Gass R; Hospital de Clínicas de Porto Alegre (HCPA), Brasil.
Plachi F; Silva FOB; Nolasco T; Tonetto MS; Goelzer LS; Muller PT; Knorst MM; Neder JA; Berton DC;
Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2024 Oct 08, pp. 104359.
Date of Electronic Publication: 2024 Oct 08.
Excess exercise ventilation (high ventilation (V̇ E )/carbon dioxide output (V̇CO 2 )) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇ E /V̇CO 2 and dyspnea in patients with early COPD. We aimed to assess whether a clinically more practical option – oral sildenafil – would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV 1 = 69.4 ± 13.5% predicted) showed higher ventilatory demands (V̇ E /V̇CO 2 ), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV 1 = 98.3 ±11.6% predicted). Contrary to our expectations, however, sildenafil (50mg; N= 15) did not change exertional V̇ E /V̇CO 2 , dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (P>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation.