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In a recent study we found that fathers’ but not mothers’ onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring’s adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents’ overweight on adult offspring’s lung function within the paternal and maternal lines. We included 929 offspring (aged 18–54, 54% daughters) of 308 fathers and 388 mothers (aged 40–66). Counterfactual-based multi-group mediation analyses by offspring’s sex (potential moderator) were used, with offspring’s prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ forced expiratory volume in one second (FEV1 ) (beta (95% CI): −144 (−272, −23) mL) and forced vital capacity (FVC) (beta (95% CI): −210 (−380, −34) mL), and a negative direct effect on sons’ FVC (beta (95% CI): −262 (−501, −9) mL); statistically significant effects on FEV1 /FVC were not observed. Mothers’ overweight before puberty had neither direct nor indirect effects on offspring’s lung function. Fathers’ overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons’ adult height but not through sons’ prepubertal overweight.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitisation as a major determinant. OBJECTIVE: We aimed to see if there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitisation, in a multi-centre population-based study. METHODS: A total of 741 subjects with current asthma and 4,155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitisation status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO was assessed in adjusted multivariate regression models and test for interaction with perennial sensitisation and asthma on the relation between UAID and FeNO were made. RESULTS: UAID were associated with higher FeNO after adjusting for perennial sensitisation, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2)% higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitisation was found in the relationship between current rhinitis and FeNO (p=0.03) and between rhinoconjunctivitis and FeNO (p=0.03). After stratification by asthma and perennial sensitisation, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitisation, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. CONCLUSIONS & CLINICAL RELEVANCE: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitisation. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant. OBJECTIVE: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study. METHODS: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made. RESULTS: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without. CONCLUSIONS & CLINICAL RELEVANCE: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflamm

Life course data on obesity may enrich the quality of epidemiologic studies analysing health consequences of obesity. However, achieving such data may require substantial resources. We investigated the use of body silhouettes in adults as a tool to reflect obesity in the past. We used large population-based samples to analyse to what extent self-reported body silhouettes correlated with the previously measured (9-23 years) body mass index (BMI) from both measured (European Community Respiratory Health Survey, N = 3 041) and selfreported (Respiratory Health In Northern Europe study, N = 3 410) height and weight. We calculated Spearman correlation between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI >= 30) at ages 30 and 45 years. Spearman correlations between measured BMI age 30 (+/- 2y) or 45 (+/- 2y) and body silhouettes in women and men were between 0.62-0.66 and correlations for self-reported BMI were between 0.58-0.70. The area under the curve for identification of obesity at age 30 using body silhouettes vs previously measured BMI at age 30 (+/- 2y) was 0.92 (95% CI 0.87, 0.97) and 0.85 (95% CI 0.75, 0.95) in women and men, respectively; for previously self-reported BMI, 0.92 (95% CI 0.88, 0.95) and 0.90 (95% CI 0.85, 0.96). Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men.

Objective: We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort. Methods: FEV1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations= 11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity >= 2 times and >= 1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV1 and FVC. Results: Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline. Conclusion: Leisure-time vigorous physical activity was associated with higher FEV1 and FVC over a 10-year period among current smokers, but not with FEV1 and FVC decline.

OBJECTIVE: To investigate the impact of physical activity on asthma in middle-aged adults, in one longitudinal analysis, and one multi-centre cross-sectional analysis. METHODS: ) and physical activity grouped by amount and frequency of lighter (no sweating/heavy breathing) and vigorous (sweating/heavy breathing) activity. RESULTS: In the Bergen longitudinal analysis, undertaking light activity 3+ times/week at baseline was associated with less follow-up asthma (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.22, 0.89), whilst an effect from undertaking vigorous activity 3+ times/week was not detected (OR 1.22, 95% CI 0.44, 2.76). The associations were attenuated with BMI adjustment. In the all-centre cross-sectional analysis an interaction was found, with the association between physical activity and asthma varying across BMI categories. CONCLUSION: These findings suggest potential longer-term benefit from lighter physical activity, whilst improvement in asthma outcomes from increasing activity intensity was not evident. Additionally, it appears the benefit from physical activity may differ according to BMI.

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8–47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2–69.9; p = 0.001). In adolescent girls we found an opposite effect (−56.5 mL; −108.3 to −4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8–47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2–69.9; p = 0.001). In adolescent girls we found an opposite effect (−56.5 mL; −108.3 to −4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8–47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2–69.9; p = 0.001). In adolescent girls we found an opposite effect (−56.5 mL; −108.3 to −4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).

A trend towards earlier menarche in women has been associated with childhood factors (e.g. obesity) and hypothesised environmental exposures (e.g. endocrine disruptors present in household products). Observational evidence has shown detrimental effects of early menarche on various health outcomes including adult lung function, but these might represent spurious associations due to confounding. To address this we used Mendelian randomization where genetic variants are used as proxies for age at menarche, since genetic associations are not affected by classical confounding. We estimated the effects of age at menarche on forced vital capacity (FVC), a proxy for restrictive lung impairment, and ratio of forced expiratory volume in one second to FVC (FEV1/FVC), a measure of airway obstruction, in both adulthood and adolescence. We derived SNP-age at menarche association estimates for 122 variants from a published genome-wide meta-analysis (N = 182,416), with SNP-lung function estimates obtained by meta-analysing three studies of adult women (N = 46,944) and two of adolescent girls (N = 3025). We investigated the impact of departures from the assumption of no pleiotropy through sensitivity analyses. In adult women, in line with previous evidence, we found an effect on restrictive lung impairment with a 24.8 mL increase in FVC per year increase in age at menarche (95% CI 1.8–47.9; p = 0.035); evidence was stronger after excluding potential pleiotropic variants (43.6 mL; 17.2–69.9; p = 0.001). In adolescent girls we found an opposite effect (−56.5 mL; −108.3 to −4.7; p = 0.033), suggesting that the detrimental effect in adulthood may be preceded by a short-term post-pubertal benefit. Our secondary analyses showing results in the same direction in men and boys, in whom age at menarche SNPs have also shown association with sexual development, suggest a role for pubertal timing in general rather than menarche specifically. We found no effect on airway obstruction (FEV1/FVC).