Improved Ventilatory Efficiency, Exercise Capacity Linked to Inhaled NO in Mild COPD

Asturias, Spain, young woman training in gym on a treadmill, legs section
This study reports on the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on VE/VCO2, dyspnoea and exercise capacity in patients with mild COPD.

The use of experimental inhaled nitric oxide (iNO) in patients with mild chronic obstructive pulmonary disease (COPD) has been shown to increase exercise capacity and improve ventilator efficiency. Results of the analysis were published in The Journal of Physiology.

A single-center, multigroup, randomized, double-blind, placebo-controlled, crossover study ( identifier: NCT03679312) was conducted in Edmonton, Alberta, Canada. Recognizing that patients with mild COPD have an exaggerated ventilator response to exercise, which is linked to dyspnea and exercise intolerance, the investigators sought to examine the effect of the selective pulmonary vasodilator iNO on an elevated ventilatory equivalent to CO2 production (VE/VCO2), dyspnea, and exercise capacity in this population. A total of 15 participants with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 COPD (forced expiratory volume in 1 second [FEV1] = 89 ± 11% predicted) with a smoking history (ie, ≥10 pack-years) and 15 age-matched healthy controls with normal lung function and a minimal smoking history (<10 pack-years) were enrolled in the study.

All of the participants completed 4 sessions over a 4-week period. Visit 1 involved a medical history, postbronchodilator pulmonary function testing, and a symptom-limited incremental cardiopulmonary cycle exercise test (CPET), to establish peak work rate. Visit 2 included a resting echocardiography session to assess cardiac function. On visits 3 and 4, which were separated by ≥24 hours, the participants completed incremental CPETs in which they were breathing either normoxic gas (placebo) or 4 ppm iNO.

Results of the study showed that iNO significantly increased peak oxygen uptake compared with placebo (1.80 ± 0.14 vs 1.53 ± 0.10 L·min–1; P <0.001). In contrast, no effect was reported among the controls. Further, at an equivalent work rate of 60 W, iNO significantly decreased (VE/VCO2) by 3.8 ± 4.2 units and dyspnea by 1.1 ± 1.2 Borg units in participants with COPD (P =.002 and P <.001, respectively). No effect was observed in the control group.

In both the COPDF and the control arms, operating lung volumes and oxygen saturation were not affected by iNO. Additionally, iNO increased peak oxygen uptake in participants with COPD, secondary to reduced (VE/VCO2) and dyspnea.

The investigators concluded that experimental manipulation of the pulmonary circulation alone can positively impact exercise capacity and dyspnea in patients with mild COPD. These findings suggest that targeting the pulmonary vasculature with more practical vasodilator therapies, such a sildenafil and pulsed iNO, may improve exercise tolerance and dyspnea in patients with mild COPD.


Phillips DB, Brotto AR, Ross BA, et al; Canadian Respiratory Research Network. Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: a randomized-control cross-over trial. J Physiol. Published online January 11, 2021. doi:10.1113/JP280913