title: Long-term prognosis of asthma, chronic obstructive pulmonary disease, and asthma-chronic obstructive pulmonary disease overlap in the Copenhagen City Heart study: a prospective population-based analysis.
abstract: Long-term prognosis of patients with characteristics of both chronic obstructive pulmonary disease (COPD) and asthma, named asthma-COPD overlap, is poorly described. We investigated the long-term prognosis of individuals with different types of chronic airway disease, with a special focus on individuals with asthma-COPD overlap.
  
  
  
  We assigned participants from the Copenhagen City Heart Study into six subgroups: healthy never-smokers, ever-smokers without asthma and COPD, those with asthma with low cumulated smoking exposure and no airflow limitation, those with COPD, those with asthma-COPD overlap with asthma onset before the age of 40 years, and those with asthma-COPD overlap with asthma onset after the age of 40 years. We defined asthma-COPD overlap as current self-reported asthma and a postbronchodilatatory forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio of less than 0·7, without any restrictions regarding smoking. We investigated the course of FEV1 decline for 18 years and risk of admission to hospital due to exacerbations or pneumonias and respiratory and all-cause mortality for 22 years. We analysed FEV1 decline in the six groups using a linear mixed-effects model.
  
  
  
  We included 8382 participants from the Copenhagen City Heart Study in our study: 2199 never-smokers, 5435 ever-smokers, 158 with asthma, 320 with COPD, 68 with asthma-COPD overlap with early-onset asthma, and 202 with asthma-COPD overlap with late-onset asthma. The multivariable-adjusted decline in FEV1 in asthma-COPD overlap with early-onset asthma was 27·3 mL (standard error 5·0) per year, which did not differ significantly from the decline of 20·9 mL (1·2) per year in healthy never-smokers (p=0·19). FEV1 decline in individuals with asthma-COPD overlap with late-onset asthma was 49·6 mL (3·0) per year, higher than the decline in asthma-COPD overlap with early-onset asthma (p=0·0001), the decline of 39·5 mL (2·5) per year in COPD (p=0·003), and the decline in healthy never-smokers (p<0·0001). Hazard ratios for hospital admissions due to exacerbations of asthma or COPD were 39·48 (95% CI 25·93-60·11) in asthma-COPD overlap with early-onset asthma, 83·47 (61·67-112·98) in asthma-COPD overlap with late-onset asthma, 23·80 (17·43-33·50) in COPD, and 14·74 (10·06-21·59) in asthma compared with never-smokers without lung disease (all p<0·0001). Life expectancy was 9·3 years (5·4-13·1) shorter in participants with asthma-COPD overlap with early-onset asthma, 12·8 years (11·1-14·6) shorter in those with asthma-COPD overlap with late-onset asthma, 10·1 years (8·6-11·5) shorter in those with COPD (all p<0·0001), and 3·3 years (1·0-5·5) shorter in those with asthma (p=0·004) than in healthy never-smokers.
  
  
  
  Prognosis of individuals with asthma-COPD overlap is poor and seems to be affected by the age of recognition of asthma, being worst in those with late asthma onset (after 40 years of age). Such patients should be followed up closely to prevent fast lung function decline and exacerbations.
  
  
  
  Capital Region of Copenhagen, Danish Heart Foundation, Danish Lung Foundation, Velux Foundation, AstraZeneca.
authors.affiliation: Institute of Public Health, Section of Social Medicine, Copenhagen University, Copenhagen, Denmark; Respiratory Section, Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark; Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University, Copenhagen, Denmark. Electronic address: peter.lange@sund.ku.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
authors.affiliation: Institute of Public Health, Section of Social Medicine, Copenhagen University, Copenhagen, Denmark; Department of Internal Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Çolak
authors.affiliation: Respiratory Section, Hvidovre Hospital, Copenhagen University, Copenhagen, Denmark.
authors.forename: Truls Sylvan
authors.initials: TS
authors.lastname: Ingebrigtsen
authors.affiliation: Centre for Respiratory Medicine and Allergy, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK; University Hospital South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.affiliation: Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University, Copenhagen, Denmark.
authors.forename: Jacob Louis
authors.initials: JL
authors.lastname: Marott
mesh_terms: D017668:Age of Onset; D000368:Aged; D001249:Asthma / Q000150:complications* / Q000503:physiopathology; D003718:Denmark; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006760:Hospitalization; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects