2012 OPEN FORUM Abstracts
EFFECTS OF MILD-MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND THE IMPACT OF TREATMENT WITH TIOTROPIUM BROMIDE.
Richard Casaburi1, Heather Paden2, Qiqi Deng2, Ahmar Iqbal3; 1Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA; 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT; 3Pfizer Inc, New York, NY
Background: Optimal clinical management of mild-moderate COPD is yet to be routinely established, as physical limitations are often unrecognized at this stage. This study aimed to characterize exercise limitation mechanisms, describe daily physical activity in GOLD I/II COPD patients vs age-/sex-matched controls, and evaluate the impact of treatment with a maintenance bronchodilator. Method: Symptomatic COPD patients (n=126) and controls (n=104) were enrolled at 15 sites (US and Canada). Subjects were m/f, =40 yr. COPD patients had dyspnea index focal score =9 and/or daily cough with sputum for 3 mo/yr in =2 consecutive years, post-bronchodilator FEV1/FVC < 70% and FEV1 =50%, and =100 mL decrease in inspiratory capacity (IC) during exercise. Controls were nonsmokers with no significant diseases. Visit 1: incremental treadmill exercise test. Visit 2: constant work rate (CWR) treadmill exercise test at 80% peak work rate from Visit 1. Visit 3: CWR test; COPD patients were randomized to daily tiotropium (Tio) or placebo. Between Visits 12 and 23: 1-wk activity monitoring. Visits 46 (COPD patients): spirometry and CWR tests; crossover treatment was separated by 4-wk washout (Visits 45). Dynamic hyperinflation was assessed using IC (baseline at rest vs peak exercise). Results: COPD patients and controls were demographically well matched; clinical characteristics were markedly different (Table). GOLD I and II groups had significant lung hyperinflation at rest, decreased activities of daily living, increased dyspnea scores and impact on work productivity vs controls. Peak exercise capacity was significantly decreased in GOLD I and II groups vs controls, with no significant difference between GOLD I and II. COPD patients had a decrease in IC with exercise, higher dyspnea scores and increased ventilatory demand on exertion during exercise vs controls. Tio improved FEV1 and reduced dynamic hyperinflation in COPD patients. It significantly improved exercise duration (change in CWR duration 57.9±24.0 s; P < 0.05) in GOLD II, but not in combined GOLD I/II or GOLD I. Conclusions: Symptomatic COPD patients showed distinct physiological impairments at rest and during exercise, as well as impacts on self-reported outcomes and daily activity; these abnormalities were largely similar in GOLD I and II. COPD patients benefited from Tio treatment, with decreased static and dynamic hyperinflation and improved lung function. Tio increased exercise duration in GOLD II patients. Sponsored Research - Boehringer Ingelheim Pharmaceuticals, Inc. Pfizer Inc Table. Demographic and baseline characteristics Values are mean±SD, except where indicated. P < 0.05: *GOLD I/II vs controls; GOLD I vs controls; GOLD II vs controls; §GOLD I vs GOLD II. BDI, Baseline Dyspnea Index; IET, Incremental Exercise Test; VSAQ, Veterans Specific Activity Questionnaire. P-value is based on 2-sample t-test with unequal variance (Satterthwaite).