RT Journal Article SR Electronic T1 Prognostic significance of chronic respiratory symptoms in individuals with normal spirometry JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1900734 DO 10.1183/13993003.00734-2019 A1 Yunus Çolak A1 Børge G. Nordestgaard A1 Jørgen Vestbo A1 Peter Lange A1 Shoaib Afzal YR 2019 UL http://erj.ersjournals.com/content/early/2019/06/12/13993003.00734-2019.abstract AB A normal spirometry is often used to preclude airway disease in individuals with unspecific respiratory symptoms. We tested the hypothesis that chronic respiratory symptoms are associated with respiratory hospitalisations and death in individuals with normal spirometry without known airway disease.We included 108 246 randomly chosen individuals aged 20–100 from a Danish population-based cohort study. Normal spirometry was defined as a pre-bronchodilator forced expiratory volume in 1 s(FEV1)/forced vital capacity(FVC)≥0.70. Chronic respiratory symptoms included dyspnoea, chronic mucus hypersecretion, wheezing, and cough. Individuals with known airway disease, i.e. chronic obstructive pulmonary disease and/or asthma, were excluded (n=10 291). We assessed risk of hospitalisations due to exacerbations of airway disease and pneumonia, and respiratory and all-cause mortality from 2003 through 2018.52 999 had normal spirometry without chronic respiratory symptoms and 30 890 had normal spirometry with chronic respiratory symptoms. During follow-up, we observed 1037 hospitalisations with exacerbation of airway disease, 5743 hospitalisations with pneumonia, and 8750 deaths, of which 463 were due to respiratory disease. Compared to individuals with normal spirometry without chronic respiratory symptoms, multivariable adjusted hazard ratios for individuals with normal spirometry with chronic respiratory symptoms were 1.62(95% confidence interval:1.20–2.18) for exacerbation hospitalisations, 1.26(1.17–1.37) for pneumonia hospitalisations, 1.59(1.22–2.06) for respiratory mortality, and 1.19(1.13–1.25) for all-cause mortality. There was a positive dose-response relationship between number of symptoms and risk of outcomes. Results were similar after 2 years follow-up, for never-smokers alone, and for each symptom separately.Chronic respiratory symptoms are associated with respiratory hospitalisations and death in individuals with normal spirometry without known airway disease.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Çolak reports personal fees from Boehringer Ingelheim and AstraZeneca outside the submitted work.Conflict of interest: Dr. Nordestgaard has nothing to disclose.Conflict of interest: Dr. Vestbo reports personal fees from GlaxoSmithKline, Chiesi pharmaceuticals, Boehringer-Ingelheim, Novartis, Almirall, AstraZeneca, personal fees from Bioxydyn, personal fees from GlaxoSmithKline, Chiesi pharmaceuticals, Novartis, AstraZeneca, Boehringer-Ingelheim, personal fees from GlaxoSmithKline, AstraZeneca, Ferring, outside the submitted work.Conflict of interest: Dr. Lange reports grants and personal fees from Almirall, grants and personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, personal fees from Novartis, grants and personal fees from GSK, personal fees from Nycomed, personal fees from Pfizer, personal fees from Mundipharma, outside the submitted work.Conflict of interest: Dr. Afzal has nothing to disclose.