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

Abstract

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DlCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DlCO 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 (V̇o2), DlCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DlCO [i.e., <lower limit of normal (LLN)] using Global Lung Function Initiative reference values. DlCO was associated with peak V̇o2 ( P = 0.006), peak work-rate ( P = 0.005), and dyspnea/V̇o2 slope ( P < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV1 and IC tertiles, peak V̇o2 and work rate were lower ( P < 0.05) in low versus normal DlCO groups. Across all tertiles, low DlCO 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 DlCO group (all P < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, DlCO<LLN was consistently associated with greater dyspnea and poorer exercise performance compared with preserved DlCO. The higher dyspnea ratings and earlier exercise termination in low DlCO groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. NEW & NOTEWORTHY Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (DlCO) 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 DlCO.