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Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generational study using a causal modelling approach: a three-generation study using a causal modelling approach

Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generational study using a causal modelling approach: a three-generation study using a causal modelling approach
Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generational study using a causal modelling approach: a three-generation study using a causal modelling approach
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 multi-generation 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; female: 52.0%) and their 274 fathers, who had participated in the ECRHS/RHINESSA generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multi-level mediation models were developed with: paternal grandmothers’ smoking in pregnancy and fathers’ smoking initiation in prepuberty as exposures; fathers' FEV1 and FVC, or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); offspring’s FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences 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 ( 0.36; 95% confidence interval: -0.63, -0.10) and FVC (-0.50; -0.80, -0.20) compared to fathers’ never smoking. Paternal grandmothers’ smoking in pregnancy had a negative direct effect on fathers’ FEV1/FVC (-0.57; -1.09, -0.05) and a negative indirect effect on offspring’s FEV1/FVC ( 0.12; -0.21, -0.03) compared to 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.
0903-1936
2002791
Accordini, Simone
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Calciano, Lucia
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Johannessen, Ane
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Benediktsdóttir, Bryndis
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Bertelsen, Randi Jacobsen
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Bråbäck, Lennart
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Dharmage, Shyamali C.
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Forsberg, Bertil
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Real, Francisco Gomez
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Holloway, John
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Holm, Mathias
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Janson, Christer
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Jõgi, Nils Oskar
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Jögi, Rain
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Malinovschi, Andrei
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Marcon, Alessandro
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Martínez-moratalla Rovira, Jesús
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Sánchez-Ramos, José Luis
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Schlunssen, Vivi
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Torén, Kjell
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Jarvis, Deborah
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Svanes, Cecilie
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Accordini, Simone
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Calciano, Lucia
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Johannessen, Ane
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Benediktsdóttir, Bryndis
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Bertelsen, Randi Jacobsen
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Bråbäck, Lennart
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Dharmage, Shyamali C.
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Forsberg, Bertil
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Real, Francisco Gomez
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Holloway, John
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Holm, Mathias
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Janson, Christer
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Jõgi, Nils Oskar
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Jögi, Rain
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Malinovschi, Andrei
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Marcon, Alessandro
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Martínez-moratalla Rovira, Jesús
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Sánchez-Ramos, José Luis
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Schlunssen, Vivi
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Torén, Kjell
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Jarvis, Deborah
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Svanes, Cecilie
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Accordini, Simone, Calciano, Lucia, Johannessen, Ane, Benediktsdóttir, Bryndis, Bertelsen, Randi Jacobsen, Bråbäck, Lennart, Dharmage, Shyamali C., Forsberg, Bertil, Real, Francisco Gomez, Holloway, John, Holm, Mathias, Janson, Christer, Jõgi, Nils Oskar, Jögi, Rain, Malinovschi, Andrei, Marcon, Alessandro, Martínez-moratalla Rovira, Jesús, Sánchez-Ramos, José Luis, Schlunssen, Vivi, Torén, Kjell, Jarvis, Deborah and Svanes, Cecilie (2021) Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generational study using a causal modelling approach: a three-generation study using a causal modelling approach. European Respiratory Journal, 58 (4), 2002791. (doi:10.1183/13993003.02791-2020).

Record type: Article

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 multi-generation 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; female: 52.0%) and their 274 fathers, who had participated in the ECRHS/RHINESSA generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multi-level mediation models were developed with: paternal grandmothers’ smoking in pregnancy and fathers’ smoking initiation in prepuberty as exposures; fathers' FEV1 and FVC, or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); offspring’s FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences 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 ( 0.36; 95% confidence interval: -0.63, -0.10) and FVC (-0.50; -0.80, -0.20) compared to fathers’ never smoking. Paternal grandmothers’ smoking in pregnancy had a negative direct effect on fathers’ FEV1/FVC (-0.57; -1.09, -0.05) and a negative indirect effect on offspring’s FEV1/FVC ( 0.12; -0.21, -0.03) compared to 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.

Text
Accordini et al 2021 ERJ67 - Accepted Manuscript
Restricted to Repository staff only until 11 March 2022.
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More information

Accepted/In Press date: 11 March 2021
e-pub ahead of print date: 1 April 2021
Published date: 1 April 2021

Identifiers

Local EPrints ID: 447752
URI: http://eprints.soton.ac.uk/id/eprint/447752
ISSN: 0903-1936
PURE UUID: 8720d785-7441-4c1c-bc6c-0c482633eecc
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 19 Mar 2021 17:31
Last modified: 30 Oct 2021 01:36

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Contributors

Author: Simone Accordini
Author: Lucia Calciano
Author: Ane Johannessen
Author: Bryndis Benediktsdóttir
Author: Randi Jacobsen Bertelsen
Author: Lennart Bråbäck
Author: Shyamali C. Dharmage
Author: Bertil Forsberg
Author: Francisco Gomez Real
Author: John Holloway ORCID iD
Author: Mathias Holm
Author: Christer Janson
Author: Nils Oskar Jõgi
Author: Rain Jögi
Author: Andrei Malinovschi
Author: Alessandro Marcon
Author: Jesús Martínez-moratalla Rovira
Author: José Luis Sánchez-Ramos
Author: Vivi Schlunssen
Author: Kjell Torén
Author: Deborah Jarvis
Author: Cecilie Svanes

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