title: Prognosis of asymptomatic and symptomatic, undiagnosed COPD in the general population in Denmark: a prospective cohort study.
abstract: COPD can be diagnosed early using spirometry, but spirometry use is only recommended in symptomatic smokers, even though early stages of COPD can be asymptomatic. We investigated the prognosis of individuals with asymptomatic and symptomatic, undiagnosed COPD in the general population in Denmark.
  
  
  
  In this prospective cohort study, we analysed data from 95 288 individuals aged 20-100 years from the Copenhagen General Population Study. 32 518 (34%) of these individuals were regarded as being at high risk for COPD (defined as individuals aged 40 years or older, with cumulative tobacco consumption of ten pack-years or higher, and without self-reported or a previous hospital contact for asthma). COPD was defined as FEV1/forced vital capacity (FVC) of less than 70% and less than the lower limit of normal, and FEV1of less than 80% of the predicted normal value. Individuals were considered undiagnosed if neither a previous COPD hospital contact, nor medical treatment for COPD, was registered. We obtained information on exacerbations and pneumonia from the National Danish Patient Registry and vital status from the National Danish Civil Registration System, and cause of death from the National Danish Causes of Death Registry. We used Cox proportional hazard models to assess risk of exacerbations, pneumonia, deaths due to respiratory causes, and deaths from all causes from 2003 to 2014.
  
  
  
  Between Nov 26, 2003, and July 10, 2013, 95 288 individuals were screened and 32 518 (34%) were at high risk of having COPD. 3699 (11%) of these participants met the COPD criteria and 2903 (78%) were undiagnosed, of whom 2052 (71%) were symptomatic. During a median follow-up of 6·1 years (IQR 4·9), we recorded 800 exacerbations, 2038 cases of pneumonia, and 2789 deaths in the 32 518 individuals at high risk of having COPD, including 152 deaths due to respiratory disease. Compared with individuals without COPD, the age and sex adjusted hazard ratio (HR) was 5·0 (95% CI 2·8-8·9) for exacerbations, 1·7 (1·3-2·2) for pneumonia, 0·7 (0·2-3·0) for death from respiratory causes, and 1·3 (1·1-1·6) for death from all causes in individuals with undiagnosed, asymptomatic COPD. Corresponding HRs were 15·5 (11·0-21·8) for exacerbations, 2·8 (2·4-3·3) for pneumonia, 4·3 (2·8-6·7) for death from respiratory causes, and 2·0 (1·8-2·3) for death from all causes in individuals with undiagnosed, symptomatic COPD.
  
  
  
  Individuals with undiagnosed, symptomatic COPD had an increased risk of exacerbations, pneumonia, and death. Individuals with undiagnosed, asymptomatic COPD had an increased risk of exacerbations and pneumonia. These findings suggest that better initiatives for early diagnosis and treatment of COPD are needed.
  
  
  
  The Danish Lung Association, the Danish Cancer Society, Herlev and Gentofte Hospital, Copenhagen University Hospital, and University of Copenhagen.
authors.affiliation: Department of Internal Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Çolak
authors.affiliation: The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Shoaib
authors.initials: S
authors.lastname: Afzal
authors.affiliation: The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Division of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.affiliation: The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; Medical Unit, Respiratory Section, Hvidovre Hospital, Copenhagen University Hospital, Hvidovre, Denmark; Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: peter.lange@sund.ku.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
mesh_terms: D000368:Aged; D058070:Asymptomatic Diseases / Q000453:epidemiology / Q000401:mortality*; D002423:Cause of Death; D003718:Denmark / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000453:epidemiology* / Q000209:etiology; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D012307:Risk Factors; D063189:Symptom Assessment; D014797:Vital Capacity