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Background: The purpose of this study was to evaluate the correlation between immediate responsiveness with the short-acting β2-agonist salbutamol and effects of treatment with the ultra-long-acting β2-agonist indacaterol in patients with chronic obstructive pulmonary disease (COPD).Methods: The REVERBREZ study was a phase IV, multicentre, open-label study in which patients with moderate-to-severe COPD received indacaterol 150 μg once-daily for 5 months. The primary endpoint was the correlation between immediate response of forced expiratory volume in 1 s (FEV1) post-inhalation of salbutamol (400 μg) at study entry and the change from baseline in trough FEV1 after 1 month of indacaterol. Secondary endpoints included dyspnoea measured by the modified Medical Research Council (mMRC) grade and health-related quality of life measured by the clinical COPD questionnaire (CCQ).Results: Of the 602 patients enrolled from 177 centres in France, 543 patients received at least one indacaterol dose, 512 patients completed 1 month of indacaterol treatment (primary endpoint), and 400 patients completed 5 months of treatment. At study entry, mean FEV1 values before and after salbutamol inhalation were 1.54 ± 0.50 L and 1.65 ± 0.53 L, respectively. Based on the magnitude of an immediate response of FEV1 after salbutamol inhalation at study entry, patients were classified into reversible (Rv, ≥12% and ≥200 mL from pre-salbutamol value; n = 106) and non-reversible (NRv, <12% or <200 mL from pre-salbutamol value; n = 431) groups. After 1 month of indacaterol treatment, mean absolute and relative difference in trough FEV1 were 100 mL and 9%, respectively. No significant correlation was found between the immediate FEV1 response to salbutamol at study entry and change from baseline in trough FEV1 after 1 month of indacaterol treatment (correlation coefficient = 0.056 [95% CI;-0.032, 0.144] for absolute response and 0.028 [95% CI;-0.06, 0.116] for relative response). At all subsequent visits, mMRC and CCQ scores, and FEV1 improved from baseline with no significant difference between the Rv and NRv groups.Conclusions: Immediate FEV1 response to salbutamol did not predict the long-term benefits observed with indacaterol treatment in patients with COPD. Patients considered reversible or non-reversible to salbutamol showed comparable improvements in lung function, dyspnoea and health-related quality of life.Trial Registration: ClinicalTrials.gov: NCT01272362 . Date: January 5, 2011. [ABSTRACT FROM AUTHOR]

The article presents the study on the features associated with chronic cough and sputum production in patients with chronic obstructive pulmonary disease (COPD) in France. Researchers reviewed data from 17 university hospitals in the country. Results of the study found no significant difference between groups for age, body mass index and comorbidities. It was concluded that chronic cough and sputum production are linked with frequent COPD exacerbations.

Background: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities. Methods: Patients were recruited from the real-life French COPD cohort "Initiatives BPCO". A low 6MWD was defined as <350 m. EID was defined by a minimum pulse oxygen saturation (SpO2)<90% and delta SpO2≥4% from baseline. Multivariate logistic regression analyses assessed the influence on 6MWD and EID of age, sex, obesity (body mass index, BMI >30 kg/m 2 ), low BMI (BMI <18.5 kg/m 2 ), modified Medical Research Council (mMRC) dyspnea scale, FEV1% pred, FVC % pred, hyperinflation and comorbidities including cardiovascular diseases. Results: Among 440 patients with available 6MWT data, a 6MWD <350 m was found in 146 patients (33%), which was positively associated in multivariate analyses with age and mMRC and negatively with resting SpO2 and FVC % pred (rescaled r 2 =0.34), whereas no comorbidity was associated with a low 6WMD. EID was found in 155 patients (35%). This was positively associated with hypertension and negatively with age, obesity, FEV1% pred and resting SpO2 (rescaled r 2 =0.37). Conclusion: 6MWD and EID exhibit different determinants in COPD with a minor impact of comorbidities limited to hypertension in EID and to obesity, which was unexpectedly associated with less EID. Other variables including age, routine resting lung function and SpO2 were weakly associated with 6MWD and EID. Altogether, these results suggest that 6MWT performance remains difficult to predict with routine clinical/functional parameters., Competing Interests: Dr Thierry Perez reports personal fees from Boehringer Ingelheim, Novartis, GSK, and Chiesi, and grants from Astra Zeneca, outside the submitted work. Professor Gaétan Deslée reports grants and personal fees from BTG/PneumRx; grants from Nuvaira; personal fees from Chiesi, grants and personal fees from AstraZeneca, outside the submitted work. Professor Pierre Régis Burgel reports personal fees from Astra-Zeneca, Boehringer Ingelheim, Chiesi, GSK, Pfizer, Teva, Vertex, and Zambon, outside the submitted work. Professor Denis Caillaud has nothing to disclose. Dr Olivier Le Rouzic reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, Lilly, Novartis, and PulmonX; non-financial support from GlaxoSmithKlein,, outside the submitted work. Dr Maeva Zysman reports personal fees and non-financial support from Boehringer ingelheim, during the conduct of the study; grants and personal fees from Novartis, grants from Fondation pour la recherche medicale; grants from Astra Zeneca; personal fees from Chiesi, outside the submitted work. Dr Roger Escamilla has nothing to disclose. Dr Gilles Jebrak has nothing to disclose. Professor Pascal Chanez has nothing to disclose. Dr Isabelle Court-Fortune reports grants and personal fees from Boehringer Ingelheim, during the conduct of the study. Dr Graziella Brinchault-Rabin has nothing to disclose. Dr Pascale Nesme-Meyer reports personal fees from Boehringer Ingelheim, outside the submitted work. Mr Jean Louis Paillasseur reports grants from iBPCO association, during the conduct of the study. Professor Nicolas Roche reports grants from Boehringer Ingelheim (France), during the conduct of the study. The authors report no other conflicts of interest in this work.

Background: The COPD "frequent exacerbator" phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations., Methods: Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters., Results: Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations., Conclusions: These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials. Little is known on the correspondence between the two methods., Methods: Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George's Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained. Correlations between mMRC and BDI scores were assessed using Spearman's correlation coefficient. An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores., Results: Data are given as median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8]. Both BDI and mMRC scores were significantly correlated at the group level (rho =-0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade. In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio. The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index., Conclusion: Dyspnea is a complex symptom with multiple determinants in COPD patients. Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable.

Background: Comorbidities are frequent in subjects with COPD, but their contribution to health-related quality of life (HRQoL) impairment is not clearly established., Methods: Cross-sectional analysis of data from the French COPD cohort Initiatives BPCO. Data were recorded in stable state and included spirometry, dyspnea (modified Medical Research Council - mMRC-scale), mood disorders (hospital anxiety-depression scale) and physician-diagnosed comorbidities including diabetes, hypertension, coronary artery disease, chronic heart failure, venous thromboembolism. HRQoL was assessed using the disease-specific St. George's Respiratory Questionnaire (SGRQ). Stepwise forward and backward multiple regression analyses were performed to examine the contribution of comorbidities to SGRQ scores., Results: Data are median [IQR]. 326 COPD subjects were analyzed: male 77%, age 65.0 [57.0; 72.0] years, FEV(1) 48.9 [34.7; 65.9]% predicted. SGRQ total score was 44.2 [30.0; 61.2]. In univariate analysis, positive correlations were found between SGRQ total scores and dyspnea and exacerbations/patient/year, whereas negative correlations were found with FEV(1). SGRQ total scores were increased in women (P = 0.06), and in subjects with low BMI, anxiety or depression (each analysis, P < 0.001), but not in subjects with cardiovascular comorbidities or diabetes. In multivariate analyses, major independent determinants of SGRQ total score included dyspnea, exacerbations/patient/year and depression. Low BMI, coronary artery disease and FEV(1) were also independently associated with SGRQ total score, but their contribution was only modest., Conclusions: These data suggest that in the presence of dyspnea and exacerbation, depression is the most important contributor to HRQoL impairment measured by SGRQ in COPD subjects, whereas other comorbidities and FEV(1) have only limited impact., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Osteoporosis is a common complication of cystic fibrosis., Objective: To determine the prevalence of osteopenia and osteoporosis in adults with cystic fibrosis and to look for factors associated with low bone mineral density (BMD) values., Methods: During this prospective 2-year study, we collected clinical data (history, body mass index, and treatments) and laboratory data (nutritional and hormonal status, markers for inflammation and bone turnover, and calcium and phosphate levels). Lung function tests and a 6-meter walking test were performed. BMD was measured at the spine, total hip, and femoral neck., Results: We included 55 patients (31 women) with a mean age of 31.9 years; 14 were homozygous and 25 heterozygous for the deltaF508 mutation and 20 (36%) had a history of fractures. BMD values indicated osteopenia in 32 (58.2%) patients and osteoporosis in 11 (20%) patients at one or more measurement sites. At all three sites, BMD values correlated with the body mass index, forced vital capacity as % predicted, and forced expiratory volume in 1 s as % predicted; at the femoral neck and total hip, BMD values correlated with the 6-meter walking test result and grip strength., Conclusion: BMD was low in 78.2% of adults with cystic fibrosis. Three factors reflecting lung disease severity were associated with low BMD values, namely, respiratory function, physical function (walking test and grip strength), and nutritional status., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) share risk factors and impair each other's prognosis., Aims: To assess the prevalence of airflow limitation (AL) compatible with COPD in a population at cardiovascular risk and to identify determinants of AL., Methods: All consecutive patients referred to the cardiovascular prevention unit of a university hospital in 2009 were studied in a cross-sectional analysis. Patients answered questionnaires on socioeconomic status, medical history and lifestyle, and underwent extensive physical examinations, biological measures and spirometry testing. AL was defined as FEV1/FVC<0.70, without any history of asthma. Determinants of AL were assessed using logistic regression., Results: The sample comprised 493 participants (mean age 57.4±11.1 years); 60% were men, 18% were current smokers, 42% were ex-smokers and 10% of patients had a history of CVD. Ten-year risk of coronary heart disease (CHD) according to the Framingham equation was intermediate (10-20%) for 25% of patients and high (>20%) for 10%. Prevalence of AL was 5.9% (95% confidence interval [CI] 4.0-8.3%) in the whole population and 4.3% (2.6-6.6%) among subjects in primary cardiovascular prevention. AL was independently associated with CVD (adjusted odds ratio 4.18, 95% CI 1.72-10.15; P=0.002) but not with Framingham CHD risk. More than 80% of patients screened with AL had not been diagnosed previously and more than one in two patients was asymptomatic., Conclusion: Patients with CVD are at increased risk of AL and thus should benefit from AL screening as they are frequently asymptomatic., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The aim of this study was first to assess the relevance of a marine sponge, Spongia officinalis, as a biomonitor of PCB. Twenty-four chlorobiphenyl congeners have been measured along a pollution gradient both in sponges and seawater. S. officinalis displays a capacity to accumulate all types of congeners. The highest concentration factors were found for hexa- and heptachlorobiphenyls. Concentrations recorded in sponges agreed quite well with the PCB concentrations of study sites. The prevalence of CB138 and CB153 definitely demonstrated the urban origin of the PCB detected, despite the ban on their production and the existence of a wastewater treatment plant since 1987. The CB138/CB153 ratio is approximately 1.2 in commercial mixtures as well as in seawater. In sponges, this ratio varies strongly in space and time, from 1 in sponges at the most polluted site to 0.3 at the reference site. This change in the ratio of these two very persistent congeners, which is not observed in seawater, indicates a metabolism of CB138 in sponges. As it was recently demonstrated for nonpersistent organic contaminants, sponges might well be able to degrade PCB, but further work is needed to identify the processes involved.