Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children

Evelien R. van Meel, Sara M. Mensink-Bout, Herman T. den Dekker, Tarunveer S. Ahluwalia, Isabella Annesi-Maesano, Syed Hasan Arshad, Nour Baïz, Henrique Barros, Andrea von Berg, Hans Bisgaard, Klaus Bønnelykke, Christian J. Carlsson, Maribel Casas, Leda Chatzi, Cecile Chevrier, Geertje Dalmeijer, Carol Dezateux, Karel Duchen, Merete Eggesbø, Cornelis van der EntMaria Fantini, Claudia Flexeder, Urs Frey, Fransesco Forastiere, Ulrike Gehring, Davide Gori, Raquel Granell, Lucy J. Griffiths, Hazel Inskip, Joanna Jerzynska, Anne M. Karvonen, Thomas Keil, Cecily Kelleher, Manolis Kogevinas, Gudrun Koppen, Claudia E. Kuehni, Nathalie Lambrechts, Susanne Lau, Irina Lehmann, Johnny Ludvigsson, Maria Christine Magnus, Erik Mélen, John Mehegan, Monique Mommers, Anne Marie Nybo Andersen, Wenche Nystad, Eva S.L. Pedersen, Juha Pekkanen, Ville Peltola, Katharine C. Pike, Angela Pinot de Moira, Costanza Pizzi, Kinga Polanska, Maja Popovic, Daniela Porta, Graham Roberts, Ana Cristina Santos, Erica S. Schultz, Marie Standl, Jordi Sunyer, Carel Thijs, Laura Toivonen, Eleonora Uphoff, Jakob Usemann, Marina Vafeidi, John Wright, Johan C. de Jongste, Vincent W.V. Jaddoe, Liesbeth Duijts

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Abstract

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Original languageEnglish
Article number2102395
JournalThe European respiratory journal
Volume60
Issue number4
DOIs
Publication statusPublished - 1 Oct 2022

Bibliographical note

Funding Information:
Conflict of interest: T.S. Ahluwalia received funding for the current manuscript from the Novo Nordisk Foundation (NNF180C0052457). I. Annesi-Maesano is member of the ATS Environment Health Policy Committee, the ERS Ethics and Integrity Committee, and the French IRD Ethics Committee. S.H. Arshad received funding for the manuscript from Asthma UK (364) and National Institutes of Health USA (R01HL082925). H. Bisgaard received funding for the current manuscript from the Lundbeck Foundation (R16-A1694), Ministry of Health (903516), Danish Council for Strategic Research (0603-00280B) and Capital Region Research Foundation. M. Eggesbø received paid honorarium for making small videos relating to allergy and asthma, by the Norwegian LHL organisation. U. Frey received funding for the manuscript from the Swiss National Science Foundation (320030_204717/1), and is chair of the National Steering Board, Swiss Personalized Health Network (SPHN). H. Inskip received funding for the manuscript from the UK Medical Research Council and the European Union, and was President for the Society for Social Medicine and Population Health. J. Jerzynska received funding for the current manuscript from the National Science Centre, Poland (DEC-2014/15/B/N27/00998). A.M. Karvonen received funding for the present manuscript from the Academy of Finland (139021, 287675, 296814, 296817, 308254), Juho Vainio Foundation, EVO/VTR funding, Pavivikki and Sakari Sohlberg Foundation, Farmers’ Social Insurance Institution (Mela), Finnish Cultural Foundation, Foundation for Pediatric Research, and the European Union (QLK4-CT-2001-0250). M. Mommers received grants from the Research Council of Norway (262700) and European Research Council (947684). A. Pinot de Moira received a Lundbeck Foundation fellowship (R264-2017-3099). V. Peltola received funding for the present manuscript from the Academy of Finland and Foundation for Pediatric Research Finland. K.C. Pike received consulting fees from Novartis and Spiriva, payment or honoraria for lectures from Novartis, and is participating on a data safety monitoring board or advisory board for Adherium. K. Polanska received funding for the current manuscript from the National Science Centre, Poland (DEC-2014/15/B/N27/00998), grant PRNF-218-AI-1/07 from Norway through the Norwegian Financial Mechanisms within the Polish–Norwegian Research Fund, and the Ministry of Science and Higher Education, Poland (PBZ-MEiN-/8/2//2006). G. Roberts is president of the BSACI. A.C. Santos received funding for the current manuscript from FCT Investigators contracts (IF/01060/2015). J. Sunyer received a grant from the European Research Council (Prenatal exposure to urban AIR pollution and pre-and postNatal Brain development (AIR-NB), 785994). J. Usemann received grants from the Palatin Foundation, University of Basel Switzerland, Swiss Cancer League and Swiss Lung Foundation, and payments or honoraria for lectures from Vertex and Zurich Lung Foundation. V.W.V. Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). L. Duijts received funding from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 (696295; 2017), the Netherlands Organisation for Health Research and Development (ZonMw; 529051014; 2017), Science Foundation Ireland (SFI/16/ERA-HDHL/3360), and the European Union (ALPHABET project). All other authors declare no conflict of interest.

Funding Information:
Conflict of interest: T.S. Ahluwalia received funding for the current manuscript from the Novo Nordisk Foundation (NNF180C0052457). I. Annesi-Maesano is member of the ATS Environment Health Policy Committee, the ERS Ethics and Integrity Committee, and the French IRD Ethics Committee. S.H. Arshad received funding for the manuscript from Asthma UK (364) and National Institutes of Health USA (R01HL082925). H. Bisgaard received funding for the current manuscript from the Lundbeck Foundation (R16-A1694), Ministry of Health (903516), Danish Council for Strategic Research (0603-00280B) and Capital Region Research Foundation. M. Eggesbø received paid honorarium for making small videos relating to allergy and asthma, by the Norwegian LHL organisation. U. Frey received funding for the manuscript from the Swiss National Science Foundation (320030_204717/1), and is chair of the National Steering Board, Swiss Personalized Health Network (SPHN). H. Inskip received funding for the manuscript from the UK Medical Research Council and the European Union, and was President for the Society for Social Medicine and Population Health. J. Jerzynska received funding for the current manuscript from the National Science Centre, Poland (DEC-2014/15/B/N27/00998). A.M. Karvonen received funding for the present manuscript from the Academy of Finland (139021, 287675, 296814, 296817, 308254), Juho Vainio Foundation, EVO/VTR funding, Pavivikki and Sakari Sohlberg Foundation, Farmers’ Social Insurance Institution (Mela), Finnish Cultural Foundation, Foundation for Pediatric Research, and the European Union (QLK4-CT-2001-0250). M. Mommers received grants from the Research Council of Norway (262700) and European Research Council (947684). A. Pinot de Moira received a Lundbeck Foundation fellowship (R264-2017-3099). V. Peltola received funding for the present manuscript from the Academy of Finland and Foundation for Pediatric Research Finland. K.C. Pike received consulting fees from Novartis and Spiriva, payment or honoraria for lectures from Novartis, and is participating on a data safety monitoring board or advisory board for Adherium. K. Polanska received funding for the current manuscript from the National Science Centre, Poland (DEC-2014/15/B/N27/00998), grant PRNF-218-AI-1/07 from Norway through the Norwegian Financial Mechanisms within the Polish–Norwegian Research Fund, and the Ministry of Science and Higher Education, Poland (PBZ-MEiN-/8/2//2006). G. Roberts is president of the BSACI. A.C. Santos received funding for the current manuscript from FCT Investigators contracts (IF/01060/2015). J. Sunyer received a grant from the European Research Council (Prenatal exposure to urban AIR pollution and pre- and postNatal Brain development (AIR-NB), 785994). J. Usemann received grants from the Palatin Foundation, University of Basel Switzerland, Swiss Cancer League and Swiss Lung Foundation, and payments or honoraria for lectures from Vertex and Zurich Lung Foundation. V.W.V. Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). L. Duijts received funding from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 (696295; 2017), the Netherlands Organisation for Health Research and Development (ZonMw; 529051014; 2017), Science Foundation Ireland (SFI/16/ERA-HDHL/3360), and the European Union (ALPHABET project). All other authors declare no conflict of interest.

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