Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD

• Published in: Journal of applied physiology (1985) 2006-10, Vol.101 (4), p.1025-1035
• Main Authors: O'Donnell, Denis E, Hamilton, Alan L, Webb, Katherine A
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Biological and medical sciences; Bronchodilator Agents - therapeutic use; Diagnostic tests; Double-Blind Method; Dyspnea - drug therapy; Dyspnea - etiology; Dyspnea - physiopathology; Exercise; Exercise Test; Female; Fundamental and applied biological sciences. Psychology; Humans; Male; Middle Aged; Physical Exertion - drug effects; Physical Exertion - physiology; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary Ventilation - drug effects; Pulmonary Ventilation - physiology; Respiratory diseases; Respiratory Mechanics - drug effects; Respiratory Mechanics - physiology; Scopolamine Derivatives - therapeutic use; Tiotropium Bromide
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01470.2005

1 Respiratory Investigation Unit, Departments of Medicine and Physiology, Queen’s University, Kingston; and 2 Boehringer Ingelheim (Canada) Ltd., Burlington, Ontario, Canada Submitted 22 November 2005 ; accepted in final form 27 April 2006 During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (V T ). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 ± 3%predicted; mean ± SE) inhaled tiotropium 18 µg or placebo once daily for 7–10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient’s maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure ( n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and V T (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 ± 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the V T response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling. chronic obstructive pulmonary disease; respiratory mechanics; tiotropium Address for reprint requests and other correspondence: D. O’Donnell, 102 Stuart St., Kingston, Ontario, Canada K7L 2V6 (e-mail: odonnell{at}post.queensu.ca )