Exacerbation frequency and course of COPD.
BACKGROUND
Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.


METHODS
This retrospective analysis of data from the 4-year UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo. Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2). Spirometry and the St George's Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).


RESULTS
In total, 5992 patients (mean age 65 years, 75% male) were randomized. Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV(1)) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units). Corresponding rates of decline in postbronchodilator FEV(1) (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium). Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium). The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium). The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.


CONCLUSIONS
Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD. Increasing rates of hospitalized exacerbations are associated with increasing risk of death.
Royal Devon and Exeter Hospital, Devon, UK. d.halpin@nhs.net
David M G
DM
Halpin
Marc
M
Decramer
Bartolome
B
Celli
Steven
S
Kesten
Dacheng
D
Liu
Donald P
DP
Tashkin
D000368:Aged; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006760:Hospitalization; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity
D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide