Exposure to particulate matter (PM10) poses a significant threat to human health. We investigated the effects of short-term exposures to PM10 sources and oxidative potential (OP), an indicator of PM related to its toxicity, on lung function in early childhood. The study is based on 435 children from the SEPAGES cohort in Grenoble, with lung function measured at 6-8 weeks (N2 multiple breath washout and tidal breathing flow-volume loop) and 3 years (oscillometry, including resistance and reactance). PM10 chemical composition and OP (ascorbic acid - AA and dithiothreitol - DTT assays) were measured on filters collected at an urban background station. PM10 concentrations were attributed to 10 different sources using a source apportionment method. Associations of short-term exposure (1-, 3-, 7- and 14-day) to each source and OP with lung function were estimated by regression models. Increased acute exposure to PM10 from traffic was associated with parameters indicating impaired lung function at 6-8 weeks and 3 years. Increased exposure to PM10 from biomass burning and primary biogenic sources was associated with lower intra-breath reactance at 3 years. Total PM10 mass and other sources showed no association, or were associated with higher lung function. Increased OPAA was consistently associated to lower child lung function. The greatest magnitude was found between 2-week exposure to mass-normalized OPAA and reduced 7-Hz-reactance at 3 years (β = -0.52 hPa×s/L 95%CI: -0.88, -0.15 per 0.07 nmol/min/μg increase). This study suggests that short-term exposure to PM10 from primary biogenic and local anthropogenic sources, mainly traffic and biomass burning, and to OP may have detrimental effects on early life lung function.

Purpose The Human Early Life Exposome (HELIX) cohort was established to assess a wide range of environmental exposures (the exposome) during early life and study the effects of the early life exposome on child and adolescent health outcomes and molecular omics signatures. Here, we describe the second follow-up of the HELIX cohort during adolescence, including measurements available and population characteristics.Participants HELIX is a collaborative study across six established and ongoing population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the United Kingdom). The cohort includes 1663 mother-child pairs recruited during pregnancy from 2003 to 2009 and followed up during childhood at 6–12 years from 2013 to 2016. This update summarises the most recent follow-up during adolescence (12–18 years) which took place from 2020 to 2022 and included 864 participants.Findings to date HELIX data have been used extensively in more than 100 publications, specifically pioneering the implementation of exposome approaches to address questions around the occurrence and effects of multiple exposures to real-life pollutant mixtures. These findings have improved our understanding of how multiple exposures co-exist and which exposures are driving the early-life exposome. Further, HELIX data have been used in exposome-wide discovery analyses to examine child health outcomes and used high-throughput omics techniques to characterise the internal exposome.Future plans Although no additional follow-up visits are currently planned, HELIX will remain an active exposome research resource for years to come. The cohort will leverage its comprehensive database and extensive biobank to investigate complex exposure-omics-health relationships and measure additional biological markers.

INTRODUCTION:Exposure to synthetic phenols is suspected to affect child respiratory health, but epidemiological findings are not consistent and studies on exposure during infancy are lacking. We aimed to investigate the association between exposure to a mixture of phenols in pregnancy and infancy and children's respiratory health. METHODS:Among 363 mother-child pairs from the Suivi de l'Exposition à la Pollution Atmosphérique durant la Grossesse et Effets sur la Santé cohort, 12 phenols were measured in weekly-pooled urine samples collected twice during pregnancy (second and third trimesters) and in infancy (2 months and 1 year). Children's lung function was assessed through tidal breathing flow-volume loops and nitrogen multiple-breath washout at 2 months, and standard and intra-breath oscillometry at 3 years. Time-specific phenol exposure profiles were identified through cluster analysis and then studied in association with respiratory health using adjusted regression models. RESULTS:Two exposure profiles were identified at each point in time, characterised by low versus high levels of several phenol compounds. Overall, high exposure profiles were associated with altered oscillometry parameters at 3 years, particularly a high profile in the second trimester with higher frequency dependence of resistance and lower volume dependence of reactance, between a high profile at 2 months and lower reactance at 7 Hz, and between a high profile at 1 year and higher area of the reactance curve, resistance at 7 Hz and volume dependence of resistance. CONCLUSION:Using repeated and accurate assessments of phenol exposure, this study provides evidence of the deleterious effects of early-life exposure to a mixture of phenols on lung function in preschool children.

The immune function is suspected to play an important role in the health effects of air pollution but it remains poorly investigated in pregnant women. One-week personal measurements of exposure to nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic diameter of ≤ 2.5 µm mass concentration (PM 2.5 ) and PM 2.5 oxidative potential (OP) were assessed in 270 pregnant women from the French cohort SEPAGES. PM filters were analyzed for PM 2.5 OP using the dithiothreitol (DTT) and the ascorbic acid (AA) assays. From a blood sample withdrawn at the end of the exposure measurement week, levels of 29 cytokines and chemokines were measured at baseline and after T cell and dendritic cell activation with phytohemagglutinin (PHA) and resiquimod (R848), respectively. Associations between each air pollutant and each cytokine were assessed using adjusted linear regression models. An increase in NO 2 exposure was associated with higher interleukin 10 (IL-10) and lower PHA-activated tumor necrosis factor (TNF). No association with PM 2.5 concentration was observed, but increased exposure to PM $${\text{OP}}^{{{\text{AA}}}}$$ OP AA was associated with lower baseline and R848-activated IL-8 and increased exposure to PM $${\text{OP}}^{\text{DTT}}$$ OP DTT was associated with higher PHA-activated IL-17A. Our study provides insights into the relationships between air pollution exposure and immune function among pregnant women.

Background Intra-breath oscillometry has been proposed as a sensitive means of detecting airway obstruction in young children. We aimed to assess the impact of early life wheezing and lower respiratory tract illness on lung function, using both standard and intra-breath oscillometry in 3 year old children. Methods History of doctor-diagnosed asthma, wheezing, bronchiolitis and bronchitis and hospitalisation for respiratory problems were assessed by questionnaires in 384 population-based children. Association of respiratory history with standard and intra-breath oscillometry parameters, including resistance at 7 Hz (R 7 ), frequency-dependence of resistance (R 7 − 19 ), reactance at 7 Hz (X 7 ), area of the reactance curve (AX), end-inspiratory and end-expiratory R (R eI , R eE ) and X (X eI , X eE ), and volume-dependence of resistance (ΔR = R eE -R eI ) was estimated by linear regression adjusted on confounders. Results Among the 320 children who accepted the oscillometry test, 281 (88%) performed 3 technically acceptable and reproducible standard oscillometry measurements and 251 children also performed one intra-breath oscillometry measurement. Asthma was associated with higher R eI , R eE , ΔR and R 7 and wheezing was associated with higher ΔR. Bronchiolitis was associated with higher R 7 and AX and lower X eI and bronchitis with higher R eI . No statistically significant association was observed for hospitalisation. Conclusions Our findings confirm the good success rate of oscillometry in 3-year-old children and indicate an association between a history of early-life wheezing and lower respiratory tract illness and lower lung function as assessed by both standard and intra-breath oscillometry. Our study supports the relevance of using intra-breath oscillometry parameters as sensitive outcome measures in preschool children in epidemiological cohorts.

Pacheco Da Silva, Emilie MS; Nadif, Rachel PhD; Dohoukpe, Eddy MS; Orsi, Laurent PhD; Quentin, Joane MS; Varraso, Raphaëlle PhD; Siroux, Valérie PhD; Dumas, Orianne PhD; Le Moual, Nicole PhD; on behalf of the Epidemiological Study on the Genetics and Environment of Asthma Author Information

ImportanceLittle is known about long-term associations of early-life exposure to extreme temperatures with child health and lung function.ObjectivesTo investigate the association of prenatal and postnatal heat or cold exposure with newborn lung function and identify windows of susceptibility.Design, Setting, and ParticipantsThis population-based cohort study (SEPAGES) recruited pregnant women in France between July 8, 2014, and July 24, 2017. Data on temperature exposure, lung function, and covariates were available from 343 mother-child dyads. Data analysis was performed from January 1, 2021, to December 31, 2021.ExposuresMean, SD, minimum, and maximum temperatures at the mother-child’s residence, estimated using a state-of-the-art spatiotemporally resolved model.Main Outcomes and MeasuresOutcome measures were tidal breathing analysis and nitrogen multiple-breath washout test measured at 2 months of age. Adjusted associations between both long-term (35 gestational weeks and first 4 weeks after delivery) and short-term (7 days before lung function test) exposure to ambient temperature and newborn lung function were analyzed using distributed lag nonlinear models.ResultsA total of 343 mother-child pairs were included in the analyses (median [IQR] maternal age at conception, 32 [30.0-35.2] years; 183 [53%] male newborns). A total of 246 mothers and/or fathers (72%) held at least a master’s degree. Among the 160 female newborns (47%), long-term heat exposure (95th vs 50th percentile of mean temperature) was associated with decreased functional residual capacity (−39.7 mL; 95% CI, −68.6 to −10.7 mL for 24 °C vs 12 °C at gestational weeks 20-35 and weeks 0-4 after delivery) and increased respiratory rate (28.0/min; 95% CI, 4.2-51.9/min for 24 °C vs 12 °C at gestational weeks 14-35 and weeks 0-1 after delivery). Long-term cold exposure (5th vs 50th percentile of mean temperature) was associated with lower functional residual capacity (−21.9 mL; 95% CI, −42.4 to −1.3 mL for 1 °C vs 12 °C at gestational weeks 15-29), lower tidal volume (−23.8 mL; 95% CI, −43.1 to −4.4 mL for 1 °C vs 12 °C at gestational weeks 14-35 and weeks 0-4 after delivery), and increased respiratory rate (45.5/min; 95% CI, 10.1-81.0/min for 1 °C vs 12 °C at gestational weeks 6-35 and weeks 0-1 after delivery) in female newborns as well. No consistent association was observed for male newborns or short-term exposure to cold or heat.Conclusions and RelevanceIn this cohort study, long-term heat and cold exposure from the second trimester until 4 weeks after birth was associated with newborn lung volumes, especially among female newborns.

CONTEXT:While strong evidence supports adverse effects of pre-natal air pollution on child's lung function, previous studies rarely considered fine particulate matter (PM2.5) or the potential role of offspring sex and no study examined the effects of pre-natal PM2.5 on the lung function of the newborn. AIM:We examined overall and sex-specific associations of personal pre-natal exposure to PM2.5 and nitrogen (NO2) with newborn lung function measurements. METHODS:This study relied on 391 mother-child pairs from the French SEPAGES cohort. PM2.5 and NO2 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 (N2MBW) 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 NO2 and PM2.5 during pregnancy was 20.2 μg/m3 and 14.3 μg/m3, respectively. A 10 μg/m3 increase in PM2.5 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/m3 increase in PM2.5. No association was found between maternal NO2 exposure and newborns lung function. CONCLUSIONS:Personal pre-natal PM2.5 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 PM2.5 effects.

Background: Fine particulate matter (PM2.5) has been found to be detrimental to respiratory health of children, but few studies have examined the effects of prenatal PM2.5 oxidative potential (OP) on lung function in infants and preschool children. Objectives: We estimated the associations of personal exposure to PM2.5 and OP during pregnancy on offspring objective lung function parameters and compared the strengths of associations between both exposure metrics. Methods: We used data from 356 mother–child pairs from the SEPAGES cohort. PM filters collected twice during a week were analyzed for OP, using the dithiothreitol (DTT) and the ascorbic acid (AA) assays, quantifying the exposure of each pregnant woman. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple-breath washout (N2MBW) test, performed at 6 wk, and airwave oscillometry (AOS) performed at 3 y. Associations of prenatal PM2.5 mass and OP with lung function parameters were estimated using multiple linear regressions. Results: In neonates, an interquartile (IQR) increase in OPvDTT (0.89 nmol/min/m3) was associated with a decrease in functional residual capacity (FRC) measured by N2MBW [β=−2.26mL; 95% confidence interval (CI): −4.68, 0.15]. Associations with PM2.5 showed similar patterns in comparison with OPvDTT but of smaller magnitude. Lung clearance index (LCI) and TBFVL parameters did not show any clear association with the exposures considered. At 3 y, increased frequency-dependent resistance of the lungs (Rrs7–19) from AOS tended to be associated with higher OPvDTT (β=0.09 hPa×s/L; 95% CI: −0.06, 0.24) and OPvAA (IQR=1.14 nmol/min/m3; β=0.12 hPa×s/L; 95% CI: −0.04, 0.27) but not with PM2.5 (IQR=6.9 μg/m3; β=0.02 hPa×s/L; 95% CI: −0.13, 0.16). Results for FRC and Rrs7–19 remained similar in OP models adjusted on PM2.5. Discussion: Prenatal exposure to OPvDTT was associated with several offspring lung function parameters over time, all related to lung volumes. https://doi.org/10.1289/EHP11155

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 (X7) and lower frequency dependence of resistance between 7 Hz and 19 Hz (R7-19) 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.

Exposure to phthalates and synthetic phenols is ubiquitous. Some of them are suspected to impact child respi-ratory health, although evidence still remains insufficient. This study investigated the associations between prenatal exposure to phthalates and phenols, individually and as a mixture, and child respiratory health assessed by objective lung function measures since 2 months of age. Among 479 mother-child pairs from the SEPAGES cohort, 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites were measured in 2 pools including each 21 urine samples collected at the 2nd and 3rd pregnancy trimesters. Lung function was measured at 2 months using tidal breathing flow-volume loops and nitrogen multiple-breath washout, and at 3 years using oscillometry. Asthma, wheezing, bronchitis and bronchiolitis were assessed by repeated questionnaires. A cluster-based analysis was applied to identify exposure patterns to phenols and phthalates. Adjusted associations between clusters as well as each individual exposure biomarker and child respiratory health were estimated by regression models. We identified four prenatal exposure patterns: 1) low concentrations of all biomarkers (reference, n = 106), 2) low phenols-moderate phthalates (n = 162), 3) high concentrations of all biomarkers except bisphenol S (n = 109), 4) high parabens-moderate other phenols-low phthalates (n = 102). At 2 months, cluster 2 infants had lower functional residual capacity and tidal volume and higher ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) and cluster 3 had lower lung clearance index and higher tPTEF/tE. Clusters were not associated with respiratory health at 3 years but in the single-pollutant models, parabens were associated with increased area of the reactance curve, bronchitis (methyl, ethyl parabens) and bronchiolitis (propyl paraben). Our results suggested that prenatal exposure to mixtures of phthalates reduced lung volume in early life. Single exposure analyses suggested associations of parabens with impaired lung function and increased risk of respiratory diseases.

Objective To evaluate the associations between the evolution of household use of cleaning products with the asthma symptom score and its evolution over 8 years. Methods Our study is based on 509 women participating in the last two surveys of the Epidemiological study on the Genetics and Environment of Asthma (EGEA) study (EGEA2: 2003–2007 (44 years, 19% current smokers) and EGEA3: 2011–2013). We assessed an asthma symptom score and the use of household cleaning products through standardised questionnaires. We studied longitudinal associations of the evolution of weekly use of irritant or spayed cleaning products with (1) the asthma symptom score at EGEA3 and a stable symptom score between EGEA2-EGEA3 (negative binomial models) and (2) the incidence/evolution of asthma symptoms between EGEA2-EGEA3 (logistic/polytomous logistic regressions). Models accounted for familial dependence and were adjusted for age, smoking status, body mass index and occupational exposure to asthmagens. Results Persistent and increased (40% and 16%, respectively) weekly use of irritants or sprays were associated with a higher risk of asthma symptoms at EGEA3 (Mean Score Ratio (MSR)=1.51 (95% CI 1.06 to 2.14) and 1.33 (95% CI 0.85 to 2.08), respectively). A decreased use (19%) was associated with a lower risk of symptoms at EGEA3, compared with a persistent use (MSR=0.59 (95% CI 0.39 to 0.88)). We also observed an association between an increased use of sprays and the incidence of asthma symptoms (OR=2.30 (95% CI 1.08 to 4.91)), compared with no weekly use of irritants/sprays. Conclusions This longitudinal study, with repeated assessment of exposure and respiratory health, supports the hypothesis that a persistent or increased weekly use of sprayed cleaning products over time may have an adverse effect on the evolution of asthma symptoms.

BACKGROUND AND AIM: Despite recognition of climate change, little is known on how ambient temperature may affect fetal development and child respiratory health. This study investigated the effect of prenatal and early postnatal exposure to ambient temperature on newborn lung function in France. METHODS: Prenatal and early postnatal mean temperature and temperature variability at the mother's residence were estimated based on a validated spatiotemporally resolved exposure model in 343 mother–child pairs from the SEPAGES cohort. Newborn lung function was assessed at two months during unsedated sleep with tidal breathing and multiple breath washout test. Associations of ambient temperature with newborns lung function were analyzed using adjusted Distributed Lag Non-linear Models (DLNM) for the whole cohort and then stratified by sex. Both chronic (the first 35 gestational weeks and the 4 weeks after birth) and acute (the 7 days before the respiratory tests) exposures were investigated. RESULTS: Among girls, chronic exposure to severe cold (the 5th percentile vs the median temperature) was robustly related to lower Functional Residual Capacity (FRC), lower tidal volume and higher respiratory rate. Chronic exposure to severe heat (the 95th percentile vs the median temperature) in girls was related to lower FRC and higher respiratory rate. Most of the significant windows of vulnerability to ambient temperature occurred between the second trimester of pregnancy and the first weeks of life. CONCLUSIONS: Prenatal and early postnatal exposure to severe cold or heat may alter lung function among infants, especially in girls. Lung volumes appeared more specifically affected than airflows. Considering children and adults respiratory health are closely linked, long-term consequences may be substantial. KEYWORDS: Ambient temperature; Climate change; DLNM; Infants; Lung function; Prenatal/Postnatal exposure; Restrictive lung disease

Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment.

Early life stages are vulnerable to environmental hazards and present important windows of opportunity for lifelong disease prevention. This makes early life a relevant starting point for exposome studies. The Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project aims to develop a toolbox of exposome tools and a Europe-wide exposome cohort that will be used to systematically quantify the effects of a wide range of community- and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways, longitudinally from early pregnancy through to adolescence. Exposome tool and data development include as follows: (1) a findable, accessible, interoperable, reusable (FAIR) data infrastructure for early life exposome cohort data, including 16 prospective birth cohorts in 11 European countries; (2) targeted and nontargeted approaches to measure a wide range of environmental exposures (urban, chemical, physical, behavioral, social); (3) advanced statistical and toxicological strategies to analyze complex multidimensional exposome data; (4) estimation of associations between the exposome and early organ development, health trajectories, and biological (metagenomic, metabolomic, epigenetic, aging, and stress) pathways; (5) intervention strategies to improve early life urban and chemical exposomes, co-produced with local communities; and (6) child health impacts and associated costs related to the exposome. Data, tools, and results will be assembled in an openly accessible toolbox, which will provide great opportunities for researchers, policymakers, and other stakeholders, beyond the duration of the project. ATHLETE’s results will help to better understand and prevent health damage from environmental exposures and their mixtures from the earliest parts of the life course onward.

Background: Measurement of respiratory function is important both in epidemiological studies and for the diagnosis of respiratory diseases in early life. Oscillometry requires minimal subject cooperation and is promising for the assessment of respiratory function in young children. Aim: to assess the feasibility and reproducibility of oscillometric measurements in 3-year-old children. Methods: Measurements were performed on 242 children who participated in the 3-year visit of the SEPAGES cohort, median (Q1, Q3) age: 3.1yr (3.0, 3.2); height: 95.4cm (95.0, 97.5), using the tremoFlo device with a 7 – 41Hz waveform. Valid tests were defined as per recommendations. Resistance at 7Hz (R7) data with a CV<15% were considered reproducible. We compared the individual mean of R7 based on all technically acceptable measures (R7_all) to the one based on the 2 first measures (R7_2) and computed the intraclass correlation coefficient (ICC) between R7_all and R7_2. Results: 225 children (94.9 %) had at least 2, and 209 (88.2%) at least 3 technically acceptable R7 measurements with a CV<15%. Of the latter, 197 (81.4%) did not require any measurement exclusion. The overall CV of R7 was: 6.7% (4.1, 10.1). The median (Q1-Q3) difference between R7_all and R7_2 was -0.006 (-0.029, 0.018) cmH2O.s/L, with an ICC=0.97. Conclusions: Our preliminary analysis demonstrates excellent feasibility and reproducibility of oscillometry in 3-year-old children. These data suggest that 2 reproducible measurements may yield a comparable outcome vs. the recommended 3. Funding: PNREST Anses, 2018/1/264 ; ERS CRC-2013-02 INCIRCLE (International Collaboration to Improve Respiratory Health in Children)

Background: The assessment of respiratory function in early-life is important, but reliable and reproducible spirometry measures are difficult to obtain in children younger than 5 years. The Forced Oscillation Technique (FOT), which requires minimal subject cooperation, is suitable in young children; its relevance in epidemiological cohorts needs further investigations. Aim: to assess the association between FOT parameters and respiratory symptoms in 3-year-old children. Methods: The study relies on 284 children who participated to the 3-year visit (still on-going) of the mother-child SEPAGES cohort. We focused on respiratory resistance (Rrs) and reactance (Xrs) at 7 Hz. For both parameters, the individual mean of the Z_scores (standardized on height and sex) of all technically acceptable measures were analyzed. Wheezing, asthma and bronchiolitis in the first 3-years of life were collected by repeated questionnaires. Results: The analysis is based on 225 children (79%) with ≥ 2 technically acceptable FOT measurements with a CV<15%. Means(sd) of Rrs7 and Xrs7 were 11.6(2.2) and -4.1(1.2) cmH2O.s/L. Ever asthma, wheezing and bronchiolitis were reported in 16%, 36% and 38% of the children. Z_score_Rrs7 was statistically higher with asthma (means(sd) were 1.06(0.76) vs. 0.64(0.82), p=0.007), bronchiolitis (0.89(0.82) vs. 0.57(0.81), p=0.02) and a non-significant trend was observed with wheezing (0.83(0.77) vs. 0.63(0.84), p=0.11). No significant association was observed for Z_score_Xrs7. Conclusion: Our preliminary analysis supports associations between respiratory resistance at 7Hz and respiratory outcomes at 3 years. Funding: PNREST_Anses_2018/1/264, ERS CRC-2013-02 INCIRCLE

Introduction: Several studies showed deleterious effects of air pollution on children respiratory health, but few relied on prenatal personal exposure estimates and lung function measures. We estimated the association between prenatal exposure to nitrogen dioxide (NO2) and lung function parameters in newborns. Methods: This study relied on SEPAGES couple-child cohort (recruitment 2014-2017 in Grenoble, France). NO2 exposure was estimated by the average concentration of NO2 measured by sensors carried by the pregnant women during 2 to 3 periods of one week. Lung Clearance Index (LCI) and Functional Residual Capacity (FRC) were measured with nitrogen multiple breath washout technique during natural sleep in the infants aged 6-10 weeks. The LCI and FRC values were corrected for the degree of hypoventilation (transient decrease of the tidal volume due to pure oxygen inhalation). Associations between prenatal NO2 exposure and LCI or FRC values were estimated by linear regression models adjusted on gestational duration, child age, sex, height and environmental tobacco smoke. Results: 862 LCI and FRC acceptable measures were obtained for 349 infants (mean(sd) age=7.0(1.1) weeks). Mean(sd) FRC and LCI measures were 106.4(18.1) and 7.6(1.1), and mean prenatal NO2 exposure was 20.0 µg/m3 (range 6-44). Higher prenatal NO2 exposure was associated with reduced FRC (estimate[95%CI] for 10ug/m3=-2.6 [-5.3; 0.2], p=0.06). No association was found with LCI. Conclusions: Increased prenatal personal NO2 exposure was borderline significantly associated with lower FRC in newborns. Further analyses considering additional pollutants and lung function parameters, and postnatal exposure are ongoing.