised by expiratory flow limitation, resulting in air trapping and lung hyperinflation.,Hyperinflation increases acutely under conditions such as exercise or exacerbations, with an accompanying sharp increase in the intensity of dyspnoea to distressing and intolerable levels.,Air trapping, causing increased lung hyperinflation, can be present even in milder COPD during everyday activities.,The resulting activity-related dyspnoea leads to a vicious spiral of activity avoidance, physical deconditioning, and reduced quality of life, and has implications for the early development of comorbidities such as cardiovascular disease.,Various strategies exist to reduce hyperinflation, notably long-acting bronchodilator treatment (via reduction in flow limitation and improved lung emptying) and an exercise programme (via decreased respiratory rate, reducing ventilatory demand), or their combination.,Optimal bronchodilation can reduce exertional dyspnoea and increase a patient's ability to exercise, and improves the chance of successful outcome of a pulmonary rehabilitation programme.,There should be a lower threshold for initiating treatments appropriate to the stage of the disease, such as long-acting bronchodilators and an exercise programme for patients with mild-to-moderate disease who experience persistent dyspnoea. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
Early identification of preventable risk factors of COPD progression is important.,Whether exacerbations have a negative impact on disease progression is largely unknown.,We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.,Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50-90%), aged ≥35 years, and a smoking history, who had ≥6 years of UK electronic medical records after initiation of maintenance therapy were studied.,Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits.,Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.,Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥1 exacerbation.,The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥1 exacerbation every year.,Patients with more years with ≥1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations.,When counting years with ≥2 exacerbations, greater effects were observed (2.19 [1.50; 2.88] mL/year excess decline per year with ≥2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis).,Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies. | Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema.,Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development.,Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS).,Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression.,ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death.,Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal.,In this review, we summarize the main findings regarding the biological role of ROS, which may contribute to COPD development, and cytoprotective mechanisms against this disease progression. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | Objectives To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD.,Design Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months.,Interviews were transcribed and analysed both thematically and as narratives.,Participants 21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients.,Setting Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9.,Results Eleven patients died during the study period.,Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together).,Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.”,Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition.,Professional carers’ familiarity with the patients’ condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease.,Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population.,Conclusions Our findings challenge current assumptions underpinning provision of end of life care for people with COPD.,The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care.,Careful assessment of possible supportive and palliative care needs should be triggered at key disease milestones along a lifetime journey with COPD, in particular after hospital admission for an exacerbation. | 1 |
The aim of the study was to determine the nutritional status and anthropometric values in a group of patients with COPD and to examine the relationship between these factors and disease severity.,A total of 105 COPD patients were included in this cross-sectional study.,The patients underwent spirometric exmination.,Mini nutritional assessment form was applied, and the anthropometric values of the patients were measured by bioelectrical impedance method.,Nutrient registration forms were given using a 3-day, 24-hour recall method to assess the nutrient uptake.,COPD severity was determined using the Global Initiative for Chronic Obstructive Lung Disease criteria, and the correlations between nutritional status and disease severity parameters were measured.,The prevalence of malnutrition in our patients with COPD was found to be 17%.,Spirometric parameters were found to be significantly lower in patients with low body mass index (BMI) and malnutrition.,As the modified Medical Research Council dyspnea scale score increased, the frequency of malnutrition increased (P=0.002).,Positive significant correlation was found between spirometric variables and muscle mass and fat external tissue volume of the patients.,Patients receiving higher protein content in diet showed a better muscle mass amount (P<0.001).,Our study results confirmed that malnutrition is an important and frequently encountered problem in COPD patients, and spirometric values of the patients with malnourishment and with low BMI are significantly lower.,We think that nutritional status should be evaluated in every COPD patient, and nutritional intake should be tailored individually. | Conventional spirometric parameters have shown poor correlation with symptoms and health status of chronic obstructive pulmonary disease (COPD).,While it is well-known that the pattern of the expiratory flow-volume curve (EFVC) represents ventilatory dysfunction, little attempts have been made to derive quantitative parameters by analyzing the curve.,In this study, we aimed to derive useful parameters from EFVC via graphic analysis and tried to validate them in patients with COPD.,Using Graphical Analysis 3.4 Vernier Software, we derived from the EFVC such parameters as area of obstruction (Ao), area of triangle (AT), area of rectangle (AR) and ratio of volume at 75 and 25 % peak expiratory flow (PEF) (0.25/0.75 V).,For validation, we reviewed clinical and spirometric data of 61 COPD patients from Seoul National University Airway Registry (SNUAR) and Korean obstructive Lung Disease (KOLD) cohorts.,Of all parameters, only RV/TLC significantly correlated with scores from St.,George’s Respiratory Questionnaire (SGRQ) (r = 0.447, p = 0.037).,Six-minute walking distance (6MWD) highly correlated with Ao/AR (r = −0.618, p = 0.005) and Ao/PEF (r = −0.581, p = 0.009) whereas neither FEV1 nor FEV1/FVC had significant correlation with 6MWD.,Ao/AR and Ao/PEF are promising parameters which correlate well with the exercising capacity of COPD patients.,The online version of this article (doi:10.1186/s12890-016-0182-8) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive airflow limitation and is associated with a chronic inflammatory response in both airways and lungs. microRNAs (miRNAs) are often highly conserved between species and have an intricate role within homeostatic conditions and immune responses.,Also, miRNAs are dysregulated in smoking-associated diseases.,We investigated the miRNA profile of 523 miRNAs by stem-loop RT-qPCR in lung tissue and cell-free bronchoalveolar lavage (BAL) supernatant of mice exposed to air or cigarette smoke (CS) for 4 or 24 weeks.,After 24 weeks of CS exposure, 31 miRNAs were differentially expressed in lung tissue and 78 in BAL supernatant.,Next, we correlated the miRNA profiling data to inflammation in BAL and lung, obtained by flow cytometry or ELISA.,In addition, we surveyed for overlap with newly assessed miRNA profiles in bronchial biopsies and with previously assessed miRNA profiles in lung tissue and induced sputum supernatant of smokers with COPD.,Several miRNAs showed concordant differential expression between both species including miR-31*, miR-155, miR-218 and let-7c.,Thus, investigating miRNA profiling data in different compartments and both species provided accumulating insights in miRNAs that may be relevant in CS-induced inflammation and the pathogenesis of COPD. | Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA).,Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD.,In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer.,Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 without COPD, undergoing pneumonectomy were enrolled.,The apoptotic index (AI) of pulmonary vascular endothelial cells was analyzed by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay.,The expression of mtTFA mRNA and protein was measured using PCR, immunohistochemistry and Western-blot.,Methylation of the mtTFA promoter was detected using bisulfite sequencing PCR.,Compared to the non-COPD group, the AI was higher, and expression of mtTFA mRNA and protein was lower in the COPD group (P<0.001).,Expression of the mtTFA protein was positively correlated with FEV1/Pre (r = 0.892, P<0.001), and negatively correlated with AI (r = −0.749, P<0.001) and smoke index (r = −0.763, P<0.001).,Percentage of mtTFA promoter methylation in the COPD patients was significantly higher compared to the non-COPD patients (P<0.05).,These results suggest that the expression of mtTFA mRNA and protein is down-regulated in the lung tissue from the COPD patients with squamous cell lung cancer, and the level of mtTFA protein is related to apoptosis of pulmonary vascular endothelial cells.,Aberrant mtTFA methylation may also play an important role in the pathogenesis of COPD. | 1 |
Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics.,The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence.,Current COPD guidelines were identified by a systematic literature search.,The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included.,Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised.,Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population.,A total of 19 COPD guidelines were included.,Systemic corticosteroids were often universally recommended to all patients with acute exacerbations.,Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms.,Objective diagnostic tests or clinical examination were only rarely recommended.,Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients.,Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
This study was performed to evaluate the effect of sex on bronchial parameters and the predicted forced expiratory volume in 1 s expressed as a percentage of the forced vital capacity (FEV1% pred) on pulmonary function testing.,The data of 359 patients with chronic obstructive pulmonary disease (COPD) with available FEV1% pred and computed tomography (CT) images were retrospectively reviewed.,FACT-Digital lung TM software (DeXin, Xi’an, China) was used to perform fully automated three-dimensional CT quantitative measurements of the bronchi.,Generation 5 to 7 bronchi were measured, and the parameters analyzed were the lumen diameter (LD), wall thickness (WT), lumen area (LA), and WA% [WA / (WA + LA) × 100%].,In the smoking, smoking cessation, and nonsmoking groups, women had a significantly larger WA% and smaller LD, WT, and LA than men.,The FEV1% pred was significantly lower in women than men in the smoking and smoking cessation groups.,The FEV1% pred was significantly higher in women than men in the nonsmoking group.,Sex-related differences may partially explain why smoking women experience more severe pulmonary function impairment than men among patients with COPD. | Recent advances in multidetector computed tomography (MDCT) facilitate acquiring important clinical information for managing patients with COPD.,MDCT can detect the loss of lung tissue associated with emphysema as a low-attenuation area (LAA) and the thickness of airways as the wall area percentage (WA%).,The percentage of small pulmonary vessels <5 mm2 (% cross-sectional area [CSA] <5) has been recently recognized as a parameter for expressing pulmonary perfusion.,We aimed to analyze the longitudinal changes in structural abnormalities using these CT parameters and analyze the effect of exacerbation and smoking cessation on structural changes in COPD patients.,We performed pulmonary function tests (PFTs), an MDCT, and a COPD assessment test (CAT) in 58 patients with COPD at the time of their enrollment at the hospital and 2 years later.,We analyzed the change in clinical parameters including CT indices and examined the effect of exacerbations and smoking cessation on the structural changes.,The CAT score and forced expiratory volume in 1 second (FEV1) did not significantly change during the follow-up period.,The parameters of emphysematous changes significantly increased.,On the other hand, the WA% at the distal airways significantly decreased or tended to decrease, and the %CSA <5 slightly but significantly increased over the same period, especially in ex-smokers.,The parameters of emphysematous change were greater in patients with exacerbations and continued to progress even after smoking cessation.,In contrast, the WA% and %CSA <5 did not change in proportion to emphysema progression.,The WA% at the distal bronchi and the %CSA <5 did not change in parallel with parameters of LAA over the same period.,We propose that airway disease and vascular remodeling may be reversible to some extent by smoking cessation and appropriate treatment.,Optimal management may have a greater effect on pulmonary vascularity and airway disease than parenchymal deconstruction in the early stage of COPD. | 1 |
Emphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated.,This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities.,Subjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled.,The percentage of low-attenuation area below −950 Hounsfield units (%LAA−950) was calculated automatically.,A calculated value of %LAA−950 that exceeded 10% was defined as emphysema.,Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models.,A total of 628 healthy subjects within the normal range of spriometric values were included.,Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (−33.9 versus −18.8 mL/year; P=0.02).,Emphysema was not associated with the development of airflow limitation during follow-up.,Incidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values.,However, an association between emphysema and future development of airflow limitation was not observed. | Chronic obstructive pulmonary disease (COPD) exacerbations have a negative impact on the quality of life of patients and the evolution of the disease.,We have investigated the prognostic value of several health-related quality of life questionnaires to predict the appearance of a composite event (new ambulatory or emergency exacerbation, hospitalization, or death) over a 1-year follow-up.,This was a multicenter, prospective, observational study.,Patients completed four questionnaires after recovering from an exacerbation (COPD Assessment Test [CAT], a Clinical COPD Questionnaire [CCQ], COPD Severity Score [COPDSS], and Airways Questionnaire [AQ20]).,Patients were followed-up until the appearance of the composite event or for 1 year, whichever came first.,A total of 497 patients were included in the study.,The majority of them were men (89.7%), with a mean age of 68.7 (SD 9.2) years, and a forced expiratory volume in 1 second of 47.1% (SD 17.5%).,A total of 303 (61%) patients experienced a composite event.,Patients with an event had worse mean scores of all questionnaires at baseline compared to patients without event: CAT=12.5 vs 11.3 (P=0.028); CCQ=2.2 vs 1.9 (P=0.013); COPDSS=12.3 vs 10.9 (P=0.001); AQ20=8.3 vs 7.5 (P=0.048).,In the multivariate analysis, only previous history of exacerbations and CAT score ≥13.5 were significant risk factors for the composite event.,A CAT score ≥13.5 increased the predictive value of previous exacerbations with an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.829-0.899; P=0.001).,The predictive value of previous exacerbations significantly increased only in one of the four trialled questionnaires, namely in the CAT questionnaire.,However, previous history of exacerbations was the strongest predictor of the composite event. | 1 |
Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear.,Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.,Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform.,Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR.,Symptoms were quantified using the visual analog scale.,At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae.,Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis.,Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α.,H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β.,In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.,At stable state, H influenzae is associated with increased airway inflammation in COPD.,The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
It can be difficult to distinguish between bronchial asthma and chronic obstructive pulmonary disease (COPD) clinically, although these conditions are associated with different profiles of inflammatory cytokines and immune cells.,This study aimed to compare T-lymphocyte subsets and inflammatory cytokines in the serum and sputum of patients with bronchial asthma and COPD who had respiratory function testing.,The study included 42 patients with bronchial asthma, 48 patients with COPD, and 45 patients with bronchial asthma complicated with COPD.,The percentage predicted values of the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), and the peak expiratory flow (PEF) rate were measured.,Serum and sputum levels of interleukin (IL)-4, IL-5, IL-9, IL-13, IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) were measured using an enzyme-linked immunosorbent assay (ELISA).,Flow cytometry measured the CD4 and CD8 T-lymphocyte subsets, and the CD4: CD8 ratio was calculated.,The FEV1, FVC, and PEF were significantly lower in patients with COPD compared with the other two patient groups.,Serum and sputum levels of IL-4, IL-5, IL-9 and IL-13 were significantly increased in the COPD patient group, and levels of TNF-α, IL-1β and IL-6 were significantly increased in the bronchial asthma patient group.,The CD4: CD8 ratio in sputum was lowest in bronchial asthma patient group and highest in COPD patient group.,The detection of serum and sputum inflammatory cytokines and T-lymphocyte subsets may distinguish between bronchial asthma and COPD. | Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression.,A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs).,PQTLs consistently replicated between the two cohorts.,Features of pQTLs were compared to previously reported expression QTLs (eQTLs).,Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests.,We identified 527 highly significant (p < 8 X 10−10) pQTLs in 38 (43%) of blood proteins tested.,Most pQTL SNPs were novel with low overlap to eQTL SNPs.,The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC).,Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes.,Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins.,The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates.,Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema.,In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms.,Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group. | 1 |
Increased lung macrophage numbers in COPD may arise from upregulation of blood monocyte recruitment into the lungs.,CCR5 is a monocyte chemokine receptor regulated by interleukin-6 (IL-6); the concentration of CCR5 ligands are known to be elevated in COPD lungs.,The objective of this study was to investigate mechanisms of monocyte recruitment to the lung in COPD, including the role of CCR5 signalling.,Ninety one COPD patients, 29 smokers (S) and 37 non-smokers (NS) underwent sputum induction, plasma sampling (to measure IL-6 and soluble IL-6 receptor [sIL-6R] by immunoassay), monocyte characterization (by flow cytometry) and monocyte isolation for cell migration and quantitative polymerase chain reaction studies.,Lung tissue was used for immunohistochemistry.,Plasma IL-6 and sIL-6R levels were increased in COPD.,Greater proportions of COPD CD14++CD16+ monocytes expressed CCR5 compared to controls.,Monocyte stimulation with IL-6 and sIL-6R increased CCR5 gene expression.,COPD monocytes demonstrated impaired migration towards sputum supernatant compared to NS (% migration, 4.4 vs 11.5, respectively; p < 0.05).,Pulmonary microvessels showed reduced monocyte recruitment (% marginated cells) in COPD compared to NS, (9.3% vs 83.1%, respectively).,The proportion of replicating Ki67+ alveolar macrophages was reduced in COPD compared to NS.,All alveolar macrophages from COPD and S expressed the anti-apoptosis marker BCL2; this protein was not present in non-smokers or COPD ex-smokers.,COPD monocytes show decreased migratory ability despite increased CCR5 expression.,Increased COPD lung macrophage numbers may be due to delayed apoptosis.,The online version of this article (doi:10.1186/s12931-017-0569-y) contains supplementary material, which is available to authorized users. | Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal.,To investigate this, we developed a protein microarray system to detect multiple cytokines in small volumes of serum.,Fourteen cytokines were measured in serum from never-smokers, ex-smokers, current smokers, and COPD patients (GOLD stages 1-3).,Certain individual circulating cytokines (particularly TNFα and IL-1β) were significantly elevated in concentration in the serum of particular COPD patients (and some current/ex-smokers without COPD) and may serve as markers of particularly significant systemic inflammation.,However, numerous circulating cytokines were raised such that their combined, but not individual, elevation was significantly associated with severity of disease, and these may be further indicators of, and contributors to, the systemic inflammatory manifestations of COPD.,The coelevation of numerous circulating cytokines in COPD is consistent with the insidious development, chronic nature, and systemic comorbidities of the disease. | 1 |
COPD exacerbations requiring hospitalization increase morbidity and mortality.,Although most COPD exacerbations are neutrophilic, approximately 10%-25% of exacerbations are eosinophilic.,We aimed to evaluate mortality and outcomes of eosinophilic and non-eosinophilic COPD exacerbations and identify new biomarkers that predict survival.,A retrospective observational cohort study was carried out in a tertiary teaching hospital from January 1, 2014 to November 1, 2014.,All COPD patients hospitalized with exacerbations were enrolled in the study at their initial hospitalization and followed-up for 6 months after discharge.,Electronic data were collected from the hospital database.,Subjects’ characteristics, hemogram parameters, CRP levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio on admission and discharge, length of hospital stay (days), readmissions, and mortality were recorded.,Patients were grouped according to peripheral blood eosinophil (PBE) levels: Group 1, >2% PBE, eosinophilic; Group 2, non-eosinophilic ≤2%.,Patient survival after hospital discharge was evaluated by Kaplan-Meier survival analysis.,A total of 1,704 patients hospitalized with COPD exacerbation were included.,Approximately 20% were classified as eosinophilic.,Six-month mortality was similar in eosinophilic and non-eosinophilic groups (14.2% and 15.2%, respectively); however, the hospital stay length and readmission rate were longer and higher in the non-eosinophilic group (P<0.001 and P<0.01, respectively).,CRP and NLR were significantly higher in the non-eosinophilic group (both P<0.01).,The platelet-to-mean platelet volume ratio was not different between the two groups.,Cox regression analysis showed that survival was negatively influenced by elevated CRP (P<0.035) and NLR (P<0.001) in the non-eosinophilic group.,Non-eosinophilic patients with COPD exacerbations with high CRP and NLR values had worse outcomes than eosinophilic patients.,PBE and NLR can be helpful markers to guide treatment decisions. | Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system.,COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system.,This study examined health care utilization and cost among these patients.,For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population.,This study involved patients who were aged 40-89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009.,Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD.,Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year.,Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use.,Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics.,The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation.,COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations.,All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations.,Severity of exacerbations, presence of cardiovascular disease, diabetes, and long-term oxygen use were associated with higher adjusted costs.,The results indicate that despite treatment with maintenance medications, COPD patients continue to have exacerbations resulting in higher costs.,New medications and disease management interventions are warranted to reduce the severity and frequency of exacerbations and the related cost impact of the disease. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations account for a substantial proportion of COPD-related costs.,To describe COPD exacerbation patterns and assess the association between exacerbation frequency and health care resource utilization (HCRU) and costs in patients with COPD in a Medicare population.,A retrospective cohort study utilizing data from a large US national health plan was conducted including patients with a COPD diagnosis during January 1, 2007 to December 31, 2012, aged 40-89 years and continuously enrolled in a Medicare Advantage Prescription Drug plan.,Exacerbation frequency, HCRU, and costs were assessed during a 24-month period following the first COPD diagnosis (follow-up period).,Four cohorts were created based on exacerbation frequency (zero, one, two, and ≥three).,HCRU and costs were compared among the four cohorts using chi-square tests and analysis of variance, respectively.,A trend analysis was performed to assess the association between exacerbation frequency and costs using generalized linear models.,Of the included 52,459 patients, 44.3% had at least one exacerbation; 26.3%, 9.5%, and 8.5% had one, two, and ≥three exacerbations in the 24-month follow-up period, respectively.,HCRU was significantly different among cohorts (all P<0.001).,In patients with zero, one, two, and ≥three exacerbations, the percentages of patients experiencing all-cause hospitalizations were 49.7%, 66.4%, 69.7%, and 77.8%, respectively, and those experiencing COPD-related hospitalizations were 0%, 40.4%, 48.1%, and 60.5%, respectively.,Mean all-cause total costs (medical and pharmacy) were more than twofold greater in patients with ≥three exacerbations compared to patients with zero exacerbations ($27,133 vs $56,033; P<0.001), whereas a greater than sevenfold difference was observed in mean COPD-related total costs ($1,605 vs $12,257; P<0.001).,COPD patients frequently experience exacerbations.,Increasing exacerbation frequency is associated with a multiplicative increase in all-cause and COPD-related costs.,This underscores the importance of identifying COPD patients at risk of having frequent exacerbations for appropriate disease management. | Mucolytics can improve disease outcome in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,The objectives of this study were to investigate the effects of erdosteine (ER), a mucolytic agent with antioxidant activity, on systemic inflammation, symptoms, recurrence of exacerbation, and time to first exacerbation postdischarge in hospitalized patients with AECOPD.,Patients admitted to hospital with AECOPD were randomized to receive either ER 900 mg daily (n=20) or a matching control (n=20).,Treatment was continued for 10 days until discharge.,Patients also received standard treatment with steroids, nebulized bronchodilators, and antibiotics as appropriate.,Serum C-reactive protein levels, lung function, and breathlessness-cough-sputum scale were measured on hospital admission and thereafter at days 10 and 30 posttreatment.,Recurrence of AECOPD-requiring antibiotics and/or oral steroids and time to first exacerbation in the 2 months (days 30 and 60) postdischarge were also assessed.,Mean serum C-reactive protein levels were lower in both groups at days 10 and 30, compared with those on admission, with significantly lower levels in the ER group at day 10.,Improvements in symptom score and forced expiratory volume in 1 second were greater in the ER than the control group, which reached statistical significance on day 10.,ER was associated with a 39% lower risk of exacerbations and a significant delay in time to first exacerbation (log-rank test P=0.009 and 0.075 at days 30 and 60, respectively) compared with controls.,Results confirm that the addition of ER (900 mg/d) to standard treatment improves outcomes in patients with AECOPD.,ER significantly reduced airway inflammation, improved the symptoms of AECOPD, and prolonged time to first exacerbation.,The authors suggest ER could be most beneficial in patients with recurring, prolonged, and/or severe exacerbations of COPD. | 1 |
Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity.,Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD.,The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells), and CD1a+ cells (Langerhans cells).,The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues.,To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE), and dendritic cells extracted from mice chronically exposed to cigarette smoke.,In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue.,Human monocyte-derived dendritic cells exposed to CSE (0.1-2%) exhibited enhanced survival in vitro when compared with control dendritic cells.,Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice.,Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1), and B cell lymphoma leukemia-x(L) (Bcl-xL), predominantly through oxidative stress.,Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not impaired.,These data indicate that COPD is associated with increased numbers of cells bearing markers associated with Langerhans cells and mature dendritic cells, and that cigarette smoke promotes survival signals and augments survival of dendritic cells.,Although CSE suppressed dendritic cell CCR7 expression, migration towards a CCR7 ligand was not diminished, suggesting that reduced CCR7-dependent migration is unlikely to be an important mechanism for dendritic cell retention in the lungs of smokers with COPD. | Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking.,Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress.,Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD.,There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients.,Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema.,Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung.,Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema.,In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed.,The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide.,Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility.,We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans recruited during exacerbations of COPD and smoking controls from the Pennsylvania Study of Chronic Obstructive Pulmonary Exacerbations (PA-SCOPE) cohort.,We assessed DNA methylation from whole blood samples in 362 African-American smokers in the PA-SCOPE cohort using the Illumina Infinium HumanMethylation27 BeadChip Array.,Final analysis included 19302 CpG probes annotated to the nearest gene transcript after quality control.,We tested methylation associations with COPD case-control status using mixed linear models.,Weighted gene comethylation networks were constructed using weighted gene coexpression network analysis (WGCNA) and network modules were analyzed for association with COPD.,There were five differentially methylated CpG probes significantly associated with COPD among African-Americans at an FDR less than 5 %, and seven additional probes that approached significance at an FDR less than 10 %.,The top ranked gene association was MAML1, which has been shown to affect NOTCH-dependent angiogenesis in murine lung.,Network modeling yielded the “yellow” and “blue” comethylation modules which were significantly associated with COPD (p-value 4 × 10-10 and 4 × 10-9, respectively).,The yellow module was enriched for gene sets related to inflammatory pathways known to be relevant to COPD.,The blue module contained the top ranked genes in the concurrent differential methylation analysis (FXYD1/LGI4, gene significance p-value 1.2 × 10-26; MAML1, p-value 2.0 × 10-26; CD72, p-value 2.1 × 10-25; and LPO, p-value 7.2 × 10-25), and was significantly associated with lung development processes in Gene Ontology gene-set enrichment analysis.,We identified 12 differentially methylated CpG sites associated with COPD that mapped to biologically plausible genes.,Network module comethylation patterns have identified candidate genes that may be contributing to racial differences in COPD susceptibility and severity.,COPD-associated comethylation modules contained genes previously associated with lung disease and inflammation and recapitulated known COPD-associated genes.,The genes implicated by differential methylation and WGCNA analysis may provide mechanistic targets contributing to COPD susceptibility, exacerbations, and outcomes among African-Americans.,Trial Registration: NCT00774176, Registry: ClinicalTrials.gov, URL: www.clinicaltrials.gov, Date of Enrollment of First Participant: June 2004, Date Registered: 04 January 2008 (retrospectively registered).,The online version of this article (doi:10.1186/s12931-016-0459-8) contains supplementary material, which is available to authorized users. | The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function. | 1 |
Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity.,Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome).,The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD.,Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled.,They further underwent a blood, induced sputum and exhaled nitric oxide collection.,Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR.,ACOS patients showed an increase of MtDNA/nDNA ratio.,Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16).,Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma.,MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56).,We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma.,Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.,The online version of this article (doi:10.1186/s12890-016-0192-6) contains supplementary material, which is available to authorized users. | 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. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | Pulmonary rehabilitation (PR) is an important treatment option for chronic obstructive pulmonary disease (COPD) patients and might contribute to a reduction in exacerbation and exacerbation-related hospitalization rate.,In this prospective study, all COPD patients that completed a comprehensive pulmonary rehabilitation program (PRP) between June 2006 and December 2012 were included.,Self-reported exacerbation and hospitalization frequency 1 year before PR was retrospectively recorded.,During the year following PR, exacerbation and hospitalization frequency was recorded with questionnaires.,For 343 patients, complete information on exacerbation and hospitalization rate was obtained.,The mean number of exacerbations decreased significantly after participating in a PRP by 1.37 exacerbations/year (95% confidence interval 1.029 to 1.717) from 4.56±3.26 exacerbations in the year preceding PR to 3.18±2.53 in the year following PR (P<0.0005).,The number of hospitalizations due to exacerbations decreased significantly by 0.68 hospitalizations/year (95% confidence interval 0.467 to 0.903) from 1.48±1.84 in the year preceding PR to 0.80±1.31 hospitalizations/year in the year following PR (P<0.0005).,The proportion of patients with a frequent exacerbation type (more than two exacerbations/year) was reduced by 24%.,Multivariate regression analysis to explore determinants that might predict reduction in exacerbation frequency or change in exacerbation pattern did not reveal clinically useful predictors, although patients with more exacerbations before PR had the highest potential for reduction.,In a large population of severely impaired COPD patients with high exacerbation rates, a significant reduction in exacerbation and hospitalization frequency was observed after participation in a comprehensive PRP. | 1 |
To examine the relationship between gastroesophageal reflux (GER) and COPD exacerbations.,We conducted a systematic search of various electronic databases for articles published up through December of 2012.,Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations) for the association between GER and COPD-as well as exacerbation rates.,Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment; and severity of airflow obstruction.,Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36).,The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001).,GER is a risk factor for COPD exacerbations.,The role of GER in COPD management should be studied in greater detail. | Introduction.,Chronic obstructive pulmonary disease (COPD) is associated with comorbidities such as cardiovascular disease, metabolic disease, osteoporosis, and anxiety and/or depression.,Although pulmonary rehabilitation programs are proven to be beneficial in patients with COPD, it is unclear whether comorbidities influence pulmonary rehabilitation outcomes.,The aim of the present review was to investigate to what extent the presence of comorbidities can affect pulmonary rehabilitation outcomes.,Methods.,The systematic literature search (Pubmed, EMBASE, and PEDro) resulted in 4 articles meeting the inclusion criteria.,The odds ratios (95% confidence intervals) of the logistic regression analyses, with comorbidities as independent variables and pulmonary rehabilitation outcomes (dyspnea, functional exercise capacity, and quality of life) as dependent variables, were used for data extraction.,Results.,Patients with anxiety and/or depression less likely improve in dyspnea.,Osteoporosis is associated with less improvements in functional exercise capacity, while cardiovascular disease does not seem to negatively impact on this outcome.,Patients with cardiovascular comorbidity will experience less positive changes in quality of life.,Conclusion.,Evidence from literature suggests that comorbidities can have a negative influence on pulmonary rehabilitation outcomes.,Screening for comorbidities in pulmonary rehabilitation settings seems useful to readdress the right patients for individually tailored pulmonary rehabilitation. | 1 |
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD.,Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear.,A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE.,We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations.,Out of 77 patients, 61 patients (79.2%) had at least one comorbidity.,During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission.,Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids.,In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30-12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60-55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01-1.19, P=0.036) were associated with frequent severe AEs.,In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04-0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs.,Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients. | 1 |
Idiopathic pulmonary fibrosis (IPF) is an age-related multifactorial disease featuring non-uniform lung fibrosis.,The decisive cellular events at early stages of IPF are poorly understood.,While the involvement of club cells in IPF pathogenesis is unclear, their migration has been associated with lung fibrosis.,In this study, we labeled club cells immunohistochemically in IPF lungs using a club cell marker Claudin-10 (Cldn10), a unique protein based on the recent report which demonstrated that the appearance of Cldn10 in developing and repairing lungs precedes other club cell markers including club cell secretory protein (CCSP).,Cldn10-positive cells in IPF lungs displayed marked pleomorphism and were found in varied arrangements, suggesting their phenoconversion.,These results were corroborated by immunogold labeling for Cldn10.,Further, immunohistochemical double-labeling for Cldn10 and α-smooth muscle actin (α-SMA) demonstrated that aberrant α-SMA signals are frequently encountered near disorganized Cldn10-positive cells in hyperplastic bronchiolar epithelium and thickened interstitium of IPF lungs.,Collectively, these data indicate that club cells actively participate in the initiation and progression of IPF through phenoconversion involving the acquisition of proliferative and migratory abilities.,Thus, our new findings open the possibility for club cell-targeted therapy to become a strategic option for the treatment of IPF. | Substantial evidence suggests that there is genetic susceptibility to chronic obstructive pulmonary disease (COPD).,To identify common genetic risk variants, we performed a genome-wide association study in 2940 cases and 1380 smoking controls with normal lung function.,We demonstrate a novel susceptibility locus at 4q22.1 in FAM13A (rs7671167, OR=0.76, P=8.6×10−8) and provide evidence of replication in one case-control and two family-based cohorts (for all studies, combined P=1.2×10−11). | 1 |
Obstructive lung disease (OLD), a major global public health problem, has been less investigated in African countries.,We assessed the prevalence and determinants of OLD in Yaounde (the capital city of Cameroon), using internationally agreed definitions.,Participants were adults (age >19 years) screened during a community-based survey between December 2013 and April 2014.,Air flow limitation (AFL) was based on a pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) below the lower limit of normal (LLN, AFL-LLN).,Chronic obstructive pulmonary disease (COPD) was based on post-bronchodilator FEV1/FVC ratio < LLN (COPD-LLN).,Of the 1287 subjects included, 51.9 % were female, 9.3 % were current smokers and their mean age was 34.4 ± 12.8 years.,Forty-nine (3.8 %, 95 % CI 2.8-4.9 %) participants had AFL-LLN.,Thirty-one subjects had COPD-LLN; giving a prevalence of COPD-LLN of (2.4 %, 95 % CI 1.6-3.3 %).,In multivariable analysis, male gender (AOR 2.42; 95 % CI 1.12-5.20) and lifetime wheezing (AOR 2.88; 95 % CI 1.06-7.81) were the determinants of COPD-LLN.,Otherwise, male sex (AOR 1.93, 95 % CI 1.00-3.73), age 40-59 years (AOR 1.99, 95 % CI 1.04-3.81) and lifetime wheezing (AOR 2.65, 95 % CI 1.13-6.20) remained as independent determinants of AFL-LLN.,Obstructive lung disease based on more accurate definitions was relatively infrequent in this population.,It is important to sensitize the medical staff and the general public about this condition which should be actively investigated in individuals aged 40 years and above. | We analyzed the chest radiographs (CXRs) of 249 clinically healthy children, 230 from southwest Mexico City and 19 from Tlaxcala.,In contrast to children from Tlaxcala, children from southwest Mexico City were chronically exposed to ozone levels exceeding the U.S.,National Ambient Air Quality Standards for an average of 4.7 hr/day and to concentrations of particulate matter (PM) with aerodynamic diameters ≤2.5 μm (PM2.5) above the annual standard.,CXRs of Mexico City children demonstrated bilateral hyperinflation (151 of 230) and increased linear markings (121 of 230).,Hyperinflation and interstitial markings were significantly more common in Mexico City children (p < 0.0002 and 0.00006 respectively).,Mexico City boys had a higher probability of developing interstitial markings with age (p = 0.004).,Computed tomography (CT) scans were obtained in 25 selected Mexico City children with abnormal CXRs.,Mild bronchial wall thickening was seen in 10 of 25, prominent central airways in 4 of 25, air trapping in 8 of 21, and pulmonary nodules in 2 of 21.,Only 7.8% of Mexico City children had abnormal lung function tests based on predicted values.,These findings are consistent with bronchiolar, peribronchiolar, and/or alveolar duct inflammation, possibly caused by ozone, PM, and lipopolysaccharide exposure.,The epidemiologic implications of these findings are important for children residing in polluted environments, because bronchiolar disease could lead to chronic pulmonary disease later in life. | 1 |
Physical activity, sedentary and sleep behaviours have strong associations with health.,This systematic review aimed to identify how clinical practice guidelines (CPGs) for the management of chronic obstructive pulmonary disease (COPD) report specific recommendations and strategies for these movement behaviours.,A systematic search of databases (Medline, Scopus, CiNAHL, EMbase, Clinical Guideline), reference lists and websites identified current versions of CPGs published since 2005.,Specific recommendations and strategies concerning physical activity, sedentary behaviour and sleep were extracted verbatim.,The proportions of CPGs providing specific recommendations and strategies were reported.,From 2370 citations identified, 35 CPGs were eligible for inclusion.,Of these, 21 (60%) provided specific recommendations for physical activity, while none provided specific recommendations for sedentary behaviour or sleep.,The most commonly suggested strategies to improve movement behaviours were encouragement from a healthcare provider (physical activity n = 20; sedentary behaviour n = 2) and referral for a diagnostic sleep study (sleep n = 4).,Since optimal physical activity, sedentary behaviour and sleep durations and patterns are likely to be associated with mitigating the effects of COPD, as well as with general health and well-being, there is a need for further COPD-specific research, consensus and incorporation of recommendations and strategies into CPGs. | COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status. | 1 |
Chronic obstructive pulmonary disease (COPD) clinical trials evaluating hard endpoints (mortality, hospitalized exacerbations) require a large number of subjects and prolonged observational periods.,We hypothesized that a composite endpoint of respiratory outcomes (CERO) can help evaluate safety and benefit in COPD trials.,Retrospective analysis of 5992 patients enrolled in the 4-year UPLIFT® trial, a randomized trial of tiotropium versus placebo in patients with moderate-to-severe COPD.,Patients were permitted to continue using their usual COPD medications except for other anticholinergics.,The CERO included deaths, respiratory failure, hospitalized exacerbations, and trial dropout due to COPD worsening.,The incidence rates (IRs) per 100 patient-years and risk ratios (RRs and 95 % CI) were determined at years 1 to 4.,The effect of treatments on CERO was similarly assessed.,A power analysis helped calculate the sample size needed to achieve outcome differences between treatments.,The CERO IRs at years 1 to 4 for tiotropium versus placebo were 16, 13, 11, and 11, and 21, 16, 14, and 13, respectively.,The RRs of CERO between tiotropium and placebo at the same time points were: RR-year 0.76 (0.67, 0.86), 0.80 (0.72, 0.88), 0.81 (0.74, 0.89), and 0.84 (0.77, 0.92).,Using the IRs and RRs, the sample size (alpha = 0.05 two-sided, 90 % power) for studies of 1, 2, 3, and 4 years would be 1546, 1392, 1216, and 1504 per treatment group, respectively, with 575, 810, 930, 1383 required events, respectively, for hypothetical, event-driven studies.,A composite endpoint incorporating relatively infrequent serious or significant COPD-related safety outcomes could be useful in clinical trials.,In UPLIFT®, CERO events were significantly reduced in patients receiving tiotropium compared with placebo.,NCT00144339.,The online version of this article (doi:10.1186/s12931-016-0361-4) contains supplementary material, which is available to authorized users. | Forced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival.,We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD.,To access the association between IC/TLC and survival in an emphysematous phenotype of COPD.,We performed a retrospective analysis of a large pulmonary function (PF) database with 39,050 entries, from April 1978 to October 2009.,Emphysematous COPD was defined as reduced FEV1/forced vital capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]).,We evaluated the association between survival in emphysematous COPD patients and the IC/TLC ratio evaluated both as dichotomous (≤25% vs >25%) and continuous predictors.,Five hundred and ninety-six patients had reported death dates.,Univariate analysis revealed that IC/TLC ≤25% was a significant predictor of death (hazard ratio [HR]: 2.39, P<0.0001).,Median survivals were respectively 4.3 (95% CI: 3.8-4.9) and 11.9 years (95% CI: 10.3-13.2).,Multivariable analysis revealed age (HR: 1.19, 95% CI: 1.14-1.24), female sex (HR: 0.69, 95% CI: 0.60-0.83), and IC/TLC ≤25% (HR: 1.69, 95% CI: 1.34-2.13) were related to the risk of death.,Univariate analysis showed that continuous IC/TLC was associated with death, with an HR of 1.66 (95% CI: 1.52-1.81) for a 10% decrease in IC/TLC.,Adjusting for age and sex, IC/TLC ≤25% is related to increased risk of death, and IC/TLC as a continuum, is a significant predictor of mortality in emphysematous COPD patients. | 1 |
Despite documented efficacy and recommendations, pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) has been underutilized.,Home-based PR was proposed as an alternative, but there were limited data.,The adequate exercise intensity was also a crucial issue.,The aim of this study was to investigate the effects of home-based PR with a metronome-guided walking pace on functional exercise capacity and health-related quality of life (HRQOL) in COPD.,The subjects participated in a 12-week home-based PR program.,Exercise intensity was initially determined by cardiopulmonary exercise test, and was readjusted (the interval of metronome beeps was reset) according to submaximal endurance test.,Six-minute walk test, pulmonary function test, cardiopulmonary exercise test, and St.,George's Respiratory Questionnaire (SGRQ) were done before and after the 12-week program, and at 6 months after completion of rehabilitation.,Thirty-three patients participated in the program.,Six-minute walking distance was significantly increased (48.8 m; P = 0.017) and the SGRQ score was also improved (-15; P < 0.001) over the six-month follow-up period after rehabilitation.,There were no significant differences in pulmonary function and peak exercise parameters.,We developed an effective home-based PR program with a metronome-guided walking pace for COPD patients.,This rehabilitation program may improve functional exercise capacity and HRQOL. | Subjective health status is the result of an interaction between physiological and psychosocial factors in patients with chronic obstructive pulmonary disease (COPD).,However, there is little understanding of multivariate explanations of subjective health status in COPD.,The purpose of this study was to explore what determines subjective health status in COPD by evaluating the relationships between background variables such as age and sex, predicted FEV1%, oxygen saturation, breathlessness, anxiety and depression, exercise capacity, and physical and mental health.,This study had a cross-sectional design, and included 100 COPD patients (51% men, mean age 66.1 years).,Lung function was assessed by predicted FEV1%, oxygen saturation by transcutaneous pulse oximeter, symptoms with the St George Respiratory Questionnaire and the Hospital Anxiety and Depression Scale, physical function with the Incremental Shuttle Walking Test, and subjective health status with the SF-36 health survey.,Linear regression analysis was used.,Older patients reported less breathlessness and women reported more anxiety (p < 0.050).,Women, older patients, those with lower predicted FEV1%, and those with greater depression had lower physical function (p < 0.050).,Patients with higher predicted FEV1%, those with more breathlessness, and those with more anxiety or depression reported lower subjective health status (p < 0.050).,Symptoms explained the greatest variance in subjective health status (35%-51%).,Symptoms are more important for the subjective health status of patients with COPD than demographics, physiological variables, or physical function.,These findings should be considered in the treatment and care of these patients. | 1 |
To examine the difference in the fractional exhaled nitric oxide (FeNO) between chronic obstructive pulmonary disease (COPD) patients with asthma-COPD overlap syndrome (ACOS) and patients with Non-ACOS COPD (Non-ACOS) and to investigate the correlation between FeNO levels and the differential cell counts of eosinophils in induced sputum, in order to explore the diagnostic value of FeNO in ACOS.,A prospective, case-control study was performed on 53 cases of ACOS group and 53 cases of Non-ACOS group in the Respiratory Medicine Outpatient of Zhangzhou Municipal TCM Hospital, Affiliated to Fujian University of Traditional Chinese Medicine.,The FeNO levels and induced sputum cell counts were determined and the correlation between FeNO levels and eosinophile percentage was analyzed by Pearson linear correlation analysis.,The FeNO levels in patients with ACOS (37[24.5-53.0]) ppb were significantly higher than those of patients with Non-ACOS (20 [15.5-24.5] ppb) (P < .01).,Also, the percentage of eosinophils in induced sputum in the ACOS group (5.70 [1.50-17.62]%) were significantly higher than those of the Non-ACOS group (0.50 [0.00-1.00]%) (P < .01).,FeNO in both groups correlated positively with the percentage of eosinophils in induced sputum (P < .01), with a correlation coefficient r of 0.521.,The area under the receiver operating curve of FeNO for the diagnosis of ACOS phenotype was 0.815 (P < .01), the sensitivity and specificity reach highest when the cut off value was 25.50 ppb.,The FeNO in patients from the ACOS group were significantly higher than those in Non-ACOS group and were moderately correlated with the percentage of eosinophils in induced sputum.,The results indicated that FeNO may be used as a diagnostic index for ACOS, in addition to the induced sputum. | The combination of asthma and chronic obstructive pulmonary disease (COPD), or ACOS is a recently defined syndrome.,The epidemiology of the condition is poorly described and previous research has suggested ACOS is associated with worse outcomes than either condition alone.,We therefore decided to complete a systematic review of the published literature.,This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines.,A structured search was performed in the PubMed, Embase, and Medline databases up to Feb 2015 to identify studies reporting incidence, prevalence, health care utilization, morbidity, or mortality in COPD and asthma.,A total of 19 studies were included in the present study.,The pooled prevalence of overlap among COPD was 27% (95% CI: 0.16-0.38, p<0.0001) and 28% (95% CI: 0.09-0.47, p = 0.0032) in the population and hospital-based studies, respectively.,We found no significant difference between ACOS and COPD in terms of gender, smoking status, lung function and 6mWD.,However, in comparison to subject with only COPD, ACOS subjects were significantly younger, had higher BMI, healthcare utilization, and lower HRQoL.,ACOS is a common condition that exists in a substantial proportion of subjects with COPD.,ACOS represents a distinct clinical phenotype with more frequent exacerbations, hospitalization, worse health-related quality of life, and higher healthcare costs than either disease alone.,There is a critical need to better define the management and treatment of this syndrome. | 1 |
Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality.,Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD.,COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme.,Assessments were performed by investigators blinded to treatment allocation.,Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups.,102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%.,Both groups had comparable characteristics at baseline.,The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only.,A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.,Pedometer-based programme produced clinically important improvements in physical activity and health status in COPDhttp://ow.ly/AmcCO | People living with chronic disease currently account for the majority of the total healthcare costs.,The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008.,This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy.,We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group.,The primary outcome was patients’ assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument.,At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system.,Patients were asked to confirm or refute their diagnosis of COPD.,Of those who responded, 1,445 (72.8%) confirmed their diagnosis.,PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients.,Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups.,No statistically significant differences were found between the control and the external control groups in any of the dimensions.,Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare.,NCT01228708. | 1 |
Social isolation is a common experience in patients with COPD but is not captured by existing patient-reported outcomes, and its association with clinical outcomes is unknown.,We prospectively enrolled adults with stable COPD who completed the University of Alabama at Birmingham Life Space Assessment (LSA) (range: 0-120, restricted Life-Space mobility: ≤60 and a marker of social isolation in older adults); six-minute walk test (6MWT), and the University of California at San Diego Shortness of Breath Questionnaire, COPD Assessment Test, and Hospital Anxiety and Depression Scale.,The occurrence of severe exacerbations (emergency room visit or hospitalization) was recorded by review of the electronic record up to 1 year after enrollment.,We determined associations between Life-Space mobility and clinical outcomes using regression analyses.,Fifty subjects had a mean ± SD %-predicted FEV1 of 42.9±15.5, and 23 (46%) had restricted Life-Space mobility.,After adjusting for age, gender, %-predicted FEV1, comorbidity count, inhaled corticosteroid/long-acting beta2-agonist use, and prior cardiopulmonary rehabilitation, subjects with restricted Life-Space had an increased risk for severe exacerbations (adjusted incidence rate ratio 4.65, 95% CI 1.19-18.23, P=0.03).,LSA scores were associated with 6MWD (R=0.50, P<0.001), dyspnea (R=−0.58, P<0.001), quality of life (R=−0.34, P=0.02), and depressive symptoms (R=−0.39, P=0.005).,Restricted Life-Space mobility predicts severe exacerbations and is associated with reduced exercise tolerance, more severe dyspnea, reduced quality of life, and greater depressive symptoms. | Background: COPD pathology involves not only the lungs but also extrapulmonary abnormalities.,Osteoporosis is one of the most important abnormalities because it may cause vertebral compression fractures and deteriorate pulmonary function.,COPD patients have many risk factors for osteoporosis, such as low BMI, decreased activity, systemic inflammation, and use of corticosteroids.,Some of these factors have been shown to deteriorate with COPD exacerbations.,We previously demonstrated the correlation between emphysema and osteoporosis and between emphysema progression and COPD exacerbations.,Thus, the hypothesis that exacerbation causes osteoporosis progression in COPD patients was investigated.,Methods: Forty-two COPD patients not on osteoporosis treatment for over 2 years were recruited.,During follow-up, exacerbations had been prospectively recorded.,Thoracic vertebral bone mineral density (BMD) was measured using chest CT, and the annual change in BMD was calculated.,The change was compared between patients with and without a history of exacerbations.,Results: The decrease in thoracic vertebral BMD was greater in patients with than in those without a history of exacerbations (median ABMD mg/ml year: −3.78 versus −0.30, p = 0.02).,Moreover, multivariate regression analysis showed that exacerbations and baseline Pa02 were independent predictors of the BMD decrease (R2 = 0.20, p = 0.007, and R2 = 0.09, p = 0.03, respectively) after adjustment for baseline age, smoking status, and airflow limitation.,Conclusions: This is the first longitudinal study to demonstrate that COPD exacerbations are independently associated with osteoporosis progression.,Osteoporosis progression should be evaluated in COPD patients, especially in those with a history of frequent exacerbations. | 1 |
To determine the underdiagnosis rate in new COPD cases at the end of a nine-year follow-up period-in the study designated "Projeto Latino-Americano de Investigação em Obstrução Pulmonar" (PLATINO, Latin-American Pulmonary Obstruction Investigation Project)-and compare that with the underdiagnosis rate during the initial phase of the study, as well as to identify the clinical features exhibited by the subjects who were not diagnosed until the end of the follow-up phase.,The study population comprised the 1,000 residents of the city of São Paulo, Brazil, who took part in the PLATINO study.,Of those, 613 participated in the follow-up phase, during which the subjects were assessed with the same instruments and equipment employed in the initial phase of the study.,We used the chi-square test or the independent sample t-test to analyze the underdiagnosis rate and to identify the characteristics of the subjects who were not diagnosed until the end of the follow-up phase.,The underdiagnosis rate for new COPD cases at the end of the nine-year follow-up period was 70.0%.,The underdiagnosis rate during the follow-up phase was 17.5% lower than that reported for the initial phase of the study.,The subjects who were not diagnosed until the end of the follow-up phase presented with fewer respiratory symptoms, better pulmonary function, and less severe disease than did those previously diagnosed with COPD.,The underdiagnosis rate for new COPD cases was lower in the follow-up phase of the study than in the initial phase.,The subjects who were not diagnosed until the end of the follow-up phase of the PLATINO study presented with the same clinical profile as did those who were not diagnosed in the initial phase.,These findings underscore the need for spirometry in order to confirm the diagnosis of COPD and provide early intervention.,Determinar a taxa de subdiagnóstico em novos casos de DPOC em uma amostra de pacientes após nove anos de seguimento do estudo "Projeto Latino-Americano de Investigação em Obstrução Pulmonar" (PLATINO) e compará-la à taxa de subdiagnóstico obtida na fase inicial do estudo, assim como identificar as características clínicas dos indivíduos subdiagnosticados na fase de seguimento.,A população desse estudo foi composta por 1.000 residentes na cidade de São Paulo que fizeram parte do estudo PLATINO.,Desses, 613 indivíduos participaram da fase de seguimento.,Os indivíduos foram avaliados utilizando-se os mesmos instrumentos e equipamentos na fase inicial do estudo.,O teste do qui-quadrado ou o teste t para amostras independentes foi utilizado para analisar a taxa de subdiagnóstico e identificar as características dos indivíduos subdiagnosticados durante a fase de seguimento.,A taxa de subdiagnóstico para novos casos da DPOC após nove anos de acompanhamento foi de 70,0%.,A taxa de subdiagnóstico na fase de seguimento foi 17,5% menor que a da fase inicial do estudo.,Os indivíduos subdiagnosticados na fase de seguimento apresentavam poucos sintomas respiratórios, função pulmonar mais preservada e menor gravidade da doença do que aqueles previamente diagnosticados com DPOC.,A taxa de subdiagnóstico na fase de seguimento foi menor que a da fase inicial do estudo.,Os indivíduos subdiagnosticados na fase de seguimento do estudo PLATINO apresentavam o mesmo perfil clínico daqueles subdiagnosticados na fase inicial.,Esses achados reforçam a necessidade da utilização da espirometria para o diagnóstico de DPOC e possibilitar a intervenção precoce. | Smoking is the main preventable cause of morbidity and mortality in our region, it being the main causative agent of chronic obstructive pulmonary disease.,There still is no consensus on the use of spirometry as a strategy for smoking cessation, given that there is insufficient scientific evidence from high quality studies to recommend the use of this technique.,This is to be a randomized, multicentre, open-label clinical trial.,A total of 444 smokers over 40 years of age will be recruited by 39 general practitioners from 22 health centers.,Primary objective of this study is to assess the effectiveness of spirometry together with information regarding the test for smoking cessation after 1 year in smokers over 40 years of age with a more than 10 pack-year history and no previous diagnosis of chronic obstructive pulmonary disease.,Groups of 45 patients who smoke will be randomly selected from the lists of the participating doctors.,The names will be sent to the corresponding doctors who will contact candidate patients and assess whether they meet the selection criteria.,Patients who meet these criteria will be randomly allocated to an intervention or control group.,For patients in both groups, a nurse will conduct an interview and perform a spirometry test to measure forced vital capacity.,Then, all patients will be referred for an appointment with their doctor for brief anti-smoking intervention, patients from the intervention group additionally being informed about the result of the spirometry test.,After 1 year, smoking status will be assessed and, in those who report that they have quit smoking, abstinence will be confirmed by co-oximetry.,Data will be analyzed on an intention-to-treat basis using the chi-squared test for outcomes and binary logistic regression if it is considered to be necessary to adjust for confounding variables.,Performing a spirometry test and providing information on pulmonary function may increase awareness of the effect of smoking among smokers who are asymptomatic or have few symptoms and make them decide to quit.,Specifically, in patients with chronic obstructive pulmonary disease it might increase levels of motivation to quit smoking in early stages of the disease.,If this strategy were to be effective, it could be included in the health promotion activities offered in primary care.,ClinicalTrials.gov Identifier: NCT01821885 | 1 |
Chronic obstructive pulmonary disease (COPD) is a very prevalent and invalidating disease.,The aim of this study was to analyze the burden borne by informal caregivers of patients with COPD.,We used the Survey on Disabilities, Personal Autonomy, and Dependency Situations (Encuesta sobre Discapacidad, Autonomía personal y Situaciones de Dependencia [EDAD]-2008) to obtain information on the characteristics of disabled individuals with COPD and their caregivers in Spain.,Additionally, statistical multivariate analyses were performed to analyze the impact that an increase in dependence would have on the problems for which caregivers provide support, in terms of health, professional, and leisure/social dimensions.,A total of 461,884 individuals with one or more disabilities and with COPD were identified, and 220,892 informal caregivers were estimated.,Results showed that 35% of informal caregivers had health-related problems due to the caregiving provided; 83% had leisure/social-related problems; and among caregivers of working age, 38% recognized having profession-related problems.,The probability of a problem arising was significantly associated with the degree of dependence of the patient receiving care.,Caregivers of patients with great dependence showed a 39% higher probability of presenting health-related problems, 27% more professional problems, and 23% more leisure problems compared with those with nondependent patients.,The results show the large impact on society in terms of the welfare of informal caregivers of patients with COPD.,A higher level of dependence was associated with more severe problems in caregivers, in all dimensions. | There are few publications on quality measurement of COPD health state according to the severity level using EQ-5D in Korea.,The present study aimed to evaluate the health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD) in terms of disease severity in Korea.,Totally two hundred patients with COPD were consecutively recruited in one tertiary hospital of Korea.,Each respondent was asked to fill out the questionnaire through a face-to-face interview after providing informed consent.,The questionnaire included general and clinical characteristics as well as the EQ-5D and Clinical COPD Questionnaire (CCQ).,HRQoL was evaluated according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and severity of breathlessness.,The adjusted mean EQ-5D index scores were 0.83, 0.88, 0.81 and 0.60 in stage I, II, III and IV, respectively.,The EQ-5D index tended to decrease with GOLD criteria.,The adjusted mean EQ-Visual Analog Scale (VAS) scores ranged from 65.1 in stage IV to 73.9 in stage I.,The CCQ total scores deteriorated with an increasing GOLD stage and severity of breathlessness (all P < 0.001).,The correlation between CCQ total score and EQ-5D index was −0.69.,Our study shows that HRQoL in COPD measured by EQ-5D and CCQ worsens with the GOLD stage and severity of breathlessness.,EQ-5D and CCQ could be useful instruments for an evaluation of HRQoL in COPD patients in Korea. | 1 |
Pulmonary rehabilitation (PR) is an effective, key standard treatment for people with COPD.,Nevertheless, low participant uptake, insufficient attendance and high drop-out rates are reported.,Investigation is warranted of the benefits achieved through alternative approaches, such as pulmonary tele-rehabilitation (PTR).,To investigate whether PTR is superior to conventional PR on 6 min walk distance (6MWD) and secondarily on respiratory symptoms, quality of life, physical activity and lower limb muscle function in patients with COPD and FEV1 <50% eligible for routine hospital-based, outpatient PR.,In this single-blinded, multicentre, superiority randomised controlled trial, patients were assigned 1:1 to 10 weeks of groups-based PTR (60 min, three times weekly) or conventional PR (90 min, two times weekly).,Assessments were performed by blinded assessors at baseline, end of intervention and at 22 weeks’ follow-up from baseline.,The primary analysis was based on the intention-to-treat principle.,The primary outcome was change in 6MWD from baseline to 10 weeks; 134 participants (74 females, mean±SD age 68±9 years, FEV1 33%±9% predicted, 6MWD 327±103 metres) were included and randomised.,The analysis showed no between-group differences for changes in 6MWD after intervention (9.2 metres (95% CI: −6.6 to 24.9)) or at 22 weeks’ follow-up (−5.3 metres (95% CI: −28.9 to 18.3)).,More participants completed the PTR intervention (n=57) than conventional PR (n=43) (χ2 test p<0.01).,PTR was not superior to conventional PR on the 6MWD and we found no differences between groups.,As more participants completed PTR, supervised PTR would be relevant to compare with conventional PR in a non-inferiority design.,Trial registration number,ClinicalTrials.gov (NCT02667171), 28 January 2016. | Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | 1 |
To obtain evidence whether the online pulmonary rehabilitation(PR) programme ‘my-PR’ is non-inferior to a conventional face-to-face PR in improving physical performance and symptom scores in patients with COPD.,A two-arm parallel single-blind, randomised controlled trial.,The online arm carried out pulmonary rehabilitation in their own homes and the face to face arm in a local rehabilitation facility.,90 patients with a diagnosis of chronic obstructive pulmonary disease (COPD), modified Medical Research Council score of 2 or greater referred for pulmonary rehabilitation (PR), randomised in a 2:1 ratio to online (n=64) or face-to-face PR (n=26).,Participants unable to use an internet-enabled device at home were excluded.,Coprimary outcomes were 6 min walk distance test and the COPD assessment test (CAT) score at completion of the programme.,A 6-week PR programme organised either as group sessions in a local rehabilitation facility, or online PR via log in and access to 'myPR’.,The adjusted mean difference for the 6 min walk test (6MWT) between groups for the intention-to-treat (ITT) population was 23.8 m with the lower 95% CI well above the non-inferiority threshold of −40.5 m at −4.5 m with an upper 95% CI of +52.2 m.,This result was consistent in the per-protocol (PP) population with a mean adjusted difference of 15 m (−13.7 to 43.8).,The CAT score difference in the ITT was −1.0 in favour of the online intervention with the upper 95% CI well below the non-inferiority threshold of 1.8 at 0.86 and the lower 95% CI of −2.9.,The PP analysis was consistent with the ITT.,PR is an evidenced-based and guideline-mandated intervention for patients with COPD with functional limitation.,A 6-week programme of online-supported PR was non-inferior to a conventional model delivered in face-to-face sessions in terms of effects on 6MWT distance, and symptom scores and was safe and well tolerated. | 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. | 1 |
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. | Two replicate, double-blind, placebo-controlled, 6-week crossover studies assessed the effect of the once-daily long-acting β2-agonist olodaterol 5 μg and 10 μg on constant work-rate cycle endurance in patients with moderate to very severe chronic obstructive pulmonary disease.,Patients received placebo, olodaterol 5 μg once daily (QD) and olodaterol 10 μg QD in a randomised order for 6 weeks each, with a 2-week washout period in between.,The primary end point was change in endurance time during constant work-rate cycle ergometry to symptom limitation at 75 % maximal work capacity after 6 weeks of treatment (2 h post-dose), based on log10-transformed data.,Key secondary end points were inspiratory capacity at isotime and intensity of breathing discomfort at isotime.,151 and 157 patients were randomised and treated in Studies 1222.37 and 1222.38, respectively, with 147 and 154 being included in the full analysis sets.,Mean endurance time at week 6 was increased compared to placebo by 14.0 % (Study 1222.37; p < 0.001) and 11.8 % (Study 1222.38; p < 0.01) with olodaterol 5 μg, and by 13.8 % (Study 1222.37; p < 0.001) and 10.5 % (Study 1222.38; p < 0.01) with olodaterol 10 μg.,Inspiratory capacity at isotime increased with olodaterol 5 μg (Study 1222.37, 0.182 L, p < 0.0001; Study 1222.38, 0.084 L, p < 0.05) and 10 μg (Study 1222.37, 0.174 L; Study 1222.38, 0.166 L; both studies, p < 0.0001), and breathing discomfort was significantly reduced in Study 1222.37 (olodaterol 5 μg, 0.77 Borg units, p < 0.001; olodaterol 10 μg, 0.63 Borg units, p < 0.01) but not Study 1222.38.,These studies provide further characterisation of the efficacy of olodaterol, showing that improvements in airflow (forced expiratory volume in 1 s) are associated with increases in inspiratory capacity and improvements in exercise endurance time.,NCT01040130 (1222.37) and NCT01040793 (1222.38).,The online version of this article (doi:10.1186/s12931-016-0389-5) contains supplementary material, which is available to authorized users. | 1 |
Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD.,Despite guideline recommendations that combined long-acting β2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk.,This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens.,The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD.,This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 µg and 2.5/5 µg) via Respimat® and twice-daily salmeterol + fluticasone propionate (50/500 µg and 50/250 µg) via Accuhaler® for 6 weeks.,The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks.,Tiotropium + olodaterol 5/5 µg and 2.5/5 µg demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 µg and 2.5/5 µg, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 µg and 50/250 µg, respectively).,Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24).,Once-daily tiotropium + olodaterol in participants with moderate-to-severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate.,Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. | 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 |
Long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) bronchodilators are key to the pharmacologic treatment of chronic obstructive pulmonary disease (COPD).,This Phase IIb study investigated the safety and efficacy of four doses of the LAMA glycopyrronium (GP) delivered using co-suspension delivery technology via metered dose inhaler (MDI).,The study was part of a wider clinical trial program performed to determine the optimal dose of GP MDI, the LABA formoterol fumarate dihydrate (FF) MDI, and glycopyrronium/formoterol fumarate dihydrate (GFF) MDI fixed-dose combination to be taken forward into Phase III studies.,In this randomized, double-blind, 7-day chronic-dosing, three-period incomplete block, cross-over study, patients with moderate-to-severe COPD received two of the four doses of GP MDI (28.8 μg, 14.4 μg, 7.2 μg, and 3.6 μg) twice daily (BID), and either placebo MDI BID or open-label ipratropium MDI 34 μg four times daily.,The primary efficacy endpoint was forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12 h (AUC0-12) relative to baseline on Day 7.,Secondary and exploratory efficacy endpoints were assessed on Days 1 and 7.,Safety and tolerability were evaluated throughout the study.,All GP MDI treatments were superior to placebo MDI for the primary efficacy endpoint (all p < 0.0001).,However, only GP MDI 28.8 μg and 14.4 μg demonstrated statistical superiority to placebo MDI for all secondary efficacy endpoints analyzed in this study, with the exception of GP MDI 14.4 μg versus placebo MDI for the proportion of patients achieving ≥12% improvement in FEV1.,No nominally significant differences were observed between GP MDI 28.8 μg and GP MDI 14.4 μg for any of the endpoints.,All doses of GP MDI were well tolerated, with no unexpected safety findings.,This study indicated that there was no advantage of GP MDI 28.8 μg compared with GP MDI 14.4 μg.,It therefore added to the evidence from the Phase I/II clinical trial program, which identified GP MDI 14.4 μg as the most appropriate dose for use in the Phase III clinical studies.,ClinicalTrials.gov (NCT01350128).,Registered May 09, 2011. | Symptoms of chronic obstructive pulmonary disease may vary throughout the day and it is important that therapeutic approaches provide 24-h symptom control.,We report the results of two phase IIIb crossover studies, PT003011 and PT003012, investigating the 24-h lung function profile of GFF MDI (glycopyrrolate/formoterol fumarate 18/9.6 μg delivered using innovative co-suspension delivery technology) administered twice daily.,Patients with moderate-to-very severe chronic obstructive pulmonary disease received 4 weeks’ treatment with each of GFF MDI, placebo MDI, and open-label tiotropium (PT003011 only).,Lung function was assessed over 24 h on day 29 of each treatment period.,The primary outcome was forced expiratory volume in 1 second area under the curve from 0 to 24 h (FEV1AUC0-24).,Other outcomes included change from baseline in average daily rescue medication use over the treatment period.,In addition, we conducted a post-hoc analysis of data pooled from both studies to further characterize the effect of GFF MDI on inspiratory capacity.,GFF MDI treatment significantly increased FEV1AUC0-24 versus placebo in studies PT003011 (n = 75) and PT003012 (n = 35) on day 29 (both studies p < 0.0001), with similar improvements in FEV1AUC versus placebo for hours 0-12 and 12-24.,In PT003011, improvements with GFF MDI versus tiotropium in FEV1AUC were greater during hours 12-24 compared to 0-12 h.,GFF MDI treatment also resulted in a significant reduction in rescue medication use versus placebo (−0.84 [p<0.0001] and −1.11 [p=0.0054] puffs/day in PT003011 and PT003012, respectively), and versus tiotropium in PT003011 (−0.44 [p=0.017] puffs/day).,A post-hoc pooled analysis showed patients treated with GFF MDI were more likely to achieve a >15% increase from baseline in inspiratory capacity than patients treated with placebo or tiotropium (72.1%, 19.0% and 47.0% of patients, respectively after the evening dose on day 29).,There were no significant safety/tolerability findings.,GFF MDI significantly improved 24-h lung function versus placebo in patients with moderate-to-very severe chronic obstructive pulmonary disease, with similar benefits in the second 12-h period compared to the first, supporting twice-daily dosing of GFF MDI.,Pearl Therapeutics, Inc.; www.clinicaltrials.gov; NCT02347072 and NCT02347085.,Registered 21 January 2015. | 1 |
Reports have suggested a reduction in exacerbations of chronic obstructive pulmonary disease (COPD) during the coronavirus disease 2019 (COVID-19) pandemic, particularly hospital admissions for severe exacerbations.,However, the magnitude of this reduction varies between studies.,Electronic databases were searched from January 2020 to May 2021.,Two independent reviewers screened titles and abstracts and, when necessary, full text to determine if studies met inclusion criteria.,A modified version of the Newcastle-Ottawa Scale was used to assess study quality.,A narrative summary of eligible studies was synthesised, and meta-analysis was conducted using a random effect model to pool the rate ratio and 95% confidence intervals (95% CI) for hospital admissions.,Exacerbation reduction was compared against the COVID-19 Containment and Health Index.,A total of 13 of 745 studies met the inclusion criteria and were included in this review, with data from nine countries.,Nine studies could be included in the meta-analysis.,The pooled rate ratio of hospital admissions for COPD exacerbations during the pandemic period was 0.50 (95% CI 0.44-0.57).,Findings on the rate of community-treated exacerbations were inconclusive.,Three studies reported a significant decrease in the incidence of respiratory viral infections compared with the pre-pandemic period.,There was not a significant relationship between exacerbation reduction and the COVID-19 Containment and Health Index (rho = 0.20, p = 0.53).,There was a 50% reduction in admissions for COPD exacerbations during the COVID-19 pandemic period compared to pre-pandemic times, likely associated with a reduction in respiratory viral infections that trigger exacerbations.,Future guidelines should consider including recommendations on respiratory virus infection control measures to reduce the burden of COPD exacerbations beyond the pandemic period. | Objectives To investigate whether the use and timing of prescription of β blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use.,Design Population based cohort study in England.,Setting UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11.,Participants Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record.,Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London.,Main outcome measure Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed β blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct.,Results Among 1063 patients with COPD, treatment with β blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years).,Patients already taking a β blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001).,Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed β blockers.,With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with β blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02).,Conclusions The use of β blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD.,Registration NCT01335672. | 1 |
Multimorbidity has already become common in primary care and will be a challenge in the future.,Primary care in Sweden participates to a great extent in the care of patients with two severe, chronic conditions: chronic obstructive pulmonary disease (COPD) and heart failure.,Both conditions are characterized by high mortality and often coexist.,Age, sex, heart failure and other comorbidities are considered to be the major predictors of mortality in patients with COPD.,We aimed to study the impact of heart failure, other comorbidities, age and sex on mortality in patients with COPD.,A register-based, prospective cohort study conducted in Blekinge County in Sweden with about 150,000 inhabitants.,The study population was comprised of people aged ≥35 years.,The data about diagnoses of COPD and heart failure came from the 2007 health care register, in which we found 984 individuals with a diagnosis of COPD.,Date of death was collected from January 1st, 2008 -August 31st, 2015.,The diagnosis-based Adjusted Clinical Groups (ACG) Case-Mix System 7.1 was used to describe comorbidity.,Each individual was assigned one of six comorbidity levels called resource utilization bands (RUB) graded from 0 to 5.,Estimated eight year mortality in patients with COPD and coexisting heart failure was seven times higher than in patients with COPD alone - odds ratio 7.06 (95% CI 3.88-12.84).,Adjusting for age and male sex resulted in odds ratio 3.75 (95% CI 1.97-7.15).,Further adjusting for other comorbidities resulted in odds ratio 3.26 (95% CI 1.70-6.25).,The mortality was strongly associated with the highest comorbidity level - RUB 5 where the odds ratio was 5.19 (95% CI 2.59-10.38).,Heart failure has an important impact on mortality in patients with COPD.,The mortality in patients with COPD and coexisting heart failure was strongly associated with age, male sex and other comorbidities.,Of those three predictors, only other comorbidities can be influenced.,Heart failure and other comorbidities should be recognized early and properly treated in order to improve survival in patients with coexisting COPD and heart failure. | An eight-item questionnaire of the COPD assessment test (CAT) is widely used to quantify the impact of COPD on the patient’s health status.,C-reactive protein (CRP) is associated with disease severity and adverse health outcomes of patients with COPD.,This study aimed to evaluate the relationship between CAT score and serum CRP levels in stable COPD patients.,We evaluated the medical records of 226 patients with CAT and serum CRP measured within a week at Samsung Medical Center between October 2013 and October 2015.,Serum CRP levels had a significantly positive relationship with CAT score (Spearman’s r=0.20, P=0.003).,Patients with elevated serum CRP levels (>0.3 mg/dL) were significantly more likely to have CAT scores of ≥14.,The adjusted odds ratio for elevated serum CRP levels in total CAT score was 1.06 (95% confidence interval, 1.02-1.09).,Among CAT components, cough (adjusted P=0.005), phlegm (adjusted P=0.001), breathlessness going up hills/stairs (adjusted P=0.005), low confidence leaving home (adjusted P=0.002), and feeling low in energy (adjusted P=0.019) were independently associated with elevated serum CRP levels.,In stable COPD patients, serum CRP levels were independently associated with total CAT score and CAT components related to respiratory symptoms, confidence leaving home, and energy. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | Two replicate, double-blind, placebo-controlled, 6-week crossover studies assessed the effect of the once-daily long-acting β2-agonist olodaterol 5 μg and 10 μg on constant work-rate cycle endurance in patients with moderate to very severe chronic obstructive pulmonary disease.,Patients received placebo, olodaterol 5 μg once daily (QD) and olodaterol 10 μg QD in a randomised order for 6 weeks each, with a 2-week washout period in between.,The primary end point was change in endurance time during constant work-rate cycle ergometry to symptom limitation at 75 % maximal work capacity after 6 weeks of treatment (2 h post-dose), based on log10-transformed data.,Key secondary end points were inspiratory capacity at isotime and intensity of breathing discomfort at isotime.,151 and 157 patients were randomised and treated in Studies 1222.37 and 1222.38, respectively, with 147 and 154 being included in the full analysis sets.,Mean endurance time at week 6 was increased compared to placebo by 14.0 % (Study 1222.37; p < 0.001) and 11.8 % (Study 1222.38; p < 0.01) with olodaterol 5 μg, and by 13.8 % (Study 1222.37; p < 0.001) and 10.5 % (Study 1222.38; p < 0.01) with olodaterol 10 μg.,Inspiratory capacity at isotime increased with olodaterol 5 μg (Study 1222.37, 0.182 L, p < 0.0001; Study 1222.38, 0.084 L, p < 0.05) and 10 μg (Study 1222.37, 0.174 L; Study 1222.38, 0.166 L; both studies, p < 0.0001), and breathing discomfort was significantly reduced in Study 1222.37 (olodaterol 5 μg, 0.77 Borg units, p < 0.001; olodaterol 10 μg, 0.63 Borg units, p < 0.01) but not Study 1222.38.,These studies provide further characterisation of the efficacy of olodaterol, showing that improvements in airflow (forced expiratory volume in 1 s) are associated with increases in inspiratory capacity and improvements in exercise endurance time.,NCT01040130 (1222.37) and NCT01040793 (1222.38).,The online version of this article (doi:10.1186/s12931-016-0389-5) contains supplementary material, which is available to authorized users. | 1 |
Emphysematous smokers with normal spirometry form a considerable proportion of the clinical population.,However, despite presenting with respiratory symptoms and activity limitation, they cannot be diagnosed with chronic obstructive lung disease (COPD) according to current criteria.,Thus, we aimed to determine whether emphysema in smokers has a different pathogenesis from that in patients with COPD.,We compared 12 pairs of lung tissue samples from emphysematous patients with normal spirometry and COPD, and determined the degree of emphysema using computed tomography.,With a focus on COPD-related pathogenesis, we independently assessed inflammatory response, protease-antiprotease balance, oxidative stress, and apoptosis in both groups.,Both groups showed similar pathological changes at a comparable degree of emphysema; the expression of inflammatory factors was comparable, with overexpression of proteases and decreased levels of antiproteases.,Moreover, there was no significant difference in the activities of glutathione and superoxide dismutase, and expression of apoptosis-related factors.,In conclusion, emphysema in smokers with normal spirometry and in patients with COPD had similar pathogenesis.,Forced expiratory volume in 1 second cannot be used as the sole diagnostic criterion in patients with COPD; early intervention is of great importance to such patients. | Atherosclerosis and COPD are both systemic inflammatory diseases that may influence each other.,The aim of the present study was to determine the prevalence of COPD in patients with cerebral and/or peripheral artery disease and to assess factors associated with the presence of COPD.,Following the diagnosis of cerebral and/or peripheral artery disease by means of duplex sonography, 166 consecutive patients underwent body plethysmography with capillary blood gas analysis.,Thereafter, blood tests with determination of different parameters such as lipid profile, inflammatory and coagulation markers were conducted in remaining 136 patients who fulfilled inclusion criteria of the study.,Thirty-six out of 136 patients suffered from COPD, mostly in early stages of the disease.,Residual volume indicating emphysema was increased (162.9%±55.9% vs 124.5%±37.0%, p<0.05) and diffusion capacity was decreased (55.1%±19.5% vs 75.3%±18.6%, p<0.05) in COPD patients vs non-COPD group.,In capillary blood gas analysis, COPD patients had lower partial pressure of oxygen (70.9±11.5 vs 75.2±11.0 mmHg, p<0.05) and higher partial pressure of carbon dioxide (36.8±7.5 vs 34.4±4.4 mmHg, p<0.05) compared with non-COPD individuals.,Presence of COPD was associated with predominance of diabetes mellitus, interleukin-8-related systemic neutrophilic inflammation and anemia.,In conclusion, COPD is highly prevalent in patients with atherosclerotic artery disease. | 1 |
In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity.,Intercostal muscle ultrasound offers a repeatable and radiation-free alternative, however requires validation.,We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters.,Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2nd and 3rd parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT.,Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91.,Inter-rater ICC was fair to excellent.,Ultrasound intercostal thickness moderately correlated with FEV1% predicted (r = 0.33) and quadriceps thickness (r = 0.31).,Echogenicity correlated negatively with FEV1% predicted (r = −0.32).,CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness.,These data confirm ultrasound of parasternal intercostal musculature is reproducible.,Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity.,This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics.,The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall. | Quantifying the improvements in lower limb or quadriceps muscle mass following resistance training (RT), is an important outcome measure in COPD.,Ultrasound is a portable, radiation free imaging technique that can measure the size of superficial muscles belonging to the quadriceps group such as the rectus femoris, but has not been previously used in COPD patients following RT.,We compared the responsiveness of ultrasound derived measures of quadriceps mass against dual energy x-ray absorptiometry (DEXA), in patients with COPD and healthy controls following a programme of high intensity knee extensor RT.,Portable ultrasound was used to assess the size of the dominant quadriceps in 45 COPD patients and 19 healthy controls-before, during, and after 8 weeks of bilateral high intensity isokinetic knee extensor RT.,Scanning was performed at the mid-thigh region, and 2 indices of quadriceps mass were measured-rectus femoris cross-sectional area (RFcsa) and quadriceps muscle thickness (Qt).,Thigh lean mass (Tdexa) was determined by DEXA.,Training resulted in a significant increase in Tdexa, RFcsa and Qt in COPD patients [5.7%, 21.8%, 12.1% respectively] and healthy controls [5.4%, 19.5%, 10.9 respectively].,The effect size for the changes in RFcsa (COPD= 0.77; Healthy=0.83) and Qt (COPD=0.36; Healthy=0.78) were greater than the changes in Tdexa (COPD=0.19; Healthy=0.26) following RT.,Serial ultrasound measurements of the quadriceps can detect changes in muscle mass in response to RT in COPD.,The technique has good reproducibility, and may be more sensitive to changes in muscle mass when compared to DEXA.,http://www.controlled-trials.com (Identifier: ISRCTN22764439) | 1 |
Chronic obstructive pulmonary disease (COPD) is combination of progressive lung diseases.,The diagnosis of COPD is generally based on the pulmonary function testing, however, difficulties underlie in prognosis of smokers or early stage of COPD patients due to the complexity and heterogeneity of the pathogenesis.,Computational analyses of omics technologies are expected as one of the solutions to resolve such complexities.,We obtained transcriptomic data by in vitro testing with exposures of human bronchial epithelial cells to the inducers for early events of COPD to identify the potential descriptive marker genes.,With the identified genes, the machine learning technique was employed with the publicly available transcriptome data obtained from the lung specimens of COPD and non-COPD patients to develop the model that can reflect the risk continuum across smoking and COPD.,The expression levels of 15 genes were commonly altered among in vitro tissues exposed to known inducible factors for earlier events of COPD (exposure to cigarette smoke, DNA damage, oxidative stress, and inflammation), and 10 of these genes and their corresponding proteins have not previously reported as COPD biomarkers.,Although these genes were able to predict each group with 65% accuracy, the accuracy with which they were able to discriminate COPD subjects from smokers was only 29%.,Furthermore, logistic regression enabled the conversion of gene expression levels to a numerical index, which we named the “potential risk factor (PRF)” index.,The highest significant index value was recorded in COPD subjects (0.56 at the median), followed by smokers (0.30) and non-smokers (0.02).,In vitro tissues exposed to cigarette smoke displayed dose-dependent increases of PRF, suggesting its utility for prospective risk estimation of tobacco products.,Our experimental-based transcriptomic analysis identified novel genes associated with COPD, and the 15 genes could distinguish smokers and COPD subjects from non-smokers via machine-learning classification with remarkable accuracy.,We also suggested a PRF index that can quantitatively reflect the risk continuum across smoking and COPD pathogenesis, and we believe it will provide an improved understanding of smoking effects and new insights into COPD. | Asthma and chronic obstructive pulmonary disease (COPD) are two common different clinical diagnoses with overlapping clinical features.,Both conditions have been increasingly studied using electronic health records (EHR).,Asthma-COPD overlap syndrome (ACOS) is an emerging concept where clinical features from both conditions co-exist, and for which, however, there is no consensus definition.,Nonetheless, we expect EHR data of people with ACOS to be systematically different from those with “asthma only” or “COPD only”.,We aim to develop a latent class model to understand the overlap between asthma and COPD in EHR data.,From the Secure Anonymised Information Linkage (SAIL) databank, we will use routinely collected primary care data recorded in or before 2014 in Wales for people who aged 40 years or more on 1st Jan 2014.,Based on this latent class model, we will train a classification algorithm and compare its performance with commonly used objective and self-reported case definitions for asthma and COPD.,The resulting classification algorithm is intended to be used to identify people with ACOS, ‘asthma only’, and ‘COPD only’ in primary care datasets. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality.,COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation.,They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation.,Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations.,Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations.,Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials.,The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD. | Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences.,Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT®], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.,Patients with ≥1 exacerbation were analyzed.,NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation.,NRSAEs were classified by diagnostic terms and organ classes.,Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.,A total of 3,960 patients had an exacerbation.,The mean age was 65 years, forced expiratory volume in 1 s (FEV1) was 38% predicted, and 74% were men.,For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33).,The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87).,The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal.,All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.,The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature. | 1 |
Acupuncture has been suggested to treat chronic obstructive pulmonary disease (COPD) in China.,However, current evidence is insufficient to draw a firm conclusion regarding the effectiveness of acupuncture in COPD.,Therefore, this multicenter, randomized, sham-controlled study was designed to evaluate the efficacy of acupuncture for treating patients with COPD.,This is a two-arm, parallel group, multicenter, randomized, sham-controlled trial with concealed allocation, and participants, assessor, and analyst blinding.,Seventy-two participants with COPD were recruited and randomly divided into 2 groups (real acupuncture group and sham acupuncture group) in a 1:1 ratio.,Patients received either real or sham needling at the same acupoints 3 times weekly for 8 weeks.,The primary outcome was dyspnea on exertion evaluated using the 6-minute walk test.,In addition, health-related quality of life was also evaluated.,Measurements were obtained at baseline and after 8 weeks of treatment.,Six-minute walking distance measurements and health-related quality of life were significantly better in the real acupuncture group than that in the sham acupuncture group.,The findings suggest that acupuncture can be used as an adjunctive therapy to reduce dyspnea in patients with COPD. | 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 |
This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung hyperinflation, and physical activity.,In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe airflow limitation received aclidinium 400 μg twice daily or placebo via Genuair®/Pressair®a for 3 weeks (2-week washout between treatment periods).,The primary endpoint was change from baseline to Week 3 in endurance time, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate.,Changes from baseline in intensity of exertional dyspnea (Borg CR10 Scale®) and trough inspiratory capacity were secondary endpoints.,Additional endpoints included changes from baseline in other spirometric, plethysmographic, and physical activity (assessed by objective accelerometer measurement) parameters.,Efficacy endpoints were analyzed using an analysis of covariance model.,In total, 112 patients were randomized and treated (mean age 60.3 years; mean post-bronchodilator forced expiratory volume in 1 s 1.7 L [56.7% predicted]; mean endurance time 485.7 s).,After 3 weeks, endurance time was significantly increased with aclidinium versus placebo (treatment difference 58.5 s; p < 0.05).,At Week 3, aclidinium significantly reduced dyspnea intensity at isotime during exercise (treatment difference -0.63; p < 0.05) and improved trough inspiratory capacity (treatment difference 78 mL; p < 0.05) versus placebo.,Significant improvements in spirometric, plethysmographic, and some physical activity parameters were observed with aclidinium versus placebo.,These results suggest that aclidinium significantly improves exercise endurance, exertional dyspnea, hyperinflation, and physical activity in patients with COPD.,ClinicalTrials.gov identifier: NCT01471171; URL: http://www.clinicaltrials.gov.,The online version of this article (doi:10.1186/1471-2466-14-209) contains supplementary material, which is available to authorized users. | The current mainstay of therapy for chronic obstructive pulmonary disease (COPD) is long-acting bronchodilators.,To date, the effect of indacaterol, a β2-agonist, on activities of daily living in COPD patients is not well understood.,The aim of this study was to evaluate the efficacy of indacaterol with regard to activities of daily living in patients with COPD.,In this nonrandomized open-label study, 23 patients with COPD were instructed to carry an accelerometer for 4 weeks without indacaterol therapy and then for another period of 4 weeks while receiving indacaterol therapy.,The number of steps, duration of moderate or greater physical activity, and energy expenditure were significantly increased after treatment with indacaterol compared with baseline data in all patients with COPD; the metabolic equivalent of task was also significantly enhanced after treatment with indacaterol.,This study provides early evidence that indacaterol improves daily physical activity in patients with COPD. | 1 |
Pneumonia poses a significant risk in patients with moderate to severe chronic obstructive pulmonary disease but data are limited on the disease phenotypes most susceptible to pneumonia.,Cluster analysis using a data-driven recursive partitioning algorithm was employed using baseline data from two pooled one-year randomized exacerbation trials (n=3,255) of fluticasone furoate/vilanterol or vilanterol alone to identify distinct patient groups at greatest risk of pneumonia or serious (hospitalization or death) pneumonia.,Five clusters were identified.,Patients at greater risk of first pneumonia had more severe obstruction (forced expiratory volume in one second/forced vital capacity <46%) and either a body mass index <19 kg/m2 (hazard ratio 7.8, 95% confidence interval 4.7-13.0; n=144) or a pneumonia history and greater comorbidities (hazard ratio 4.8, 95% confidence interval 3.0-7.7; n=374) relative to the cluster with the lowest pneumonia risk (reference; n=1310).,Multiple comorbidities and use of psychoanaleptics also contributed to an increased risk of pneumonia in more obstructed patients.,Independent of cluster, use of inhaled corticosteroids was associated with pneumonia (hazard ratio 1.89, 95% confidence interval 1.25-2.84) and serious pneumonia (hazard ratio 2.92, 95% confidence interval 1.40-6.01).,Cluster analysis can identify patient populations at risk for serious safety outcomes and inform risk management strategies to optimize patient management.,The greatest risk for pneumonia was in subjects with multiple pneumonia risk factors. | The relationship between prior health care utilization and respiratory medication prescriptions in an unselected population of patients with COPD is not known.,We determined the prescribed respiratory medications and respiratory and nonrespiratory health care encounters in 523 Veterans with COPD at the Cincinnati Veterans Affairs Medical Center between 2000 and 2005.,Prescribed treatments were compared with the GOLD guidelines and each patient was classified as receiving less medications than recommended in the guidelines (<G), medications according to the guidelines (=G), or more medications than recommended (>G).,Respiratory medications were <G for 54%, =G in 33%, and >G for 14% of the patients studied.,For GOLD stages 1 and 2, <G patients had the fewest and >G patients the most prior respiratory encounters during a 12 month period (0.31 ± 0.073 (0.21, 0.47), 0.75 ± 0.5 (0.37, 1.5), 1.1 ± 0.27 (0.74, 1.6) visits/person/year, <G, =G, >G, respectively, mean + standard error of mean (SEM) (95% confidence limits) 2 degrees of freedom (df) ANOVA P < 0.001 for prescription effect).,For GOLD stages 3 and 4, <G was associated with significantly fewer prior respiratory visits than was =G (0.78 ± 0.11 (0.6, 1.0) and 2.4 ± 0.47 (1.9, 3.1) visits/person/year, respectively, P < 0.001).,There were no differences in nonrespiratory health care visits for GOLD stages 1 and 2 by prescription level (3.1 ± 0.24 (2.6, 3.5), 3.1 ± 0.46 (2.1, 4.6) and 4.1 ± 0.55 (3.3, 5.1) visits/person/year, <G, =G, >G respectively, 2 df ANOVA P = 0.096) or for GOLD stages 3 and 4 (3.6 ± 0.25 (3.2, 4.1) and 4.0 ± 0.44 (3.3, 4.9) visits/person/year, <G and =G, respectively, P = 0.36).,Respiratory medications prescribed for an unselected population with a broad range of COPD severity complied poorly with the GOLD pharmacologic treatment guidelines but correlated with the number of prior respiratory health care visits. | 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. | Being overweight or obese is associated with a higher rate of survival in patients with advanced chronic obstructive pulmonary disease (COPD).,This paradoxical relationship indicates that the influence of nutritional status on functional parameters should be further investigated.,To investigate the impact of nutritional status on body composition, exercise capacity and respiratory muscle strength in severe chronic obstructive pulmonary disease patients.,Thirty-two patients (nine women) were divided into three groups according to their body mass indices (BMI): overweight/obese (25 ≤ BMI ≤ 34.9 kg/m2, n=8), normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2, n=17) and underweight (BMI <18.5 kg/m2, n=7).,Spirometry, bioelectrical impedance, a six-minute walking distance test and maximal inspiratory and expiratory pressures were assessed.,Airway obstruction was similar among the groups (p=0.30); however, overweight/obese patients had a higher fat-free mass (FFM) index [FFMI=FFM/body weight2 (mean±SEM: 17±0.3 vs.,15±0.3 vs.,14±0.5 m/kg2, p<0.01)], exercise capacity (90±8 vs. 79±6 vs. 57±8 m, p=0.02) and maximal inspiratory pressure (63±7 vs. 57±5 vs. 35±8 % predicted, p=0.03) in comparison to normal weight and underweight patients, respectively.,In addition, on backward multiple regression analysis, FFMI was the unique independent predictor of exercise capacity (partial r=0.52, p<0.01).,Severe chronic obstructive pulmonary disease (COPD) patients who were overweight or obese had a greater FFM, exercise capacity and inspiratory muscle strength than patients with the same degree of airflow obstruction who were of normal weight or underweight, and higher FFM was independently associated with higher exercise capacity.,These characteristics of overweight or obese patients might counteract the drawbacks of excess weight and lead to an improved prognosis in COPD. | 1 |
Evidence suggests that there is an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD).,An important etiological link between COPD and CHD may be an underlying systemic inflammatory process.,Given that COPD patients are at greater risk of cardiovascular mortality, understanding the burden of CHD on COPD patients could permit future risk attenuation.,Longitudinal cohort analyses of the Third National Health and Nutrition Examination Survey from 1988-1994 were performed. 3,681 individuals ≥40 years of age with good quality spirometry data were included.,Participants were divided into 5 groups: 1) no COPD, no CHD; 2) COPD without inflammation, no CHD; 3) COPD with inflammation, no CHD; 4) CHD only, and 5) CHD + COPD.,A novel “inflammatory” COPD designation included those with COPD and clinical evidence of inflammation (i.e., CRP ≥95.24 nmol/L).,The risk for CHD mortality was significant only for the CHD group (HR 5.56, 95% CI 3.24-9.55) and the COPD + CHD group (HR 5.02, 95% CI 2.83-8.90).,Similarly, the risk for cardiovascular disease (CVD) mortality was significant only for the CHD group (HR 4.25, 95% CI 2.70-6.69) and the CHD + COPD group (HR 4.12, 95% CI 2.60-6.54) after adjusting for nonmodifiable CHD risk factors (age, gender, race/ethnicity, family history of CHD).,After adjusting for modifiable CHD risk factors (diabetes, BMI, physical activity, systolic blood pressure, cholesterol, and smoking), hazard ratios of the two groups remained similar but attenuated.,For total mortality, the risk was significant for the four groups: the non-inflammatory COPD group; the COPD with inflammation group, the CHD group, and the COPD + CHD group.,Our study did not confirm that inflammatory COPD may be a CHD risk equivalent.,However, due to the small size of the “inflammatory” COPD group, further prospective replication and validation is needed.,Moreover, given that COPD results from inflammation, the systemic inflammation associated with COPD may have worsened comorbid conditions and may have lead to the increased total mortality found in the COPD with inflammation and COPD + CHD groups which requires further investigation. | Cardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge.,The factors associated with cTnT elevation in COPD are not known.,From our hospital's database, all patients admitted with COPD exacerbation in 2000-03 were identified. 441 had measurement of cTnT performed.,Levels of cTnT ≥ 0.04 μg/l were considered elevated.,Clinical and historical data were retrieved from patient records, hospital and laboratory databases.,Odds ratios for cTnT elevation were calculated using logistic regression.,120 patients (27%) had elevated cTnT levels.,The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration.,The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20-1.94) for a 5 × 106/ml increase in neutrophils, 1.21 (1.12-1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69-0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09-1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15-1.82) for a 10 point increase in CIIS.,Multiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD.,The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury. | 1 |
C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial.,Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations.,A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year.,Episodes of exacerbations meeting Anthonisen’s criteria type I-II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood.,A total of 380 episodes were recorded.,Full microbiological analysis was available in 265 samples.,Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus.,Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0-28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6-79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8-93.7) (P<0.014).,H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9-167.9) and 74.1 mg/L (IQR 42.0-220.7), respectively.,In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission.,In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46-4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12-8.44) were independent predictors after adjustment for baseline characteristics.,CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated.,CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission.,Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease. | Chronic Obstructive Pulmonary Disease (COPD) influences different aspects of patient’s health-related quality of life (HRQL).,While disease-specific HRQL instruments focus on symptoms and functional impairments, generic instruments cover a broader view on health.,This study compares the generic EQ-5D-3 L and two disease-specific questionnaires (St.-George’s Respiratory Questionnaire (SGRQ-C), COPD Assessment Test (CAT)) in a comprehensive spectrum of COPD disease grades with particular attention on comorbidities and assesses the discriminative abilities of these instruments.,Using data from the baseline visit of the German COPD cohort COSYCONET, mean HRQL scores in different COPD grades were compared by linear regression models adjusting for age, sex, education, smoking status, BMI, and low vs. high number of comorbidities or a list of several self-reported comorbid conditions.,Discriminative abilities of HRQL instruments to differentiate between COPD grades were assessed by standardized mean differences.,In 2,291 subjects in COPD GOLD grades 1-4 EQ-5D-3 L utility, EQ-5D VAS, SGRQ, and CAT were found able to discriminate between COPD grades, with some limitations for the EQ-5D utility in mild disease.,Both generic and disease-specific HRQL instruments reflected the burden of comorbid conditions.,The SGRQ showed the best discrimination between COPD grades and was less influenced by comorbidities, while EQ-5D utility put a higher weight on comorbid conditions.,For all instruments, psychiatric disorders and peripheral artery disease showed the strongest negative associations with HRQL.,All HRQL instruments considered reflect considerable impairment of HRQL in COPD patients, worsening with increasing COPD grade and number of comorbidities.,Findings may support clinical assessment, choice of HRQL instrument in future studies, and parameterization of decision-analytic models.,The online version of this article (doi:10.1186/s12890-016-0238-9) contains supplementary material, which is available to authorized users. | 1 |
It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD).,The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD.,National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008.,Comorbidities were obtained from the Swedish Hospital Discharge Register.,Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion.,The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, PaO2 breathing air, FEV1, smoking history and year of inclusion.,In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period.,No patient was lost to follow-up.,Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios).,Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes.,Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68-0.77; P<0.001).,Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD. | Severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is a common reason for emergency room (ER) visit about which little has been documented from India.,Prospective study of the clinical presentation and predictors of outcome in 116 patients presenting with severe AE-COPD requiring admission to the medical intensive care unit between January 2000 and December 2004.,Their mean age was 62.1 ± 9.8 years.,There were 102 males.,Mean duration of COPD was 7.2 ± 5.8 years.,All males were smokers (22.3 ± 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis.,All women were exposed to domestic fuel.,Associated co-morbid illnesses were present in 81 patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28 (54.3%) had two or more co-morbid illnesses.,Evidence of past pulmonary tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II diabetes mellitus had active PTB.,Arterial blood gas analysis revealed respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%).,Invasive mechanical ventilation was required in 18 patients.,Sixteen (13.7%) patients died.,Stepwise multivariate logistic regression analysis revealed need for invasive ventilation (OR 45.809, 95%CI 607.46 to 3.009;p < 0.001); presence of co-morbid illness (OR 0.126, 95%CI 0.428 to 0.037;p < 0.01) and hypercapnia (OR 0.114, 95%CI 1.324 to 0.010;p < 0.05) were predictors of death.,Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD difficult and also contribute to mortality.,High prevalence of past PTB and active PTB in patients with AE-COPD suggests an intriguing relationship between smoking, PTB and COPD which merits further study. | 1 |
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems.,Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.,Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency.,Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database.,Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.,Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001).,The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs.,Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6).,Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.,Comorbidity burden determines elevated utilization for COPD patients.,Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients. | 1 |
Low 25-hydroxyvitamin D (25[OH]D) levels, commonly observed in chronic obstructive pulmonary disease (COPD), are associated with muscle weakness in elderly populations, and vitamin D supplementation appears to improve muscle strength and decrease falls in older individuals.,We tested the effect of vitamin D supplementation on physical performance in patients with COPD.,Patients were randomized to daily cholecalciferol (2000 IU) or placebo for 6 weeks.,The primary outcome was the 6-week change in Short Physical Performance Battery (SPPB) score.,Secondary outcomes included changes in the St George’s Respiratory Questionnaire (SGRQ) score, and serum 25(OH)D.,Thirty-six participants (mean age 68 years, all Caucasian males, mean forced expiratory volume in one second 33% of predicted) completed the study.,Despite an increase in 25(OH)D levels in the intervention arm to a mean of 32.6 ng/mL (versus 22.1 ng/mL in the placebo arm), there was no difference in improvements in either SPPB scores (0.3 point difference; 95% confidence interval −0.8 to 1.5; P = 0.56) or SGRQ scores (2.3 point difference; 95% confidence interval −2.3 to 6.9; P = 0.32).,Among patients with severe COPD, 2000 IU of daily vitamin D for 6 weeks increased 25(OH)D to a level widely considered as normal.,However, compared with placebo, short-term vitamin D supplementation had no discernible effect on a simple measure of physical performance. | COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported.,Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40-76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls.,Levels <20 ng/mL defined deficiency.,Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models.,COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI.,Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29).,Summertime decreased the risk of vitamin D deficiency (OR = 0.22).,COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels. | 1 |
Coronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020.,No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.,We systematically searched electronic databases from inception to March 24, 2020.,Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.,Study quality was assessed using a modified version of the Newcastle-Ottawa Scale.,We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).,In total, 123 abstracts were screened and 61 full-text manuscripts were reviewed.,A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients.,All studies were included in the meta-analysis.,The crude case fatality rate of COVID-19 was 7.4%.,The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively.,COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)].,This was associated with higher mortality (60%).,Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications.,The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers.,Current smokers also had a higher mortality rate of 38.5%.,Although COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD.,Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate.,Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers. | Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD).,However, little is known about viral etiology related to AECOPD in Asia.,We aimed to study the viral etiology of AECOPD in Hong Kong.,Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005.,Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture.,Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge.,There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 ± 7.7 years [± SD]; 160 men).,Mean FEV1 was 39.6 ± 18.9% of predicted normal, and FEV1/FVC ratio was 58.0 ± 15.2%.,Fifty-eight episodes (22.1%) yielded positive viral PCR results.,The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%).,The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture.,The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV1 ≥ 50%, ≥ 30 to 50%, and < 30% of predicted normal.,Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year,Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong.,These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD. | 1 |
Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined.,This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype.,A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited.,Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]).,The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions.,A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included.,In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations.,Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%).,Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006).,The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001).,Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001).,One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease.,The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment. | Mortality due to chronic obstructive pulmonary disease continues to rise, whereas mortality rates related to cardiovascular disease appear to be slowing, or even declining.,This is due at least in part to more widespread use of preventative therapies that have been shown to reduce cardiovascular mortality, raising the question of whether appropriate use of therapies for chronic obstructive pulmonary disease which potentially reduce mortality could have a similar impact.,This article discusses approaches used successfully in managing heart disease and considers whether these can be applied to chronic obstructive pulmonary disease and whether a better understanding of the strongest predictors of mortality in chronic obstructive pulmonary disease is needed.,It reviews the role of inhaled corticosteroids, both alone and in combination with long-acting β2-agonists, in individuals with chronic obstructive pulmonary disease, including the role of combination therapy with inhaled corticosteroids/long-acting β2-agonists (budesonide/formoterol or salmeterol/fluticasone propionate) in decreasing exacerbations and improving health status, potentially providing survival benefits in chronic obstructive pulmonary disease.,This review also discusses the potential impact of treatments indicated for cardiovascular disease on chronic obstructive pulmonary disease and possible links between the two diseases. | 1 |
The 2018 Global Initiative for Chronic Obstructive Lung Disease Report reveals that the blood eosinophil count could forecast the risk of flare-ups.,This study explored the correlations of blood eosinophils with fractional exhaled nitric oxide (FeNO) and pulmonary function parameters in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,The data of patients with AECOPD at our hospital admitted between July 2018 and June 2019 were retrospectively analyzed.,All patients were stratified into an eosinophilic group (≥2%) or a noneosinophilic group (<2%) based on the peripheral eosinophil count per centum.,Cross-sectional analysis was performed to compare clinical characteristics, percentage of eosinophils, FeNO, and pulmonary function between the 2 groups.,After applying the inclusion/exclusion criteria, 247 patients were included.,FeNO values were higher in eosinophilic group (n=97) than in noneosinophilic group (n=150) (P=0.005).,The forced expiratory volume in 1 second% predicted (FEV1% predicted), FEV1, and forced vital capacity (FVC) were higher in the eosinophilic group than in the noneosinophilic group (P=0.043; P=0.040; and P=0.011, respectively).,Blood eosinophilia showed positive correlations with FeNO (P=0.004) and spirometry variables (FEV1 [% predicted], P=0.003; FEV1, P<0.001; and FVC, P<0.001).,An FeNO level of 22.5 ppb was the best cutoff value to predict blood eosinophilia (P=0.000).,Blood eosinophil count is a likely biomarker that can predict positive relationship with FeNO values and pulmonary function parameters. | Chronic obstructive pulmonary disease (COPD) patients may experience an acute exacerbation (AECOPD) that requires hospitalisation.,The length of hospital stay (LHS) has a great economic impact on the health-care system.,Knowing the predictors of prolonged LHS could help to identify possible interventions.,We performed a prospective study to identify the clinical predictors of prolonged LHS in patients hospitalised for AECOPD.,We divided the study sample by LHS into normal (≤7 days) and prolonged LHS (> 7 days) groups.,Outcomes were the need for non-invasive and invasive mechanical ventilation (NIMV and IMV), intensive care unit (ICU) admission, and the 3-year mortality.,We enrolled 437 patients, of which 213 and 224 had normal LHS and prolonged LHS, respectively.,Patients with a prolonged LHS had more prior hospitalisations for AECOPD, a worse mMRC (modified Medical Research Council) dyspnoea score, a higher prevalence of long-term oxygen therapy and a higher rate of congestive heart disease.,During the current admission, this group also tended to require NIMV, IMV and ICU admission and the mortality risks at 6 months, 1 year and 3 years were higher.,In the multivariate regression analysis, an mMRC dyspnoea score ≥ 2 (odds ratio-OR 2.24; 95% confidence interval-CI 1.34 to 3.74; p = 0.002) and the presence of acute respiratory acidosis (OR 2.75; 95% CI 1.49 to 5.05; p = 0.001) predicted a prolonged LHS at admission.,The presence of an mMRC ≥2 and acute respiratory acidosis at admission independently increased the risk of a prolonged LHS for AECOPD. | 1 |
Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease.,Epithelial mesenchymal transition (EMT) has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant.,In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL) and what type of EMT is present on the basis of vascularity.,We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker) and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls.,Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker), vimentin (mesenchymal marker), and S100A4 (fibroblast epitope).,Type-IV collagen was stained to demonstrate vessels.,There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P<0.001), vimentin (P<0.001), S100A4 (P<0.001), and fragmentation (P<0.001), but this was less than that in large airways.,Notably, there was no hypervascularity in small airway reticular basement membrane as in large airways.,Epithelial activation and S100A4 expression were related to airflow obstruction.,EMT is active in small airways, but less so than in large airways in CAL, and may be relevant to the key pathologies of chronic obstructive pulmonary disease, small airway fibrosis, and airway cancers. | 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 |
Our starting point is that relatively new findings into the pathogenesis and pathophysiology of airway disease in smokers that lead to chronic obstructive pulmonary disease (COPD) need to be reassessed as a whole and integrated into “mainstream” thinking along with traditional concepts which have stood the test of time.,Such a refining of the accepted disease paradigm is urgently needed as thinking on therapeutic targets is currently under active reconsideration.,We feel that generalised airway wall “inflammation” is unduly over-emphasised, and highlight the patchy and variable nature of the pathology (with the core being airway remodelling).,In addition, we present evidence for airway wall disease in smokers/COPD as including a hypocellular, hypovascular, destructive, fibrotic pathology, with a likely spectrum of epithelial-mesenchymal transition states as significant drivers of this remodelling.,Furthermore, we present data from a number of research modalities and integrate this with the aetiology of lung cancer, the role of chronic airway luminal colonisation/infection by a specific group of “respiratory” bacteria in smokers (which results in luminal inflammation) and the central role for oxidative stress on the epithelium.,We suggest translation of these insights into more focus on asymptomatic smokers and early COPD, with the potential for fresh preventive and therapeutic approaches.,We discuss the pathogenesis and pathophysiology of COPD, emphasising their need to be reassessed as a whole and integrated with traditional concepts to refine the disease paradigm.,This is urgently needed to open-up thinking about therapeutic targets.https://bit.ly/3pTyrsi | Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease.,Epithelial mesenchymal transition (EMT) has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant.,In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL) and what type of EMT is present on the basis of vascularity.,We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker) and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls.,Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker), vimentin (mesenchymal marker), and S100A4 (fibroblast epitope).,Type-IV collagen was stained to demonstrate vessels.,There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P<0.001), vimentin (P<0.001), S100A4 (P<0.001), and fragmentation (P<0.001), but this was less than that in large airways.,Notably, there was no hypervascularity in small airway reticular basement membrane as in large airways.,Epithelial activation and S100A4 expression were related to airflow obstruction.,EMT is active in small airways, but less so than in large airways in CAL, and may be relevant to the key pathologies of chronic obstructive pulmonary disease, small airway fibrosis, and airway cancers. | 1 |
Asthma-COPD overlap (ACO) is difficult to diagnose because it is characterized by persistent airflow limitation, and patients present with several manifestations that are usually associated with both asthma and COPD.,In this retrospective study, we aimed to evaluate the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and blood eosinophil counts for the clinical diagnosis of ACO.,A total of 121 patients were divided into two study groups, COPD alone or ACO, which was based on criteria from the joint document by the Global Initiative for Asthma and the Global initiative for chronic Obstructive Lung Disease.,From July 2014 to April 2017, FeNO levels and blood eosinophil counts were measured in specimens from patients naïve to inhaled corticosteroids (ICS) and those using ICS.,Receiver operating characteristic curve analysis was used to determine the cutoff values of FeNO and blood eosinophil levels that provided the best differential diagnosis between ACO and COPD.,Among a total of 121 patients, 65 patients were diagnosed with COPD and 56 patients with ACO.,The FeNO level was higher in patients with ACO than in patients with COPD (median 24.5 vs 16.0 ppb, respectively; P<0.01).,Among patients naïve to ICS, the area under the receiver operating characteristic curve of FeNO values was 0.726, and the optimal diagnostic cutoff level of FeNO was 25.0 ppb, with 60.6% sensitivity and 87.7% specificity for differentiating ACO from COPD.,FeNO (≥25.0 ppb) combined with blood eosinophil counts (≥250/μL) showed 96.1% specificity.,These results demonstrate that the FeNO level combined with blood eosinophil count is useful for the differential diagnosis between ACO and COPD. | Fractional exhaled nitric oxide (FeNO) is an easy, sensitive, reproducible, and noninvasive marker of eosinophilic airway inflammation.,Accordingly, FeNO is extensively used to diagnose and manage asthma.,Patients with COPD who share some of the features of asthma have a condition called asthma-COPD overlap syndrome (ACOS).,The feasibility of using FeNO to differentiate ACOS patients from asthma and COPD patients remains unclear.,From February 2013 to May 2016, patients suspected with asthma and COPD through physician’s opinion were subjected to FeNO measurement, pulmonary function test (PFT), and bronchial hyperresponsiveness or bronchodilator test.,Patients were divided into asthma alone group, COPD alone group, and ACOS group according to a clinical history, PFT values, and bronchial hyperresponsiveness or bronchodilator test.,Receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in diagnosing ACOS.,The optimal operating point was also determined.,A total of 689 patients were enrolled in this study: 500 had asthma, 132 had COPD, and 57 had ACOS.,The FeNO value in patients with ACOS was 27 (21.5) parts per billion (ppb; median [interquartile range]), which was significantly higher than that in the COPD group (18 [11] ppb).,The area under the ROC curve was estimated to be 0.783 for FeNO.,Results also revealed an optimal cutoff value of >22.5 ppb FeNO for differentiating ACOS from COPD patients (sensitivity 70%, specificity 75%).,FeNO measurement is an easy, noninvasive, and sensitive method for differentiating ACOS from COPD.,This technique is a new perspective for the management of COPD patients. | 1 |
Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly.,They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD).,They should not be prescribed in mild or moderate disease.,In COPD ICS are associated with side-effects including risk of pneumonia.,We quantified appropriateness of prescribing and examined the risks and costs associated with overuse.,Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations.,We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision.,3537 patients had a diagnosis of COPD.,Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated.,Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common.,An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03).,Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated.,The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS.,Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm.,In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven. | 1 |
A multidimensional assessment of COPD was recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2013 and revised in 2017.,We examined the ability of the GOLD 2017 and the new 16 subgroup (1A-4D) classifications to predict clinical outcomes, including exacerbation and mortality, and compared them with the GOLD 2013 classifications.,Patients with COPD were recruited from January 2006 to December 2017.,The predictive abilities of grades 1-4 and groups A-D were examined through a logistic regression analysis with receiver operating curve estimations and area under the curve (AUC).,A total of 553 subjects with COPD were analyzed.,The mortality rate was 48.6% during a median follow-up period of 5.2 years.,Both the GOLD 2017 and the 2013 group A-D classifications had good predictive ability for total and severe exacerbations, for which the AUCs were 0.79 vs 0.77 and 0.79 vs 0.78, respectively.,The AUCs for the GOLD 2017 groups A-D, grades 1-4, and the GOLD 2013 group A-D classifications were 0.70, 0.66, and 0.70 for all-cause mortality and 0.73, 0.71, and 0.74 for respiratory cause mortality, respectively.,Combining the spirometric staging with the grouping for the GOLD 2017 subgroups (1A-4D), the all-cause mortality rate for group B and D patients was significantly increased from subgroups 1B-4B (27.7%, 50.6%, 53.3%, and 69.2%, respectively) and groups 1D-4D (55.0%, 68.8%, 82.1%, and 90.5%, respectively).,The AUCs of subgroups (1A-4D) were 0.73 and 0.77 for all-cause and respiratory mortality, respectively; the new classification was determined more accurate than the GOLD 2017 for predicting mortality (P<0.0001).,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor among COPD patients.,Combining the spirometric staging with the grouping increased the predictive ability for all-cause and respiratory mortality.,We validate the ability of the GOLD 2017 and 16 subgroup (1A-4D) classifications to predict clinical outcome for COPD patients.,The GOLD 2017 classification performed well by identifying individuals at risk of exacerbation, but its predictive ability for mortality was poor.,The new 16 subgroup (1A-4D) classification combining the spirometric 1-4 staging and the A-D grouping increased the predictive ability for mortality and was better than the GOLD 2017 for predicting all-cause and respiratory mortality among COPD patients. | To evaluate risk factors associated with exacerbation frequency in primary care.,Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts.,Retrospective observational cohort study.,Electronic medical records database (England and Wales).,58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink.,Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted.,Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics.,Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models.,During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none).,Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer).,Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. | 1 |
A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear.,Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable.,To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases.,We recruited 59 outpatients with MetS and 76 outpatients with COPD.,After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29).,A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%.,More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease.,MetS+COPD patients exhibited significantly higher C-peptide levels.,We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers.,Finally, a negative association emerged between smoking and vitamin D.,We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance.,Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development. | Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality.,RSV is able to evade antiviral defenses to persist in the lungs of COPD patients.,Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established.,Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice.,RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice.,This infiltration of cells was most pronounced around the vasculature and bronchial airways.,By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure.,Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression.,In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure.,RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity.,This is significant as these phosphatases counter smoke-induced inflammation and protease expression.,Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice.,Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. | 1 |
Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally.,Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments.,MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis.,Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC.,These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF).,Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD.,Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease.,Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion. | Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema.,Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses.,To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire.,In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations.,We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD.,In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences.,This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs.,This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy.,The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006.,Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period.,Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.,15857 patients were enrolled -9911 males, mean age: 76 years (SD 10).,Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%.,A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD.,On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863).,Occurrence and type of exacerbations drove the direct healthcare cost.,Less than one quarter of patients presented claims for pulmonary function tests.,COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes.,A more tailored approach to the management of COPD patients is required. | 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 |
Identifying patients at risk of exacerbations and managing them appropriately to reduce this risk represents an important clinical challenge.,Numerous treatments have been assessed for the prevention of exacerbations and their efficacy may differ by patient phenotype.,Given their centrality in the treatment of COPD, there is strong rationale for maximizing bronchodilation as an initial strategy to reduce exacerbation risk irrespective of patient phenotype.,Therefore, in patients assessed as frequent exacerbators (>1 exacerbation/year) we propose initial bronchodilator treatment with a long-acting muscarinic antagonist (LAMA)/ long-acting β2-agonist (LABA).,For those patients who continue to experience >1 exacerbation/year despite maximal bronchodilation, we advocate treating according to patient phenotype.,Based on currently available data on adding inhaled corticosteroids (ICS) to a LABA, ICS might be added to a LABA/LAMA combination in exacerbating patients who have an asthma-COPD overlap syndrome or high blood eosinophil counts, while in exacerbators with chronic bronchitis, consideration should be given to treating with a phosphodiesterase (PDE)-4 inhibitor (roflumilast) or high-dose mucolytic agents.,For those patients who experience frequent bacterial exacerbations and/or bronchiectasis, addition of mucolytic agents or a macrolide antibiotic (e.g. azithromycin) should be considered.,In all patients at risk of exacerbations, pulmonary rehabilitation should be included as part of a comprehensive management plan.,The online version of this article (doi:10.1186/s12931-016-0425-5) contains supplementary material, which is available to authorized users. | Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated.,Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture.,We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013.,The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention.,Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD.,Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy).,Severe COPD (defined as postbronchodilator FEV1 < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture.,The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up.,This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture. | 1 |
Randomized controlled trials (RCTs) indicate that long-acting bronchodilator combinations, such as β2-agonist (LABA)/muscarinic antagonist (LAMA), have favorable efficacy compared with commonly used COPD treatments.,The objective of this analysis was to compare the efficacy and safety of LABA/LAMA with LAMA or LABA/inhaled corticosteroid (ICS) in adults with stable moderate-to-very-severe COPD.,This systematic review and meta-analysis (PubMed/MEDLINE, Embase, Cochrane Library and clinical trial/manufacturer databases) included RCTs comparing ≥12 weeks’ LABA/LAMA treatment with LAMA and/or LABA/ICS (approved doses only).,Eligible studies were independently selected by two authors using predefined data fields; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.,Eighteen studies (23 trials) were eligible (N=20,185).,LABA/LAMA significantly improved trough forced expiratory volume in 1 second (FEV1) from baseline to week 12 versus both LAMA and LABA/ICS (0.07 L and 0.08 L, P<0.0001), with patients more likely to achieve clinically important improvements in FEV1 of >100 mL (risk ratio [RR]: 1.33, 95% confidence interval [CI]: [1.20, 1.46] and RR: 1.44, 95% CI: [1.33, 1.56], respectively, the number needed to treat being eight and six, respectively).,LABA/LAMA improved transitional dyspnea index and St George’s Respiratory Questionnaire scores at week 12 versus LAMA (both P<0.0001), but not versus LABA/ICS, and reduced rescue medication use versus both (P<0.0001 and P=0.001, respectively).,LABA/LAMA significantly reduced moderate/severe exacerbation rate compared with LABA/ICS (RR 0.82, 95% CI: [0.75, 0.91]).,Adverse event (AE) incidence was no different for LABA/LAMA versus LAMA treatment, but it was lower versus LABA/ICS (RR 0.94, 95% CI: [0.89, 0.99]), including a lower pneumonia risk (RR 0.59, 95% CI: [0.43, 0.81]).,LABA/LAMA presented a lower risk for withdrawals due to lack of efficacy versus LAMA (RR: 0.66, 95% CI: [0.51, 0.87]) and due to AEs versus LABA/ICS (RR: 0.83, 95% CI: [0.69, 0.99]).,The greater efficacy and comparable safety profiles observed with LABA/LAMA combinations versus LAMA or LABA/ICS support their potential role as first-line treatment options in COPD.,These findings are of direct relevance to clinical practice because we included all currently available LABA/LAMAs and comparators, only at doses approved for clinical use. | Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent.,This analysis evaluated the incremental cost-effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective.,A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) was used.,Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council ≥2).,Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials).,Spanish utility values were derived from a published local observational study.,Unitary health care costs (€2015) were obtained from local sources.,A 3-year time horizon was selected, and 3% discount was applied to effects and costs.,Results were expressed as cost/quality-adjusted life years (QALYs).,Univariate and probabilistic sensitivity analysis (PSA) was performed.,UMEC/VI produced additional 0.03 QALY and €590 vs TIO, leading to an ICER of €21,475/QALY.,According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of €30,000/QALY.,UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective. | 1 |
Chronic obstructive pulmonary disease (COPD), characterized by persistent airflow limitation, was a disease mediated by a combination of inflammatory factors, immune cells, and immune mediators.,COPD was an inflammatory and autoimmune disease involving T‐lymphocytes triggered by cigarette smoke and other factors that progressively affected the bronchi, lung parenchyma, and pulmonary blood vessels.,LncRNAs were reported to be implicated in COPD pathogenesis and development.,Non‐smokers, smokers (non‐COPD), and COPD patients were randomly selected in an established COPD surveillance cohort.,Demographic and clinical information of all subjects were collected.,Pulmonary function was measured by post‐bronchodilator testing. qRT‐PCR and ELISA assays were performed to detect the expression levels of lncRNA LUCAT1, miR‐181a‐5p, and inflammatory cytokines.,An in vitro exposure model was constructed using cigarette smoke extract (CSE)‐induced human bronchial epithelial (16HBE) cells.,The dual‐luciferase reporter and RNA pull‐down assays were used to detect the binding relationship between lncRNA LUCAT1 and miR‐181a‐5p; meanwhile, Spearman's correlation assay was used to verify the correlation between lncRNA LUCAT1 and miR‐181a‐5p.,Afterward, the lncRNA LUCAT1 silencing plasmid was constructed and co‐transfected with a miR‐181a‐5p inhibitor to evaluate the effects on CSE‐induced 16HBE cell proliferation and apoptosis.,Finally, a Western blot assay was utilized to determine the mechanism of lncRNA LUCAT1/miR‐181a‐5p/Wnt/β‐catenin axis in COPD.,LncRNA LUCAT1 was upregulated in the serums of COPD patients.,Correlation analysis further confirmed the strong correlation between LUCAT1 expression and inflammatory cytokines IL‐1β, IL‐6, and TNF‐α.,Receiver operating characteristic (ROC) analysis verified the potential of LUCAT1 in COPD diagnosis.,After treatment with CSE, LUCAT1 was significantly increased while its target miR‐181a‐5p was decreased in 16HBE cells.,Cell proliferation and apoptosis assays showed that LUCAT1 silencing alleviated CSE’s effects on 16HBE cell proliferation and apoptosis.,Mechanically, rescue assays demonstrated that miR‐181a‐5p inhibition could partially counteract the impact of LUCAT1 on COPD progression through the Wnt/β‐catenin pathway.,LncRNA LUCAT1 may be a valuable indicator for differentiating COPD.,Moreover, LncRNA LUCAT1/miR‐181‐5p/Wnt/β‐catenin axis behaved as a critical role in COPD development, shedding new sights for clinical treatment.,Chronic obstructive pulmonary disease (COPD) was a chronic, non‐homogeneous lung disease characterized by persistent excessive inflammation that led to tissue remodeling, alveolar damage, airflow limitation, and accelerated lung function decline.,The clinical manifestations of COPD include chronic cough, coughing sputum, dyspnea, and acute exacerbation in the presence of infections and other triggering factors.,Pulmonary function tests were the primary means of confirming the diagnosis of COPD (Respiratory Care, 57, 2012 and 165).,Appropriate drug therapy can effectively relieve symptoms, reduce the number and frequency of acute exacerbations, improve exercise tolerance, and improve quality of life.,Cigarette smoking was a significant risk factor for COPD.,Inhaled cigarette smoke first encountered respiratory epithelial cells, causing the release of pro‐inflammatory mediators such as interleukin (IL)‐1, IL‐6, and tumor necrosis factor (TNF)‐α.,Although inflammation‐based airway injury was recognized as a core feature of COPD, the underlying mechanism was unclear.,From the results, we found that lncRNA LUCAT1 was upregulated in the serums of COPD patients.,Correlation analysis further confirmed the strong correlation between LUCAT1 expression and inflammatory cytokines IL‐1β, IL‐6, and TNF‐α.,Receiver operating characteristic (ROC) analysis verified the potential of LUCAT1 in COPD diagnosis.,After treatment with CSE, LUCAT1 was significantly increased, while its target miR‐181a‐5p was decreased in 16HBE cells.,Cell proliferation and apoptosis assays showed that LUCAT1 silencing alleviated CSE’s effects on 16HBE cell proliferation and apoptosis.,Mechanically, rescue assays demonstrated that miR‐181a‐5p inhibition could partially counteract the impact of LUCAT1 on COPD progression through the Wnt/β‐catenin pathway.,In sum, lncRNA LUCAT1 may be a valuable indicator for differentiating COPD.,Moreover, lncRNA LUCAT1/miR‐181‐5p/Wnt/β‐catenin axis behaved as a critical role in COPD development, shedding new sights for clinical treatment. | COPD has complex etiologies involving both genetic and environmental determinants.,Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD).,Nonetheless, AATD patients present a heterogeneous clinical evolution, which has not been completely explained by sociodemographic or clinical factors.,Here we performed the gene expression profiling of blood cells collected from mild and severe COPD patients with PiZZ AATD.,Our aim was to identify differences in messenger RNA (mRNA) and microRNA (miRNA) expressions that may be associated with disease severity.,Peripheral blood mononuclear cells from 12 COPD patients with PiZZ AATD (6 with severe disease and 6 with mild disease) were used in this pilot, high-throughput microarray study.,We compared the cellular expression levels of RNA and miRNA of the 2 groups, and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms.,We also integrated the miRNA and the differentially expressed putative target mRNA.,For data analyses, we used the R statistical language R Studio (version 3.2.5).,The severe and mild COPD-AATD groups were similar in terms of age, gender, exacerbations, comorbidities, and use of augmentation therapy.,In severe COPD-AATD patients, we found 205 differentially expressed genes (DEGs) (114 upregulated and 91 downregulated) and 28 miRNA (20 upregulated and 8 downregulated) compared to patients with mild COPD-AATD disease.,Of these, hsa-miR-335-5p was downregulated and 12 target genes were involved in cytokine signaling, MAPK/mk2, JNK signaling cascades, and angiogenesis were much more highly expressed in severe compared with mild patients.,Despite the small sample size, we identified downregulated miRNA (hsa-miR-335) and the activation of pathways related to inflammation and angiogenesis on comparing patients with severe vs mild COPD-AATD.,Nonetheless, our findings warrant further validation in large studies. | 1 |
Exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by acute enhancement of airway neutrophilic inflammation under oxidative stress and can be involved in emphysema progression.,However, pharmacotherapy against the neutrophilic inflammation and emphysema progression associated with exacerbation has not been established.,Thioredoxin-1 has anti-oxidative and anti-inflammatory properties and it can ameliorate neutrophilic inflammation through anti-chemotactic effects and prevent cigarette smoke (CS)-induced emphysema.,We aimed to determine whether thioredoxin-1 can suppress neutrophilic inflammation and emphysema progression in a mouse model of COPD exacerbation and if so, to reveal the underlying mechanisms.,Mice were exposed to CS and then challenged with polyinosine-polycytidylic acid [poly(I:C)], an agonist for virus-induced innate immunity.,Airway neutrophilic inflammation, oxidative stress and lung apoptosis were enhanced in smoke-sensitive C57Bl/6, but not in smoke-resistant NZW mice.,Exposure to CS and poly(I:C) challenge accelerated emphysema progression in C57Bl/6 mice.,Thioredoxin-1 suppressed neutrophilic inflammation and emphysema progression.,Poly(I:C) caused early neutrophilic inflammation through keratinocyte-derived chemokine and granulocyte-macrophage colony-stimulating factor (GM-CSF) release in the lung exposed to CS.,Late neutrophilic inflammation was caused by persistent GM-CSF release, which thioredoxin-1 ameliorated.,Thioredoxin-1 enhanced pulmonary mRNA expression of MAP kinase phosphatase 1 (MKP-1), and the suppressive effects of thioredoxin-1 on prolonged GM-CSF release and late neutrophilic inflammation disappeared by inhibiting MKP-1.,Using a mouse model of COPD exacerbation, we demonstrated that thioredoxin-1 ameliorated neutrophilic inflammation by suppressing GM-CSF release, which prevented emphysema progression.,Our findings deepen understanding of the mechanisms underlying the regulation of neutrophilic inflammation by thioredoxin-1 and indicate that thioredoxin-1 could have potential as a drug to counteract COPD exacerbation. | Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain.,This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.,Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects.,In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.,Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort.,Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects.,In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups.,Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.,MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression.,Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. | 1 |
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. | Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject. | 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. | Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in patients with chronic obstructive pulmonary disease (COPD).,It is unclear whether the risk of pneumonia varies for different inhaled agents, particularly fluticasone and budesonide, and increases with the dose and long-term duration of use.,We formed a new-user cohort of patients with COPD treated during 1990-2005.,Subjects were identified using the Quebec health insurance databases and followed through 2007 or until a serious pneumonia event, defined as a first hospitalisation for or death from pneumonia.,A nested case-control analysis was used to estimate the rate ratio (RR) of serious pneumonia associated with current ICS use, adjusted for age, sex, respiratory disease severity and comorbidity.,The cohort included 163 514 patients, of which 20 344 had a serious pneumonia event during the 5.4 years of follow-up (incidence rate 2.4/100/year).,Current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63 to 1.75).,The risk was sustained with long-term use and declined gradually after stopping ICS use, disappearing after 6 months (RR 1.08; 95% CI 0.99 to 1.17).,The rate of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93 to 2.10), increasing with the daily dose, but was much lower with budesonide (RR 1.17; 95% CI 1.09 to 1.26).,ICS use by patients with COPD increases the risk of serious pneumonia.,The risk is particularly elevated and dose related with fluticasone.,While residual confounding cannot be ruled out, the results are consistent with those from recent randomised trials. | 1 |
Asthma-COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease.,However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized.,To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected.,This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma.,The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS.,Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135).,The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves.,Only sputum NGAL levels could differentiate ACOS from asthma (P<0.001 and P<0.001) and COPD (P<0.05 and P=0.002) in the discovery and replication cohorts, respectively.,Sputum NGAL levels were independently correlated with the percentage of pre-bronchodilator forced expiratory volume in 1 second predicted in multivariate analysis in the discovery and replication cohorts (P=0.001 and P=0.002, respectively).,In conclusion, sputum biomarkers reflecting both airway inflammation and remodeling of the tissue show potential in differentiation between asthma, COPD, and ACOS. | The diagnostic criteria of asthma-COPD overlap syndrome (ACOS) are controversial.,Emphysema is characteristic of COPD and usually does not exist in typical asthma patients.,Emphysema in patients with asthma suggests the coexistence of COPD.,Quantitative computed tomography (CT) allows repeated evaluation of emphysema noninvasively.,We investigated the value of quantitative CT measurements of emphysema in the diagnosis of ACOS.,This study included 404 participants; 151 asthma patients, 125 COPD patients, and 128 normal control subjects.,All the participants underwent pulmonary function tests and a high-resolution CT scan.,Emphysema measurements were taken with an Airway Inspector software.,The asthma patients were divided into high and low emphysema index (EI) groups based on the percentage of low attenuation areas less than −950 Hounsfield units.,The characteristics of asthma patients with high EI were compared with those having low EI or COPD.,The normal value of percentage of low attenuation areas less than −950 Hounsfield units in Chinese aged >40 years was 2.79%±2.37%.,COPD patients indicated more severe emphysema and more upper-zone-predominant distribution of emphysema than asthma patients or controls.,Thirty-two (21.2%) of the 151 asthma patients had high EI.,Compared with asthma patients with low EI, those with high EI were significantly older, more likely to be male, had more pack-years of smoking, had more upper-zone-predominant distribution of emphysema, and had greater airflow limitation.,There were no significant differences in sex ratios, pack-years of smoking, airflow limitation, or emphysema distribution between asthma patients with high EI and COPD patients.,A greater number of acute exacerbations were seen in asthma patients with high EI compared with those with low EI or COPD.,Asthma patients with high EI fulfill the features of ACOS, as described in the Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines.,Quantitative CT measurements of emphysema may help in diagnosing ACOS. | 1 |
Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis.,Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group.,To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial.,343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014.,This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application.,The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators.,PA was measured using accelerometry during 1 week preceding randomisation and during week 12.,Secondary outcomes included exercise capacity and health status.,Analyses were based on modified intention to treat.,Both groups were comparable at baseline in terms of factors influencing PA.,At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit - upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001).,The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG.,In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG.,Other health status outcomes did not differ.,The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone.,NCT02158065. | The effectiveness of clinic-based pulmonary rehabilitation in advanced COPD is well established, but few data exist for less severe patients treated in alternative settings.,The purpose of this study was to investigate whether a novel, community-based exercise program (CBE) was feasible and effective for patients with moderate COPD.,Nineteen patients with moderate COPD (mean FEV1 62%) and self-reported exercise impairment were randomized to 12-weeks of progressive endurance and strength training at a local health club under the guidance of a certified personal trainer, or to continuation of unsupervised habitual physical activity.,Outcomes assessed at baseline and 12 weeks included session compliance, intensity adherence, treadmill endurance time, muscle strength, dyspnea, and health status.,Compliance was 94% and adherence was 83%.,Comparisons between CBE and control groups yielded the following mean (SEM) differences in favor of CBE: endurance time 134 (74) seconds versus -59 (49) seconds (P = 0.041) and TDI 5.1 (0.8) versus -0.2 (0.5) (P < 0.001).,The CBE group increased muscle strength (weight lifted) by 11.8 kilograms per subject per week of training (P < 0.001).,SGRQ was not significantly changed.,We demonstrated the feasibility and effectiveness of a novel community-based exercise program involving health clubs and personal trainers for patients with moderate COPD.,ClinicalTrials.gov Identifier NCT01985529. | 1 |
Telemonitoring (TM) of patients with COPD has gained much interest, but studies have produced conflicting results.,We aimed to investigate the effect of TM with the option of video consultations on quality of life (QoL) in patients with severe COPD.,COPD patients at high risk of exacerbations were eligible for the 6-month study and a total of 281 patients were equally randomized to either TM (n=141) or usual care (n=140).,TM comprised recording of symptoms, oxygen saturation, spirometry, and video consultations.,Algorithms generated alerts if readings breached thresholds.,Both groups filled in a health-related QoL questionnaire (15D©) and the COPD Assessment Test (CAT) at baseline and at 6 months.,Within-group differences were analyzed by paired t-test.,Most of the enrolled patients had severe COPD (86% with Global Initiative for Chronic Obstructive Lung Disease stage 3 or 4 and 45% with admission for COPD within the last year, respectively).,No difference in drop-out rate and mortality was found between the groups, and likewise there was no difference in 15D or CAT at baseline.,At 6 months, a significant improvement of 0.016 in 15D score (p=0.03; minimal clinically important difference 0.015) was observed in the TM group (compared to baseline), while there was no improvement in the control group −0.003 (p=0.68).,After stratifying 15D score at baseline to <0.75 or ≥0.75, respectively, there was a significant difference in the <0.75 TM group of 0.037 (p=0.001), which is a substantial improvement.,No statistically significant changes were found in CAT score.,Compared to the nonintervention group, TM as an add-on to usual care over a 6-month period improved QoL, as assessed by the 15D questionnaire, in patients with severe COPD, whereas no difference between groups was observed in CAT score. | Aims of this cross-sectional study were to assess health status and care dependency in patients with advanced chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF) and to identify correlates of an impaired health status.,The following outcomes were assessed in outpatients with advanced COPD (n = 105) or CHF (n = 80): clinical characteristics; general health status (EuroQol-5 Dimensions (EQ-5D); Assessment of Quality of Life instrument (AQoL); Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)); disease-specific health status (St.,Georges Respiratory Questionnaire (SGRQ), Minnesota Living with Heart Failure Questionnaire (MLHFQ)); physical mobility (timed ‘Up and Go’ test); and care dependency (Care Dependency Scale).,Patients with advanced COPD or CHF have an impaired health status and may be confronted with care dependency.,Multiple regression analyses have shown that physical and psychological symptoms, care dependency and number of drugs were correlated with impaired health status in advanced COPD or CHF, while demographic and clinical characteristics like age, gender, disease severity and co-morbidities were not correlated.,Clinical care should regularly assess symptom burden and care dependency to identify patients with advanced COPD or CHF at risk for an impaired health status. | 1 |
Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined.,This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype.,A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited.,Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George’s Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]).,The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions.,A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included.,In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations.,Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%).,Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006).,The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001).,Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001).,One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease.,The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment. | 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 |
Hospitalizations for COPD are associated with poor patient prognosis.,Length of stay (LOS) of COPD admissions in a large urban area and patient and hospital factors associated with it are described.,Retrospective longitudinal study.,All COPD patients registered with London general practitioners and admitted as an emergency with COPD (2006-2010), not having been admitted with COPD in the preceding 12 months were included.,Association of patient and hospital characteristics with mean LOS of COPD admissions was assessed.,Association between hospital and LOS was determined by negative binomial regression.,The total number of admissions was 38,504, from 22,462 patients.,The mean LOS for first admissions fell by 0.8 days (95% confidence interval [CI]: 0.7-1.5) from 8.2 to 7.0 days between 2006 and 2010.,Seventy-nine percent of first admissions were ≤10 days, with a mean LOS of 3.7 days (2009-2010).,The mean LOS of successive COPD admissions of the same patients was the same or less throughout the study period.,The interval between successive admissions fell from a mean of 357 days between the first and second admission to a mean of 19 days after eight admissions.,Age accounted for 2.3% of the variance in LOS.,Socioeconomic deprivation did not predict LOS.,Fewer discharges happened at the weekend (1,893/day) than on weekdays (5,218/day).,The mean LOS varied between hospitals, from 4.9 days (95% CI: 3.8-5.9) to 9.5 days (95% CI: 8.6-10.3) when adjusting for clustering, age, sex, and socioeconomic deprivation.,The fall in LOS of the first COPD admission between 2006 and 2010 reflects international trends.,The stability of LOS in successive admissions suggests that increasing severity of disease does not affect recovery time from an exacerbation.,Variations between hospitals of nearly 5 days in LOS for COPD admissions suggests that significant improvements in patient outcomes and in savings in health care utilization could be made in hospitals with longer LOS. | The time of year when patients experience exacerbations of chronic obstructive pulmonary disease is a much-overlooked feature of the disease.,The higher incidence of exacerbations in winter has important consequences for patients in terms of increased morbidity and mortality.,The seasonality also imposes a considerable burden on already-overloaded health care services, with both primary care consultations and hospital admissions increasing in number.,The seasonality of exacerbations varies with latitude, and is greater in more temperate climates, where there may be less protection from outdoor and indoor cold exposure.,The precise causes of the seasonality are unknown, but thought to be partly due to the increased prevalence of respiratory viral infections circulating in cold, damp conditions.,Increased susceptibility to viral infection may also be a mechanism mediated through increased airway inflammation or possibly reduced vitamin D levels.,The seasonality of exacerbations informs us about the triggers of exacerbations and suggests possible strategies to reduce their number. | 1 |
The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials.,Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 μg once daily (n = 2 studies), indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4), FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2), SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1).,All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained.,Treatment-by-covariate interactions were included where possible to improve the similarity of the trials.,Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and transitional dyspnea index at 12 weeks.,Based on the results without adjustment for covariates, indacaterol 75 μg resulted in a greater improvement in FEV1 at 12 weeks compared with FOR/BUD 9/160 μg (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with SAL/FP 50/250 μg (0.00 L [−0.07-0.07]) and SAL/FP 50/500 μg (0.01 L [−0.04-0.05]).,For transitional dyspnea index, data was available only for indacaterol 75 μg versus SAL/FP 50/500 μg (−0.49 points [−1.87-0.89]).,Based on results of a network meta-analysis with and without covariates, indacaterol 75 μg is expected to be at least as efficacious as FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500 μg) in terms of lung function.,In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data. | Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD).,There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β2-agonists, and long-acting β2-agonists such as formoterol.,Significant research has been performed to investigate the efficacy, safety and tolerability of formoterol in the therapeutic field of COPD.,Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol.,In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its efficacy improves when administered in combination with ipratropium.,Formoterol has been shown to better reduce dynamic hyperinflation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium.,Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients’ quality of life and disease symptoms.,Formoterol has a favorable safety profile and is better tolerated than theophylline.,Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD. | 1 |
The use of information and communication technologies to manage chronic diseases allows the application of integrated care pathways, and the optimization and standardization of care processes.,Decision support tools can assist in the adherence to best-practice medicine in critical decision points during the execution of a care pathway.,The objectives are to design, develop, and assess a clinical decision support system (CDSS) offering a suite of services for the early detection and assessment of chronic obstructive pulmonary disease (COPD), which can be easily integrated into a healthcare providers' work-flow.,The software architecture model for the CDSS, interoperable clinical-knowledge representation, and inference engine were designed and implemented to form a base CDSS framework.,The CDSS functionalities were iteratively developed through requirement-adjustment/development/validation cycles using enterprise-grade software-engineering methodologies and technologies.,Within each cycle, clinical-knowledge acquisition was performed by a health-informatics engineer and a clinical-expert team.,A suite of decision-support web services for (i) COPD early detection and diagnosis, (ii) spirometry quality-control support, (iii) patient stratification, was deployed in a secured environment on-line.,The CDSS diagnostic performance was assessed using a validation set of 323 cases with 90% specificity, and 96% sensitivity.,Web services were integrated in existing health information system platforms.,Specialized decision support can be offered as a complementary service to existing policies of integrated care for chronic-disease management.,The CDSS was able to issue recommendations that have a high degree of accuracy to support COPD case-finding.,Integration into healthcare providers' work-flow can be achieved seamlessly through the use of a modular design and service-oriented architecture that connect to existing health information systems. | To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined.,Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature.,Existing knowledge such as genotype - phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data.,Different approaches to this challenge exist but so far none has proven entirely satisfactory.,To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies.,Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases.,From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data.,We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects.,The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene - disease and gene - compound data which are used for subsequent data analysis, modelling and simulation.,Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development. | 1 |
Patients with COPD have an increased risk of cardiovascular disease.,Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated.,We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.,Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment.,In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined.,These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.,On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar.,The IL-6 was also increased (p < 0.05).,Twenty-two patients completed study assessments.,In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01).,Total cholesterol and ISWT also improved (p < 0.05).,On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.,Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD. | Reticular basement membrane (RBM) thickening has been variably associated with asthma and chronic obstructive pulmonary disease (COPD).,Even if RBM thickness is similar in both diseases, its composition might still differ.,To assess whether RBM thickness and composition differ between asthma and COPD.,We investigated 24 allergic asthmatics (forced expiratory volume in one second [FEV1] 92% predicted), and 17 nonallergic COPD patients (FEV1 60% predicted), and for each group a control group of similar age and smoking habits (12 and 10 persons, respectively).,Snap-frozen sections of bronchial biopsies were stained with hematoxylin/eosin and for collagen I, III, IV, V, laminin and tenascin.,RBM thickening was assessed by digital image analysis.,Relative staining intensity of each matrix component was determined.,Mean (SD) RBM thickness was not significantly different between asthma and COPD 5.5 (1.3) vs 6.0 (1.8) μm, but significantly larger than in their healthy counterparts, ie, 4.7 (0.9) and 4.8 (1.2) μm, respectively.,Collagen I and laminin stained significantly stronger in asthma than in COPD.,Tenascin stained stronger in asthma than in healthy controls of similar age, and stronger in COPD controls than in asthma controls (p < 0.05).,RBM thickening occurs both in asthma and COPD.,We provide supportive evidence that its composition differs in asthma and COPD. | 1 |
The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).,Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities.,COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities.,Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD.,First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection?,Secondly, do inhaled corticosteroids offer protection against COVID-19?,And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients?,This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.,This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19https://bit.ly/36PKzEO | To estimate the prevalence of both cardiometabolic and other co‐morbidities in patients with COVID‐19, and to estimate the increased risk of severity of disease and mortality in people with co‐morbidities.,Medline, Scopus and the World Health Organization website were searched for global research on COVID‐19 conducted from January 2019 up to 23 April 2020.,Study inclusion was restricted to English language publications, original articles that reported the prevalence of co‐morbidities in individuals with COVID‐19, and case series including more than 10 patients.,Eighteen studies were selected for inclusion.,Data were analysed using random effects meta‐analysis models.,Eighteen studies with a total of 14 558 individuals were identified.,The pooled prevalence for co‐morbidities in patients with COVID‐19 disease was 22.9% (95% CI: 15.8 to 29.9) for hypertension, 11.5% (9.7 to 13.4) for diabetes, and 9.7% (6.8 to 12.6) for cardiovascular disease (CVD).,For chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cerebrovascular disease and cancer, the pooled prevalences were all less than 4%.,With the exception of cerebrovascular disease, all the other co‐morbidities presented a significantly increased risk for having severe COVID‐19.,In addition, the risk of mortality was significantly increased in individuals with CVD, COPD, CKD, cerebrovascular disease and cancer.,In individuals with COVID‐19, the presence of co‐morbidities (both cardiometabolic and other) is associated with a higher risk of severe COVID‐19 and mortality.,These findings have important implications for public health with regard to risk stratification and future planning. | 1 |
The 2013 GOLD classification system for COPD distinguishes four stages: A (low symptoms, low exacerbation risk), B (high symptoms, low risk), C (low symptoms, high risk) and D (high symptoms, high risk).,Assessment of risk is based on exacerbation history and airflow obstruction, whatever results in a higher risk grouping.,The previous system was solely based on airflow obstruction.,Earlier studies compared the predictive performance of new and old classification systems with regards to mortality and exacerbations.,The objective of this study was to compare the ability of both classifications to predict the number of future (total and severe) exacerbations and mortality in a different patient population, and to add an outcome measure to the comparison: lung function decline.,Patient-level data from the UPLIFT trial were used to analyze 4-year survival in a Weibull model, with GOLD stages at baseline as covariates.,A generalized linear model was used to compare the numbers of exacerbations (total and severe) per stage.,Analyses were repeated with stages C and D divided into substages depending on lung function and exacerbation history.,Lung function decline was analysed in a repeated measures model.,Mortality increased from A to D, but there was no difference between B and C.,For the previous GOLD stages 2-4, survival curves were clearly separated.,Yearly exacerbation rates were: 0.53, 0.72 and 0.80 for stages 2-4; and 0.35, 0.45, 0.58 and 0.74 for A-D.,Annual rates of lung function decline were: 47, 38 and 26 ml for stages 2-4 and 44, 48, 38 and 39 for stages A-D.,With regards to model fit, the new system performed worse at predicting mortality and lung function decline, and better at predicting exacerbations.,Distinguishing between the sub-stages of high-risk led to substantial improvements.,The new classification system is a modest step towards a phenotype approach.,It is probably an improvement for the prediction of exacerbations, but a deterioration for predicting mortality and lung function decline.,ClinicalTrials.gov NCT00144339 (September 2, 2005).,The online version of this article (doi:10.1186/1471-2466-14-163) contains supplementary material, which is available to authorized users. | 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) is a leading cause of mortality and of loss of disability-adjusted life years worldwide.,It often is accompanied by the presence of comorbidity.,To systematically review the influence of COPD comorbidity on generic health-related quality of life (HRQoL).,A systematic review approach was used to search the databases Pubmed, Embase and Cochrane Library for studies evaluating the influence of comorbidity on HRQoL in COPD.,Identified studies were analyzed according to study characteristics, generic HRQoL measurement instrument, COPD severity and comorbid HRQoL impact.,Studies using only non-generic instruments were excluded.,25 studies met the selection criteria.,Seven studies utilized the EQ-5D, six studies each used the SF-36 or SF-12.,The remaining studies used one of six other instruments each.,Utilities were calculated by four EQ-5D studies and one 15D study.,Patient populations covered both early and advanced stages of COPD and ranged from populations with mostly stage 1 and 2 to studies with patients classified mainly stage 3 and 4.,Evidence was mainly created for cardiovascular disease, depression and anxiety as well as diabetes but also for quantitative comorbid associations.,Strong evidence is pointing towards the significant negative association of depression and anxiety on reduced HRQoL in COPD patients.,While all studies found the occurrence of specific comorbidities to decrease HRQoL in COPD patients, the orders of magnitude diverged.,Due to different patient populations, different measurement tools and different concomitant diseases the study heterogeneity was high.,Facilitating multimorbid intervention guidance, instead of applying a parsimony based single disease paradigm, should constitute an important goal for improving HRQoL of COPD patients in research and in clinical practice. | Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems.,Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.,Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency.,Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database.,Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.,Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001).,The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs.,Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6).,Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.,Comorbidity burden determines elevated utilization for COPD patients.,Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients. | 1 |
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations.,We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities.,We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses.,Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci.,Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.,Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.,Pulmonary function is influenced by environmental factors, lifestyle, and genetics.,Here, in a multiethnic GWAS meta-analysis for pulmonary function traits, the authors identify over 50 additional genetic loci, a subset of which are specific for European, African, Asian, or Hispanic/Latino ancestry. | Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC).,Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047).,We identified three novel loci not previously associated with pulmonary function.,SNPs in or near DNER (smallest P JMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest P JMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest P JMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction.,The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated.,We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue.,DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers.,Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects. | 1 |
We aimed to study the adverse outcomes of symptomatic and asymptomatic non-obstructed individuals and those with mild COPD longitudinally in participants from three Latin-American cities.,Two population-based surveys of adults with spirometry were conducted for these same individuals with a 5- to 9-year interval.,We evaluated the impact of respiratory symptoms (cough, phlegm, wheezing or dyspnea) in non-obstructed individuals, and among those classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1, COPD on exacerbation frequency, mortality and FEV1 decline, compared with asymptomatic individuals without airflow obstruction or restriction.,Non-obstructed symptomatic individuals had a marginal increased risk of mortality (HR 1.3; 95% CI 0.9-1.94), increased FEV1 decline (−4.5 mL/year; 95% CI −8.6, −0.4) and increased risk of 2+ exacerbations in the previous year (OR 2.6; 95% CI 1.2-6.5).,Individuals with GOLD stage 1 had a marginal increase in mortality (HR 1.5; 95% CI 0.93-2.3) but a non-significant impact on FEV1 decline or exacerbations compared with non-obstructed individuals.,The presence of respiratory symptoms in non-obstructed individuals was a predictor of mortality, lung-function decline and exacerbations, whereas the impact of GOLD stage 1 was mild and inconsistent.,Respiratory symptoms were associated with asthma, current smoking, and the report of heart disease.,Spirometric case-finding and treatment should target individuals with moderate-to-severe airflow obstruction and those with restriction, the groups with consistent increased mortality. | Influence of tuberculosis (TB) on the natural course of COPD has not been well known.,This study was designed to investigate the effects of history of TB on the long-term course of COPD.,Patients hospitalized with COPD exacerbation were consecutively included (n=598).,Cases were classified into two categories: those with TB history and those without.,Clinical, demographic, and radiological features were meticulously recorded, and patients were followed up for hospitalizations due to exacerbation and for overall mortality.,A total of 93 patients (15%) had a history of TB.,On average, patients with past TB history were 4 years younger than the rest of the patients (P=0.002).,Our study revealed that patients with past TB were diagnosed with COPD 4 years earlier and died 5 years earlier as compared to the patients without TB.,In addition, in the past TB group, rate of hospital admissions per year was higher compared to the group that lacked TB history (2.46±0.26 vs 1.56±0.88; P=0.001).,Past TB group had higher arterial carbon dioxide tension (PaCO2) and lower forced expiratory volume in 1 second (FEV1; P=0.008 and P=0.069, respectively).,Median survival was 24 months for patients who had past TB and 36 months for those who had not.,Kaplan-Meier analysis revealed that although 3-year survival rate was lower in patients with past TB, it was not statistically significant (P=0.08).,Cox regression analysis showed that while factors such as age, PaCO2, hematocrit, body mass index (BMI) and Charlson index affected mortality rates in COPD patients (P<0.05), prior history of TB did not.,Our results showed that a history of TB caused more hospitalizations, reduced respiratory functions and increased PaCO2.,It was found that, despite similarity of the overall mortality, COPD diagnosis and death occurred 5 years earlier in patients with past TB.,We conclude that history of TB has an important role in the natural course of COPD. | 1 |
This study investigated the efficacy and safety of budesonide/formoterol (B/F) and tiotropium combination in the management of chronic obstructive pulmonary disease (COPD) in Chinese patients.,Between January 2015 and November 2017, 113 eligible Chinese patients with COPD were included and divided into an intervention group and a control group.,Sixty-three patients in the intervention group underwent B/F combined tiotropium, while 50 patients in the control group received tiotropium alone.,The primary outcome was severity of dyspnea on exertion (DOE), measured by the 6-minute walk test (6MWT) scale.,The secondary outcomes included lung function, measured by the forced expiratory volume in 1 second (FEV1), quality of life, measured by the St.,George's Respiratory Questionnaire (SGRQ), and adverse events.,All outcomes were measured at the end of 12-week treatment.,B/F and tiotropium combination showed greater efficacy in DOE (P < .01), lung function (P < .01), and quality of life (P < .01), compared with tiotropium alone at the end of 12-week treatment.,In addition, adverse events in both groups were similar and tolerable.,The findings suggest that B/F and tiotropium combination can be used as an effective treatment in Chinese patients with COPD. | To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD).,Systematic review and network meta-analysis (NMA).,208 randomised clinical trials (RCTs) including 134 692 adults with COPD.,LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo.,The proportion of patients with moderate-to-severe exacerbations.,The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes.,NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26 141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol.,Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve).,NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%).,NMA was conducted on CVM (37 RCTs, 55 156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR).,Triamcinolone acetonide was the most harmful (SUCRA=81%).,NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol.,The most harmful agent was fluticasone/salmeterol (SUCRA=89%).,NMA was conducted for arrhythmia; no statistically significant differences between agents were identified.,Many inhaled agents are available for COPD, some are safer and more effective than others.,Our results can be used by patients and physicians to tailor administration of these agents.,PROSPERO # CRD42013006725. | 1 |
The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape.,The pandemic’s impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood.,We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations.,We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments.,Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years.,For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes.,Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations.,Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages.,There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33).,In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81).,The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths.,This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.,The online version contains supplementary material available at 10.1186/s12916-021-02000-w. | The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood.,We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD.,Prospective cohort study.,Outpatient Department, London Chest Hospital, London, UK.,Thirty-nine patients with COPD.,We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation.,Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed.,A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae.,Rhinovirus was identified in 19.6% of exacerbations.,The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048).,Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens.,In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone.,The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity. | 1 |
Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world.,The underlying pathophysiological mechanisms have been the focus of extensive research in the past.,The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue.,Both types of cells express chemokines and chemokine receptors, making them sensitive to modifications of concentration gradients.,Cigarette smoke exposure and recurrent exacerbations, directly and indirectly, impact the expression of chemokines and chemokine receptors.,Here, we provide an overview of the evidence regarding chemokines involvement in COPD, and we hypothesize that a dysregulation of this tightly regulated system is critical in COPD evolution, both at a stable state and during exacerbations.,Targeting chemokines and chemokine receptors could be highly attractive as a mean to control both chronic inflammation and bronchial remodeling.,We present a special focus on the CXCL8-CXCR1/2, CXCL9/10/11-CXCR3, CCL2-CCR2, and CXCL12-CXCR4 axes that seem particularly involved in the disease pathophysiology. | It is known that tissue macrophages derive not only from blood monocytes but also from yolk sac or fetal liver, and the tissue of residence guides their function.,When isolated, they lose tissue specific signatures, hence studies of human macrophages should be ideally done directly in the tissue.,The aim of this study was to investigate directly in human lung tissue the polarization of alveolar macrophage (AM), classic (M1) or alternative (M2), in health and disease, using COPD as a model.,Surgical lungs from 53 subjects were studied: 36 smokers whose FEV1 varied from normal to severe COPD, 11 non-smokers and 6 normal donors. iNOS and CD206 immunohistochemistry was used to quantify the percentage of AM polarized as M1 or M2 in lung sections.,The percentage of M1 and M2 increased progressively with smoking and COPD severity, from 26% to 84% for M1 and from 7% to 78% for M2.,In donors 74% of AM were negative for M1 and 93% for M2.,Confocal microscopy showed co-localization of M1 and M2 in the same AM in severe COPD.,In normal lungs alveolar macrophages were mostly non-polarized.,With smoking and COPD severity, M1 and M2 polarization increased significantly and so did the co-expression of M1 and M2 in the same alveolar macrophage.,The online version of this article (doi:10.1186/s12931-017-0522-0) contains supplementary material, which is available to authorized users. | 1 |
This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the ‘Dutch hypothesis’ of whether these are essentially the same or different pathological conditions.,Bronchoscopic biopsies were stained with anti-collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied.,The Rbm in COPD was fragmented, non-homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls.,Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001].,The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, μm2/mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics.,The characteristics of Rbm remodelling are quite different in asthma and COPD. | The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4.,These cells are also present in the basal epithelium.,Such changes are likely hallmarks of epithelial mesenchymal transition (EMT).,We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.,Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells).,The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope".,Slides were double stained for S100A4 and cytokeratin(s).,In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003.,Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003.,Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.,These data provide additional support for active EMT in COPD airways. | 1 |
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. | 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. | We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | 1 |
In chronic obstructive pulmonary disease (COPD) apoptotic bronchial epithelial cells are increased, and their phagocytosis by alveolar macrophages (AM) is decreased alongside bacterial phagocytosis.,Epithelial cellular lipids, including those exposed on uncleared apoptotic bodies, can become oxidized, and may be recognized and presented as non-self by antigen presenting cells.,CD1b is a lipid-presenting protein, previously only described in dendritic cells.,We investigated whether CD1b is upregulated in COPD AM, and whether lipid oxidation products are found in the airways of cigarette smoke (CS) exposed mice.,We also characterise CD1b for the first time in a range of macrophages and assess CD1b expression and phagocytic function in response to oxidised lipid.,Bronchoalveolar lavage and exhaled breath condensate were collected from never-smoker, current-smoker, and COPD patients and AM CD1b expression and airway 8-isoprostane levels assessed.,Malondialdehyde was measured in CS-exposed mouse airways by confocal/immunofluorescence.,Oxidation of lipids produced from CS-exposed 16HBE14o- (HBE) bronchial epithelial cells was assessed by spectrophotometry and changes in lipid classes assessed by mass spectrometry.,16HBE cell toxicity was measured by flow cytometry as was phagocytosis, CD1b expression, HLA class I/II, and mannose receptor (MR) in monocyte derived macrophages (MDM).,AM CD1b was significantly increased in COPD smokers (4.5 fold), COPD ex-smokers (4.3 fold), and smokers (3.9 fold), and AM CD1b significantly correlated with disease severity (FEV1) and smoking pack years.,Airway 8-isoprostane also increased in smokers and COPD smokers and ex-smokers.,Malondialdehyde was significantly increased in the bronchial epithelium of CS-exposed mice (MFI of 18.18 vs 23.50 for control).,Oxidised lipid was produced from CS-exposed bronchial epithelial cells (9.8-fold of control) and showed a different overall lipid makeup to that of control total cellular lipid.,This oxidised epithelial lipid significantly upregulated MDM CD1b, caused bronchial epithelial cell toxicity, and reduced MDM phagocytic capacity and MR in a dose dependent manner.,Increased levels of oxidised lipids in the airways of COPD patients may be responsible for reduced phagocytosis and may become a self-antigen to be presented by CD1b on macrophages to perpetuate disease progression despite smoking cessation. | Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment.,The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status.,Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD.,Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD.,Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems.,It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism.,In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group).,After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species.,Later, the comparisons of individual lipids were performed between controls and patients with COPD.,Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers.,Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated.,Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD.,Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change.,In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers.,Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity.,Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years.,Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD.,Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD. | 1 |
For patients with acute exacerbation of COPD (AECOPD), type 2 diabetes mellitus (T2DM) as comorbidity have poor outcomes.,However, data on the impact of previously diagnosed and new- diagnosed T2DM in such a patient population is lacking.,Inpatients diagnosed with AECOPD in the department of Pulmonary and Critical Care Medicine of The First Hospital of China Medical University during 2011-2017 were enrolled.,Data on demography, prevalence of type 2 DM, other comorbidities, hospital stays and laboratory tests (including arterial partial pressure of oxygen [PaO2]) results were recorded.,Results were compared with AECOPD patients having previously diagnosed and new-diagnosed type 2 diabetes.,Markers associated with development of type 2 DM and the prognosis of AECOPD patients were identified.,Of the 196 patients enrolled in this study, the overall prevalence of T2DM was 26%.,The PaO2 in the newly diagnosed T2DM group was considerably lower versus non-diabetic group.,The T2DM group had a longer hospital stay and higher troponin level versus the non-diabetic group.,AECOPD patients with T2DM were found to be correlated with hypertension.,Age, need for assisted ventilation, increased troponin, and elevated fasting blood glucose on admission were risk factors for death in hospitalized AECOPD patients.,AECOPD patients had a higher prevalence of T2DM than the general population; T2DM comorbidity caused lower PaO2, longer hospital stays, and increased troponin.,Poor blood glucose control may increase the risk of death in AECOPD patients. | AUDIPOC is a nationwide clinical audit that describes the characteristics, interventions and outcomes of patients admitted to Spanish hospitals because of an exacerbation of chronic obstructive pulmonary disease (ECOPD), assessing the compliance of these parameters with current international guidelines.,The present study describes hospital resources, hospital factors related to case recruitment variability, patients’ characteristics, and adherence to guidelines.,An organisational database was completed by all participant hospitals recording resources and organisation.,Over an 8-week period 11,564 consecutive ECOPD admissions to 129 Spanish hospitals covering 70% of the Spanish population were prospectively identified.,At hospital discharge, 5,178 patients (45% of eligible) were finally included, and thus constituted the audited population.,Audited patients were reassessed 90 days after admission for survival and readmission rates.,A wide variability was observed in relation to most variables, hospital adherence to guidelines, and readmissions and death.,Median inpatient mortality was 5% (across-hospital range 0-35%).,Among discharged patients, 37% required readmission (0-62%) and 6.5% died (0-35%).,The overall mortality rate was 11.6% (0-50%).,Hospital size and complexity and aspects related to hospital COPD awareness were significantly associated with case recruitment.,Clinical management most often complied with diagnosis and treatment recommendations but rarely (<50%) addressed guidance on healthy life-styles.,The AUDIPOC study highlights the large across-hospital variability in resources and organization of hospitals, patient characteristics, process of care, and outcomes.,The study also identifies resources and organizational characteristics associated with the admission of COPD cases, as well as aspects of daily clinical care amenable to improvement. | 1 |
•COPD is a risk factor for lung cancer beyond their shared aetiology.,•Both are driven by oxidative stress.,•Both are linked to cellular aging, senescence and telomere shortening.,•Both have been linked to genetic predisposition.,•Both show altered epigenetic regulation of gene expression.,COPD is a risk factor for lung cancer beyond their shared aetiology.,Both are driven by oxidative stress.,Both are linked to cellular aging, senescence and telomere shortening.,Both have been linked to genetic predisposition.,Both show altered epigenetic regulation of gene expression.,Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden.,Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking.,Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging.,In the majority of smokers, the burden of smoking may be dealt with by the body’s defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms.,However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great.,Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation.,Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments. | Reactive oxygen species (ROS) participate in the pathogenesis of emphysema.,Among ROS-producing enzymes, NOX NADPH oxidases are thought to be responsible for tissue injury associated with several lung pathologies.,To determine whether NOX2 and/or NOX1 participate in the development of emphysema, their expression patterns were first studied by immunohistochemistry in the lungs of emphysematous patients.,Subsequently, we investigated their contribution to elastase-induced emphysema using NOX2- and NOX1-deficient mice.,In human lung, NOX2 was mainly detected in macrophages of control and emphysematous lungs, while NOX1 was expressed in alveolar epithelium and bronchial cells.,We observed an elevated number of NOX2-positive cells in human emphysematous lungs, as well as increased NOX2 and NOX1 mRNA expression in mouse lungs following elastase exposure.,Elastase-induced alveolar airspace enlargement and elastin degradation were prevented in NOX2-deficient mice, but not in NOX1-deficient mice.,This protection was independent of inflammation and correlated with reduced ROS production.,Concomitantly, an elevation of sirtuin 1 (SIRT1) level and a decrease of matrix metalloproteinase-9 (MMP-9) expression and activity were observed in alveolar macrophages and neutrophils.,We addressed the specific role of macrophage-restricted functional NOX2 in elastase-induced lung emphysema using Ncf1 mutant mice and Ncf1 macrophage rescue mice (Ncf1 mutant mice with transgenic expression of Ncf1 only in CD68-positive mononuclear phagocytes; the MN mouse).,Compared to WT mice, the lack of functional NOX2 led to decreased elastase-induced ROS production and protected against emphysema.,In contrast, ROS production was restored specifically in macrophages from Ncf1 rescue mice and contributes to emphysema.,Taken together, our results demonstrate that NOX2 is involved in the pathogenesis of human emphysema and macrophage-specific NOX2 participates in elastase-induced emphysema through the involvement of SIRT1/MMP-9 pathways in mice. | 1 |
‘Clinically important deterioration’ (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations.,ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg.,This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.,A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV1; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George’s Respiratory Questionnaire (SGRQ) total score (≥4 units).,A ‘sustained’ CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time.,CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV1 was also measured at weeks 1 and 18.,AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05).,Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01).,AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV1 and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).,AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.,Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011.,Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.,The online version of this article (doi:10.1186/s12931-017-0583-0) contains supplementary material, which is available to authorized users. | 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. | 1 |
It is still unclear whether signs of neutrophil mobilization in the blood of patients with chronic obstructive pulmonary disease represent true systemic events and how these relate to bacterial colonization in the airways.,In this study, we evaluated these issues during clinically stable periods and during exacerbations in smokers with obstructive pulmonary disease and chronic bronchitis (OPD-CB).,Over a period of 60 weeks for each subject, blood samples were repeatedly collected from 60 smokers with OPD-CB during clinically stable periods, as well as during and after exacerbations.,Myeloperoxidase (MPO) and neutrophil elastase (NE) protein and mRNA, growth of bacteria in sputum, and clinical parameters were analyzed.,Ten asymptomatic smokers and ten never-smokers were included as controls.,We found that, during clinically stable periods, neutrophil and NE protein concentrations were increased in smokers with OPD-CB and in the asymptomatic smokers when compared with never-smokers.,During exacerbations, neutrophil and MPO protein concentrations were further increased in smokers with OPD-CB, without a detectable increase in the corresponding mRNA during exacerbations.,However, MPO and NE protein and mRNA displayed positive correlations.,During exacerbations, only increased neutrophil concentrations were associated with growth of bacteria in sputum.,Among patients with low transcutaneous oxygen saturation during exacerbations, PaO2 (partial oxygen pressure) correlated with concentrations of MPO and NE protein and neutrophils in a negative manner.,There are signs of systemic neutrophil mobilization during clinically stable periods and even more so during exacerbations in chronic obstructive pulmonary disease.,In this condition, MPO and NE may share a cellular origin, but its location remains uncertain.,Factors other than local bacteria, including hypoxemia, may be important for driving systemic signs of neutrophil mobilization. | Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes.,Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.,To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.,In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV1 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation.,Sputum total cell counts (9.0 versus 7.9 × 106/mL), eosinophils (0.3 versus 0.2 × 106/mL), neutrophils (6.1 versus 5.8 × 106/mL), and lymphocytes (0.07 versus 0.02 × 106/mL) increased significantly during an exacerbation compared to stable disease.,A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation.,These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-α (TNF-α) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection.,Sputum TNF-α level during an exacerbation had the best test characteristics to predict a bacterial infection.,Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations.,The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways.,Sputum TNF-α is a candidate marker for predicting airway bacterial infection. | 1 |
The 1-minute sit-to-stand (STS) test could be valuable to assess the level of exercise tolerance in chronic obstructive pulmonary disease (COPD).,There is a need to provide the minimal important difference (MID) of this test in pulmonary rehabilitation (PR).,COPD patients undergoing the 1-minute STS test before PR were included.,The test was performed at baseline and the end of PR, as well as the 6-minute walk test, and the quadriceps maximum voluntary contraction (QMVC).,Home and community-based programs were conducted as recommended.,Responsiveness to PR was determined by the difference in the 1-minute STS test between baseline and the end of PR.,The MID was evaluated using distribution and anchor-based methods.,Forty-eight COPD patients were included.,At baseline, the significant predictors of the number of 1-minute STS repetitions were the 6-minute walk distance (6MWD) (r=0.574; P<10−3), age (r=−0.453; P=0.001), being on long-term oxygen treatment (r=−0.454; P=0.017), and the QMVC (r=0.424; P=0.031).,The multivariate analysis explained 75.8% of the variance of 1-minute STS repetitions.,The improvement of the 1-minute STS repetitions at the end of PR was 3.8±4.2 (P<10−3).,It was mainly correlated with the change in QMVC (r=0.572; P=0.004) and 6MWD (r=0.428; P=0.006).,Using the distribution-based analysis, an MID of 1.9 (standard error of measurement method) or 3.1 (standard deviation method) was found.,With the 6MWD as anchor, the receiver operating characteristic curve identified the MID for the change in 1-minute STS repetitions at 2.5 (sensibility: 80%, specificity: 60%) with area under curve of 0.716.,The 1-minute STS test is simple and sensitive to measure the efficiency of PR.,An improvement of at least three repetitions is consistent with physical benefits after PR. | Resistance training (RT) is thought to be effective in preventing muscle depletion, whereas endurance training (ET) is known to improve exercise capacity and health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD).,Our objectives were to assess the efficiency of combining RT with ET compared with ET alone.,We identified eligible studies through a systematic multi-database search.,One author checked titles and abstracts for relevance using broad inclusion criteria, whilst two independent authors checked the full-text copies for eligibility.,Two authors independently extracted data, and we assessed the risk of bias and quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation guidelines.,We included 11 randomized controlled trials (331 participants) and 2 previous systematic reviews.,The meta-analyses showed equal improvements in HRQoL, walking distance and exercise capacity.,However, we found moderate quality evidence of a significant increase in leg muscle strength favouring a combination of RT and ET (standardized mean difference of 0.69 (95% confidence interval: 0.39-0.98).,In conclusion, we found significantly increased leg muscle strength favouring a combination of RT with ET compared with ET alone.,Therefore, we recommend that RT should be incorporated in rehabilitation of COPD together with ET. | 1 |
The immunopathology of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking.,In the last quarter of the century, the analysis of specimens obtained from the lower airways of COPD patients compared with those from a control group of age-matched smokers with normal lung function has provided novel insights on the potential pathogenetic role of the different cells of the innate and acquired immune responses and their pro/anti-inflammatory mediators and intracellular signalling pathways, contributing to a better knowledge of the immunopathology of COPD both during its stable phase and during its exacerbations.,This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.,This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function. | Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD), including the chronic inflammatory process, emphysema, and altered innate immune response.,Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF)-α, interferon-γ, interleukin (IL)-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP), and growth factors such as transforming growth factor-β.,The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations.,While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable.,In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines.,The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor.,Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in COPD.,The two largest studies that have been reported in the literature involve the use of blocking antibody to TNFα and CXCL8 (IL-8), and neither has provided benefit.,Blocking the actions of CXCL8 through its CXCR2 receptor blockade was not successful either.,Studies of antibodies against IL-17, IL-18, IL-1β, and TSLP are currently either being undertaken or planned.,There is a need to carefully phenotype COPD and discover good biomarkers of drug efficacy for each specific target.,Specific groups of COPD patients should be targeted with specific anticytokine therapy if there is evidence of high expression of that cytokine and there are features of the clinical expression of COPD that will respond. | 1 |
Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals.,We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes.,By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs).,The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls.,Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2.,Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins.,The eQTLs for IREB2 and CHRNA5 were not in LD.,Seventy-four additional eQTL SNPs were associated with COPD at p<0.01.,These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6.,Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus. | In addition to smoking, genetic predisposition is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD).,Genetic association studies of new candidate genes in COPD may lead to improved understanding of the pathogenesis of the disease.,Two proposed casual single nucleotide polymorphisms (SNP) (rs1051740, rs2234922) in microsomal epoxide hydrolase (EPHX1) and three SNPs (rs1801282, rs1800571, rs3856806) in peroxisome proliferator-activated receptor gamma (PPARG), a new candidate gene, were genotyped in a case-control study (272 COPD patients and 301 controls subjects) in Hungary.,Allele frequencies and genotype distributions were compared between the two cohorts and trend test was also used to evaluate association between SNPs and COPD.,To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested in logistic regression analysis.,Association between haplotypes and COPD outcome was also assessed.,The distribution of imputed EPHX1 phenotypes was significantly different between the COPD and the control group (P = 0.041), OR for the slow activity phenotype was 1.639 (95% CI = 1.08- 2.49; P = 0.021) in our study.,In logistic regression analysis adjusted for both variants, also age and pack-year, the rare allele of His447His of PPARG showed significant association with COPD outcome (OR = 1.853, 95% CI = 1.09-3.14, P = 0.0218).,In haplotype analysis the GC haplotype of PPARG (OR = 0.512, 95% CI = 0.27-0.96, P = 0.035) conferred reduced risk for COPD.,The "slow" activity-associated genotypes of EPHX1 were associated with increased risk of COPD.,The minor His447His allele of PPARG significantly increased; and the haplotype containing the minor Pro12Ala and the major His447His polymorphisms of PPARG decreased the risk of COPD. | 1 |
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