Lydiane Agier1, Xavier Basagaña2, Lea Maitre2, Berit Granum3, Philippa K Bird4, Maribel Casas2, Bente Oftedal3, John Wright4, Sandra Andrusaityte5, Montserrat de Castro2, Enrique Cequier3, Leda Chatzi6, David Donaire-Gonzalez2, Regina Grazuleviciene5, Line S Haug3, Amrit K Sakhi3, Vasiliki Leventakou7, Rosemary McEachan4, Mark Nieuwenhuijsen2, Inga Petraviciene5, Oliver Robinson8, Theano Roumeliotaki7, Jordi Sunyer2, Ibon Tamayo-Uria2, Cathrine Thomsen3, Jose Urquiza2, Antonia Valentin2, Rémy Slama1, Martine Vrijheid2, Valérie Siroux9. 1. Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Inserm, CNRS, University Grenoble Alpes, Institute for Advanced Biosciences (IAB), U1209 Joint Research Center, Grenoble, France. 2. ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. 3. Norwegian Institute of Public Health, Oslo, Norway. 4. Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK. 5. Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania. 6. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Social Medicine, University of Crete, Heraklion, Greece; Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands. 7. Department of Genetics and Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands. 8. ISGlobal, Barcelona, Spain; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. 9. Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Inserm, CNRS, University Grenoble Alpes, Institute for Advanced Biosciences (IAB), U1209 Joint Research Center, Grenoble, France. Electronic address: valerie.siroux@univ-grenoble-alpes.fr.
Abstract
BACKGROUND: Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children. METHODS: In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures. FINDINGS: In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions. INTERPRETATION: Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease. FUNDING: European Community's Seventh Framework Programme (HELIX project).
BACKGROUND: Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children. METHODS: In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures. FINDINGS: In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions. INTERPRETATION: Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease. FUNDING: European Community's Seventh Framework Programme (HELIX project).
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