There are conflicting data regarding the magnitude and determinants of chronic obstructive pulmonary disease (COPD) risk in farmers.In a cross-sectional study of 917 nonfarming working controls and 3787 farmers aged 40-75 years, we assessed respiratory symptoms, tobacco exposure, job history (without direct exposure measurement) and lung function. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion ( post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70) and by the Quanjer reference equation ( post-bronchodilator FEV1/FVC

Prostacyclin analogues targeting the prostacyclin pathway are used to treat patients with pulmonary arterial hypertension (PAH), and are given either by an intravenous, subcutaneous or inhaled route [1]. Continuous i.v. infusion of epoprostenol has received the strongest recommendation for treatment of the most severe forms of PAH [2], mainly because it is the only PAH-specific drug that was demonstrated to give an improvement in survival in a randomised controlled study [3]. Due to drawbacks associated with its i.v. administration, epoprostenol is preferentially offered to young, high-risk patients [2]. For PAH patients in New York Heart Association (NYHA) functional class (FC) III/IV with severe haemodynamic impairment, epoprostenol can be combined with an endothelin receptor antagonist (ERA) and a phosphodiesterase type-5 (PDE-5) inhibitor to achieve sustained clinical and haemodynamic efficacy [4, 5].Selexipag is a prostacyclin receptor agonist whose molecular structure is different from the prostacyclin analogues that can be orally administered with few side-effects [6,7]. Therefore, while selexipag has been developed for the treatment of PAH, it is not considered equivalent to prostacyclin analogues [1,2]. Nevertheless, due to recurrent catheter-related infections and/or problems with patient acceptance, several physicians have attempted to replace i.v. epoprostenol with selexipag in selected patients. The current literature provides some reports and case-series of successful transitions from a prostacyclin analogue to selexipag. The available data are, however, fragmentary because of 1) the small number of cases; 2) the type of drug administered before the transition (mainly treprostinil (i.v. or s.c.) or inhaled prostacyclin); and 3) the absence of long-term haemodynamic follow-up. As not all prostacyclin analogues and/or all routes of administration are equivalent for the treatment of PAH [1], we aimed to investigate the consequences of transition from i.v. epoprostenol to oral selexipag.The study population consisted of all patients with PAH enrolled in the French PH Network registry treated for at least 3 months with i.v. epoprostenol, who have been transitioned to oral selexipag, and with at least one evaluation, including a right heart catheterisation, while on selexipag. Clinical and haemodynamic characteristics of patients were collected at the time of first diagnosis of PAH, at the time of transition (while receiving epoprostenol, just before the initiation of selexipag), and at first and last evaluations on selexipag. Continuous variables were compared using a Wilcoxon signed-ranked test and categorical variables were compared using a McNemar test or a cumulative logic marginal model for variables with two categories and three or more categories, respectively [8]. A Bonferroni correction was applied to correct for multiple tests and, thus, a p-value lower than 0.025 was considered as significant.We identified eight patients with PAH (idiopathic, n=5; heritable, n=2; associated with a connective t...

Although they did not present with chronic activity-related dyspnoea, subjects with a postbronchodilator FEV1/FVC

Asthma is a widespread respiratory disease caused by complex contribution from genetic, environmental and behavioral factors. For several decades, its sensitivity to environmental factors has been investigated in single exposure (or single family of exposures) studies, which might be a narrow approach to tackle the etiology of such a complex multifactorial disease. The emergence of the exposome concept, introduced by C. Wild (2005), offers an alternative to address exposure–health associations. After presenting an overview of the exposome concept, we discuss different statistical approaches used to study the exposome–health associations and review recent studies linking multiple families of exposures to asthma-related outcomes. The few studies published so far on the association between the exposome and asthma-related outcomes showed differences in terms of study design, population, exposome definition and statistical methods used, making their results difficult to compare. Regarding statistical methods, most studies applied successively univariate (Exposome-Wide Association Study (ExWAS)) and multivariate (adjusted for co-exposures) (e.g., Deletion–Substitution–Addition (DSA) algorithm) regression-based models. This latest approach makes it possible to assess associations between a large set of exposures and asthma outcomes. However, it cannot address complex interactions (i.e., of order ≥3) or mixture effects. Other approaches like cluster-based analyses, that lead to the identification of specific profiles of exposure at risk for the studied health-outcome, or mediation analyses, that allow the integration of information from intermediate biological layers, could offer a new avenue in the understanding of the environment–asthma association. European projects focusing on the exposome research have recently been launched and should provide new results to help fill the gap that currently exists in our understanding of the effect of environment on respiratory health.

Background: Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate.Objective: To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. Methods:The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for

IntroductionThe current definition of chronic obstructive pulmonary disease (COPD) associates persistent airflow limitation and chronic respiratory symptoms. Agricultural work has been associated with an increased risk of developing COPD, but the prevalence and definition of the disease vary greatly between studies. This meta-analysis aimed to assess the association between agricultural work and COPD using the most widely used definitions of the disease.MethodsInclusion criteria were: (1) design: cross-sectional or longitudinal, (2) groups: at least one group of farmers and a control group of non-farmers, (3) outcome: prevalence or unadjusted OR of COPD, airflow limitation and/or chronic bronchitis, (4) study subjects: groups of exposed subjects comprising ≥30 individuals and with a mean age ≥40 years and (5) language: English and French language, full-length, original publications in peer-reviewed journals.ResultsIn total, 22 manuscripts were included in the meta-analysis. Eight studies assessed only the prevalence of airflow limitation, nine assessed only the prevalence of chronic bronchitis and four assessed the prevalence of both these parameters. Only one assessed the prevalence of COPD according to its current definition, and this study also provided the prevalence of airflow limitation. Ten studies showed a positive association between farming exposure and airflow limitation or chronic bronchitis, and 12 showed no association (OR (95% CI)=1.77 (1.50 to 2.08), p<0.001). Cattle, swine, poultry and crop farming were associated with either airflow limitation or chronic bronchitis.ConclusionAlthough some features of COPD are associated with some agricultural work, well-designed studies with appropriate diagnostic criteria should be conducted to draw strong conclusions about the relationship between COPD and farming.

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide () is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning into membrane conductance (diffusing capacity) for carbon monoxide () and alveolar capillary blood volume () through combined measurement of and transfer factor of the lung for nitric oxide () is more effective to identify pulmonary hypertension in SSc patients compared with alone. Here, the objective was to determine whether combined- partitioned with recently refined equations could more accurately detect pulmonary hypertension than alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients., and were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for (0.82, 95% CI 0.79-0.85) and (0.80, 95% CI 0.76-0.83), but lower for (0.75, 95% CI 0.71-0.78) and (0.66, 95% CI 0.62-0.70).Compared with alone, combined- does not add capability to detect pulmonary hypertension in unselected SSc patients.

Pseudomonas aeruginosa is the main cause of chronic airway infection in cystic fibrosis (CF). However, for unclear reasons some patients are never colonized by P. aeruginosa. The objectives of this study were to better define the clinical, genetic, and microbiological characteristics of such a subpopulation and to identify predictive factors of non-colonization with P. aeruginosa. The French CF patient registry 2013–2014 was used to identify CF patients aged ≥ 20 years. The clinical outcomes, CF Transmembrane conductance Regulator (CFTR) genotypes, and microbiological data of patients reported positive at least once for P. aeruginosa (“Pyo” group, n = 1,827) were compared to those of patients with no history of P. aeruginosa isolation (“Never” group, n = 303). Predictive factors of non-colonization by P. aeruginosa were identified by multivariate logistic regression model with backward selection. Absence of aspergillosis (odds ratio (OR) [95% CI] = 1.64 [1.01–2.66]), absence of diabetes (2.25 [1.21–4.18]), pancreatic sufficiency (1.81 [1.30–2.52]), forced expiratory volume 1 (FEV1) ≥ 80% (3.03 [2.28–4.03]), older age at CF diagnosis (1.03 [1.02–1.04]), and absence of F508del/F508del genotype (2.17 [1.48–3.19]) were predictive clinical factors associated with absence of infection (“Never” group). Microbiologically, this same group was associated with more frequent detection of Haemophilus influenzae and lower rates of Stenotrophomonas maltophilia, Achromobacter xylosoxidans and Aspergillus spp. (all p<0.01) in sputum. This study strongly suggests that the absence of pulmonary colonization by P. aeruginosa in a minority of CF adults (14.2%) is associated with a milder form of the disease. Recent progress in the development of drugs to correct CFTR deficiency thus may be decisive in the control of P. aeruginosa lung infection.