PT - JOURNAL ARTICLE AU - Rikke Bjersand Sunde AU - Jonathan Thorsen AU - Casper-Emil Tingskov Pedersen AU - Jakob Stokholm AU - Klaus Bønnelykke AU - Bo Chawes AU - Hans Bisgaard TI - Prenatal tobacco exposure and risk of asthma and allergy outcomes in childhood AID - 10.1183/13993003.00453-2021 DP - 2021 Jan 01 TA - European Respiratory Journal PG - 2100453 4099 - http://erj.ersjournals.com/content/early/2021/06/25/13993003.00453-2021.short 4100 - http://erj.ersjournals.com/content/early/2021/06/25/13993003.00453-2021.full AB - Background Harmful effects of prenatal tobacco exposure and possible interaction with 17q12-21 genetic variants have been shown for some asthma outcomes in childhood, whereas findings related to allergy outcomes are more inconsistent. This study aimed to examine the effect of prenatal tobacco exposure and relation to 17q12-21 genotype on a wide array of asthma and allergy-related outcomes in early childhood.Methods Prenatal tobacco exposure was determined by maternal smoking during 3rd trimester (yes/no) in 411 children from the COPSAC2000 birth cohort with clinical follow-up till age 7 years. The rs7216389 SNP was used as main representative of the 17q12-21 locus. Asthma endpoints included asthma diagnosis, exacerbations, episodes with troublesome lung symptoms and lower respiratory tract infections (LRTI), spirometry, plethysmography, bronchial responsiveness to methacholine, exercise and cold dry air. Allergy-related endpoints included aeroallergen sensitisation, allergic rhinitis, fractional exhaled nitric oxide, blood eosinophil count and urine eosinophil protein X levels. Statistical analyses were done using Cox regression, linear regression, logistic regression and Quasi-Poisson regression.Results Prenatal tobacco exposure increased the risk of asthma (adjusted hazard ratio (aHR)=2.05, (95% CI 1.13; 3.73), p=0.02)), exacerbations (aHR=3.76, (2.05; 6.91), p<0.001), number of LRTIs (aIRR=1.87, (1.34; 2.55), p<0.001), and associated with decreased spirometry indices (FEV1: aMD=−0.07 L (−0.13; −0.005), p=0.03, MMEF: aMD=−0.19 L·s−1 (−0.34; −0.04), p=0.01) and increased bronchial responsiveness to methacholine (PD20: aGMR=0.55 (0.31; 0.96), p=0.04). In contrast, there was no association with any allergy-related endpoints. The effect on asthma depended on 17q12-21 genotype with an increased risk only among children without risk alleles.Conclusion Prenatal tobacco exposure was associated with asthma dependent on 17q12-21 genotype and with exacerbations, lung function and bronchial responsiveness, but not with any allergy-related outcomes. This suggests that tobacco exposure in utero leads to adverse lung developmental/structural effects rather than susceptibility to develop allergy and Type 2 inflammation.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Rikke Bjersand Sunde has nothing to disclose.Conflict of interest: Jonathan Thorsen has nothing to disclose.Conflict of interest: Casper-Emil Tingskov Pedersen has nothing to disclose.Conflict of interest: Jakob Stokholm has nothing to disclose.Conflict of interest: Klaus Bønnelykke has nothing to disclose.Conflict of interest: Bo Chawes has nothing to disclose.Conflict of interest: Hans Bisgaard.