Pre-pubertal smoke exposure of fathers and increased risk of offspring asthma: a possible transgenerational effect

Abstract

Asthma is a major non-communicable disease in children [1]. Pre-and post-natal exposure to tobacco smoke are major risk factors for childhood asthma [1,2]. While there is evidence that mothers' intrauterine exposure to second-hand smoke is associated with asthma in the offspring [3,4], there is also increasing concern that fathers who start smoking before completing puberty may elevate the risk of asthma in their offspring [4,5]. The suggestion is that this may be as a result of epigenetic changes to sperm precursor (stem) cells during gonadal maturation [4,5]. However, this is rather speculative, and as yet little is actually known about whether fathers' passive smoke exposure throughout childhood to puberty is indeed associated with increased asthma risk in their offspring.We investigated this potential association using data from 1689 father-offspring pairs in the Tasmanian Longitudinal Health Study (TAHS). Offspring in this study were the probands in TAHS [6], where their childhood asthma and hay fever status had been reported by their parents at age 7 years, in 1968. Offspring asthma was defined as more than one attack of asthma/wheezy breathing by this age of 7 years, and was classified as allergic asthma if they had both asthma and hay fever during the same period. Fathers of the probands reported their personal lifetime active smoking history and also pre-pubertal passive smoke exposure (between 0 and 15 years) from their own parents (i.e. offspring paternal grandparents) in the 2010 follow-up survey. The study was approved by human ethics review committees at the Universities of Melbourne (approval number: 040375), Tasmania (040375.1) and New South Wales (08094), Alfred Hospital (1118/04), and Royal Brisbane and Women's Hospital Health Service District (2006/037).We used logistic regression for offspring asthma at age 7 years (asthma versus no asthma), and multinomial logistic regression for offspring asthma phenotypes (non-allergic asthma versus no asthma; allergic asthma versus no asthma). Analyses were adjusted for fathers' educational levels, and prior asthma history. These potential confounders were identified by directed acyclic graph models. The analyses were additionally adjusted and stratified for fathers' lifetime active smoking history. In addition, we investigated potential interaction between fathers' pre-pubertal passive smoke exposure and lifetime active smoking, using a likelihood ratio test. We also combined fathers' pre-pubertal passive smoke exposure (yes/no) and fathers' lifetime active smoking history (yes/no), and categorised them into four groups (as: no/no (reference), yes/no, no/yes, yes/yes) and fitted this new variable in the analyses.Fathers' passive smoke exposure before 15 years of age was associated with increased odds of offspring non-allergic asthma by 7 years of age (adjusted multinomial odds ratio (aMOR) 1.59, 95% CI 1.09-2.32) (adjusted model 1) (table 1). After further stratifying by fathers' lifetime active smoking history, the association between fathers' passive sm...

Preconception origins of asthma, allergies and lung function: The influence of previous generations on the respiratory health of our children

“…To date, only one murine study has investigated sperm miRNAs after inhalation smoke exposure in the key puberty window [92], demonstrated to be important in human epidemiological studies [32,33,36,93]. Although the counts and morphological integrity of the spermatozoa as well as the proliferation of spermatogonia of smoke-exposed fathers remained intact, 13 miRNAs were upregulated and 32 downregulated and were predicted to target mRNAs associated with lung and early embryo development.…”

“…Regarding mother's smoking and offspring lung health, a role of mother's preconception smoking on offspring asthma or lung function is not identified, as investigated for only preconception smoking [32] and for early onset smoking [33][34]36]. For comparison, the well-known effects of maternal smoking in pregnancy are replicated in these studies.…”

Seven days in medicine: 14-20 September 2022

“…The risk of non-allergic asthma in children increased by 59% if their fathers were exposed to secondhand smoke in childhood, in a comparison with children whose fathers were not exposed. The risk was higher, at 72%, if their fathers had been exposed to secondhand smoke and gone on to smoke themselves 6…”

Social determinants of respiratory health from birth: still of concern in the 21st century?

“…This is even though they may be a harbinger of future COPD [1], adult bronchiectasis [2], and early morbidity and mortality from respiratory and all-cause disease [3]. Furthermore, it is not widely enough appreciated that early adverse exposures not merely have lifetime effects on the child, but also have effects on that child's children and even grandchildren [4][5][6]. Early means before birth and even pre-conception.…”

“…If a woman smokes, even if her daughters do not smoke, her grandchildren are more likely to develop asthma [ 4 , 5 ]. Men who are passively exposed to tobacco are more likely to father children with asthma [ 6 ]. Urgent action is needed to break these transgenerational cycles of disease.…”