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International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)

International audience; This report is based on proceedings from the Exposure Assessment Tools for Hypersensitivity Pneumonitis (HP) Workshop, sponsored by the American Thoracic Society, that took place on May 18, 2019, in Dallas, Texas. The workshop was initiated by members from the Environmental, Occupational, and Population Health and Clinical Problems Assemblies of the American Thoracic Society. Participants included international experts from pulmonary medicine, occupational medicine, radiology, pathology, and exposure science. The meeting objectives were to 1) define currently available tools for exposure assessment in evaluation of HP, 2) describe the evidence base supporting the role for these exposure assessment tools in HP evaluation, 3) identify limitations and barriers to each tool's implementation in clinical practice, 4) determine which exposure assessment tools demonstrate the best performance characteristics and applicability, and 5) identify research needs for improving exposure assessment tools for HP. Specific discussion topics included history-taking and exposure questionnaires, antigen avoidance, environmental assessment, specific inhalational challenge, serum-specific IgG testing, skin testing, lymphocyte proliferation testing, and a multidisciplinary team approach. Priorities for research in this area were identified.

Background Comorbidities including cardiovascular diseases are very common in chronic obstructive pulmonary disease (COPD) secondary to tobacco smoking and contribute to the overall severity of the disease. In non-smoking COPD, which accounts for about 25% of COPD cases worldwide, current knowledge on the frequency and determinants of comorbidities remains scarce. The aims of the current study were to assess the frequency of major comorbidities and to evaluate their determinants in a group of non-selected patients with mild-to-moderate COPD who were exposed to organic dust (dairy farmers), to tobacco smoking, or to both, and in controls without COPD who were exposed to organic dust (dairy farmers), or to tobacco smoking, or to both, or who were without exposure. Patients and Methods A total of 4665 subjects (2323 dairy farmers and 2342 non-farmers) including 355 patients with COPD and 4310 controls with normal spirometry were recruited through a large COPD screening program. Self-reported physician-diagnosed diseases with plausible links to COPD were recorded in this cross-sectional study. Results Whatever the exposure, cardiovascular comorbidities were not more frequent in patients with COPD than their counterparts without airflow limitation. A higher risk of major cardiovascular comorbidities was associated with tobacco smoking and a lower risk was associated with exposure to organic dusts. Conclusion Tobacco smoking (but not COPD) is associated with higher frequency of cardiovascular comorbidities. By contrast, being a dairy farmer exposed to organic dusts is associated with a lower frequency of the same comorbidities. This reinforces the crucial need for controlling established cardiovascular risk factors even in patients with mild-to-moderate COPD.

Background The observation that COPD is an independent risk factor for cardiovascular disease (CVDs) comes from comparisons between smokers with COPD and smokers without COPD. The mechanisms that explain increased risk of CVD in patients with COPD are still unclear. Objectives The goal of this study was to assess systemic arterial stiffness (a predictor of CVD mortality) and to evaluate its determinants in a group of patients with mild to moderate COPD secondary to organic dust exposure, tobacco smoking, or both. Methods Systemic arterial stiffness was assessed by using aortic pulse wave velocity (aPWV). Measurements were made in 142 patients with COPD and 155 healthy control subjects matched for age, sex, BMI, and tobacco smoking, exposed to tobacco smoking (n = 56/70 for COPD/control subjects, respectively), organic dusts (n = 44/48), or both (n = 42/37). Results aPWV was higher in COPD than in healthy controls in subjects exposed to tobacco smoking and to both organic dusts and tobacco smoking. By contrast, among never smokers exposed to organic dusts, patients with COPD and matched control subjects had similar aPWV. Multivariate analysis of the 142 patients with COPD (exposed to tobacco smoking and/or to organic dusts) showed that tobacco smoking was associated with high aPWV. Moreover, soluble suppression of tumorigenicity 2, a marker of major cardiovascular events, was correlated with aPWV in these patients. Conclusions Analysis of an unselected group of patients with COPD with different causes suggests that: (1) COPD by itself is not sufficient to explain increased aPWV; and (2) tobacco smoking is a risk factor for elevated aPWV in COPD.

Introduction Proper diagnosis of COPD remains a challenge. Spirometry testing in primary care may help to reduce misdiagnosis, but its reliability as a diagnostic instrument needs to be assessed. Objectives To investigate (1) the validity of spirometry testing performed in primary care and (2) the accuracy of the diagnostic of airflow limitation obtained by these tests. Methods Subjects attending a COPD screening programme had screening spirometry performed either by general practitioners (GPs) or by trained nurses or technicians, who had all received two 3-hour training sessions. Subjects with airflow limitation and a subset of subjects with normal spirometry at screening were invited to undergo confirmatory spirometry performed by trained nurses in a pulmonary function laboratory. Results Of the 4610 subjects who attended the screening sessions, 96.5% had a valid screening spirometry test. A total of 392 subjects attended the confirmatory sessions. Values measured by screening spirometry were satisfactory compared with those of confirmatory spirometry (rc = 0.83). Taking confirmatory spirometry as reference, the positive predictive value of screening spirometry for the diagnosis of persistent airflow limitation was 93% with a specificity of 95%. Agreement for the diagnosis of persistent airflow limitation was substantial (k = 0.80). Conclusion Spirometry performed in primary care by trained personnel reliably identifies persistent airflow limitation. This may encourage pulmonologists to collaborate with primary care providers with the aim of improving appropriate diagnosis of COPD.

BACKGROUND: Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain inconsistent. The aim of this study was to investigate the association between pre- and post-natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis). METHODS: A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6 years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded. RESULTS: Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11-2.48 and for food allergy: aOR 3.01, 95% CI 1.22-7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4 years (aOR 2.73, 95% CI 1.66-4.49) and also suggested a dose-response relationship. A tendency was observed with asthma between 3 and 6 years (aOR 1.65, 95% CI 0.95-2.86). CONCLUSIONS: Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post-natal exposure to antibiotics in children born in rural settings.

Compensation for occupational pulmonary diseases requires the establishment of guidelines based on standardized and objective criteria, in order to provide compensation that is as fair as possible to patients who suffer from them. A review of the elements necessary for the examination of an individual file was carried out by a working group. It is accepted that respiratory functional exploration is the key element in assessing the level of permanent disability in all of these conditions, with the exception of thoracic malignancies. Guiding scales have been developed for the respiratory impairment of three types of conditions: occupational asthma, thoracic malignancy, and other respiratory diseases. Additional criteria for increasing the permanent disability level are also proposed in order to take into account professional prejudice, in particular the possibility or not of continuing the occupational activity, in the same job or after changing to another. For certain respiratory diseases, a periodic reassessment of the initially attributed permanent disability level is recommended as well as the initial one at the time of definitive cessation of occupational activity.

Inflammatory response in patients with COPD secondary to organic dust exposure (OD-COPD) is poorly understood. We therefore aimed to characterize inflammatory and immune profile from peripheral blood mononuclear cells (PBMC) in a group of patients with mild-to-moderate COPD secondary to organic dust exposure (OD-COPD), tobacco smoking (T-COPD), or both. We compared T, B and NK cells distribution and inflammatory (TNF-α, Il-1β, IL-6), type 1 (IFN-γ), type 2 (IL-4, IL-13) and type 3 (IL-17) immunity related cytokines at baseline, and after stimulation with LPS, flagellin and CD3/CD28 beads in all COPD groups. OD-COPD displayed significantly lower NK cells and CD8+ T cells compared with controls. After flagellin stimulation, T-COPD had significantly lower IL-13 levels than OD-COPD and controls (p 0.05) whereas IFN-γ tended to be lower in OD-COPD. All COPD groups displayed higher IL-1β and IL-17 than controls after CD3/CD28 stimulation. Inflammatory responses in OD-COPD were different from T-COPD. OD-COPD displayed higher levels of type 2 immunity related cytokines.

IntroductionInterstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives.MethodsThe consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro, by studying the production and secretion of the corresponding mutated proteins and ex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented.ResultsFor the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6–65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic.DiscussionThis study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

Case Presentation A 35-year-old man was admitted for recurrent episodes of pneumonia. He complained of a 2-month history of exertional dyspnea and productive cough with whitish and viscous sputum which was poorly responsive to antibiotic therapy. He also reported a weight loss of 5 kg since the first symptoms appeared. There was no dysphagia, fever, or chest pain. He currently did not use medication and did not have a relevant medical history except a current 10 pack-year smoking history. He did not report any history of trauma or respiratory exposure to fats.

International audience; Background: There are chronic forms of hypersensitivity pneumonitis (cHP) that can progress to pulmonary fibrosis. There is no recommended treatment for patients whose respiratory condition continues to deteriorate in spite of antigen avoidance. Whether rituximab may be beneficial to patients with cHP is unknown. The aim of this study was to describe the course of 20 patients with cHP under rituximab therapy.Methods: This retrospective study was conducted from November 2018 to July 2019 in 7 French university hospitals. Forced Vital Capacity (FVC) was measured 6 months before rituximab therapy onset (M - 6), at rituximab onset (M0), and 6 months later (M+6).Results: FVC decreased significantly in the 6 months preceding the introduction of rituximab (65% [44; 112%] at M - 6 versus 59% [39; 102%] at M0; p = 0.0001), but it did not differ significantly from that at 6 months after the introduction of rituximab (61% [38; 99%]). The decline in FVC between M0 and M+6 (-3% [-15; +19%]) was significantly less than between M - 6 and M0 (-8% [-21; 0%]) (p = 0.0002). Between M0 (37% [16; 73%]) and M + 6 (45% [15; 70%]), the median DLCO remained stable (p = 0.12). DLCO improved at M+6 in 5 of the 8 patients (63%) for whom a DLCO value was available at M+6 improved their DLCO.Conclusion: Rituximab seems well tolerated, and may lead to stabilization or improvement of lung function in some patients.

International audience; Background - Although farming is often considered a risk factor for COPD, data regarding the burden and characteristics of COPD in dairy farmers are sparse and conflicting. Objectives - To characterize COPD in dairy farmers. Methods - 4788 subjects entered two parallel COPD screening programs, one in agricultural workers and one in general practice from 2011 to 2015. Subjects with COPD were invited to participate in the characterization phase of the study. Those who accepted were included in two subgroups: dairy farmers with COPD (DF-COPD) (n = 101) and non-farmers with COPD (NF-COPD) (n = 85). Patients with COPD were frequency-matched with subjects with normal spirometry for age, sex and tobacco smoking (pack-years and status) (DF-controls n = 98, NF-controls n = 89). All subjects from these four groups underwent lung function and exercise testing, questionnaires and blood analysis. Results - The frequency of COPD in dairy farmers was 8.0% using the GOLD criterion and 6.2% using the lower limit of normal criterion and was similar in non-farming subjects (7.3% and 5.2%, respectively) although dairy farmers had lower tobacco consumption (screening phase). DF-COPD had better pulmonary function, exercise capacity and quality of life, fewer symptoms and comorbidities than NF-COPD, and higher levels of some Th2 biomarkers (MCP-2, periostin) (characterization phase). In farmers, COPD was not related to occupational exposure factors, supporting the role of host factors. Conclusion - COPD secondary to organic dust exposure (dairy farming) appears less severe and associated with fewer comorbidities than COPD secondary to tobacco smoking.

Secondary spontaneous pneumothorax (SSP) occurs in the context of underlying pulmonary disease. Our objectives were to estimate the relationship between SSP and short term air pollution exposure with nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 μm (PM10). Patients with SSP were included between June 1, 2009 and May 31, 2013, in 14 Emergency Departments in France. In this case–crossover design study, PM10, NO2, and O3 data were collected hourly from monitoring stations. Quantitative values, fast increase in air pollutant concentration, and air quality threshold exceedance were retained. These assessments were calculated for each of the 4 days prior to the event (Lag 1–Lag 4) for all case and control period, and for the entire exposure period. A total of 135 patients with SSP were included, with a mean age of 55.56 (SD 18.54) years. For short term exposure of PM10, NO2 and O3, no differences were observed between case and control periods in terms of quantitative values of air pollutant exposure (P > 0.68), fast increase in concentration (P > 0.12) or air quality threshold exceedance (P > 0.68). An association between O3 exposures cannot be ruled out, especially when considering the Lag 2 prior to the event and in warm seasons.

Interstitial lung diseases (ILDs) can be caused by mutations in theThe consequences of the 11For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic

International audience; Purpose: Respiratory hazards of farming have been identified for centuries, with little focus on gender differences. We used data from the AGRICOH consortium, a collective of prospective cohorts of agricultural workers, to assess respiratory disease prevalence among adults in 18 cohorts representing over 200,000 farmers, farm workers, and their spouses from six continents.Methods: Cohorts collected data between 1992 and 2016 and ranged in size from 200 to >128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.

Secondary spontaneous pneumothorax (SSP) occurs in the context of underlying pulmonary disease. Our objectives were to estimate the relationship between SSP and short term air pollution exposure with nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 μm (PM10). Patients with SSP were included between June 1, 2009 and May 31, 2013, in 14 Emergency Departments in France. In this case–crossover design study, PM10, NO2, and O3 data were collected hourly from monitoring stations. Quantitative values, fast increase in air pollutant concentration, and air quality threshold exceedance were retained. These assessments were calculated for each of the 4 days prior to the event (Lag 1–Lag 4) for all case and control period, and for the entire exposure period. A total of 135 patients with SSP were included, with a mean age of 55.56 (SD 18.54) years. For short term exposure of PM10, NO2 and O3, no differences were observed between case and control periods in terms of quantitative values of air pollutant exposure (P > 0.68), fast increase in concentration (P > 0.12) or air quality threshold exceedance (P > 0.68). An association between O3 exposures cannot be ruled out, especially when considering the Lag 2 prior to the event and in warm seasons.

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis, (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country’s history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.

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), pConclusionAlthough 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.

International audience; Background The effect of exposure to micro-organisms on allergic diseases has been well studied. The protective effect of early food diversity against allergic diseases was previously shown in the PASTURE cohort study. The consumption of cheese, a food potentially rich in microbial diversity, deserves further examination. We aimed to evaluate whether cheese consumption is associated with allergic diseases. Methods In the PASTURE study (birth cohort in 5 European countries), data on feeding practices, environmental factors and allergic diseases were collected by questionnaires from birth to 6 years (N=931). Cheese consumption at 18 months of age was quantified in terms of frequency and diversity (i.e., number of consumed types among 6 types: hard pressed, semi-pressed, soft, blue, fresh cheese, from the farm). Multiple logistic regressions were performed to evaluate the effect of cheese consumption on atopic dermatitis (AD), food allergy (FA), allergic rhinitis, asthma and atopic sensitization at 6 years after adjustment for confounders of atopy. Results Cheese consumption (vs. non-consumption) had a significant protective effect on AD (OR=0.51 [0.29-0.90], p=0.02) and FA (OR=0.32, [0.15-0.71], p=0.004), but no effect on atopic sensitization, allergic rhinitis and asthma at 6 years. This effect on AD and FA may be related to the diversity of consumed cheeses (OR=0.64 [0.48-0.85] per cheese type, p=0.002; OR=0.55 [0.33-0.92], p=0.02, respectively). Conclusions Although reverse causality cannot totally be ruled out, cheese diversity at 18 months had a protective effect against AD and FA at 6 years in addition to the protective effect of diversity of other foods.

International audience; Bird fancier's lung (BFL) is a pulmonary disease caused by inhalation of avian proteins. The involvement of the microorganisms of droppings has been assumed in the past and this idea still persists today. Our study aimed to compare by immunoprecipitation assay the detection of antibodies against both droppings and microorganisms in the sera of patients (n=15) and asymptomatic exposed controls (n=18). We found that 14/15 BFL patients had negative serological results for isolated microorganisms of the droppings, only one positive against Enterobacter sakasakii. Serological arguments were in accordance with diagnosis in 87 % of cases by testing à la carte antigens from each bird dropping versus 20 % using the standard antigenic panel. Otherwise, the microorganisms antigens issued from dropping flora were negative in 93 % of cases. Consequently, it's preferable to use the total extract from the patient's bird droppings to establish the serodiagnosis of the disease.

Background Chronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis. Methods A list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, interquartile range = 0 on a 5-point Likert scale (1, strongly agree; 2, tend to agree; 3, neither agree nor disagree; 4, disagree; 5, strongly disagree). Results In two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by patients with ILD for readability and usability. Conclusions This Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.

Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments (PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (beta = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.Growing up in the rich microbial environment of a farm strongly influences the maturation of the gut microbiome in the first year of life, which helps protect against the development of asthma in children.

International audience; Exposure to organic dusts is an independent causative factor of chronic obstructive pulmonary disease (COPD). Unhealthy dietary patterns have been associated with poor lung function in smokers. This study investigated whether dietary patterns were associated with post-bronchodilator airway obstruction, a hallmark of COPD, in dairy farmers exposed to organic dusts. All subjects were identified by screening programs and patients with airflow obstruction were matched with subjects with normal spirometry. Six groups were compared, defined by their exposures (non-smoking dairy farmers, smokers ≥ 10 pack-years with no occupational exposure, and smoking dairy farmers) and the presence or absence of post-bronchodilator airflow obstruction, resulting in 321 study subjects. The Alternative Healthy Eating Index (AHEI) score was calculated based on an adapted food frequency questionnaire. Mean total AHEI scores were similar in all groups. Comparison between smokers with post-bronchodilator airway obstruction and subjects with post-bronchodilator airway obstruction related to occupational exposure found minimal differences in dietary patterns: dairy farmers had lower scores for the ratio of white to red meat and higher scores for cereal fiber consumption. As in previous studies, smokers with post-bronchodilator airway obstruction exhibited higher lipid intakes and lower carbohydrate intakes than their counterparts with normal spirometry. No evidence of any meaningful difference in dietary patterns was found between subjects with post-bronchodilator airway obstruction detected by screening and healthy controls, either in dairy farmers or in smokers with no occupational exposure.

OBJECTIVES: Lack of microbiota accessible carbohydrates (MAC) can drive gut commensal extinctions. Infant formula lacks the MAC found in breastmilk, human milk oligosaccharides (HMOs). As a result, a switch from breastmilk feeding (high MAC) to formula (low MAC) may drive extinctions of infant gut commensals. METHODS: The prevalence of Bifidobacterium longum subsp. infantis, a bacterium that efficiently consumes HMOs, was compared in cohorts from Austria, Bangladesh, Finland, Gambia, Germany, Switzerland, and United States. Scientific literature reports that both Bangladesh and Gambia have long duration breastfeeding without a history of prevalent formula use; Bangladesh has a mean duration of breastfeeding of 31.9 months and Gambia has a median duration of breastfeeding >18 months. This contrasts with European countries and the US, who all have median duration of breastfeeding 50% relative abundance Bifidobacterium) despite the low frequency of colonization with B. infantis. The R0 of B. infantis transmission varied by country. CONCLUSIONS: The prevalence of infant colonization with B. infantis may be sensitive to breastfeeding duration in populations. Our data supports the concept that lack of MAC drives commensal extinctions, and suggests that deliberate intervention may be needed to restore B. infantis, a bacteria that benefits infant health. More studies are needed, particularly to determine whether species of Bifidobacterium other than B. infantis are sensitive to breastfeeding duration, and to understand the impact of different types of Bifidobacterium on infant health. FUNDING SOURCES: NIH awards F32HD093185 (DHT), AT007079 (DAM), and AT008759 (DAM).

Rationale: A link is established between air pollution and respiratory diseases. Very few studies evaluated this link with primary spontaneous pneumothorax (PSP). Contrasted results, low statistical power and methodological limits of these studies brought us to evaluate in a more thorough way this link. Objectives: (1) to estimate the relation between PSP and air pollutants namely nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 μm (PM10); (2) to investigate a time lag effect between these pollutants and occurrence of PSP. Methods: This study has a case-crossover design. Subjects aged ≥18 years admitted from 1st June 2009 to 31st May 2013, in 14 Emergency Departments centers on the French territory. Were excluded: patients with traumatic, secondary, recurrent or history of previous pneumothorax. NO2, O3 and PM10 data were collected hourly in monitoring stations. Three exposure assessments were retained: quantitative values, fast increase concentration of air pollutants and peak of pollution. These assessments were calculated for the entire exposure period and for each of the four days of all case and control periods. Results: 948 subjects included. Whatever the pollutant considered, no differences were observed between case and control periods, regardless of whether the quantitative values of air pollutants exposure (p > 0.09), fast increase concentration (p > 0.46) and peak of pollution (p > 0.20). Conclusions: We failed to show a relation between PSP and short-term air pollution exposure to low levels of NO2 and PM10. An association between O3 exposure and PSP cannot be ruled out. An impact at higher exposure level, and/or a potentiating effect of different meteorological factors remain to be demonstrated. Keywords: Pneumothorax, Air pollution, Case-crossover study

The observation that COPD is an independent risk factor for cardiovascular disease (CVDs) comes from comparisons between smokers with COPD and smokers without COPD. The mechanisms that explain increased risk of CVD in patients with COPD are still unclear.The goal of this study was to assess systemic arterial stiffness (a predictor of CVD mortality) and to evaluate its determinants in a group of patients with mild to moderate COPD secondary to organic dust exposure, tobacco smoking, or both.Systemic arterial stiffness was assessed by using aortic pulse wave velocity (aPWV). Measurements were made in 142 patients with COPD and 155 healthy control subjects matched for age, sex, BMI, and tobacco smoking, exposed to tobacco smoking (n = 56/70 for COPD/control subjects, respectively), organic dusts (n = 44/48), or both (n = 42/37).aPWV was higher in COPD than in healthy controls in subjects exposed to tobacco smoking and to both organic dusts and tobacco smoking. By contrast, among never smokers exposed to organic dusts, patients with COPD and matched control subjects had similar aPWV. Multivariate analysis of the 142 patients with COPD (exposed to tobacco smoking and/or to organic dusts) showed that tobacco smoking was associated with high aPWV. Moreover, soluble suppression of tumorigenicity 2, a marker of major cardiovascular events, was correlated with aPWV in these patients.Analysis of an unselected group of patients with COPD with different causes suggests that: (1) COPD by itself is not sufficient to explain increased aPWV; and (2) tobacco smoking is a risk factor for elevated aPWV in COPD.

Allergic mechanisms related to environmental and occupational exposure have been suggested to contribute to the development of chronic obstructive pulmonary disease (COPD). Objectives To investigate the relationships between atopy markers, persistent airflow limitation (PAL) and occupational exposure in dairy farmers. Methods Clinical and biological (total IgE and 21 allergen specific IgE) markers of atopy were assessed in 101 dairy farmers with PAL (DF-PAL), 85 non-farmers with PAL (NF-PAL) (both groups were prospectively included from a screening program performed between 2011 and 2015), and matched controls, i.e. 98 farmers without PAL (DF-controls) and 89 non-farming subjects without PAL (NF-controls). Occupational exposure in farmers was estimated using a validated questionnaire. Results Prevalence of allergy history was significantly higher in DF-PAL and in NF-PAL than in controls. Polysensitization, and sensitization to seasonal and food allergens were more frequent in DF-PAL than in DF-controls, respectively: 13.8% vs 1% (adjusted odds ratio (aOR): 17.5 (2.2–134), 11.9% vs 3.1% (aOR: 4.4 (1.2–7.2) and 16.8% vs 4.1% (aOR: 5.2 (1.7–7.2)). The prevalence of atopy markers was similar between NF-PAL patients and NF-controls. Conclusions PAL in farmers is associated with a high rate of markers of atopy, supporting atopy as a risk indicator. Clinical trial registered with ClinicalTrials.gov (NCT02540408). Electronic supplementary material The online version of this article (10.1186/s12931-019-1082-2) contains supplementary material, which is available to authorized users.

Copd: think about occupational exposures! Unfortunately, the occupational exposures of COPD are still poorly taught and poorly researched, although they account for 15 to 20% of all COPD. The clinician must know them well and therefore systematically seek them for any newly diagnosed case. A thorough and rigorous professional interview allows to trace the entire professional career, even when the patient smokes. The main exposures in industrial and agricultural sectors are described. Recognition of COPD in occupational diseases is only possible in France since a few years, in a restrictive way. The prevention of occupational COPD (reduction or elimination of environmental pollution in the workplace) is likely to reduce the incidence of COPD in exposed workers. A regular monitoring to detect early COPD (spirometry) is needed.Bpco : pensez aussi aux causes professionnelles ! Mal connues, les causes professionnelles des bronchopneumopathies chroniques obstructives (BPCO) sont encore peu enseignées et mal recherchées, bien qu’à l'origine de 15 à 20 % des BPCO. Le clinicien doit bien les connaître et donc les rechercher systématiquement devant tout cas nouvellement diagnostiqué. Un interrogatoire professionnel complet et rigoureux permet de retracer toute la carrière professionnelle, même lorsqu’il existe une intoxication tabagique avérée. Les principales expositions en milieu industriel et en secteur agricole sont décrites. La reconnaissance des BPCO en maladie professionnelle n’est possible en France que depuis quelques années, de façon encore très limitative. La prévention des BPCO d’origine professionnelle (réduction ou suppression des pollutions de l’environnement du travail) est susceptible de diminuer l’incidence de cette pathologie chez les travailleurs exposés. Ils doivent bénéficier d’une surveillance régulière nécessaire pour dépister une BPCO débutante (spirométrie).

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

Occupational characteristics of dairy farming COPD and controls. (DOCX 20 kb)

Background: Childhood asthma is often preceded by early wheeze. Usually, wheezing episodes are recorded retrospectively, which may induce recall bias. Aims and objectives: The aim of this study was to investigate true-positive recall of parent-reported wheeze at 1year of age, its determinants, and its implications for asthma and lung function at 6years of age. Methods: The PASTURE (Protection Against Allergy—Study in Rural Environments) study followed 880 children from rural areas in 5 European countries from birth to age 6years. Wheeze symptoms in the first year were asked weekly. At age 6, parent-reported asthma diagnosis was ascertained and lung function measurements were conducted. Correct parental recall of wheeze episodes at the end of the first year was assessed for associations with lung function, asthma, and the asthma risk locus on chromosome 17q21. Results: Parents correctly recalled wheeze after the first year in 54% of wheezers. This true-positive recall was determined by number of episodes, timing of the last wheeze episode, and parental asthma. Independently from these determinants, true-positive recall predicted asthma at age 6years (odds ratio 4.54, 95% confidence interval (CI) [1.75-14.16]) and impaired lung function (β=−0.62, 95% CI [−1.12; −0.13], P-value=.02). Associations were stronger in children with asthma risk SNPs on chromosome 17q21. Conclusion: Correct parental recall of wheezing episodes may reflect clinical relevance of early wheeze and its impact on subsequent asthma and lung function impairment. Questions tailored to parental perception of wheezing episodes may further enhance asthma prediction.

Supplementary methods (DOCX 25 kb)

Adjusted odds ratios for markers of atopy in the whole population considering three tested indicators (DOCX 17 kb)

International audience; INTRODUCTION:Playing a wind instrument is an increasingly reported cause of hypersensitivity pneumonitis. However, current knowledge about contamination of wind instruments by fungi and specific fungal sensitization is scarce. Therefore, we aimed: (i) to assess the current prevalence and type of fungal contamination of wind instruments, (ii) to identify potential risk factors associated with instrument contamination, and (iii) to evaluate the prevalence of sensitization to these fungi among musicians.MATERIAL AND METHODS:Musicians from music schools in eastern France and who played a wind instrument were prospectively recruited (NCT01487850). The mouthpiece and the reed of their instrument were sampled to quantify the magnitude and type of fungi. Each subject had a physical examination, a mycological analysis of saliva and a blood sample in search of serum precipitins against the most frequent fungi isolated from instruments. The results were compared with those of 40 healthy non-exposed controls.RESULTS:Forty musicians playing a wind instrument (bassoon, clarinet, oboe, saxophone) were included. (i) 95% of wind instruments were colonized by fungi, mainly with Phoma spp., Penicillium spp. and Rhodotorula mucilaginosa; (ii) absence of systematic drying of the instrument was a main contributing factor; (iii) serum precipitins were significantly more present in the musicians' sera than in control sera and were consistent with the fungi present in their instrument.CONCLUSION:This study reveals a constant and specific fungal contamination among wind reed instruments with a significant sensitization among musicians, pleading in favour of regular instrument cleaning. Physicians should be aware of this possible source of antigenic exposure.

A 52-year-old non-smoking beautician using a skincare device spraying steam and ozone (a "vapozone" facial steamer) was referred for progressive dyspnea and dry cough during working periods. Although spirometry was normal, she had decreased diffusing capacity of the lung for carbon monoxide, bronchiolitis with air trapping on high-resolution CT scan and 60% lymphocytosis by bronchoalveolar lavage. Twenty-six antigens were tested and serum-specific precipitins were found mainly against Pseudomonas sp. and Mycobacterium mucogenicum. Cultures from her skincare device isolated Pseudomonas sp. Outcome was favorable with cessation of occupational exposure to the device, without any medication. This is the first report of a case of HP in a beautician due to steam contaminated by Pseudomonas sp. from a vapozone. HP, and not only asthma and contact dermatitis, should be suspected in beauticians with respiratory symptoms. Am. J. Ind. Med. 59:1041-1045, 2016. © 2016 Wiley Periodicals, Inc.