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Oxidative stress is a prominent pathway for the health effects associated with fine particulate matter (PM 2.5 ) exposure. Oxidative potential (OP) of PM has been associated to several health endpoints, but studies on its impact on biomarkers of oxidative stress remains insufficient. 300 pregnant women from the SEPAGES cohort (France) carried personal PM 2.5 samplers for a week and OP was measured using ascorbic acid (AA) and dithiothreitol (DTT) assays, and normalized by 1) PM 2.5 mass (OP m ) and 2) sampled air volume (OP v ). A pool of three urine spots collected on the 7th day of PM sampling was analyzed for biomarkers, namely 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and 8-isoprostaglandin-F2α (8-isoPGF2α). Associations were investigated using adjusted multiple linear regressions. OP effects were additionally investigated by stratifying by median PM 2.5 concentration (14 μg m -3 ). In the main models, no association was observed with 8-isoPGF2α, nor MDA. An interquartile range (IQR) increase in OP m AA exposure was associated with increased 8-OHdG (percent change: 6.2 %; 95 % CI: 0.2 % to 12.6 %). In the stratified analysis, exposure to OP m AA was associated with 8-OHdG for participants exposed to low levels of PM 2.5 (percent change: 11.4 %; 95 % CI: 3.3 % to 20.1 %), but not for those exposed to high levels (percent change: -1.0 %; 95 % CI: -10.6 % to 9.6 %). Associations for OP m DTT also followed a similar pattern (p-values for OP m AA -PM and OP m DTT -PM interaction terms were 0.12 and 0.11, respectively). Overall, our findings suggest that OP m AA may be associated with increased DNA oxidative damage. This association was not observed with PM 2.5 mass concentration exposure. The effects of OP m AA in 8-OHdG tended to be stronger at lower (below median) vs. higher concentrations of PM 2.5 . Further epidemiological, toxicological and aerosol research are needed to further investigate the OP m AA effects on 8-OHdG and the potential modifying effect of PM mass concentration on this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 (FEV 1 ) 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 FEV 1 . 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Poly- and perfluoroalkyl substances (PFAS) are used in a wide range of products. Experimental studies suggested impaired lung development and pro-inflammatory response following exposure to some PFAS. We aimed to assess the associations between prenatal exposure to PFAS and children respiratory health., Methods: The study is based on 433 mother-child pairs. 26 PFAS were measured in maternal serum collected during pregnancy. Lung function parameters were measured at 2 months using tidal breathing flow-volume loops and multiple-breath nitrogen washout and at 36 months using oscillometry. Incidence of respiratory health diseases (asthma, wheeze, bronchitis, bronchiolitis) in the first 36 months of life was assessed by repeated questionnaires. A cluster-based analysis was applied to identify prenatal PFAS exposure patterns. Adjusted linear and logistic regressions were performed to assess the associations between PFAS exposure patterns as well as individual PFAS, and each respiratory health parameter., Results: We excluded 13 PFAS due to low quantification (<5%). Relying on the 13 remaining PFAS, we identified three exposure clusters, characterized by low (N = 163), medium (N = 236) and high (N = 51) pregnancy PFAS concentrations. Compared to children belonging to the low exposure group, children in the moderate exposure group had higher reactance at 7 Hz (X 7 ) and lower frequency dependence of resistance between 7 Hz and 19 Hz (R 7-19 ) at 36 months, suggesting better lung function. No association of any exposure metric was detected with respiratory diseases in the first 3 years of life., Conclusions: Our study relying on both mixture and uni-pollutant analyses, does not provide evidence for a deleterious effect of prenatal PFAS exposure on respiratory health at an early age., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: While strong evidence supports adverse effects of pre-natal air pollution on child's lung function, previous studies rarely considered fine particulate matter (PM 2.5 ) or the potential role of offspring sex and no study examined the effects of pre-natal PM 2.5 on the lung function of the newborn., Aim: We examined overall and sex-specific associations of personal pre-natal exposure to PM 2.5 and nitrogen (NO 2 ) with newborn lung function measurements., Methods: This study relied on 391 mother-child pairs from the French SEPAGES cohort. PM 2.5 and NO 2 exposure was estimated by the average concentration of pollutants measured by sensors carried by the pregnant women during repeated periods of one week. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple breath washout (N 2 MBW) test, performed at 7 weeks. Associations between pre-natal exposure to air pollutants and lung function indicators were estimated by linear regression models adjusted for potential confounders, and then stratified by sex., Results: Mean exposure to NO 2 and PM 2.5 during pregnancy was 20.2 μg/m 3 and 14.3 μg/m 3 , respectively. A 10 μg/m 3 increase in PM 2.5 maternal personal exposure during pregnancy was associated with an adjusted 2.5 ml (2.3%) decrease in the functional residual capacity of the newborn (p-value = 0.11). In females, functional residual capacity was decreased by 5.2 ml (5.0%) (p = 0.02) and tidal volume by 1.6 ml (p = 0.08) for each 10 μg/m 3 increase in PM 2.5 . No association was found between maternal NO 2 exposure and newborns lung function., Conclusions: Personal pre-natal PM 2.5 exposure was associated with lower lung volumes in female newborns, but not in males. Our results provide evidence that pulmonary effects of air pollution exposure can be initiated in utero. These findings have long term implications for respiratory health and may provide insights into the underlying mechanisms of PM 2.5 effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status., Objective: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations., Methods: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO 2 , PM 2.5 and PM 10 annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status., Results: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO 2 , PM 2.5 and PM 10 concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status., Conclusion: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations., Competing Interests: Declaration of competing interest MJA holds investigator initiated grants for unrelated research from Pfizer, Boehringer-Ingelheim, Sanofi and GSK. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi. He has also received a speaker's fee from GSK., (Copyright © 2022. Published by Elsevier B.V.)

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 (FEV 1 ) (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 FEV 1 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 FEV 1 (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 FEV 1 (%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 FEV 1 in adults with asthma. None of the exposures revealed significant association when considered independently., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: While uncontrolled asthma in adults is frequent in Europe, the impact of socioeconomic position (SEP) was little investigated. We aimed to investigate the respective association of individual- and area-level SEP with uncontrolled asthma among French elderly women., Methods: Analyses were conducted in the Asthma-E3N study, among participants with current asthma (i.e., asthma attacks, treatment, or symptoms in previous year). Asthma control was evaluated using Asthma Control Test (uncontrolled: score ≤19); SEP was defined at both individual- and area-level, using educational level (low, medium, high), the French Deprivation index (tertiles defined at national level), and by merging them in a combined-SEP index. Associations between SEP and asthma control were estimated for 2258 women by logistic regression adjusted for age. Analyses were stratified by asthma controller medication use estimated through a drug reimbursement database., Results: Women were 70 years on average and 24% had uncontrolled asthma. A low educational level (11%) was associated with an increased risk of uncontrolled asthma [odds ratio (95% confidence interval) = 1.9 (1.4,2.6)], especially among women not using controller medication [3.1 (1.9,5.1)]. Using the combined-SEP index, the highest risk of uncontrolled asthma was observed among women with the most disadvantaged socioeconomic profile (low educational level and low-SEP neighborhood) [2.5 (1.5,4.2)]., Conclusions: Women with low SEP had more often uncontrolled asthma, which might be partly explained by inadequate asthma treatment. To achieve the best management of asthma for elderly patients, a specific attention should be given not only to disadvantaged population and neighborhoods, but also to disadvantaged populations in affluent neighborhoods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: To which extent serum cytokines may predict asthma control in adults remains understudied., Objectives: We investigated cross-sectional and longitudinal associations between cytokine profiles and asthma outcomes., Methods: Serum interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels were determined in 283 adults with current asthma from the 2nd survey of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2). Participants were followed-up seven years later. Asthma symptom control was assessed according to GINA 2015 guidelines. Cytokine profiles were identified by principal component (PC) analyses, and expressed as above/below the median., Results: The first two PCs captured 82.5% of the variability. While all seven cytokines scored high on PC1, only IL-1Ra and IL-10 scored high on PC2. At EGEA2, neither PC1 nor PC2 were related to exacerbations, asthma attacks, asthma symptom control, lung function, or allergic diseases. High level of PC1 (above the median) was associated with higher blood neutrophil counts (P = 0.02), while high level of PC2 was associated with lower IgE levels (P = 0.04). High level of PC2 at EGEA2 was associated with lower bronchial hyperresponsiveness (adjusted(a) OR[95%CI] = 0.46[0.23; 0.91]) and with subsequent lower risk of worsening asthma control and attacks (aOR[95%CI] = 0.24[0.09; 0.60]; 0.31[0.11; 0.85] respectively)., Conclusions: Serum cytokine profiles with high levels of IL-1Ra and IL-10 were associated with lower subsequent risks of worsening asthma control and attacks in adults. This study adds new findings for the role of serum cytokine profiles to help identifying adults with subsequent risk of asthma burden that could be targeted for specific therapies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Bleach is widely used for household cleaning. Although it is recognized that occupational use of bleach may have adverse respiratory health effects, it is unknown whether common domestic use of bleach may be a risk factor for asthma., Aim: To assess whether the domestic use of bleach for home cleaning is associated with asthma and other respiratory outcomes., Methods: Questionnaire-based information on respiratory symptoms and cleaning habits and data from skin prick-tests, bronchial responsiveness challenge and white blood cells were analyzed in 607 women participating in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). Bleach use was evaluated in 3 categories (<1 day/week; 1-3 days/week; 4-7 days/week "frequent")., Results: Overall, 37% of the women reported using bleach weekly. Women using bleach frequently (11%) were more likely to have current asthma as compared to non-users (adjusted Odds-Ratio (aOR) = 1.7; 95% Confidence Interval (95%CI) 1.0-3.0). Among women with asthma, frequent use of bleach was significantly associated with higher blood neutrophil cell counts. Bleach use was significantly associated with non-allergic asthma (aOR 3.3; 95%CI 1.5-7.1), and more particularly with non-allergic adult-onset asthma (aOR 4.9; 95%CI 2.0-11.6). Consistently, among women without allergic sensitization, significant positive associations were found between use of bleach and bronchial hyperresponsiveness, asthma like-symptoms and chronic cough. No association was observed for allergic asthma., Conclusions: Frequent use of bleach for home-cleaning is associated with non-allergic adult-onset asthma, elevated neutrophil counts and lower-airway symptoms in women., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To investigate the usefulness of a self-reported respiratory health transition question over 10 years through reliability, ability to capture long-term asthma trajectory and predictive ability., Settings: In two 20-year cohorts (Asthma-E3N, n = 16,371, 61-88 years; EGEA, n = 1254, 27-82 years), perceived 10-year change in respiratory health ("Overall, in the last 10 years, do you think that your bronchial or respiratory health has changed?" if yes: "Has it improved/deteriorated?") was studied in relation with change in respiratory medication dispensation and lung function, with change in asthma status measured over the same period of time, and with subsequent asthma-related outcomes., Results: Perceived deterioration (14% in Asthma-E3N) was associated with increased dispensations of respiratory medications over time (from 17% with >2 dispensations in 2004 to 26% in 2010). Report of perceived deterioration (13% in EGEA) was related to a lung function decline steeper by 9.3 mL/year as compared to perceived improvement. In both cohorts, change (improvement or deterioration) was more often perceived by participants with than without asthma (>45% vs <20%) and was dominant among participants with persistent current asthma (77%). Perceived deterioration was related to poorer asthma control 7 years later and to higher use of oral corticosteroids in the following 18 months., Conclusion: The proposed simple self-reported respiratory health transition question over 10 years allows predicting part of the long-term trajectory of asthma., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma., Methods: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006-2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1-7) and the generic SF-36 (scores range: 0-100) were used., Results: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (-1, p = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains., Conclusion: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The association between smoking and asthma remains unclear and has mostly been assessed in cross-sectional studies, with potential selection bias ("healthy smoker effect")., Aims: Using a longitudinal approach, the aims were to assess whether 1) childhood asthma modifies smoking initiation, 2) active smoking influences asthma incidence in adults and 3) active smoking among subjects with asthma influences the persistence of the disease or the 12-year evolution in lung function in children and adults., Methods: Subjects (513 children and 1190 adults) were recruited and followed-up for 12 years in the context of the EGEA study (Epidemiological study on the Genetics and Environment of Asthma)., Results: Childhood asthma was not associated with a decreased probability of starting active smoking (Hazard Ratio, HR = 0.96; 95% confidence interval (CI): 0.72, 1.27). Smoking at baseline was associated with a higher risk for asthma incidence in adulthood (HR = 1.95, 95% CI: 1.00, 3.77). Among subjects with asthma, smoking was unrelated to lung function evolution; however, among children with moderate to severe asthma at inclusion, smoking tended to slow down the lung function growth (P = 0.04)., Conclusion: These findings support the hypothesis that childhood asthma does not prevent smoking initiation and confirm that active smoking has a deleterious role on asthma. Altogether this study emphasizes the importance of active smoking as a serious public health problem particularly for children and women., (Copyright © 2011. Published by Elsevier Ltd.)