Date of Award
Doctor of Philosophy (Medical Science)
Medical Sciences (Division of Physiology/Pharmacology)
N.L. Jones, P.M. O'Byrne
Because the relationship between pulmonary function and exercise tolerance is highly variable in COPD, other contributing factors were investigated. Physiological factors that contribute to exercise tolerance must contribute to the symptoms limiting exercise, thus the symptoms limiting exercise in COPD and their contributing factors were explored, including an investigation of novel mechanisms to explore the reported tiotropium bromide-mediated improvement in exercise tolerance in COPD.
We conducted a retrospective, cross-sectional analysis of 4,424 COPD patients and 4,221 healthy subjects; referred to McMaster University Medical Center for exercise testing. Multiple linear regression, ridge regression, and MANOVA were utilized to determine the factors contributing to exercise tolerance, important symptoms limiting exercise, and factors contributing to dyspnea.
A randomized, double-blind, placebo-controlled, crossover study of 20 COPD subjects was performed. Repeated measures ANOVA was utilized to determine effects of 3 weeks tiotropium bromide vs. 3 weeks placebo on cardiac output and efficiency of gas exchange during exercise.
MBC, DLCO, and quadriceps strength were the three major, independent, contributors to exercise capacity (MPO = -206.3 + 5.1*Quadriceps Strength + 1.8*MBC + 10.0*DLCO, r2 = 0.677). MANOVA further illustrated this.
Dyspnea, alone or in equal combination with leg effort, was the most important symptom limiting exercise in COPD. VE and MBC were the two major, independent, contributors to dyspnea (Dyspnea = 0.95 + 0.08*VE + -0.01*MBC, r2 = 0.457). The increase in dyspnea with VE was much greater than the decrease with MBC.
Tiotropium bromide did not significantly (p = 0.72) improve the efficiency of gas exchange for oxygen, significantly worsened (p = 0.005) the efficiency of gas exchange for carbon dioxide, and did not improve cardiac output.
We concluded the reported tiotropium bromide-mediated improvement in exercise tolerance in COPD is not mediated through improvements in gas exchange efficiency and/or cardiac output.
Young, Aaron W., "ANTICHOLINERGIC THERAPY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: NOVEL MECHANISMS OF ACTION" (2011). Open Access Dissertations and Theses. Paper 5486.
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