Juan Pablo López-Cervantes

Background: Father's adolescent smoking and overweight affect respiratory health in offspring, suggesting that paternal puberty exposures may influence offspring biological ageing through preconception epigenetic mechanisms. Methods: We analyzed epigenetic age acceleration using four validated epigenetic clocks derived from blood DNA methylation in 892 RHINESSA offspring (mean age 27 years), linked to parental data on smoking and body shapes from RHINE/ECRHS. Linear regression examined parental smoking initiation (≤15 or >15 years) and overweight body shape (childhood/puberty or age 30) in relation to offspring epigenetic age acceleration, adjusting for offspring sex, age and parental socioeconomic status. Sensitivity analyses accounted for offspring smoking and BMI. Results: PCHorvath (β 1.53; 95% CI 0.02, 2.9), PCGrimAge (1.21; 0.03, 2.1), DunedinPACE (0.04; -0.001, 0.1) and PCPhenoAge (1.92; -0.3, 4.2) were accelerated in daughters of fathers who started smoking ≤15 years. Likewise, PCHorvath (2.25; 1.2, 3.3), PCGrimAge (1.36; -0.2, 2.9), DunedinPACE (0.07; 0.01, 0.1) and PCPhenoAge (3.11; 1.8, 4.4) were accelerated in daughters and sons of fathers who had been overweight in childhood and puberty. These results remained largely unchanged after additional adjustments or stratification in sensitivity analyses. No associations were found for maternal smoking or overweight in puberty. Conclusions: Epigenetic ageing is accelerated in offspring of fathers who smoked or were overweight in puberty, independent of offspring lifestyle. These findings suggest that adolescent boys' environment and lifestyle may be critical for next-generation health.

Evidence suggests that a father’s smoking in puberty may adversely impact respiratory health in offspring, possibly through epigenetic changes in germ cells. This study investigates whether snus use starting in or after puberty influences respiratory health in future offspring. We analysed Swedish data from RHINE (Respiratory Health in Northern Europe) parents and RHINESSA (Respiratory Health in Northern Europe, Spain and Australia) offspring by using mixed-effect logistic regression to assess the links between paternal snus initiation around puberty and offspring asthma, chronic bronchitis, rhinitis, and eczema, adjusting for paternal and offspring smoking. We identified 1090 offspring–father pairs. The offspring’s median age was 29 years (17–51) and 55% were women. The maternal line (n = 1421) was not analysed, as n = 89) had a higher risk of current allergic asthma [odds ratio (OR) 1.42; 95% confidence interval (CI) 1.02–1.97], at least three asthma symptoms with allergy (OR 1.13; 95% CI 1.10–1.21), chronic bronchitis (OR 2.17; 95% CI 1.04–4.54), and eczema (OR 1.45; 95% CI 1.27–1.65). Fathers’ snus use starting after puberty (n = 252) showed no consistent associations with offspring outcomes. The effect estimates were consistent after excluding offspring using snus in puberty. Paternal snus use starting in puberty was associated with a higher risk of asthma and other respiratory and allergic symptoms in offspring. These findings support the hypothesis that exposures in puberty may impact future generations’ respiratory health, possibly through epigenetic changes. This highlights the need for research on exposures during this period and actions to prevent habits that could negatively impact future offspring’s health.

Background: Research suggests preconception exposure to smoking may impact offspring lung health, and that epigenetic mechanisms may be at play. Thus, parental snus initiation before offspring conception may potentially influence asthma risk in offspring. Aims: To investigate the association of parental snus use before conception with offspring asthma. Methods: Data from the population-based Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study (2013-16) across Norway, Sweden, Denmark, Iceland and Estonia were analyzed. Parental reports (from one parent) on their age of snus initiation were categorized as never (reference), preconception (≥2 years before offspring birth), and postconception (after offspring birth). Offspring asthma (never/ever) was reported by the parent. Logistic regressions clustered by study center and adjusted for parental age, sex, and offspring sex were conducted. Sensitivity analyses included never-smoking parents and sex-specific parent-offspring pairs. Results: This two-generation analysis included 2005 parent-offspring pairs (mean age: parent, 36 years; offspring, 9 years). Offspring of parents who reported preconception snus use (198 pairs) had higher asthma risk (OR 1.94; 95%CI 1.23-3.10) compared to offspring of never-snus users (1706 pairs). This association remained for offspring of never-smoking parents (90 pairs; 2.29; 1.12-4.30). Sex-specific analyses revealed associations in father-daughter only (2.86; 1.29-6.36). Weaker associations were found with postconception snus use. Conclusions: Parental snus use before conception may possibly increase asthma risk in offspring, even among children of never-smoking parents.

Objectives To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms. Design Cross-sectional analysis of a population-based cohort. Setting Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019. Participants 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study. Main outcome measures Current asthma and asthma symptoms. Results The median age of study participants was 28 years (range 15–53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (β-coefficient (β) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; β 0.16; 95% CI −0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years. Conclusions Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product.

Background: Evidence suggests an association of oral moist tobacco (snus) with higher risk of asthma, asthma-symptoms, and chronic bronchitis among never smokers. However, there is no knowledge of whether time at snus initiation plays a role for respiratory outcomes. Objective: To investigate associations of snus use starting in puberty (≤15 years of age) and after, with asthma and asthma-like symptoms. Methods: Questionnaire data on tobacco habits and respiratory outcomes were obtained in Norway, Sweden, Denmark, Iceland, and Estonia from 9002 responders [median age 29 years (15-72); 58% females] from the Respiratory Health In Northern Europe, Spain and Australia (RHINESSA) study in 2013-16. Time at snus initiation was classified as never (reference), ≤15, or >15 years of age. Multilevel logistic regression models adjusted for age and smoking, and stratified by sex were used to analyze associations of time at snus initiation and 1) asthma-like symptoms (≥3 vs. vs. no). Results: Snus use was reported by 20.4% of the participants of whom 21.7% had started in puberty. Women using snus in puberty had a higher OR for asthma-like symptoms (OR 2.54; 95%CI 1.37-4.70) and for asthma medication/attacks (OR 1.70; 95%CI 0.87-3.31) compared to never users. No significant effect could be identified for early onset snus use in males (OR 1.15; 95%CI 0.74-1.79) or late initiation in either of the sexes. Conclusions: Many snus users in Northern Europe start consumption at an early age. Our results indicate that use of snus starting in puberty could increase the risk of respiratory symptoms in women.