Dynamic relationship of diffusing capacity and pulmonary alveolar vascular recruitment during exercise in chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of global morbidity and mortality. COPD has multiple etiologies. Irreversible pulmonary-alveolar capillary damage is one of them which can be assessed by diffusing capacity of the lungs for carbon monoxide (DLCO). The primary objective was to study the use of DLCO in predicting exercise limitation in COPD. The secondary objective was to evaluate the role of dietary nitrate precursor (beetroot juice) in improving alveolar gas exchange, pulmonary vascular function, and exercise intolerance in COPD. A third (mainly exploratory) aim was to study the expansion of pulmonary gas exchange surface area during exercise and its correlation with pulse wave velocity (PWV) as a surrogate of arterial stiffness. 32 patients with mild to severe COPD were tested. Cycle ergometry on day 1 was performed. DLCO, noninvasive indices of gas exchange, pulmonary vascular capacitance, cardiac eutput (Qc), Exhaled nitric oxide (exNO), and other respiratory variables were measured before and after ergometry. Patients were randomized to 8 days of beetroot juice or placebo and on day 8 the above protocol was repeated. Effects of high nitrate juice intake on indices of arterial stiffness (Appendix D) were studied by aortic PWV and central aortic pressure (cAP) before and after exercise. Only the single breath DLCO relative to Qc and body weight were significant resting predictors of exercise intolerance. COPD patients who did expand gas exchange surface area during exercise relative to Qc had a more preserved exercise capacity. Beetroot juice showed a (non significant) trend in improving exercise performance and pulmonary gas exchange surface area. The juice significantly lowered blood pressure, increased exNO and improved the patient overall wellbeing through objective scoring. The juice did not affect PWV before exercise in this cohort, but there was an effect of dietary nitrate on brachial systolic and pulse pressure, aortic pulse pressure and reflection magnitude determined from cAP. The three sets of novel experiments showed that exercise limitation in COPD is affected by alveolar-capillary gas exchange impairment attributed to impairment of pulmonary capillary recruitment. DLCO is a good measure of pulmonary vascular health and exercise intolerance in COPD. Dietary nitrate did neither significantly improve alveolar gas exchange nor improve indices of arterial stiffness in this cohort, though positive trends were observed.