Associations between combined urban and lifestyle factors and respiratory health in European children.

INTRODUCTION: Previous studies identified some environmental and lifestyle factors independently associated with children respiratory health, but few focused on exposure mixture effects. This study aimed at identifying, in pregnancy and in childhood, combined urban and lifestyle environment profiles associated with respiratory health in children. METHODS: This study is based on the European Human Early-Life Exposome (HELIX) project, combining six birth cohorts. Associations between profiles of pregnancy (38 exposures) and childhood (84 exposures) urban and lifestyle factors, identified by clustering analysis, and respiratory health were estimated by regression models adjusted for confounders. RESULTS: Among the 1033 included children (mean ± standard-deviation (SD) age: 8.2 ± 1.6 years old, 47% girls) the mean ± SD forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were 99 ± 13% and 101 ± 14%, respectively, and 12%, 12% and 24% reported ever-asthma, wheezing and rhinitis, respectively. Four profiles of pregnancy exposures and four profiles of childhood exposures were identified. Compared to the reference childhood exposure profile (low exposures), two exposure profiles were associated with lower levels of FEV1. One profile was characterized by few natural spaces in the surroundings and high exposure to the built environment and road traffic. The second profile was characterized by high exposure to meteorological factors and low levels of all other exposures and was also associated with an increased risk of ever-asthma and wheezing. A pregnancy exposure profile characterized by high exposure levels to all risk factors, but a healthy maternal lifestyle, was associated with a lower risk of wheezing and rhinitis in children, compared to the reference pregnancy profile (low exposures). CONCLUSION: This comprehensive approach revealed pregnancy and childhood profiles of urban and lifestyle exposures associated with lung function and/or respiratory conditions in children. Our findings highlight the need to pursue the study of combined exposures to improve prevention strategies for multifactorial diseases such as asthma.

Environmental exposures in early-life and general health in childhood.

BACKGROUND: Early-life environmental exposures are suspected to be involved in the development of chronic diseases later in life. Most studies conducted so far considered single or few exposures and single-health parameter. Our study aimed to identify a childhood general health score and assess its association with a wide range of pre- and post-natal environmental exposures. METHODS: The analysis is based on 870 children (6-12 years) from six European birth cohorts participating in the Human Early-Life Exposome project. A total of 53 prenatal and 105 childhood environmental factors were considered, including lifestyle, social, urban and chemical exposures. We built a general health score by averaging three sub-scores (cardiometabolic, respiratory/allergy and mental) built from 15 health parameters. By construct, a child with a low score has a low general health status. Penalized multivariable regression through Least Absolute Shrinkage and Selection Operator (LASSO) was fitted in order to identify exposures associated with the general health score. FINDINGS: The results of LASSO show that a lower general health score was associated with maternal passive and active smoking during pregnancy and postnatal exposure to methylparaben, copper, indoor air pollutants, high intake of caffeinated drinks and few contacts with friends and family. Higher child's general health score was associated with prenatal exposure to a bluespace near residency and postnatal exposures to pets, cobalt, high intakes of vegetables and more physical activity. Against our hypotheses, postnatal exposure to organochlorine compounds and perfluorooctanoate were associated with a higher child's general health score. CONCLUSION: By using a general health score summarizing the child cardiometabolic, respiratory/allergy and mental health, this study reinforced previously suspected environmental factors associated with various child health parameters (e.g. tobacco, air pollutants) and identified new factors (e.g. pets, bluespace) warranting further investigations.

Exposome Profiles and Asthma among French Adults.

Rationale: Although previous studies in environmental epidemiology focused on single or a few exposures, a holistic approach combining multiple preventable risk factors is needed to tackle the etiology of multifactorial diseases such as asthma. Objectives: To investigate the association between combined socioeconomic, external environment, early-life environment, and lifestyle-anthropometric factors and asthma phenotypes. Methods: A total of 20,833 adults from the French NutriNet-Santé cohort were included (mean age, 56.2 yr; SD, 13.2; 72% women). The validated asthma symptom score (continuous) and asthma control (never asthma, controlled asthma, and uncontrolled asthma) were considered. The exposome (n = 87 factors) covered four domains: socioeconomic, external environment, early-life environment, and lifestyle-anthropometric. Cluster-based analyses were performed within each exposome domain, and the identified profiles were studied in association to asthma outcomes in negative binomial (asthma symptom score) or multinomial logistic (asthma control) regression models. Measurements and Main Results: In total, 5,546 (27%) individuals had an asthma symptom score ⩾1, and 1,206 (6%) and 194 (1%) had controlled and uncontrolled asthma, respectively. Three early-life exposure profiles ("high passive smoking-own dogs," "poor birth parameters-daycare attendance-city center," or "⩾2 siblings-breastfed" compared with "farm-pet owner-molds-low passive smoking") and one lifestyle-anthropometric profile ("unhealthy diet-high smoking-overweight" compared with "healthy diet-nonsmoker-thin") were associated with more asthma symptoms and uncontrolled asthma. Conclusions: This large-scale exposome-based study revealed early-life and lifestyle exposure profiles that were at risk for asthma in adults. Our findings support the importance of multiinterventional programs for the primary and secondary prevention of asthma, including control of specific early-life risk factors and promotion of a healthy lifestyle in adulthood.

Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort.

BACKGROUND: Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate. OBJECTIVE: To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. METHODS: The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate). RESULTS: Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively). CONCLUSION: Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.

Profile of exposures and lung function in adults with asthma: An exposome approach in the EGEA study.

BACKGROUND: Environmental research on multifactorial health outcomes calls for exposome approaches able to assess the joint effect of multiple exposures. OBJECTIVE: Our aim was to identify profiles of exposure to lifestyle/environmental factors associated with lung function in adults with asthma using a cluster-based approach. METHODS: We used data from 599 adults of the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA) (mean age 39.0 years, 52% men) who ever had asthma. Exposures to 53 lifestyle/environmental factors were assessed by questionnaires or geographic information systems-based models. A two-step approach was developed: 1) exposome dimension reduction by selecting factors showing association with forced expiratory volume in 1 s (FEV1) (p < 0.20) in an exposome-wide association study (ExWAS), 2) clustering analysis using the supervised Bayesian Profile Regression (sBPR) to group individuals according to FEV1 level and to their profile of exposure to a reduced set of uncorrelated exposures (each paired correlation<0.70) identified in step 1. RESULTS: The ExWAS identified 21 factors showing suggestive association with FEV1 (none significant when controlling for multiple tests). The sBPR conducted on 15 uncorrelated exposures identified in step 1, revealed 3 clusters composed of 30, 115 and 454 individuals with a mean ± SD FEV1(%pred) of 79% ± 21, 90% ± 19 and 93% ± 16, respectively. Cluster 1 was composed of individuals with heavy smoking, poor diet, higher outdoor humidity and proximity to traffic, while cluster 2 and 3 included individuals with moderate/low levels of exposure to these factors. DISCUSSION: This exposome study identified a specific profile of joint lifestyle and environmental factors, associated with a low FEV1 in adults with asthma. None of the exposures revealed significant association when considered independently.

Concurrence of 1- and 3-Min Sit-to-Stand Tests with the 6-Min Walk Test in Idiopathic Pulmonary Fibrosis.

BACKGROUND: In idiopathic pulmonary fibrosis (IPF), some physiological parameters measured during a 6-min walk test (6-MWT) impart reliable prognostic information. Sit-to-stand tests (STSTs) are field exercise tests that are easier to implement than the 6-MWT in daily practice. OBJECTIVES: The aims of the study were to test the reproducibility and compare 2 STSTs (the 1-min STST [1-STST] and the semi-paced 3-min chair rise test [3-CRT]) in IPF, and to determine if selected physiological parameters (speed of displacement and changes in pulse oxygen saturation [SpO2]) are interchangeable between the STSTs and the 6-MWT. METHODS: Thirty-three patients with stable IPF were studied in 3 French expert centers. To test reproducibility, intra-class correlations (ICCs) of parameters measured during tests performed 7-14 days apart were calculated. To test interchangeability, the agreement and correlation of physiological responses measured during STSTs and during 6-MWT were studied. RESULTS: Vertical displacements and changes in SpO2 during both STSTs were reproducible, with ICCs ranging from 0.78 [0.63-0.87] to 0.95 [0.92-0.97]. Vertical displacements during 1-STST and 3-CRT were correlated with 6-MWT distance (correlation coefficients (r) of 0.72 and 0.77, respectively; p < 0.001). Similarly, correlations were found between changes in SpO2 measured during the 2 STSTs and the 6-MWT, with coefficients ranging from 0.73 to 0.91 (p < 0.001). Distance walked and SpO2 during 6-MWT were well estimated from vertical displacement and SpO2 during the 2 STSTs, respectively. CONCLUSION: The correlations found between the 2 STSTs and the 6-MWT suggest that STSTs may be of interest to assess displacement and exercise-induced changes in SpO2 in IPF patients.

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.

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).

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.

Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis.

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

Smoking habits in French farmers: a cross-sectional study.

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.

Asymptomatic subjects with airway obstruction have significant impairment at exercise.

BACKGROUND: The relevance of screening for airway obstruction in subjects not complaining of COPD symptoms may depend on the definition of airway obstruction. Response to exercise in asymptomatic subjects with persistent airway obstruction as defined by a postbronchodilator FEV1/FVC <5th centile lower limit of normal (LLN) remains unknown. METHODS: Dyspnoea (Borg scale), exercise tolerance and ventilatory constraints on tidal volume expansion were assessed in 20 consecutive asymptomatic subjects with persistent mild airway obstruction detected by screening (postbronchodilator FEV1/FVC z-score: -2.14±0.29; FEV1 z-score: -1.02±0.64) undergoing incremental cycle cardiopulmonary exercise testing, compared with 20 healthy controls with normal spirometry matched for age, sex, body mass index and smoking history (FEV1/FVC z-score: -0.13±0.57; FEV1 z-score: 0.32±0.67) and with 20 symptomatic patients with COPD matched for the same characteristics (FEV1/FVC z-score: -2.36±0.51; FEV1 z-score: -1.02±0.48). RESULTS: Asymptomatic subjects with airway obstruction had higher dyspnoea ratings than controls during incremental exercise. Asymptomatic subjects with airway obstruction had also peak oxygen consumption and peak power output that were lower than controls, and similar to those observed in patients with COPD. Although less frequent than in COPD, dynamic hyperinflation was more frequent in asymptomatic subjects with airway obstruction than in controls (85%, 50% and 10%, respectively; p=0.01 in asymptomatic subjects vs controls and p=0.04 vs COPD). CONCLUSIONS: Although they did not present with chronic activity-related dyspnoea, subjects with a postbronchodilator FEV1/FVC

Prevalence and risk factors for COPD in farmers: a cross-sectional controlled study.

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

Determinants of immunoglobulin G responses to respiratory syncytial virus and rhinovirus in children and adults.

Introduction: Exposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults. Methods: The study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels. Results: In children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels. In adults (43.5 ± 16.7 years old, 48% men), younger age, female sex, lower BMI, active smoking and all seasons except summer were associated with higher RV-specific IgG levels. Older age, active smoking and all seasons except summer were associated with higher RSV-specific IgG levels. Conclusion: Personal and seasonal determinants of RSV- and RV-specific IgG levels seem to vary according to the respiratory virus type and between children and adults, suggesting different patterns of responses along the life course.

The exposome concept: how has it changed our understanding of environmental causes of chronic respiratory diseases?

The exposome approach can help us better understand multifactorial respiratory diseases through multidisciplinary collaboration, harmonised resources and use of sophisticated methods addressing combined exposures and longitudinal data. https://bit.ly/3Ng9MNn.

Insight into the relationship between forced vital capacity and transfer of the lungs for carbon monoxide in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Forced vital capacity (FVC) is routinely used to quantify the severity and identify the progression of idiopathic pulmonary fibrosis (IPF). Although less commonly used, lung transfer of carbon monoxide (TLCO) correlates better with the severity of IPF than does FVC. METHODS: Aiming at studying how FVC behaves in relation to TLCO, we analysed cross-sectional data from 430 IPF patients, of which 221 had at least 2 assessments (performed 2.4 ± 1.9 years apart) available for longitudinal analyses. Thresholds for identifying "abnormal" FVC and TLCO values were the statistically-defined lower limits of normal (LLN). For patients with longitudinal data, mean annual absolute declines of FVC and TLCO were calculated. RESULTS: The correlation between FVC and TLCO (%predicted) was weak (R2=0.21). FVC was "abnormal" (i.e.,