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

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.
Funding Agencies|Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Swedish Child Diabetes Foundation (Barndiabetesfonden); JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden (FORSS); Swedish Council for Working Life and Social Research [FAS2004-1775]; Ostgota Brandstodsbolag; UK Medical Research Council; Wellcome [217065/Z/19/Z]; University of Bristol; Swedish Heart Lung Foundation; ALF Region Stockholm; SFO Epidemiology Karolinska Institutet; European Research Council [757919, ERC-2014-CoG-648916]; Programme Grants for Applied Research funding scheme [RP-PG-0407-10044]; Wellcome Trust [WT101597MA]; Swiss National Science Foundation [320030_163311, SNF: 320030-182628, 320030-162820, 3233-069348, 3200-069349]; Italian Ministry of Health; Lundbeck Foundation [R16-A1694, 195/04, R100-A9193, R264-2017-3099]; Ministry of Health [903516]; Danish Council for Strategic Research [0603-00280B]; Capital Region Research Foundation; Danish National Research Foundation; Danish Regional Committees; Egmont Foundation; March of Dimes Birth Defects Foundation; Novo Nordisk Foundation; Danish Medical Research Council [SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B]; Innovation Fund Denmark [0603-00294B (09-067124)]; Nordea Foundation [02-2013-2014]; University of Copenhagen; Danish Council for Independent Research [DFF-4183-00594, DFF-4183-00152]; Foundation for Medical Research (FRM); National Institute for Research in Public health; French Ministry of Health (DGS); French Ministry of Research; INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs; French National Institute for Health Education (INPES); European Union [733206]; Diabetes National Research Program; Mutuelle Generale de lEducation Nationale complementary health insurance (MGEN); French national agency for food security; European Community [261357]; Erasmus MC Rotterdam; Erasmus University Rotte