Background: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). Methods: Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999-2002 and in 2010-2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999-2002 with incidence of restrictive pattern and airflow limitation in 2010-2013 were also assessed. Findings: Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14). Interpretation: Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health. Funding: EU H2020, grant agreement no.633212. ; The current study is part of the Ageing for Lungs in European Cohorts (ALEC) study (www.alecstudy.org), ALEC has received funding from the European Union's Horizon 2020 research and innovation program [grant agreement No. 633212]. The coordination of the ECRHS was supported by the European Commission [grant agreement no. QLK4-CT-1999–01237] and the Medical Research Council [grant agreement no. 92091]. The hormones measures at ECRHS III were funded by the Norwegian Research Council [grant agreement no. 228174]. Hormones measures at ECRHS II were funded by the local budget of the ECRHS Paris team, INSERM U700, Epidemiology, with further support from the Comité National contre les Maladies Respiratoires (CNMR), the centre d'Investigation Clinique (CIC), Bichat Hospital, and the French Agence Nationale de la Recherche (ANR). Bodies funding the local studies are listed in the Online Supplement. The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Introduction: The study aim was to examine the association of snoring and nocturnal gastro-oesophageal reflux (nGOR) with respiratory symptoms and lung function, and if snoring and/or nGOR associated with a steeper decline in lung function. Methods: Data from the third visit of the European Community Respiratory Health Survey (ECRHS) was used for cross-sectional analysis. Pre- and post-bronchodilator spirometry was performed, and information on sleep, nGOR and respiratory symptoms was collected (n=5715). Habitual snoring and nGOR were assessed by questionnaire reports. Pre-bronchodilator spirometry from ECRHS I, II and III (20 years follow-up) were used to analyse lung function changes by multivariate regression analysis. Results: Snoring and nGOR were independently associated with a higher prevalence of wheeze, chest tightness, breathlessness, cough and phlegm. The prevalence of any respiratory symptom was 79% in subjects with both snoring and nGOR versus 56% in those with neither (p<0.001). Subjects with both snoring and nGOR had more frequent exacerbations (adjusted prevalence 32% versus 19% among "no snoring, no nGOR", p=0.003). Snoring but not nGOR was associated with a steeper decline in forced expiratory volume in 1 s over 10 years after adjusting for confounding factors (change in % predicted -5.53, versus -4.58 among "no snoring", p=0.04) and forced vital capacity (change in % predicted -1.94, versus -0.99 among "no snoring", p=0.03). Conclusions: Adults reporting both habitual snoring and nGOR had more respiratory symptoms and more frequent exacerbations of these symptoms. Habitual snoring was associated with a steeper decline in lung function over time. ; The ALEC Study is funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement number 633212. Funding information for this article has been deposited with the Crossref Funder Registry.
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 Download ; Objective: Regular physical activity may be associated with improved lung function via reduced systemic inflammation, although studies exploring this mechanism are rare. We evaluated the role of C-reactive protein in blood, which is a common marker of systemic inflammation, on the association of physical activity with forced expiratory volume in one second and forced vital capacity. Methods: Cross-sectional data on spirometry, C-reactive protein levels and self-reported physical activity (yes/no; ≥2 times and ≥1hr per week of vigorous physical activity) were available in the European Community Respiratory Health Survey (N = 2347 adults, 49.3% male, 28-56 years-old). A subsample was also assessed 10 years later using the International Physical Activity Questionnaire, and tertiles of Metabolic Equivalent of Task-minutes per week spent in vigorous, moderate and walking activities were calculated (N = 671, 49.6% male, 40-67 years-old). Adjusted cross-sectional mixed linear regression models and the "mediate" package in "R" were used to assess the presence of mediation. Results: Despite positive significant associations between nearly all physical activity metrics with forced expiratory volume in one second and forced vital capacity, there was no evidence that C-reactive protein levels played a role. An influence of C-reactive protein levels was only apparent in the smaller subsample when comparing the medium to low tertiles of moderate activity (mean difference [95% CIs]: 21.1ml [5.2, 41.9] for forced expiratory volume in one second and 17.3ml [2.6, 38.0] for forced vital capacity). Conclusions: In a population of adults, we found no consistent evidence that the association of physical activity with forced expiratory volume in one second or forced vital capacity is influenced by the level of C-reactive protein in blood. ; European Union ...
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
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 Download ; Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood. ; European Union's Horizon 2020 Research ...
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
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
Publisher's version (útgefin grein) ; Background: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). Methods: Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999–2002 and in 2010–2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999–2002 with incidence of restrictive pattern and airflow limitation in 2010–2013 were also assessed. Findings: Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14). Interpretation: Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health. ; The current study is part of the Ageing for Lungs in European Cohorts (ALEC) study ( www.alecstudy.org ), ALEC has received funding from the European Union's Horizon 2020 research and innovation program [grant agreement No. 633212]. The coordination of the ECRHS was supported by the European Commission [grant agreement no. QLK4-CT-1999–01237] and the Medical Research Council [grant agreement no. 92091]. The hormones measures at ECRHS III were funded by the Norwegian Research Council [grant agreement no. 228174]. Hormones measures at ECRHS II were funded by the local budget of the ECRHS Paris team, INSERM U700, Epidemiology, with further support from the Comité National contre les Maladies Respiratoires (CNMR), the centre d'Investigation Clinique (CIC), Bichat Hospital, and the French Agence Nationale de la Recherche (ANR). Bodies funding the local studies are listed in the Online Supplement. The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. ; Peer Reviewed
Publisher's version (útgefin grein) ; Background Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy. Methods The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20–44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates. Findings Over 20 years the prevalence of 'wheeze' and 'wheeze in the absence of a cold' decreased (−2.4%, 95% CI −3.5 to −1.3%; −1.5%, 95% CI −2.4 to −0.6%, respectively) but the prevalence of asthma attacks, use of asthma medication and hay fever/nasal allergies increased (0.6%, 95% CI 0.1 to 1.11; 3.6%, 95% CI 3.0 to 4.2; 2.7%, 95% CI 1.7 to 3.7). Changes were similar in the first 10 years compared with the second 10 years, except for hay fever/nasal allergies (increase seen in the first 10 years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hay fever/nasal allergies at baseline. Interpretation European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hay fever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing. ; ECRHS I: The coordination of ECRHS I was supported by the European Commission. The following grants helped fund the local studies. Australia: Asthma Foundation of Victoria, Allen and Hanbury's, Belgium: Belgian Science Policy Office, National Fund for Scientific Research, Denmark: Aarhus (R Dahl, M Iversen), Estonia: Estonian Science Foundation, grant no. 1088, France: Ministère de la Santé, Glaxo France, Insitut Pneumologique d'Aquitaine, Contrat de Plan Etat-Région Languedoc-Rousillon, CNMATS, CNMRT (90MR/10, 91AF/6), Ministre delegué de la santé, RNSP, France; GSF, Germany: Bundes minister für Forschung und Technologie, Greece: The Greek Secretary General of Research and Technology, Fisons, Astra and Boehringer-Ingelheim; Italy: Ministero dell'Università e della Ricerca Scientifica e Tecnologica, CNR, Regione Veneto grant RSF no. 381/05.93, Netherlands Dutch Ministry of Wellbeing, Public Health and Culture and the Netherlands Asthma Foundation, Norway: Norwegian Research Council project no. 101422/310; Portugal: Glaxo Farmacêutica Lda, Sandoz Portugesa, Spain: Fondo de Investigación Sanitaria (#91/0016-060-05/E, 92/0319 and #93/0393), Hospital General de Albacete, Hospital General Juan Ramón Jiménez, Dirección Regional de Salud Pública (Consejería de Sanidad del Principado de Asturias), CIRIT (1997 SGR 00079) and Servicio Andaluz de Salud; Sweden: The Swedish Medical Research Council, the Swedish Heart Lung Foundation, the Swedish Association against Asthma and Allergy; Switzerland: Swiss National Science Foundation grant 4026- 28099; UK: National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority. ECRHS II: The coordination of ECRHS II was supported by the European Commission. The following grants helped fund the local studies. Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code, G.0402.00), University of Antwerp, Flemish Health Ministry; Estonia: Tartu Estonian Science Foundation grant no. 4350, France: (All) Programme Hospitalier de Recherche Clinique—Direction de la Recherche Clinique (DRC) de Grenoble 2000 number 2610, Ministry of Health, Ministère de l'Emploi et de la Solidarité, Direction Génerale de la Santé, Centre Hospitalier Universitaire (CHU) de Grenoble, Bordeaux: Institut Pneumologique d'Aquitaine; Grenoble: Comite des Maladies Respiratoires de l'Isere Montpellier: Aventis (France), Direction Regionale des Affaires Sanitaires et Sociales Languedoc-Roussillon; Paris: Union Chimique Belge-Pharma (France), Aventis (France), Glaxo France, Germany: Erfurt GSF—National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code, FR1526/1-1), Hamburg: GSF—National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code, MA 711/4-1), Iceland: Reykjavik, Icelandic Research Council, Icelandic University Hospital Fund; Italy: Pavia GlaxoSmithKline Italy, Italian Ministry of University and Scientific and Technological Research (MURST), Local University Funding for Research 1998 and 1999; Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico—Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte Verona: Ministero dell'Universita e della Ricerca Scientifica (MURST), Glaxo Wellcome SPA, Norway: Bergen: Norwegian Research Council, Norwegian Asthma and Allergy Association, Glaxo Wellcome AS, Norway Research Fund; Spain: Fondo de Investigacion Santarias (grant codes, 97/0035-01, 99/0034-01 and 99/0034 02), Hospital Universitario de Albacete, Consejeria de Sanidad; Barcelona: Sociedad Espanola de Neumologıa y Cirugıa Toracica, Public Health Service (grant code, R01 HL62633-01), Fondo de Investigaciones Santarias (grant codes, 97/0035-01, 99/0034-01 and 99/0034-02), Consell Interdepartamentalde Recerca i Innovacio Tecnologica (grant code, 1999SGR 00241), Instituto de Salud Carlos III; Red de Centros de Epidemiologıa y Salud Publica, C03/09, Red de Bases moleculares y fisiologicas de las Enfermedades Respiratorias, C03/011, and Red de Grupos Infancia y Medio Ambiente G03/176; Huelva: Fondo de Investigaciones Santarias (grant codes, 97/0035-01, 99/0034-01 and 99/0034-02); Galdakao: Basque Health Department Oviedo: Fondo de Investigaciones Sanitaria (97/0035-02, 97/0035, 99/0034-01, 99/0034-02, 99/0034-04, 99/0034-06, 99/350, 99/0034--07), European Commission (EU-PEAL PL01237), Generalitat de Catalunya (CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Española de Neumología y Cirugía Torácica (SEPAR R01 HL62633-01), Red de Centros de Epidemiología y Salud Pública (C03/09), Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias (C03/011) and Red de Grupos Infancia y Medio Ambiente (G03/176);97/0035-01, 99/0034-01 and 99/0034-02); Sweden: Göteborg, Umea, Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research, Swedish Asthma and Allergy Foundation, Swedish Cancer and Allergy Foundation, Swedish Council for Working Life and Social Research (FAS), Switzerland: Basel Swiss National Science Foundation, Swiss Federal Office for Education and Science, Swiss National Accident Insurance Fund; UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign). ECRHS III: The coordination of ECRHS III was supported by the Medical Research Council (grant no. 92091). The following grants helped fund the local studies. Australia: National Health and Medical Research Council, Belgium: Antwerp South, Antwerp City: Research Foundation Flanders (FWO), grant code G.0.410.08.N.10 (both sites), Estonia: Tartu-SF0180060s09 from the Estonian Ministry of Education. France: (All) Ministère de la Santé. Programme Hospitalier de Recherche Clinique (PHRC) National 2010. Bordeaux: INSERM U897 Université Bordeaux Segalen, Grenoble: Comite Scientifique AGIRadom 2011. Paris: Agence Nationale de la Santé, Région Ile de France, domaine d'intérêt majeur (DIM) Germany : Erfurt: German Research Foundation HE 3294/10-1, Hamburg: German Research Foundation MA 711/6-1, NO 262/7-1, Iceland: Reykjavik, The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation, California, USA, Orkuveita Reykjavikur (Geothermal plant), Vegagerðin (The Icelandic Road Administration, ICERA). Italy: All Italian centres were funded by the Italian Ministry of Health, Chiesi Farmaceutici SpA. In addition, Verona was funded by Cariverona Foundation, Education Ministry (MIUR). Norway: Norwegian Research council grant no 214123, Western Norway Regional Health Authorities grant no 911631, Bergen Medical Research Foundation. Spain: Fondo de Investigación Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud , Sociedad Española de Neumología y Cirurgía Torácica (SEPAR 1001/2010); Sweden: All centres were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association, The Swedish Association against Lung and Heart Disease. Fondo de Investigación Sanitaria (PS09/02457), Barcelona: Fondo de Investigación Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigación Sanitaria (FIS 09/01511), Huelva: Fondo de Investigación Sanitaria (FIS PS09/02185), and Servicio Andaluz de Salud Oviedo: Fondo de Investigación Sanitaria (FIS PS09/03190). Sweden: All centres were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association, The Swedish Association against Lung and Heart Disease. Swedish Research Council for Health, Working Life and Welfare (FORTE) Göteborg : Also received further funding from the Swedish Council for Working Life and Social Research. Umea also received funding from Vasterbotten Country Council ALF grant. Switzerland: The Swiss National Science Foundation (grant nos 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099). The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, The Canton's Government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais and Zürich, the Swiss Lung League, the Canton's Lung League of Basel Stadt/Basel, Landschaft, Geneva, Ticino, Valais and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, UK: Medical Research Council (grant no 92091). Support was also provided by the National Institute for Health Research through the Primary Care Research Network. ; Peer Reviewed
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).