Prenatal tobacco exposure and risk of asthma and allergy outcomes in childhood

Abstract

BackgroundHarmful 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.MethodsPrenatal 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.ResultsPrenatal 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.ConclusionPrenatal 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.