RT Journal Article
T1 Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach
A1 Accordini, Simone
A1 Sánchez Ramos, José Luis
A1 Svanes, Cecilie
AB Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited.We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18–47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers’ smoking in pregnancy and fathers’ smoking initiation in prepuberty as exposures; fathers’ forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Δ) in expected z-scores related to fathers’ and grandmothers’ smoking history.Fathers’ smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Δz-score –0.36, 95% CI −0.63– −0.10) and FVC (−0.50, 95% CI −0.80– −0.20) compared with fathers’ never smoking. Paternal grandmothers’ smoking in pregnancy had a negative direct effect on fathers’ FEV1/FVC (−0.57, 95% CI −1.09– −0.05) and a negative indirect effect on offspring's FEV1/FVC (−0.12, 95% CI −0.21– −0.03) compared with grandmothers’ not smoking before fathers’ birth nor during fathers’ childhood.Fathers’ smoking in prepuberty and paternal grandmothers’ smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.
PB European Respiratory Society
SN 0903-1936
SN 1399-3003 (electrónico)
YR 2021
FD 2021
LK http://hdl.handle.net/10272/20844
UL http://hdl.handle.net/10272/20844
LA eng
NO Accordini S, Calciano L, Johannessen A, et al. Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach. Eur Respir J 2021; 58: 2002791 [DOI: 10.1183/13993003.02791-2020].
NO The present analyses are part of the Research Council of Norway FRIPRO project (led byC. Svanes) and the ALEC Study (www.alecstudy.org; led by D. Jarvis). The present manuscript contributes to ALEC Workpackage 2 (led by C. Svanes). The RHINESSA Principal Investigators (PIs)/vice-PIs and ECRHS PIs/teammembers are listed in the supplementary material.
DS Repositorio Institucional de la Universidad de Huelva
RD 1 jun 2026