Presence Of Chronic Bronchitis Research Articles

Expression of human Interferon Regulatory Factor 3 (IRF-3) in alveolar macrophages relates to clinical and functional traits in COPD.

IntroductionChronic obstructive pulmonary disease (COPD) is a frequent cause of morbidity and mortality. Dysregulated and enhanced immune-inflammatory responses have been described in COPD. Recent data showed impaired immune responses and, in particular, of interferon (IFNs) signaling pathway in these patients.AimTo evaluate in peripheral lung of COPD patients, the expression of some of the less investigated key components of the innate immune responses leading to IFN productions including: IFN-receptors (IFNAR1/IFNAR2), IRF-3 and MDA-5. Correlations with clinical traits and with the inflammatory cell profile have been assessed.MethodsLung specimens were collected from 58 subjects undergoing thoracic surgery: 22 COPD patients, 21 smokers with normal lung function (SC) and 15 non-smoker controls (nSC). The expression of IFNAR1, IFNAR2, IRF-3 and MDA-5, of eosinophils and activated NK cells (NKp46+) were quantified in the peripheral lung by immunohistochemistry.ResultsA significant increase of IRF-3 + alveolar macrophages were observed in COPD and SC compared with nSC subjects. However, in COPD patients, the lower the levels of IRF-3 + alveolar macrophages the lower the FEV1 and the higher the exacerbation rate. The presence of chronic bronchitis (CB) was also associated with low levels of IRF-3 + alveolar macrophages. NKp46 + cells, but not eosinophils, were increased in COPD patients compared to nSC patients (p < 0.0001).ConclusionsSmoking is associated with higher levels of innate immune response as showed by higher levels of IRF-3 + alveolar macrophages and NKp46 + cells. In COPD, exacerbation rates, severe airflow obstruction and CB were associated with lower levels of IRF-3 expression, suggesting that innate immune responses characterize specific clinical traits of the disease.

Clinical significance of chronic bronchitis in different racial groups

BackgroundsLimited data are available on racial differences in the clinical features of chronic bronchitis (CB) patients with chronic obstructive pulmonary disease (COPD). In this study, we aimed to compare clinical features among CB patients of different races. We also analyzed the clinical significance of CB, defined classically and based on the COPD Assessment Test (CAT), to validate the CAT-based definition.MethodsWe analyzed patient data extracted from the Korean COPD Subgroup Study (KOCOSS) cohort (2012–2021) and US Genetic Epidemiology of COPD (COPDGene) study (2008–2011). We compared clinical characteristics among CB and non-CB patients of three different races using two CB definitions.ResultsIn this study, 3,462 patients were non-Hispanic white (NHW), 1,018 were African American (AA), and 1,793 were Asian. The proportions of NHW, AA, and Asian patients with CB according to the classic definition were 27.4%, 20.9%, and 10.7%, compared with 25.2%, 30.9%, and 23.0% according to the CAT-based definition, respectively. The risk of CB prevalence was highest in NHW and lowest in Asian COPD patients. Among all races, CB patients were more likely to be current smokers, have worse respiratory symptoms and poorer health-related quality of life (HrQoL), and to have decreased lung function and exercise capacity. Most of these characteristics showed similar associations with the outcomes between the two definitions of CB. A binominal regression model revealed that CB patients of all races had an increased risk of future exacerbations according to both CB definitions, except for Asian patients with classically defined CB.ConclusionsThe presence of CB was associated with worse respiratory symptoms, HrQoL, exercise capacity and lung function, and more exacerbations, regardless of race or CB definition. The CAT-based definition may be more useful for assessing the risk of future exacerbations in Asian COPD patients.

Chronic Bronchitis Affects Outcomes in Smokers without Chronic Obstructive Pulmonary Disease (COPD).

Background. Chronic bronchitis (CB) importantly affects outcomes in smokers with COPD, but the effects on smokers without COPD are less well known and less emphasized. The aim of our study was to investigate the possible effects of CB on clinical outcomes in smokers without COPD (noCOPD) and compare them with the effects in smokers with COPD (COPD). Methods. For that purpose, we studied 511 smokers, 302 with and 209 without COPD, followed for 10 years in an academic COPD ambulatory setting. Chronic bronchitis was defined as the presence of cough and sputum production for at least 3 months in each of two consecutive years. All subjects underwent clinical and functional examination with spirometry, diffusion capacity (DLco), 6-min walking test (6MWT), mMRC Dyspnoea Scale, COPD Assessment Test (CAT), and recording of annual frequency of exacerbations. All-cause mortality during follow-up was recorded. Results. 27% of noCOPD and 45% of COPD had CB. noCOPD with CB had lower FEV1 and DLco, worse 6MWT, more dyspnoea, a higher number of exacerbations and lower survival than noCOPD without CB. CB did not affect FEV1 decline in noCOPD but it significantly did in COPD. Conclusions. The presence of chronic bronchitis in smokers without COPD will significantly affect symptoms, quality of life, and survival, underlining the importance of recognizing the condition and managing it accordingly.

Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease.

Phosphodiesterase (PDE) 4 inhibitors prevent the metabolism of cyclic adenosine monophosphate, thereby reducing inflammation. Inhaled PDE4 inhibitors aim to restrict systemic drug exposure to enhance the potential for clinical benefits (in the lungs) versus adverse events (systemically). The orally administered PDE4 inhibitor roflumilast reduces exacerbation rates in the subgroup of chronic obstructive pulmonary disease patients with a history of exacerbations and the presence of chronic bronchitis, but can cause PDE4 related adverse effects due to systemic exposure. CHF6001 is an inhaled PDE4 inhibitor, while inhaled ensifentrine is an inhibitor of both PDE3 and PDE4; antagonism of PDE3 facilitates smooth muscle relaxation and hence bronchodilation. These inhaled PDE inhibitors have both reported positive findings from early phase clinical trials, and have been well tolerated. Longer term trials are needed to firmly establish the clinical benefits of these drugs.

Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases.

Selective phosphodiesterase (PDE) inhibitors are a class of nonsteroid anti-inflammatory drugs for treating chronic inflammatory diseases. Modulation of systemic and airway inflammation is their pivotal mechanism of action. Furthermore, PDE inhibitors modulate cough reflex and inhibit airway mucus secretion. Roflumilast, a selective PDE4 inhibitor, has been extensively studied for the efficacy and safety in chronic obstructive pulmonary disease (COPD) patients. According to the mechanisms of action, the potential roles of PDE inhibitors in treating chronic respiratory diseases including severe asthma, asthma-COPD overlap (ACO), noncystic fibrosis bronchiectasis, and chronic cough are discussed. Since roflumilast inhibits airway eosinophilia and neutrophilia in COPD patients, it reduces COPD exacerbations in the presence of chronic bronchitis in addition to baseline therapies. The clinical studies in asthma patients have shown the comparable efficacy of roflumilast to inhaled corticosteroids for improving lung function. However, the clinical trials of roflumilast in severe asthma have been limited. Although ACO is common and is also associated with poor outcomes, there is no clinical trial regarding its efficacy in patients with ACO despite a promising role in reducing COPD exacerbation. Since mucus hypersecretion is a result of neutrophil secretagogue in patients with chronic bronchitis, experimental studies have shown that PDE4s are regulators of the cystic fibrosis transmembrane conductance regulator (CFTR) in human airway epithelial cells. Besides, goblet cell hyperplasia is associated with an increased expression of PDE. Bronchiectasis and chronic bronchitis are considered neutrophilic airway diseases presenting with mucus hypersecretion. They commonly coexist and thus lead to severe disease. The role of roflumilast in noncystic fibrosis bronchiectasis is under investigation in clinical trials. Lastly, PDE inhibitors have been shown modulating cough from bronchodilation, suppressing transient receptors potential (TRP), and anti-inflammatory properties. Hence, there is the potential role of the drug in the management of unexplained cough. However, clinical trials for examining its antitussive efficacy are pivotal. In conclusion, selective PDE4 inhibitors may be potential treatment options for chronic respiratory diseases apart from COPD due to their promising mechanisms of action.

Prevalence of chronic bronchitis against a background of abdominal obesity in young people aged 25–44 in Novosibirsk

Aim . To study the prevalence of chronic bronchitis (CB) against the background of abdominal obesity (AO) in young people aged 25–44 in Novosibirsk. Materials and methods . A simultaneous population survey of the population of 25–44 year-olds in Novosibirsk was carried out. The study included 906 people (414 men and 492 women). AO was recorded with a waist circumference of more than 94 cm in men and more than 80 cm in women. CB was recorded according to standardized epidemiological (questionnaire, pulmonary questionnaire) and functional (spirometry) criteria. Results. The prevalence of AO and CB in the population was 42.9% and 8.7%, respectively; in men 43.2% and 7.7%; in women 42.7% and 9.6%. The prevalence of CB against the background of AO in the population was 1.95 times higher ( p = 0.003) compared with individuals with CB without AO (OR = 2.08 [CI 1.302–3.333]). In women, the prevalence of CB against the background of AO was 2.15 times higher ( p = 0.005) compared with women with CB without AO (OR = 2.35 [CI 1.267–4.359]). The prevalence of CB in smokers in the population was 1.65 times higher ( p = 0.015) compared with non-smokers (OR = 1.72 [CI 1.081–2.739]). In male smokers, the prevalence of CB was 2.02 times higher ( p = 0.031) compared with non-smoking men (OR = 2.15 [CI 1.020–4.514]). The multivariate logistic regression analysis showed that in people aged 25–44, the presence of CB is associated with smoking [Exp(B) = 1.966, p = 0.006] and the presence of AO [Exp(B) = 2.091, p = 0.003]. Conclusion . Significant effects of AO and smoking on the development of CB in the population of 25–44 year-olds as a whole were revealed. At the same time, in men aged 25–44, the relative risk of developing CB is significantly affected by smoking, and in women aged 25–44, by the presence of AO.

Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease.

In chronic obstructive pulmonary disease (COPD) patients with exacerbations despite optimized bronchodilator therapy, roflumilast and chronic azithromycin are recommended options. Roflumilast is recommended in severe COPD patients with chronic bronchitis, whereas chronic azithromycin is more broadly indicated. The comparative effectiveness between these 2 treatments to reduce exacerbation rate remains unclear. Our objective was analysis of the Veterans Health Administration (VHA) database (medication and claims data without lung function or presence of chronic bronchitis or tobacco use) to compare the effectiveness of roflumilast and azithromycin on hospitalizations and mortality. The primary outcome of the study was cumulative incidences of first COPD-related and all-cause hospitalization. Sensitivity analysis on hospitalizations was conducted for VHA patients who also had Medicare. In 1302 roflumilast and 2573 azithromycin patients, the all-cause mortality rates at 1 year were 19% and 15%, respectively. The median times-to-all-cause death were 47 months (interquartile range [IQR] 16-81) for the roflumilast and 48 months (IQR 20-83) for the azithromycin groups. Roflumilast was associated with higher mortality (hazard ratio [HR] 1.16; 95% confidence interval [CI], 1.04-1.29). Roflumilast showed no significant association for COPD-related hospitalization (subdistribution HR [SHR]=1.14, 95% CI, 1.00-1.29) and all-cause hospitalization (HR 1.07, 95% CI, 0.97-1.18). For patients with Medicare (N=2030), roflumilast was associated with higher COPD-related (SHR 1.21; 95% CI, 1.05-1.41) and all-cause (SHR 1.23; 95% CI, 1.09-1.38) hospitalizations. Roflumilast was associated with higher hazard ratios for death, COPD-related hospitalizations, and all-cause hospitalizations in COPD patients only after adjustment for VHA and external Medicare events. Prospective clinical trials are needed to directly compare the relative efficacy of these therapies.

Smoking-associated increase in mucins 1 and 4 in human airways

RationaleSmoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD.MethodsMucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sex-matched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot.ResultsThe levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers.ConclusionsSmoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease.

Phenotypic characteristics of COPD patients with a smoking history in POPE-study in the Russian Federation

Chronic obstructive pulmonary disease is a significant problem for Russian healthcare. The identification of different clinical phenotypes of the disease may allow individualizing approaches to the treatment of patients with this pathology, while there is insufficient data on the phenotypic characteristics of patients with COPD in Eastern and Central Europe. Methods . The article presents data from 356 outpatient patients with COPD with a smoking history of more than 10 pack/years, who were included in the study randomly without prior selection or invitation. 57.6% of persons were patients without frequent exacerbations. Patients with frequent exacerbations were 33.7% (without the presence of chronic bronchitis – 9.3% and with the presence of chronic bronchitis – 24.4%). An overlap of bronchial asthma and COPD was revealed in 8.7% of the included patients. According to the GOLD (2011), 7% of patients belong to group A, 26.4% to group B, 4.2% to group C, and 63.4% to group D. Results . This paper presents the results of the Russian part of the international POPE-study (Phenotypes of COPD in Central and Eastern Europe), which contains data on COPD clinical phenotypes in Russian patients with a verified diagnosis of COPD. A detailed description of spirometric data, comorbid pathology, and prescribed medications depending on clinical phenotypes is given. A high level of administration of inhaled glucocorticosteroids was revealed, which even patients without frequent exacerbations received in 54% of cases. Conclusion . The obtained data will help to develop optimal approaches to eliminate discrepancies between clinical recommendations for managing patients with COPD and actual clinical practice in Russia.

Introducing the New COPD Pocket Consultant Guide App: Can A Digital Approach Improve Care? A Statement of the COPD Foundation.

The COPD Foundation has tried to address gaps in chronic obstructive pulmonary disease (COPD) care by providing COPD Pocket Consultant Guide cards to U.S. health care providers. Since launching the card in 2007, there have been numerous updates and more than 800,000 of these cards have been distributed at no charge to health care professionals. The most recent versions have concentrated on presenting an algorithm for COPD management based on 7 severity domains: spirometry, symptoms, exacerbations, oxygen requirements, the presence of chronic bronchitis or emphysema and comorbidities. To increase the usability and reach of this tool, the COPD Pocket Consultant Guide is now available as an app for iOS and Android. This updated version of the app includes new COPD and asthma/COPD overlap flow charts; an interactive therapy chart that takes into account modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and spirometry scores; anxiety and depression screeners; up-to-date medication charts in both brand and generic formats; a checklist to aid in determining when a patient should be referred to a pulmonologist and more. Potential use of the COPD Pocket Consultant Guide app in clinical care is discussed.

Chronic bronchitis is associated with severe exacerbation and prolonged recovery period in Chinese patients with COPD: a multicenter cross-sectional study.

Chronic bronchitis (CB) is closely associated with the frequency and severity of chronic obstructive pulmonary disease (COPD) exacerbation. However, little is known about the impact of CB on COPD exacerbations, severe and non-severe, and on recovery from an exacerbation. We conducted a nation-wide multicenter cross-sectional survey in China between September 2007 and December 2008. Eleven hospitals participated in this study. Patients' demographic information, presence of CB, overall numbers of COPD exacerbation and severe exacerbation leading to emergency visit, hospitalization and intensive care unit (ICU) stay in the past year, recovery period following the last exacerbation, and well- or poor-recovery were recorded. A total of 1,101 patients with COPD were enrolled and 890 (80.8%) had CB. Patients with CB reported more history of frequent exacerbations (≥2/patient/year) (59.6% vs. 50.7%, P=0.019) and severe exacerbation (% emergency visit ≥1: 28.0% vs. 16.6%, P=0.001; % hospitalization ≥1: 51.2% vs. 28.0%, P<0.001; %ICU stay ≥1: 6.5% vs. 1.9%, P=0.009). Recovery period following the last exacerbation was longer in patients with CB (19.0±16.2 vs. 15.2±14.7 days, P=0.003) and more patients with CB reported poor recovery (85.8% vs. 78.4%, P=0.003). Multivariate analyses showed that CB was independently associated with severe exacerbation requiring emergency visit (adjusted OR, 1.512, P=0.048) and hospitalization (adjusted OR, 2.031, P<0.001) and prolonged recovery period (adjusted regression coefficient 2.861, P=0.030). CB is associated with frequent exacerbations of COPD in Chinese population, especially severe exacerbations requiring emergency visit and hospitalization admission. Additionally, CB significantly prolongs recovery period following COPD exacerbation.

Current asthma contributes as much as smoking to chronic bronchitis in middle age: a prospective population-based study.

Background and objectivePersonal smoking is widely regarded to be the primary cause of chronic bronchitis (CB) in adults, but with limited knowledge of contributions by other factors, including current asthma. We aimed to estimate the independent and relative contributions to adult CB from other potential influences spanning childhood to middle age.MethodsThe population-based Tasmanian Longitudinal Health Study cohort, people born in 1961, completed respiratory questionnaires and spirometry in 1968 (n=8,583). Thirty-seven years later, in 2004, two-thirds responded to a detailed postal survey (n=5,729), from which the presence of CB was established in middle age. A subsample (n=1,389) underwent postbronchodilator spirometry between 2006 and 2008 for the assessment of chronic airflow limitation, from which nonobstructive and obstructive CB were defined. Multivariable and multinomial logistic regression models were used to estimate relevant associations.ResultsThe prevalence of CB in middle age was 6.1% (95% confidence interval [CI]: 5.5, 6.8). Current asthma and/or wheezy breathing in middle age was independently associated with adult CB (odds ratio [OR]: 6.2 [95% CI: 4.6, 8.4]), and this estimate was significantly higher than for current smokers of at least 20 pack-years (OR: 3.0 [95% CI: 2.1, 4.3]). Current asthma and smoking in middle age were similarly associated with obstructive CB, in contrast to the association between allergy and nonobstructive CB. Childhood predictors included allergic history (OR: 1.3 [95% CI: 1.1, 1.7]), current asthma (OR: 1.8 [95% CI: 1.3, 2.7]), “episodic” childhood asthma (OR: 2.3 [95% CI: 1.4, 3.9]), and parental bronchitis symptoms (OR: 2.5 [95% CI: 1.6, 4.1]).ConclusionThe strong independent association between current asthma and CB in middle age suggests that this condition may be even more influential than personal smoking in a general population. The independent associations of childhood allergy and asthma, though not childhood bronchitis, as clinical predictors of adult CB raise the possibility of some of this burden having originated in childhood.

Twenty-five year trends in prevalence of chronic bronchitis and the trends in relation to smoking

The present study examines how the trends in the prevalence of chronic bronchitis during the last three decades associate with changes in smoking habits during the same period. Altogether 47 896 subjects aged 25-74 years were examined in six independent cross-sectional population surveys repeated every five years between 1982 and 2007 in Finland. The presence of chronic bronchitis, smoking habits and other risk factors were measured by standard questionnaires. During the study, the prevalence of chronic bronchitis was significantly higher in men than in women. In men aged 25-64 years, the prevalence of chronic bronchitis decreased from 19% in 1982 to 13% in 2007 (p for trend <0.001). The corresponding decrease in women aged 25-64 years was from 13% to 11% (p for trend 0.009). In men aged 65-74 years, the prevalence of chronic bronchitis decreased from 24% to 19% (p for trend 0.032). Simultaneously, male smoking decreased and smoking in middle-aged women increased. However, adjusting for the changes in smoking habits did not change the declining trends in the prevalence of chronic bronchitis. The significant declining trend in chronic bronchitis was seen separately in male current smokers and in male and female never smokers aged 45-74 years and the declining trend was the greatest in male current smokers. In general, female smokers with chronic bronchitis had smoked less than their male counterparts. There was a declining trend in the prevalence of chronic bronchitis which was probably explained by both a decrease in smoking and by other factors.

Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy.

Daily azithromycin decreases acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but long-term side effects are unknown. To identify the types of exacerbations most likely to be reduced and clinical subgroups most likely to benefit from azithromycin, 250 mg daily, added to usual care. Enrollment criteria included irreversible airflow limitation and AECOPD requiring corticosteroids, emergency department visit, or hospitalization in the prior year or use of supplemental oxygen. Recurrent events and cumulative incidence analyses compared treatment received for AECOPD by randomization group, stratified by subgroups of interest. Cox proportional hazards models estimated treatment effects in subgroups adjusted for age, sex, smoking status, FEV1% predicted, concomitant COPD medications, and oxygen use. Azithromycin was most effective in reducing AECOPD requiring both antibiotic and steroid treatment (n = 1,113; cumulative incidence analysis, P = 0.0002; recurrent events analysis, P = 0.002). No difference in treatment response by sex (P = 0.75), presence of chronic bronchitis (P = 0.19), concomitant inhaled therapy (P = 0.29), or supplemental oxygen use (P = 0.23) was observed. Older age and milder Global Initiative for Chronic Obstructive Lung Disease stage were associated with better treatment response (P = 0.02 and 0.04, respectively). A significant interaction between treatment and current smoking was seen (P = 0.03) and azithromycin did not reduce exacerbations in current smokers (hazard ratio, 0.99; 95% confidence interval, 0.71-1.38; P = 0.95). Azithromycin is most effective in preventing AECOPD requiring both antibiotic and steroid treatment. Adjusting for confounders, we saw no difference in efficacy by sex, history of chronic bronchitis, oxygen use, or concomitant COPD therapy. Greater efficacy was seen in older patients and milder Global Initiative for Chronic Obstructive Lung Disease stages. We found little evidence of treatment effect among current smokers. Clinical trial registered with www.clinicaltrials.gov (NCT0011986 and NCT00325897).

Serum free light chains and the adaptive immune response in usual and alpha-1-antitrypsin deficiency-related chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition with a complex pathophysiology. In COPD, the immune response involves the adaptive immune system, although the antigenic stimulus driving this response is unknown. During the process of antibody synthesis an excess of free light chains (FLCs) are produced and secreted into the circulation. High polyclonal FLC concentrations have been found in several autoimmune and inflammatory conditions such as systemic lupus erythematosus and rheumatoid arthritis. Thus, FLCs are being investigated as a biomarker of immune activation, disease activity, and severity in these conditions. Our aim was to establish whether serum FLCs could be a marker of phenotypic variation or predict poor outcome in patients with usual and alpha-1-antitrypsin deficiency (A1ATD)-related COPD. MethodsWe measured FLC concentrations in 294 COPD patients with A1ATD-related and 85 patients with usual COPD using the Freelite serum FLC assay (The Binding Site Ltd, Birmingham, UK). We then compared combined (κ and λ) FLC (cFLC) concentrations in different subgroups defined by the presence of chronic bronchitis, colonisation of the lower respiratory tract, and subsequent mortality. In addition, we measured the estimated glomerular filtration rate (eGFR) of patients included in the study. FindingsOur preliminary data showed that in A1ATD-related COPD and usual COPD, cFLC concentrations were significantly higher in patients with chronic bronchitis than in those without bronchitis (p=0·008 vs p=0·047). Patients with A1ATD-related COPD who were chronically colonised with pathogenic organisms in their stable state also had significantly higher cFLC concentrations than did those who were not colonised (p=0·036). A multiple regression analysis showed that eGFR and the presence of chronic bronchitis significantly predicted cFLC concentrations in patients with A1ATD: renal function was the strongest predictor (β=−0·326, p<0·0001) followed by the presence of chronic bronchitis (β=0·147, p=0·01). A similar trend was seen in the usual COPD group although this did not meet statistical significance (eGFR β=−0·220, p=0·055; chronic bronchitis β=0·224, p=0·061). The 33 A1ATD patients who subsequently died also had significantly higher cFLC concentrations (p=0·005) than did those still alive. InterpretationThe higher cFLC concentrations in patients with A1ATD-related COPD who have chronic bronchitis and colonised lower respiratory tracts could mean that there is a greater adaptive immune response in these individuals. The drive behind this response might come directly from microorganisms or through self-perpetuating autoimmune events. Within the specialty of COPD clinical management, there is a move towards a more individualised approach to treating different clinical phenotypes. Measurement of serum FLCs might have a potential role as a biomarker to help stratify patients. The higher cFLC concentrations in patients with renal impairment is unsurprising in view of their renal clearance, but raised polyclonal FLCs have also been shown to be a predictor of mortality in the general population. Our mortality results suggest that FLCs could have a role in risk stratification for patients with COPD, but further investigation is needed. FundingGrifols Therapeutics.

S62 Polyclonal free light chains: a potential biomarker for immune activation in alpha-1-antitrypsin deficiency (A1ATD) related chronic obstructive pulmonary disease

IntroductionA1ATD is a hereditary condition associated with the premature onset of chronic obstructive pulmonary disease (COPD). In COPD, the immune response within the lung is known to involve cells of...

Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in the Lower Airways in COPD

Cigarette smoke and smoking-induced inflammation decrease cystic fibrosis transmembrane conductance regulator (CFTR) activity and mucociliary transport in the nasal airway and cultured bronchial epithelial cells. This raises the possibility that lower airway CFTR dysfunction may contribute to the pathophysiology of COPD. We compared lower airway CFTR activity in current and former smokers with COPD, current smokers without COPD, and lifelong nonsmokers to examine the relationships between clinical characteristics and CFTR expression and function. Demographic, spirometry, and symptom questionnaire data were collected. CFTR activity was determined by nasal potential difference (NPD) and lower airway potential difference (LAPD) assays. The primary measure of CFTR function was the total change in chloride transport (Δchloride-free isoproterenol). CFTR protein expression in endobronchial biopsy specimens was measured by Western blot. Compared with healthy nonsmokers (n = 11), current smokers (n = 17) showed a significant reduction in LAPD CFTR activity (Δchloride-free isoproterenol, -8.70 mV vs -15.9 mV; P = .003). Similar reductions were observed in smokers with and without COPD. Former smokers with COPD (n = 7) showed a nonsignificant reduction in chloride conductance (-12.7 mV). A similar pattern was observed for CFTR protein expression. Univariate analysis demonstrated correlations between LAPD CFTR activity and current smoking, the presence of chronic bronchitis, and dyspnea scores. Smokers with and without COPD have reduced lower airway CFTR activity compared with healthy nonsmokers, and this finding correlates with disease phenotype. Acquired CFTR dysfunction may contribute to COPD pathogenesis.

Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD.

BackgroundAs chronic obstructive pulmonary disease (COPD) is a heterogeneous disease it is unlikely that all patients will benefit equally from a given therapy. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, has been shown to improve lung function in moderate and severe COPD but its effect on exacerbations in unselected populations was inconclusive. This led to the question of whether a responsive subset existed that could be investigated further.MethodsThe datasets of two previous replicate, randomized, double-blind, placebo-controlled, parallel-group studies (oral roflumilast 500 μg or placebo once daily for 52 weeks) that were inconclusive regarding exacerbations were combined in a post-hoc, pooled analysis to determine whether roflumilast reduced exacerbations in a more precisely defined patient subset.ResultsThe pooled analysis included 2686 randomized patients. Roflumilast significantly decreased exacerbations by 14.3% compared with placebo (p = 0.026). Features associated with this reduction were: presence of chronic bronchitis with or without emphysema (26.2% decrease, p = 0.001), presence of cough (20.9% decrease, p = 0.006), presence of sputum (17.8% decrease, p = 0.03), and concurrent use of inhaled corticosteroids (ICS; 18.8% decrease, p = 0.014). The incidence of adverse events was similar with roflumilast and placebo (81.5% vs 80.1%), but more patients in the roflumilast group had events assessed as likely or definitely related to the study drug (21.5% vs 8.3%).ConclusionsThis post-hoc, pooled analysis showed that roflumilast reduced exacerbation frequency in a subset of COPD patients whose characteristics included chronic bronchitis with/without concurrent ICS. These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment.Trials registrationClinicalTrials.gov identifiers: NCT00076089 and NCT00430729.

Risk Factors for Benign Prostatic Hyperplasia in South Korean Men

Objectives: Benign prostatic hyperplasia (BPH) is the most common prostate disease in middle-aged and elderly men, and leads to severe impairment in later life. Despite the significant effect on public health, the causes of BPH have received little attention. Identifying risk factors for BPH is crucial for understanding the etiology and for determining effective interventions or targeting strategies. Methods: This survey was performed in two steps: (1) a pilot study was first conducted prior to the main study in order to estimate baseline characteristics, and (2) the main study investigated the prevalence and risk factors of BPH using clinical diagnostic tests and a questionnaire. A total of 641 males, aged 50–79 years, participated in this community-based cross-sectional study. Results: Age was the only significant demographic risk factor of BPH. The presence of chronic bronchitis and a high prostate-specific antigen (PSA) level increased the risk by three- and twofold, respectively. The risk decreased as drinking frequency increased. Physical activity 3–5 times/week reduced the risk relative to being active less than twice per week; however, engaging in physical activity nearly everyday increased the risk 1.7-fold relative to being active up to twice per week. Conclusions: Although BPH has been considered a disease that is unavoidable with advancing age, the clear identification and control of the underlying risk factors might allow effective prevention by placing a special emphasis on those at risk.

Chronic bronchitis among French adults: high prevalence and underdiagnosis.

The aims of this survey were to determine the prevalence of symptoms indicative of chronic bronchitis (CB) in the French adult population, to identify the role of risk factors for CB, and to assess rates of CB diagnosis and pulmonary function testing (PFT) in the presence of CB. A representative sample of 14,076 individuals aged > or = 25 yrs completed a self-administered questionnaire on symptoms, comorbidities, smoking history, sociodemographical data, and diagnosis and care by physicians. The prevalence of CB was 4.1% and the prevalence of chronic cough and/or expectoration was 11.7%. In individuals with comorbidity, these figures were 10.4% and 24.4%, respectively. Smoking was associated with an increased frequency of CB. In subjects with CB, 44.6% had PFT (spirometry or peak expiratory flow measurement), 24% were diagnosed as having CB, and 7.2% received care. Rates of diagnosis, PFT, and follow-up were lower in young individuals and in those without comorbidity. PFT and follow-up were less common in current smokers. Prevalence of chronic bronchitis in French adults is high and similar in magnitude to that of other industrialised countries. Comorbidities and tobacco smoking increase the frequency of chronic bronchitis symptoms. Chronic bronchitis is too infrequently diagnosed, investigated and cared for.