While the impact of early life acetaminophen on asthma risk is still not clear, potential interactions with Glutathione S-Transferase (GST) genes due to reduced antioxidant function in particular polymorphisms, and possible impact on lung function, have never been investigated in adolescents.
We aimed to investigate associations between early life acetaminophen use, adolescent asthma and lung function and to assess potential interactions by GST polymorphisms.
Acetaminophen use was recorded 18 times up to 2 years of age (n=575, 92.7%). Participants were genotyped for GST polymorphisms (GSTM1/T1/P1) (n=429, 69.2%). Asthma and lung function were measured at 12 (n=365, 58.9%) and 18 years (n=413, 66.6%). Regression models assessed associations and interactions.
Doubling of days of acetaminophen use was associated with reduced pre-bronchodilator (BD) Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV/FVC) (β-coefficient=-0.10 [95%CI -0·19, -0·01]) and Mid-Expiratory Flow (MEF) (-0.09 [-0·18, 0]) at 18 years, but this association was not found when restricted for non-respiratory reasons, suggesting confounding by indication. However, in children with GSTM1 null and GSTT1 present, increasing acetaminophen use for non-respiratory reasons was associated with reduced FEV and MEF at 18 years (interaction between GSTM1/T1 and acetaminophen p<0·05). Increased acetaminophen use was associated with asthma at 18 years for children with GSTP1 Ile/Ile (OR=1·66, 1·07, 2·57), but not other GSTP1 genotypes.
These novel findings need to be investigated for consistency in other studies but suggest that children carrying risk genotypes may be susceptible to respiratory consequences from acetaminophen use.

Copyright © 2020. Published by Elsevier Inc.