Low resting diffusion capacity, dyspnea, and exercise intolerance in chronic obstructive pulmonary disease.

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (Dl) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both Dl decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (V̇o), Dl, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low Dl [i.e., <lower limit of normal (LLN)] using Global Lung Function Initiative reference values. Dl was associated with peak V̇o ( = 0.006), peak work-rate ( = 0.005), and dyspnea/V̇o slope ( < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV and IC tertiles, peak V̇o and work rate were lower ( < 0.05) in low versus normal Dl groups. Across all tertiles, low Dl groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal Dl group (all < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, Dl<LLN was consistently associated with greater dyspnea and poorer exercise performance compared with preserved Dl. The higher dyspnea ratings and earlier exercise termination in low Dl groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (Dl) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal Dl.