Denis Caillaud

Clinical COPD phenotypes: a novel approach using principal component and cluster analyses

Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV1) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George’s Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0–73.0) yrs; FEV1 was 48.9 (34.1–66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV1) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.

Cough and Sputum Production Are Associated With Frequent Exacerbations and Hospitalizations in COPD Subjects

BACKGROUND Epidemiologic studies indicate that chronic cough and sputum production are associated with increased mortality and disease progression in COPD subjects. Our objective was to identify features associated with chronic cough and sputum production in COPD subjects. METHODS Cross-sectional analysis of data were obtained in a multicenter (17 university hospitals in France) cohort of COPD patients. The cohort comprised 433 COPD subjects (65 +/- 11 years; FEV(1), 50 +/- 20% predicted). Subjects with (n = 321) and without (n = 112) chronic cough and sputum production were compared. RESULTS No significant difference was observed between groups for age, FEV(1), body mass index, and comorbidities. Subjects with chronic cough and sputum production had increased total mean numbers of exacerbations per patient per year (2.20 +/- 2.20 vs 0.97 +/- 1.19, respectively; p < 0.0001), moderate exacerbations (1.80 +/- 2.07 vs 0.66 +/- 0.85, respectively; p < 0.0001), and severe exacerbations requiring hospitalizations (0.43 +/- 0.95 vs 0.22 +/- 0.56, respectively; p < 0.02). The total number of exacerbations per patient per year was the only variable independently associated with chronic cough and sputum production. Frequent exacerbations (two or more per patient per year) occurred in 55% vs 22% of subjects, respectively, with and without chronic cough and sputum production (p < 0.0001). Chronic cough and sputum production and decreased FEV(1) were independently associated with an increased risk of frequent exacerbations and frequent hospitalizations. CONCLUSIONS Chronic cough and sputum production are associated with frequent COPD exacerbations, including severe exacerbations requiring hospitalizations.

Long-term exposure to close-proximity air pollution and asthma and allergies in urban children

The aim of this study was to evaluate the impact of urban air pollution, assessed through reliable indicators of exposure, on asthma and allergies in schoolchildren. A validated dispersion model combining data on traffic conditions, topography, meteorology and background pollution was used to relate 3-yrs averaged concentrations of major urban pollutants at the sites of schools to skin prick tests, exercise-induced asthma and reported asthma and allergies in 6,683 children (9–11 yrs) attending 108 schools randomly selected in six French communities. For the 4,907 children who had resided at their current address for the past 3 yrs, asthma (exercise induced, past year and lifetime) was significantly positively associated with benzene, SO2, particles with a 50% cut-off aerodynamic diameter of 10 &mgr;m (PM10), nitrogen oxides (NOx) and CO. In the same children, eczema (lifetime and past year) was significantly positively associated with benzene, PM10, NO2, NOx and CO, lifetime allergic rhinitis with PM10 and sensitisation to pollens with benzene and PM10. Among the 2,213 children residing at their current address since birth, the associations persisted for lifetime asthma with benzene (adjusted OR per interquartile range (95% CI) 1.3 (1.0–1.9)) and PM10 (1.4 (1.0–2.0)), and for sensitisation to pollens with volatile organic compounds (1.3 (1.0–1.9)) and PM10 (1.2 (1.0–1.9)). Accurately modelled urban air pollution was associated with some measures of childhood asthma and allergies.

Clinical COPD phenotypes identified by cluster analysis: validation with mortality

To the Editors: Because forced expiratory volume in 1 s is a poor descriptor of chronic obstructive pulmonary disease (COPD) heterogeneity [1], interest has emerged regarding the identification of clinically relevant COPD phenotypes [2, 3]. We recently reported the usefulness of applying mathematical models ( i.e. principal component and cluster analyses) to multiple variables for the identification of clinical phenotypes in a cohort of COPD subjects [4]. These original analyses allowed the description of four COPD groups, which we called “clinical COPD phenotypes” [4]. This terminology was based on the classical definition of “phenotype”, referring to the observable characteristics (including respiratory manifestations and comorbidities) of patients. Recently, a panel of experts proposed the following modified definition for clinical COPD phenotypes: “a single or combination of disease attributes that describes differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)” [2 …

Relationship between blood eosinophils, clinical characteristics, and mortality in patients with COPD

In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan–Meier analysis. Three sets of analyses were performed to compare patients with ≥2% versus <2%, ≥3% versus <3%, and ≥4% versus <4% Eos. Eos was available in 458 patients (mean age: 62 years, 72% male, mean forced expiratory volume in 1 second: 51% pred), including 235 patients with Eos ≥2% (49%), 149 with Eos ≥3% (33%), and 90 with Eos ≥4% (20%). For all cutoffs, there was no difference between Eos+ and Eos− groups in univariate analyses except for diabetes and SGRQ score (more frequent and more impaired, respectively, in lower Eos categories). In particular, there was no difference in exacerbation rate, history of asthma, or three-year survival. In conclusion, regardless of the cutoff, Eos+ COPD patients exhibited no specific characteristic in terms of symptoms, lung function, exacerbation rate, and prognosis. These findings suggest that the association of higher Eos with exacerbations reported in previous studies could be population specific, which does not support generalizing the use of Eos as a biomarker for COPD phenotyping.

Asthma–COPD overlap syndrome (ACOS) vs ‘pure’ COPD: a distinct phenotype?

Some studies suggest that asthma–COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real‐life cohort of patients with COPD.

Association between occupational exposure and the clinical characteristics of COPD

BackgroundThe contribution of occupational exposures to COPD and their interaction with cigarette smoking on clinical pattern of COPD remain underappreciated. The aim of this study was to explore the contribution of occupational exposures on clinical pattern of COPD.MethodsCross-sectional data from a multicenter tertiary care cohort of 591 smokers or ex-smokers with COPD (median FEV1 49%) were analyzed. Self-reported exposure to vapor, dust, gas or fumes (VDGF) at any time during the entire career was recorded.ResultsVDGF exposure was reported in 209 (35%) subjects aged 31 to 88 years. Several features were significantly associated with VDGF exposure: age (median 68 versus 64 years, p < 0.001), male gender (90% vs 76%; p < 0.0001), reported work-related respiratory disability (86% vs 7%, p < 0.001), current wheezing (71% vs 61%, p = 0.03) and hay fever (15.5% vs 8.5%, p < 0.01). In contrast, current and cumulative smoking was less (p = 0.01) despite similar severity of airflow obstruction.ConclusionIn this patient series of COPD patients, subjects exposed to VDGF were older male patients who reported more work-related respiratory disability, more asthma-like symptoms and atopy, suggesting that, even in smokers or ex-smokers with COPD, occupational exposures are associated with distinct patients characteristics.

Prevalence and association of asthma and allergic sensitization with dietary factors in schoolchildren: data from the french six cities study

BackgroundThe prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study.MethodsCross-sectional studies were performed among 7432 schoolchildren aged 9–11 years in Bordeaux, Clermont-Ferrand, Créteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions.ResultsAsthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56–0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07–2.05]) and having lunch at the canteen 1–2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52–0.96]), lifetime asthma (0.76 [0.60–0.96]) and allergic sensitization (0.80 [0.67–0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50–0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47–3.93] and 1.51 [1.17–2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43–0.87]. None of the dietary factors was associated with BHR.ConclusionsDiet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy.

Relationships between molds and asthma suggesting non-allergic mechanisms. A rural-urban comparison.

A fungal index, based on specific microbial volatile organic compounds (MVOCs) emission, was employed and related to asthma in children from rural and urban dwellings after stratification on the children atopic status.

Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children

Objective The purpose of this study was to examine the association between pre and post environmental tobacco smoke (ETS) exposure and behavioral problems in schoolchildren. Methods In the cross-sectional 6 cities Study conducted in France, 5221 primary school children were investigated. Pre- and postnatal exposure to secondhand tobacco smoke at home was assessed using a parent questionnaire. Child’s behavioral outcomes (emotional symptoms and conduct problems) were evaluated by the Strengths and Difficulties Questionnaire (SDQ) completed by the parents. Results ETS exposure during the postnatal period and during both pre- and postnatal periods was associated with behavioral problems in children. Abnormal emotional symptoms (internalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.72 (95% Confidence Interval (CI)= 1.36-2.17), whereas the OR was estimated to be 1.38 (95% CI= 1.12-1.69) in the case of postnatal exposure only. Abnormal conduct problems (externalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.94 (95% CI= 1.51-2.50), whereas the OR was estimated to be 1.47 (95% CI=1.17-1.84) in the case of postnatal exposure only. Effect estimates were adjusted for gender, study center, ethnic origin, child age, low parental education, current physician diagnosed asthma, siblings, preterm birth and single parenthood. Conclusion Postnatal ETS exposure, alone or in association with prenatal exposure, increases the risk of behavioral problems in school-age children.