Inflammatory and immunological profile in COPD secondary to organic dust exposure.

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-1ß, 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-1ß 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.

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study.

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.

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer.

INTRODUCTION: Interstitial 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. METHODS: The 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. RESULTS: For 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. DISCUSSION: This 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.

Characterization of chronic obstructive pulmonary disease in dairy farmers.

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.

TNF-α-induced protein 3 is a key player in childhood asthma development and environment-mediated protection.

BACKGROUND: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-α-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, mediates environmentally induced asthma protection. OBJECTIVE: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. METHODS: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective" farms or LPS. NF-κB signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. RESULTS: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P < .05), reflecting their increased inflammatory status. Ex vivo farm dust or LPS stimulation restored TNFAIP3 expression to healthy levels in asthmatic patients and shifted NF-κB signaling-associated gene expression toward an anti-inflammatory state (P < .001). Farm/rural children had lower expression, indicating tolerance induction by continuous environmental exposure. Newborns with asthma at school age had reduced TNFAIP3 expression at birth, suggesting TNFAIP3 as a possible biomarker predicting subsequent asthma. CONCLUSION: Our data indicate TNFAIP3 as a key regulator during childhood asthma development and its environmentally mediated protection. Because environmental dust exposure conferred the anti-inflammatory effects, it might represent a promising future agent for asthma prevention and treatment.

Is atopy a risk indicator of chronic obstructive pulmonary disease in dairy farmers?

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).

The protective effect of cheese consumption at 18 months on allergic diseases in the first 6 years.

BACKGROUND: The effect of exposure to microorganisms 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 (ie, number of consumed types among 6 types: hard pressed, semipressed, soft, blue, fresh cheese, and 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. nonconsumption) 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). CONCLUSION: 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.

High levels of butyrate and propionate in early life are associated with protection against atopy.

BACKGROUND: Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma. METHODS: We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation. RESULTS: Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation. CONCLUSION: Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.

Association between antibiotic treatment during pregnancy and infancy and the development of allergic diseases.

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.

Parents know it best: Prediction of asthma and lung function by parental perception of early wheezing episodes.

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 1 year of age, its determinants, and its implications for asthma and lung function at 6 years 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 6 years. 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 6 years (odds ratio 4.54, 95% confidence interval (CI) [1.75-14.16]) and impaired lung function (ß = -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.

COPD, airflow limitation and chronic bronchitis in farmers: a systematic review and meta-analysis.

INTRODUCTION: The 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. METHODS: Inclusion 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. RESULTS: In 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. CONCLUSION: Although 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.

Dietary Patterns and Prevalence of Post-bronchodilator Airway Obstruction in Dairy Farmers Exposed to Organic Dusts.

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.

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

Microbial exposure to dairy farmers' dwellings and COPD occurrence.

Dairy farming is a risk factor for chronic obstructive pulmonary disease (COPD). The aim was to determine predictive markers either in blood samples or in dwelling dust samples by comparing COPD and healthy controls with or without farming activity. Dust was collected and analyzed by real-time quantitative PCR. ELISA and DELFIA® were performed to assay the level of specific IgG and IgE of 10 targeted microorganisms. The dwelling exposure of farmers was higher than in the non-farmers (Especially Eurotium amstelodami and Lichtheimia corymbifera). The IgG response against Wallemia sebi and Saccharopolyspora rectivirgula was more often higher in the farmers than the non-farmers. However, exposure and sensitization to the microorganisms tested cannot explain the occurrence of COPD in the dairy farmers' population. COPD development is probably caused by multiple factors associated with exposure over a period of several years.

Functional phenotypes determined by fluctuation-based clustering of lung function measurements in healthy and asthmatic cohort participants.

RATIONALE: Asthma is characterised by inflammation and reversible airway obstruction. However, these features are not always closely related. Fluctuations of daily lung function contain information on asthma phenotypes, exacerbation risk and response to long-acting ß-agonists. OBJECTIVES: In search of subgroups of asthmatic participants with specific lung functional features, we developed and validated a novel clustering approach to asthma phenotyping, which exploits the information contained within the fluctuating behaviour of twice-daily lung function measurements. METHODS: Forced expiratory volume during the first second (FEV1) and peak expiratory flow (PEF) were prospectively measured over 4 weeks in 696 healthy and asthmatic school children (Protection Against Allergy - Study in Rural Environments (PASTURE)/EFRAIM cohort), and over 1 year in 138 asthmatic adults with mild-to-moderate or severe asthma (Pan-European Longitudinal Assessment of Clinical Course and BIOmarkers in Severe Chronic AIRway Disease (BIOAIR) cohort). Using enrichment analysis, we explored whether the method identifies clinically meaningful, distinct clusters of participants with different lung functional fluctuation patterns. MEASUREMENTS AND MAIN RESULTS: In the PASTURE/EFRAIM dataset, we found four distinct clusters. Two clusters were enriched in children with well-known clinical characteristics of asthma. In cluster 3, children from a farming environment predominated, whereas cluster 4 mainly consisted of healthy controls. About 79% of cluster 3 carried the asthma-risk allele rs7216389 of the 17q21 locus. In the BIOAIR dataset, we found two distinct clusters clearly discriminating between individuals with mild-to-moderate and severe asthma. CONCLUSIONS: Our method identified dynamic functional asthma and healthy phenotypes, partly independent of atopy and inflammation but related to genetic markers on the 17q21 locus. The method can be used for disease phenotyping and possibly endotyping. It may identify participants with specific functional abnormalities, potentially needing a different therapeutic approach.

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.

BACKGROUND: Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. OBJECTIVE: We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). METHODS: Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. RESULTS: The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. CONCLUSIONS: LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.

[COPD: think about occupational exposures!] / Bpco : pensez aussi aux causes professionnelles !

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).

Exposure to Farm Animals and Risk of Lung Cancer in the AGRICAN Cohort.

Epidemiologic studies have found lower risks of lung cancer in farmers. However, little is known about the types of agricultural activities concerned. In the Agriculture and Cancer cohort, we assessed the relationship between animal farming and lung cancer by investigating the types of animals, tasks, and timing of exposure. Analyses included 170,834 participants from the Agriculture and Cancer (AGRICAN) cohort in France. Incident lung cancers were identified through linkage with cancer registries from enrollment (2005-2007) to 2011. A Cox model, adjusting for pack-years of cigarette smoking, was used to calculate hazard ratios and 95% confidence intervals. Lung cancer risk was inversely related to duration of exposure to cattle (≥40 years: hazard ratio = 0.60, 95% confidence interval: 0.41, 0.89; P for trend < 0.01) and to horse farming (≥20 years: hazard ratio = 0.64, 95% confidence interval: 0.35, 1.17; P for trend = 0.09), especially for adenocarcinomas, but not with poultry or pig farming. More pronounced decreased risks were reported among individuals who had cared for animals, undertaken milking, and who had been exposed to cattle in infancy. Our study provides strong evidence of an inverse association between lung cancer and cattle and horse farming. Further research is warranted to identify the etiologic protective agents and biological mechanisms.

Enhanced T helper 1 and 2 cytokine responses at birth associate with lower risk of middle ear infections in infancy.

BACKGROUND: Respiratory tract infections and their symptoms are frequent during early childhood, but their risk factors, including the effect of early immune regulation, are less known. The aim of the study was to analyze whether stimulated cord blood cytokine production is associated with the frequency of respiratory tract infection symptoms or infections during the first year of life. METHODS: The study population consisted of children of mothers from farm or non-farm rural environment from Austria, Finland, Germany, and Switzerland who participated in a prospective birth cohort study (PASTURE: Protection against Allergy-Study in Rural Environments) (N = 550). Cord blood samples were stimulated with the combination of phorbol ester and ionomycin (P/I) for 24 h, and the production of IL-5, IL-10, TNF-α, and IFN-γ was determined using ELISA. Information about infectious morbidity was collected using weekly diaries. RESULTS: P/I-stimulated production of IL-5 (adjusted risk ratio (aRR) for ≤median production, 0.37; 95% confidence interval (CI), 0.25-0.55, aRR for >median production, 0.41; 95% CI, 0.27-0.61 vs. production median production, 0.39; 95% CI, 0.25-0.62 vs. production