Objective: We integratively assessed the effect of different indoor and outdoor environmental exposures early in life on respiratory and allergic health conditions among children from (sub-) urban areas. Methods: This study included children participating in four ongoing European birth cohorts located in three different geographical regions: INMA (Spain), LISAplus (Germany), GINIplus (Germany) and BAMSE (Sweden). Wheezing, bronchitis, asthma and allergic rhinitis throughout childhood were assessed using parental-completed questionnaires. We designed “environmental scores” corresponding to different indoor, green- and grey-related exposures (main analysis, a-priori-approach). Cohort-specific associations between these environmental scores and the respiratory health outcomes were assessed using random-effects meta-analyses. In addition, a factor analysis was performed based on the same exposure information used to develop the environmental scores (confirmatory analysis, data-driven-approach). Results: A higher early exposure to the indoor environmental score increased the risk for wheezing and bronchitis within the first year of life (combined adjusted odds ratio: 1.20 [95% confidence interval: 1.13–1.27] and 1.28 [1.18–1.39], respectively). In contrast, there was an inverse association with allergic rhinitis between 6 and 8 years (0.85 [0.79–0.92]). There were no statistically significant associations for the outdoor related environmental scores in relation to any of the health outcomes tested. The factor analysis conducted confirmed these trends. Conclusion: Although a higher exposure to indoor related exposure through occupants was associated with an increased risk for wheezing and bronchitis within the 1st year, it might serve as a preventive mechanism against later childhood allergic respiratory outcomes in urbanized environments through enhanced shared contact with microbial agents.

This study was funded by Grants from UE (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), and from Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/0178, 11/01007, 11/02591, 11/02038, 13/1944, 13/2032, 14/0891, and 14/1687) and the Conselleria de Sanitat, Generalitat Valenciana. The BAMSE study has been supported by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Research Council Formas, the Swedish Environment Protection Agency, the European Community's Seventh Framework Program (FP7/2007–2011 under grant agreement no. 211250), the Swedish Asthma and Allergy Association Research Foundation, and the Stockholm County Council. Christina Tischer is a recipient of a European Respiratory Society Fellowship (RESPIRE2 – 2015– 7251). Payam Dadvand is funded by a Ramón y Cajal fellowship (RYC-2012-10995) awarded by the Spanish Ministry of Economy and Competitiveness. Elaine Fuertes is supported by a Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2015; proposal number 704268).