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

被引：31

作者：

Accordini, Simone ^{[1
]}

Calciano, Lucia ^{[1
]}

Johannessen, Ane ^{[2
]}

Benediktsdottir, Bryndis ^{[3
]}

Bertelsen, Randi Jacobsen ^{[4
,5
]}

Braback, Lennart ^{[6
]}

Dharmage, Shyamali C. ^{[7
]}

Forsberg, Bertil ^{[6
]}

Real, Francisco Gomez ^{[4
,8
]}

Holloway, John W. ^{[9
]}

Holm, Mathias ^{[10
]}

Janson, Christer ^{[11
]}

Jogi, Nils O. ^{[4
,12
]}

Jogi, Rain ^{[12
]}

Malinovschi, Andrei ^{[13
]}

Marcon, Alessandro ^{[1
]}

Rovira, Jesus Martinez-Moratalla ^{[14
]}

Sanchez-Ramos, Jose Luis ^{[15
]}

Schlunssen, Vivi ^{[16
]}

Toren, Kjell ^{[10
]}

Jarvis, Deborah ^{[17
,18
]}

Svanes, Cecilie ^{[2
]}

机构：

[1] Univ Verona, Dept Diagnost & Publ Hlth, Unit Epidemiol & Med Stat, Verona, Italy

[2] Univ Bergen, Ctr Int Hlth, Dept Global Publ Hlth & Primary Care, Bergen, Norway

[3] Univ Iceland, Fac Med, Reykjavik, Iceland

[4] Univ Bergen, Dept Clin Sci, Bergen, Norway

[5] Oral Hlth Ctr Expertise Western Norway Vestland, Bergen, Norway

[6] Umea Univ, Dept Publ Hlth & Clin Med, Sect Sustainable Hlth, Umea, Sweden

[7] Univ Melbourne, Sch Populat & Global Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic, Australia

[8] Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway

[9] Univ Southampton, Fac Med, Human Dev & Hlth, Southampton, Hants, England

[10] Univ Gothenburg, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden

[11] Uppsala Univ, Dept Med Sci Resp Allergy & Sleep Res, Uppsala, Sweden

[12] Tartu Univ Hosp, Lung Clin, Tartu, Estonia

[13] Uppsala Univ, Dept Med Sci Clin Physiol, Uppsala, Sweden

[14] Complejo Hosp Univ Albacete CHUA, Serv Neurol, Serv Salud Castilla La Mancha SESCAM, Albacete, Spain

[15] Univ Huelva, Dept Nursing, Huelva, Spain

[16] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark

[17] Imperial Coll London, Fac Med, Natl Heart & Lung Inst, London, England

[18] Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England

来源：

EUROPEAN RESPIRATORY JOURNAL | 2021年 / 58卷 / 04期

基金：

英国医学研究理事会; 欧盟地平线“2020”;

关键词：

MEDIATION ANALYSIS; NICOTINE EXPOSURE; EPIGENETIC INHERITANCE; CIGARETTE-SMOKING; RISK-FACTORS; ODDS RATIO; ASTHMA; CHILDHOOD; PREGNANCY; WEIGHT;

D O I：

10.1183/13993003.02791-2020

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

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 (Delta) 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 (Delta z-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.

引用

页数：13

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