title: Adverse health consequences in COPD patients with rapid decline in FEV1--evidence from the UPLIFT trial.
abstract: BACKGROUND
  The rate of decline in forced expiratory volume in 1 second (FEV1) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV1 with other endpoints.
  
  
  METHODS
  Retrospective analysis of UPLIFT® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily in chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV1 was analysed with random co-efficient regression. Patients were categorised according to quartiles based on the rate of decline (RoD) in post-bronchodilator FEV1. The St George's Respiratory Questionnaire (SGRQ) total score, exacerbations and mortality were assessed within each quartile.
  
  
  RESULTS
  Mean (standard error [SE]) post-bronchodilator FEV1 increased in the first quartile (Q1) by 37 (1) mL/year. The other quartiles showed annualised declines in FEV1 (mL/year) as follows: Q2 = 24 (1), Q3 = 59 (1) and Q4 = 125 (2). Age, gender, respiratory medication use at baseline and SGRQ did not distinguish groups. The patient subgroup with the largest RoD had less severe lung disease at baseline and contained a higher proportion of current smokers. The percentage of patients with ≥ 1 exacerbation showed a minimal difference from the lowest to the largest RoD, but exacerbation rates increased with increasing RoD. The highest proportion of patients with ≥ 1 hospitalised exacerbation was in Q4 (Q1 = 19.5% [tiotropium], 26% [control]; Q4 = 33.8% [tiotropium] and 33.1% [control]). Time to first exacerbation and hospitalised exacerbation was shorter with increasing RoD. Rate of decline in SGRQ increased in direct proportion to each quartile. The group with the largest RoD had the highest mortality.
  
  
  CONCLUSIONS
  Patients can be grouped into different RoD quartiles with the observation of different clinical outcomes indicating that specific (or more aggressive) approaches to management may be needed.
  
  
  BACKGROUND
  ClinicalTrials.gov number, NCT00144339.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA. skesten@uptakemedical.com
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
authors.forename: Marc
authors.initials: M
authors.lastname: Decramer
authors.forename: Dacheng
authors.initials: D
authors.lastname: Liu
authors.forename: Donald
authors.initials: D
authors.lastname: Tashkin
mesh_terms: D000368:Aged; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000401:mortality* / Q000503:physiopathology*; D012189:Retrospective Studies; D012602:Scopolamine Derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D000069447:Tiotropium Bromide
chemical_list: D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide