title: Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms.
  
  
  METHODS
  We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end.
  
  
  RESULTS
  Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year (P<0.001), despite similar smoking exposure.
  
  
  CONCLUSIONS
  Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.).
authors.affiliation: From the Institute of Public Health, Section of Social Medicine (P.L.), Respiratory Section, Hvidovre Hospital (P.L.), Copenhagen City Heart Study, Frederiksberg Hospital (P.L., G.B.J., J.L.M., P.S.), and the Department of Respiratory Medicine, Gentofte Hospital (J.V.), Copenhagen University, Copenhagen, and University of Southern Denmark, Odense (G.B.J.) - all in Denmark; Brigham and Women's Hospital, Harvard Medical School, Boston (B.C., M.D., C.A.O., V.P.-P.); Servei de Pneumologia, Thorax Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona (A.A.), and Fundació Clínic per a la Recerca Biomèdica (R.F.) - both in Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (A.A., R.F.) and Instituto de Investigación Hospital Universitario de la Princesa, Universidad Autónoma de Madrid (UAM), Cátedra UAM-Linde (J.B.S.) - both in Madrid; Arizona Respiratory Center, University of Arizona, Tucson (S.G., F.D.M.); Universidad Autónoma de Chile, Santiago, Chile (P.M.-C.); University of Colorado, Denver, Denver (P.M.); Lovelace Respiratory Research Institute (H.P., Y.T.) and University of New Mexico (A.S.) - both in Albuquerque; and the Respiratory and Allergy Research Group, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom (J.V.).
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.forename: Gorm
authors.initials: G
authors.lastname: Boje Jensen
authors.forename: Miguel
authors.initials: M
authors.lastname: Divo
authors.forename: Rosa
authors.initials: R
authors.lastname: Faner
authors.forename: Stefano
authors.initials: S
authors.lastname: Guerra
authors.forename: Jacob Louis
authors.initials: JL
authors.lastname: Marott
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Martinez
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Camblor
authors.forename: Paula
authors.initials: P
authors.lastname: Meek
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Owen
authors.forename: Hans
authors.initials: H
authors.lastname: Petersen
authors.forename: Victor
authors.initials: V
authors.lastname: Pinto-Plata
authors.forename: Peter
authors.initials: P
authors.lastname: Schnohr
authors.forename: Akshay
authors.initials: A
authors.lastname: Sood
authors.forename: Joan B
authors.initials: JB
authors.lastname: Soriano
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000503:physiopathology*; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult