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Abstract Background Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. Methods To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). Results 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. Conclusion These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.

Abstract 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).

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 steady increase of IgE-dependent allergic diseases after the Second World War is a unique phenomenon in the history of humankind. Numerous cross-sectional studies, comprehensive longitudinal cohort studies of children living in various types of environment, and mechanistic experimental studies have pointed to the disappearance of “protective factors” related to major changes in lifestyle and environment. A common unifying concept is that of the immunoregulatory role of the gut microbiota. This review focuses on the protection against allergic disorders that is provided by the farming environment and by exposure to microbial diversity. It also questions whether and how microbial bioengineering will be able in the future to restore an interplay that was beneficial to the proper immunological development of children in the past and that was irreversibly disrupted by changes in lifestyle. The protective “farming environment” includes independent and additional influences: contact with animals, stay in barns/stables, and consumption of unprocessed milk and milk products, by mothers during pregnancy and by children in early life. More than the overall quantity of microbes, the biodiversity of the farm microbial environment appears to be crucial for this protection, as does the biodiversity of the gut microbiota that it may provide. Use of conventional probiotics, especially various species or strains of Lactobacillus and Bifidobacterium, has not fulfilled the expectations of allergists and pediatricians to prevent allergy. Among the specific organisms present in cowsheds that could be used for prevention, Acinetobacter (A.) lwoffii F78, Lactococcus (L.) lactis G121, and Staphylococcus (S.) sciuri W620 seem to be the most promising, based on experimental studies in mouse models of allergic respiratory diseases. However, the development of a new generation of probiotics based on very productive research on the farming environment faces several obstacles that cannot be overcome without a close collaboration between microbiologists, immunologists, and bioengineers, as well as pediatricians, allergists, specialists of clinical trials, and ethical committees.

Abstract Background Farmers are exposed to multiple air contaminants that may interact with tobacco smoking in the development of respiratory diseases. Farmers are currently considered to smoke less than non-farmers, but precise data in different categories of age and farming activities are lacking. Methods Smoking habits were studied in a cross-sectional study involving 4105 farmers and 996 non-farming controls aged 40–74 years in 9 French departments between October 2012 and May 2013. Three age groups were defined (40–54, 55–64 and 65-74years). Farmers were divided into four activity groups, namely cattle breeders, livestock farmers working in confined spaces, crop farmers and others. Smoking prevalence was compared between farmers and controls, and odds ratios (ORs) for smoking adjusted for age were calculated. Results The adjusted OR for ever-smoking was lower among farmers than among non-farmers in all age categories, but the ORs for current smoking were similar in farmers and controls. Smoking prevalence varied according to the type of farming activity, and was lower than in non-farming controls only among cattle breeders and confined livestock farmers. In farmers, the proportion of smokers was higher in the youngest age categories compared with the older age classes. Conclusions Our results confirm that the prevalence of ever-smokers is lower in farmers than in non-farmers. Nevertheless, our data show that active smoking prevalence is similar in farmers and in non-farmers. This suggests that farmers, just like non-farmers, should be targeted by primary prevention campaigns against smoking.

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

This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host–microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

This review is the summary of a workshop on small airways disease, which took place in Porquerolles, France in November 2011. The purpose of this workshop was to review the evidence on small airways (bronchiolar) involvement under various pathophysiological circumstances, excluding asthma and chronic obstructive pulmonary disease. Histopathological patterns associated with small airways disease were reviewed, including cellular and obliterative bronchiolitis. Many pathophysiological conditions have been associated with small airways disease including airway infections, connective tissue diseases and inflammatory bowel diseases, bone marrow and lung transplantation, common variable immunodeficiency disorders, diffuse panbronchiolitis, and diseases related to environmental exposures to pollutants, allergens and drugs. Pathogenesis, clinical presentation, a computed tomography scan and pulmonary function test findings are reviewed, and therapeutic options are described with the objective of providing an integrative approach to these disorders.

The use of recombinant antigens has been shown to improve both the sensitivity and the standardization of the serological diagnosis of Farmer's lung disease (FLD). The aim of this study was to complete the panel of recombinant antigens available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known to be involved in FLD. L. corymbifera proteins were thus separated by 2D electrophoresis and subjected to western blotting with sera from 7 patients with FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins were identified by mass spectrometry based on a protein database specifically created for this study and subsequently produced as recombinant antigens. The ability of recombinant antigens to discriminate patients with FLD from controls was assessed by ELISA performed with sera from FLD patients (n = 41) and controls (n = 43) recruited from five university hospital pneumology departments of France and Switzerland. Forty-one FLD-associated immunoreactive proteins from L. corymbifera were identified. Six of them were produced as recombinant antigens. With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl dehydrogenase was the most effective antigen for discriminating FLD patients from HEC. ELISA performed with the putative proteasome subunit alpha type as an antigen was especially specific (88.6%) and could thus be used for FLD confirmation. The production of recombinant antigens from L. corymbifera represents an additional step towards the development of a standardized ELISA kit for FLD diagnosis.

A new survey coordinated by the French expert centres for rare pulmonary diseases investigated French pulmonologists' diagnostic and therapeutic practice for idiopathic pulmonary fibrosis (IPF) and explored changes since a previous survey in 2011–2012. From May 16 to August 30, 2014, 524 pulmonologists were contacted. Those following at least one patient with IPF were invited to complete a questionnaire administered by telephone or e-mail. 166 (31.7%) pulmonologists, 161 (97%) of whom had participated to the first survey, completed the questionnaire. Of those, 46% and 52%, respectively, discussed the cases with radiologists and pathologists. Out of 144 pulmonologists practicing outside of expert centres, 80% indicated referring patients to those centres. The 2013 French practical guidelines for IPF were known by 92% of pulmonologists involved in IPF, 96% of whom considered them appropriate for practice. The multidisciplinary discussion form for IPF diagnosis was known by 74% and considered appropriate by 94%. Diagnosis and management resulted from multidisciplinary discussion in 50% of the cases. About 58% of patients were diagnosed with “mild to moderate IPF” as defined by forced vital capacity ≥50% of the predicted value and diffusing capacity for carbon monoxide ≥35% of predicted. At the time of the survey, 31% of physicians were using pirfenidone to treat patients with “mild-to-moderately severe IPF” and 30% generally prescribed no treatment. Substantial improvement has occurred since the 2011–2012 survey with regard to knowledge of guidelines and proper management of IPF. Early diagnosis still needs to be improved through the network of expert centres.

Farmer's lung (FL) is a common type of hypersensitivity pneumonitis. It is often considered that fibrosis is the most frequent finding in chronic FL. Nevertheless, three cohort studies have suggested that some patients with chronic FL may develop emphysema. We aimed to evaluate the current prevalence of emphysema in active FL, to describe the radiological and functional features of emphysema in active FL, and to identify risk factors associated with emphysema in this population.Patients aged over 18 years with active FL were prospectively recruited through the SOPHIA study (CPP Est; P-2009-521), between 2007 and 2015. Each patient had complete medical history screening, clinical examination, high resolution computed tomodensitometry, bronchoalveolar lavage, pulmonary function tests and serum precipitins.Among 33 patients with active FL, the prevalence of emphysema in this series of incident active FL cases was higher (48.5%) than that of fibrosis (12%) and was not dependent on smoking habits. Most patients with emphysema did not have lung hyperinflation. The possible risk factors for emphysema in active FL were a longer duration of exposure to organic dusts, and at a higher level.Emphysema is found in half of patients with active FL and may be influenced by exposure patterns.