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AbstractThe management of occupational asthma (OA) may be influenced by several factors and removal from exposure is the main tertiary prevention approach, but it is not always feasible without personal and socioeconomic consequences. Reducing the delay between the onset of suggestive symptoms of OA and the diagnosis of OA is associated with a better prognosis. Workers' education to increase awareness to trigger agents and a medical surveillance program directed especially at at-risk workers could be helpful in reducing this latency time. An early identification of workers who develop rhinitis and conjunctivitis which often precede the onset of asthma symptoms could be important for an early identification of OA. This is particularly important for cases of asthma caused by high-molecular-weight sensitizers and in the early years of employment. The availability of financial support and compensation measures for workers with OA may influence the latency time before diagnosis and, consequently, may influence the OA outcomes. In conclusion, there is a need for high-quality cohort studies that will increase knowledge about risk factor that may influence the timing of diagnosis of OA. This knowledge will be useful for implementation of future surveillance and screening programs in workplaces.

Background: The premenstrual syndrome (PMS) causes clinically relevant psychological and physical symptoms in up to 20% of women of reproductive age. To date, no studies have investigated the relationship between PMS and residential surrounding greenspace, although a green living environment has been reported to have beneficial associations with overall and reproductive health. Objective: To investigate whether lifelong exposure to residential surrounding greenspace is associated with PMS and whether such an association is mediated by BMI, air pollution or physical activity. Methods: This study used data collected in 2013-2015 from 1069 Scandinavian women aged 18-49 years, participating in RHINESSA, a European multi-centre and population-based cohort. Satellite-derived Normalised Difference Vegetation Index was used as a proxy of greenspace. Presence of eight common PMS symptoms and their sum (PMS symptom count) were used as outcomes. The associations were assessed by adjusted multilevel logistic and negative binomial regressions. Subsequently we carried out mediation analyses for physical activity, BMI and air pollution exposure. Results: Higher exposure to residential surrounding greenspace was associated with "Anxiety or tension" (Odds Ratio 0.82, 95% Confidence Interval (CI): 0.70 - 0.95), "Depression or hopelessness" (0.84, 0.73 - 0.98), "Difficulty with sleeping" (0.82, 0.68 - 1.00) and "Breast tenderness and abdominal bloating" (0.84, 0.71 - 0.99) before or around the start of the menstrual period. There was also an association with a lower PMS symptom count (Risk Ratio: 0.94, 95% CI: 0.91 - 0.99). These associations were robust to sensitivity analyses and were not mediated by BMI, physical activity or air pollution. Conclusions: Living in greener areas may be beneficial against PMS symptoms. Further studies are needed to confirm these novel findings and to explore the underlying biological mechanisms. ; Kai Triebner has received a postdoctoral fellowship from the University of Bergen. Payam Dadvand is funded by a Ramón y Cajal fellowship (Grant: RYC-2012–10995) awarded by the Spanish Ministry of Economy and Finance. The present analyses are part of a project funded by the Norwegian Research Council (Grant: 228174). Co-ordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230,827 and 273838), ERC StG project BRuSH #804199, the European Union's Horizon 2020 research and innovation programme under grant agreement No. 633,212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911892 and 911631). Study centre Bergen has further received local funding from the above-named grants for study establishment and co-ordination and in addition from the World University Network, the Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association. Iana Markevych is supported from the "NeuroSmog: Determining the impact of air pollution on the developing brain" (Nr. POIR 040.04.00-1763/18-00) which is implemented as part of the TEAM-NET programme of the Foundation for Polish Science, co-financed from EU resources, obtained from the European Regional Development Fund under the Smart Growth Operational Programme. The funding sources were not involved in the conduct of the research and/or preparation of the article, in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication.

Publisher's version (útgefin grein). ; Background Tobacco consumption is the largest avoidable health risk. Understanding changes of smoking over time and across populations is crucial to implementing health policies. We evaluated trends in smoking initiation between 1970 and 2009 in random samples of European populations. Methods We pooled data from six multicentre studies involved in the Ageing Lungs in European Cohorts consortium, including overall 119,104 subjects from 17 countries (range of median ages across studies: 33–52 years). We estimated retrospectively trends in the rates of smoking initiation (uptake of regular smoking) by age group, and tested birth cohort effects using Age-Period-Cohort (APC) modelling. We stratified all analyses by sex and region (North, East, South, West Europe). Results Smoking initiation during late adolescence (16–20 years) declined for both sexes and in all regions (except for South Europe, where decline levelled off after 1990). By the late 2000s, rates of initiation during late adolescence were still high (40–80 per 1000/year) in East, South, and West Europe compared to North Europe (20 per 1000/year). Smoking initiation rates during early adolescence (11–15 years) showed a marked increase after 1990 in all regions (except for North European males) but especially in West Europe, where they reached 40 per 1000/year around 2005. APC models supported birth cohort effects in the youngest cohorts. Conclusion Smoking initiation is still unacceptably high among European adolescents, and increasing rates among those aged 15 or less deserve attention. Reducing initiation in adolescents is fundamental, since youngsters are particularly vulnerable to nicotine addiction and tobacco adverse effects. ; This study has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 633212. DJ has received support from the European Union and the Medical Research Council. National funders who supported data collection in the original cohort and cross-sectional studies are listed in S2 Appendix. The funders had no role in the writing of the manuscript or the decision to submit it for publication. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication. ; Peer Reviewed

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files ; Tobacco consumption is the largest avoidable health risk. Understanding changes of smoking over time and across populations is crucial to implementing health policies. We evaluated trends in smoking initiation between 1970 and 2009 in random samples of European populations. We pooled data from six multicentre studies involved in the Ageing Lungs in European Cohorts consortium, including overall 119,104 subjects from 17 countries (range of median ages across studies: 33-52 years). We estimated retrospectively trends in the rates of smoking initiation (uptake of regular smoking) by age group, and tested birth cohort effects using Age-Period-Cohort (APC) modelling. We stratified all analyses by sex and region (North, East, South, West Europe). Smoking initiation during late adolescence (16-20 years) declined for both sexes and in all regions (except for South Europe, where decline levelled off after 1990). By the late 2000s, rates of initiation during late adolescence were still high (40-80 per 1000/year) in East, South, and West Europe compared to North Europe (20 per 1000/year). Smoking initiation rates during early adolescence (11-15 years) showed a marked increase after 1990 in all regions (except for North European males) but especially in West Europe, where they reached 40 per 1000/year around 2005. APC models supported birth cohort effects in the youngest cohorts. Smoking initiation is still unacceptably high among European adolescents, and increasing rates among those aged 15 or less deserve attention. Reducing initiation in adolescents is fundamental, since youngsters are particularly vulnerable to nicotine addiction and tobacco adverse effects. ; European Union's Horizon 2020 research and innovation programme European Union Medical Research Council

Publisher's version (útgefin grein) ; Emerging evidence suggests that parents' preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39–65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18–49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers' smoking onset before conception of the offspring (onset ≥15 years) was associated with higher BMI in the offspring when adult (β 0.551, 95%CI: 0.174–0.929, p = 0.004). Mothers' preconception and postnatal smoking onset was associated with higher offspring BMI (onset <15 years: β1.161, 95%CI 0.378–1.944; onset ≥15 years: β0.720, 95%CI 0.293–1.147; onset after offspring birth: β2.257, 95%CI 1.220–3.294). However, mediation analysis indicated that these effects were fully mediated by parents' postnatal pack years, and partially mediated by parents' BMI and offspring smoking. Regarding FMI, sons of smoking fathers also had higher fat mass (onset <15 years β1.604, 95%CI 0.269–2.939; onset ≥15 years β2.590, 95%CI 0.544–4.636; and onset after birth β2.736, 95%CI 0.621–4.851). There was no association between maternal smoking and offspring fat mass. We found that parents' smoking before conception was associated with higher BMI in offspring when they reached adulthood, but that these effects were mediated through parents' pack years, suggesting that cumulative smoking exposure during offspring's childhood may elicit long lasting effects on offspring BMI. ; Co-ordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230827 and 273838), ERC StG project BRuSH #804199, the European Union's Horizon 2020 research and innovation program under grant agreement No. 633212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911892 and 911631). Study centres have further received local funding from the following: Bergen: the above grants for study establishment and co-ordination, and, in addition, World University Network (RDF and Sustainability grant), Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association. Albacete and Huelva: SEPAR. Fondo de Investigación Sanitaria (FIS PS09). Gøteborg, Umeå and Uppsala: the Swedish Lung Foundation, the Swedish Asthma and Allergy Association. Reykjavik: Iceland University. Melbourne: NHMRC, Melbourne University, Tartu: the Estonian Research Council (Grant No. PUT562). Århus: The Danish Wood Foundation (Grant No. 444508795), the Danish Working Environment Authority (Grant No. 20150067134). The RHINE study received funding by Norwegian Research Council, Norwegian Asthma and Allergy Association, Danish Lung Association, Swedish Heart and Lung Foundation, Vårdal Foundation for Health Care Science and Allergy Research, Swedish Asthma and Allergy Association, Swedish Lung Foundation, Icelandic Research Council, and Estonian Science Foundation. The co-ordination of ECRHS was supported by European Union's Horizon 2020 research and innovation program under grant agreement No. 633212 (the ALEC Study), the European Commission frameworks 5 and 7 (ECRHS I and II) and the Medical Research Council (ECRHS III). ; Peer Reviewed

Publisher's version (útgefin grein). ; Background: Menopause is associated with a number of adverse health effects and its timing has been reported to be influenced by several lifestyle factors. Whether greenspace exposure is associated with age at menopause has not yet been investigated. Objective: To investigate whether residential surrounding greenspace is associated with age at menopause and thus reproductive aging. Methods: This longitudinal study was based on the 20-year follow-up of 1955 aging women from a large, population-based European cohort (ECRHS). Residential surrounding greenspace was abstracted as the average of satellite-based Normalized Difference Vegetation Index (NDVI) across a circular buffer of 300 m around the residential addresses of each participant during the course of the study. We applied mixed effects Cox models with centre as random effect, menopause as the survival object, age as time indicator and residential surrounding greenspace as time-varying predictor. All models were adjusted for smoking habit, body mass index, parity, age at menarche, ever-use of contraception and age at completed full-time education as socio-economic proxy. Results: An increase of one interquartile range of residential surrounding greenspace was associated with a 13% lower risk of being menopausal (Hazard Ratio: 0.87, 95% Confidence Interval: 0.79–0.95). Correspondingly the predicted median age at menopause was 1.4 years older in the highest compared to the lowest NDVI quartile. Results remained stable after additional adjustment for air pollution and traffic related noise amongst others. Conclusions: Living in greener neighbourhoods is associated with older age at menopause and might slow reproductive aging. These are novel findings with broad implications. Further studies are needed to see whether our findings can be replicated in different populations and to explore the potential mechanisms underlying this association. ; Kai Triebner has received a postdoctoral fellowship from theUniversity of Bergen. Payam Dadvand is funded by a Ramón y Cajalfellowship (Grant: RYC-2012-10995) awarded by the Spanish Ministryof Economy and Finance. The present analyses are part of a projectfunded by the Norwegian Research Council (Grant: 228174).Coordination of the ECRHS I was supported by the EuropeanCommission as part of the"Quality of Life"program and the authorsand participants are grateful to the late C. Baya and M. Hallen for theirhelp during the study and K. Vuylsteek and the members of the COMACfor their support. Coordination of the ECRHS II was supported by theEuropean Commission as part of the"Quality of Life"program (Grant:QLK4-CT-1999-01237). The coordination of the ECRHS 3 was fundedthrough the Medical Research Council (Grant: 92091). NDVI calcula-tions were conducted within the framework of the Ageing Lungs InEuropean Cohorts study that was funded by the European Union'sHorizon 2020 research and innovation program under (Grant: 633212).Bodies funding the local studies are listed in the online data supple-ment. The funding sources were not involved in the conduct of theresearch and/or preparation of the article, in study design, in the col-lection, analysis and interpretation of data, in the writing of the reportor in the decision to submit the article for publication. ; Peer Reviewed

Publisher's version (útgefin grein). ; Background: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. Objective: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. Methods: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. Results: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. Conclusion: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health. ; This study was funded by the European Union's Horizon 2020 research and innovation program as part of the ALEC study (Ageing Lungs in European Cohorts study, grant no. 633212). The RHINESSA generation study also received funding by the Research Council of Norway (grant nos. 214123 and 228174), the Bergen Medical Research Foundation (Norway), the Western Norwegian Regional Health Authorities (grant nos. 912011, 911892, and 911631), the Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association, the Danish Woods Foundation (grant no. 444508795), the Danish Working Environment Authority (grant no. 20150067134), the Swedish Lung Foundation, the Swedish Asthma and Allergy Association, and the Estonian Research Council (grant no. PUT562). The funding agencies had no direct role in the conduct of the study; the collection, management, statistical analysis, and interpretation of the data; and the preparation or approval of the manuscript. ; Peer Reviewed

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files ; We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort. ; 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. ; 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. ; 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. ; European Union

Publisher's version (útgefin grein) ; Objectives: Menopause involves hypoestrogenism, which is associated with numerous detrimental effects, including on respiratory health. Hormone replacement therapy (HRT) is often used to improve symptoms of menopause. The effects of HRT on lung function decline, hence lung ageing, have not yet been investigated despite the recognized effects of HRT on other health outcomes. Study design: The population-based multi-centre European Community Respiratory Health Survey provided complete data for 275 oral HRT users at two time points, who were matched with 383 nonusers and analysed with a two-level linear mixed effects regression model. Main outcome measures: We studied whether HRT use was associated with the annual decline in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Results: Lung function of women using oral HRT for more than five years declined less rapidly than that of nonusers. The adjusted difference in FVC decline was 5.6 mL/y (95%CI: 1.8 to 9.3, p = 0.01) for women who had taken HRT for six to ten years and 8.9 mL/y (3.5 to 14.2, p = 0.003) for those who had taken it for more than ten years. The adjusted difference in FEV1 decline was 4.4 mL/y (0.9 to 8.0, p = 0.02) with treatment from six to ten years and 5.3 mL/y (0.4 to 10.2, p = 0.048) with treatment for over ten years. Conclusions: In this longitudinal population-based study, the decline in lung function was less rapid in women who used HRT, following a dose-response pattern, and consistent when adjusting for potential confounding factors. This may signify that female sex hormones are of importance for lung ageing. ; Kai Triebner has received a postdoctoral fellowship from the University of Bergen. The present analyses are part of a project funded by the Norwegian Research Council (Project No. 228174) as well as part of the Ageing Lungs in European Cohorts (ALEC) Study (www.alecstudy.org), which has received funding from the European Union's Horizon 2020 research and innovation program (Grant No. 633212). The European Commission supported the European Community Respiratory Health Survey, as part of the "Quality of Life" program. Bodies funding the local studies are listed in the online data supplement. The funding sources had no involvement in the conduct of the research and/or preparation of the article, in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. ; Peer Reviewed

Publisher's version (útgefin grein) ; 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 self-reported (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. ; The project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 633212. The co-ordination of ECRHS I and ECRHS I was supported by the European Commission. The co-ordination of ECRHS III was supported by the Medical Research Council (Grant Number 92091). The co-ordination of the RHINE study is led by Professor C. Janson at the Uppsala University. The funding sources for the local ECRHS and RHINE studies are provided in the on-line supplement. ; Peer Reviewed

To access publisher's full text version of this article click on the hyperlink below ; Very few studies have examined whether a long-term beneficial effect of physical activity on lung function can be influenced by living in polluted urban areas. We assessed whether annual average residential concentrations of nitrogen dioxide (NO Associations between repeated assessments (at 27-57 and 39-67 years) of being physically active (physical activity: ≥2 times and ≥1 h per week) and forced expiratory volume in 1 s (FEV Among current smokers, physical activity and lung function were positively associated regardless of air pollution levels. Among never-smokers, physical activity was associated with lung function in areas with low/medium NO ; European Union

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files ; 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 self-reported (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. ; European Union Medical Research Council European Commission

Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01–2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01–1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17–2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02–1.55). Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception. Funding: European Union (Horizon 2020, GA-633212).

Publisher's version (útgefin grein) ; Background Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01–2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01–1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17–2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02–1.55). Conclusions Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception. ; The present analyses are part of the Ageing Lungs in European Cohorts (ALEC) Study [www.alecstudy.org], which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 633212. The coordination of the European Community Respiratory Health Survey (ECRHS) was supported by the European Commission (phases 1 and 2) and the Medical Research Council (phase 3). Local funding agencies for the ECRHS are reported in the Supplementary Appendix, available as Supplementary data at IJE online. Conflict of interest: J.W.H. reports grants from the European Union's Horizon 2020 programme (633212), the Medical Research Council UK (MC_PC_15078) and the National Institutes of Health USA (R01 AI091905, R01 AI121226) during the conduct of the study. R.J. reports grants from the Estonian Research Council (personal grant No. 562) during the conduct of the study, grants/grants pending from the Estonian Research Council (personal research grant No. 562), personal fees for consulting and lecturing from GlaxoSmithKline, Boehringer and Novartis and travel/accommodation/meeting expenses paid by GlaxoSmithKline and Boehringer, outside the submitted work. C.R. reports personal fees for consulting and lecturing from ALK, Astra Zeneca, GSK, Boheringer and Novartis, outside the submitted work. A.G.C. reports grants from Chiesi Farmaceutici and GlaxoSmithKline Italy, during the conduct of the study. P.D. reports personal fees for consulting and lecturing from ALK and Stallergenes Greer and personal fees for consulting from Circassia, Chiesi Farmaceutici, ThermofisherScientific and Menarini, outside the submitted work. D.J. reports grants from the Medical Research Council and the European Union's Horizon 2020 programme, during the conduct of the study. All other authors declare no competing interests. ; Peer Reviewed

Publisher's version (útgefin grein) ; Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV 1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV 1 declines. We found no association between weight change profiles and FEV 1 /FVC decline. Conclusion: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life. ; Funding The present analyses are part of the ageing lungs in european cohorts (alec) study (www.alecstudy.org), which has received funding from the european Union's horizon 2020 research and innovation programme under grant agreement no. 633212. The local investigators and funding agencies for the european community respiratory health survey are reported in the online supplement. isglobal is a member of the cerca Programme, generalitat de catalunya. ; Peer Reviewed