Abstract
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 years from a Danish population-based cohort study. Normal spirometry was defined as a pre-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio ≥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 individuals had normal spirometry without chronic respiratory symptoms and 30 890 individuals 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 with 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% CI 1.20–2.18) for exacerbation hospitalisations, 1.26 (95% CI 1.17–1.37) for pneumonia hospitalisations, 1.59 (95% CI 1.22–2.06) for respiratory mortality and 1.19 (95% CI 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 of 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.
Abstract
Chronic respiratory symptoms are associated with respiratory hospitalisations and death in individuals with normal spirometry. Persistent symptoms should lead to further investigations for airway disease even with normal spirometry. http://bit.ly/2ZnnO3T
Footnotes
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Author contributions: Y. Çolak and S. Afzal had full access to all data in the study and had final responsibility for the decision to submit for publication. Y. Çolak, B.G. Nordestgaard, J. Vestbo, P. Lange and S. Afzal contributed to the study concept and design. Y. Çolak, B.G. Nordestgaard, J. Vestbo, P. Lange and S. Afzal collected, analysed or interpreted the data. Y. Çolak wrote the draft manuscript. Y. Çolak, B.G. Nordestgaard, J. Vestbo, P. Lange and S. Afzal revised the manuscript for important intellectual content. Y. Çolak did the statistical analyses. B.G. Nordestgaard obtained funding. B.G. Nordestgaard provided administrative, technical or material support. S. Afzal supervised the study.
Support statement: Funded by the Lundbeck Foundation. The funder did not participate in the design and conduct of the study; collection, management, analysis or interpretation of the data; or in preparation, review or approval of the manuscript; or decision to submit the manuscript for publication. J. Vestbo is supported by the NIHR Manchester Biomedical Research Centre (Manchester, UK). Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: Y. Çolak reports personal fees from Boehringer Ingelheim and AstraZeneca outside the submitted work.
Conflict of interest: B.G. Nordestgaard has nothing to disclose.
Conflict of interest: J. Vestbo reports personal fees for consultancy from GlaxoSmithKline, Chiesi Pharmaceuticals, Boehringer Ingelheim, Novartis, Almirall, AstraZeneca and Bioxydyn, personal fees for lecturing from GlaxoSmithKline, Chiesi Pharmaceuticals, Novartis, AstraZeneca, Boehringer Ingelheim, outside the submitted work.
Conflict of interest: P. Lange reports grants and personal fees from Almirall, Boehringer Ingelheim and GlaxoSmithKline, personal fees from AstraZeneca, Novartis, Nycomed, Pfizer and Mundipharma, outside the submitted work.
Conflict of interest: S. Afzal has nothing to disclose.
- Received April 11, 2019.
- Accepted June 11, 2019.
- Copyright ©ERS 2019