Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: A randomized‐control cross‐over trial
Bibliographic record
Abstract
Key points Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO 2 production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on / , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced / and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD. Abstract Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO 2 production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower / and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized‐control cross‐over study, 15 patients with mild COPD (FEV 1 = 89 ± 11% predicted) and 15 healthy controls completed symptom‐limited cardiopulmonary exercise tests while breathing normoxic gas or 40 ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80 ± 0.14 vs . 1.53 ± 0.10 L·min –1 , P < 0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60 W, iNO reduced / by 3.8 ± 4.2 units ( P = 0.002) and dyspnoea by 1.1 ± 1.2 Borg units ( P < 0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced / and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased / , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".