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

Simone Accordini; Lucia Calciano; Ane Johannessen; Bryndis Benediktsdóttir; Randi Jacobsen Bertelsen; Lennart Bråbäck; Shyamali C Dharmage; Bertil Forsberg; Francisco Gómez Real; John W Holloway; Mathias Holm; Christer Janson; Nils O Jõgi; Rain Jõgi; Andrei Malinovschi; Alessandro Marcon; Jesús Martínez-Moratalla Rovira; José Luis Sánchez-Ramos; Vivi Schlünssen; Kjell Torén; Deborah Jarvis; Cecilie Svanes

doi:10.1183/13993003.02791-2020

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 Oct 21;58(4):2002791. doi: 10.1183/13993003.02791-2020. Print 2021 Oct.

Authors

Simone Accordini^{1

2}, Lucia Calciano^{3

2}, Ane Johannessen⁴, Bryndis Benediktsdóttir⁵, Randi Jacobsen Bertelsen^{6

7}, Lennart Bråbäck⁸, Shyamali C Dharmage⁹, Bertil Forsberg⁸, Francisco Gómez Real^{6

10}, John W Holloway¹¹, Mathias Holm¹², Christer Janson¹³, Nils O Jõgi^{6

14}, Rain Jõgi¹⁴, Andrei Malinovschi¹⁵, Alessandro Marcon³, Jesús Martínez-Moratalla Rovira¹⁶, José Luis Sánchez-Ramos¹⁷, Vivi Schlünssen¹⁸, Kjell Torén¹², Deborah Jarvis^{19

20

21}, Cecilie Svanes^{4

21}

Affiliations

¹ Unit of Epidemiology and Medical Statistics, Dept of Diagnostics and Public Health, University of Verona, Verona, Italy simone.accordini@univr.it.
² Equal contribution as first authors.
³ Unit of Epidemiology and Medical Statistics, Dept of Diagnostics and Public Health, University of Verona, Verona, Italy.
⁴ Centre for International Health, Dept of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
⁵ Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
⁶ Dept of Clinical Science, University of Bergen, Bergen, Norway.
⁷ Oral Health Centre of Expertise in Western Norway/Vestland, Bergen, Norway.
⁸ Section of Sustainable Health, Dept of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
⁹ Allergy and Lung Health Unit, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
¹⁰ Dept of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
¹¹ Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
¹² Occupational and Environmental Medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹³ Dept of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.
¹⁴ Lung Clinic, Tartu University Hospital, Tartu, Estonia.
¹⁵ Dept of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
¹⁶ Servicio de Neumología, Complejo Hospitalario Universitario de Albacete (CHUA), Servicio de Salud de Castilla-La Mancha (SESCAM), Albacete, Spain.
¹⁷ Dept of Nursing, University of Huelva, Huelva, Spain.
¹⁸ Dept of Public Health, Aarhus University, Aarhus, Denmark.
¹⁹ Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
²⁰ MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
²¹ Equal contribution as last authors.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Adult Children
Child
Forced Expiratory Volume
Humans
Lung
Middle Aged
Nicotiana
Pregnancy
Smoking / adverse effects
Tobacco Smoke Pollution* / adverse effects
Vital Capacity
Young Adult

Substances

Tobacco Smoke Pollution