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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 ; Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects. Keywords: Bronchodilatation; Epidemiology; FeNO; Lung function. ; UK Research & Innovation (UKRI) Medical Research Council UK (MRC) European Commission Spanish Government Generalitat ...

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

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