What is it about?
Interstitial lung disease (ILD) is a group of lung conditions that cause scarring of the lungs, making it difficult to breathe and stay physically active. Some people with ILD also develop high blood pressure in the lungs (pulmonary hypertension), which can further reduce exercise capacity. Inhaled nitric oxide (iNO) is a treatment that relaxes blood vessels in the lungs and may improve blood flow. Several clinical trials have evaluated whether iNO helps people with ILD become more active, but the results have been inconsistent. We combined the results of all available randomized clinical trials comparing iNO with placebo. Across four studies involving 274 participants, we found that iNO did not meaningfully improve the distance patients could walk in six minutes or the amount of moderate-to-vigorous physical activity they performed. The overall rate of side effects was also similar between the two groups. These findings suggest that current evidence does not support the routine use of inhaled nitric oxide to improve exercise capacity in patients with ILD.
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Why is it important?
Patients with ILD often experience severe limitations in daily physical activity, and effective treatments to improve functional capacity remain limited. Inhaled nitric oxide has attracted interest because it selectively dilates blood vessels in well-ventilated areas of the lungs and may improve oxygen delivery without causing widespread low blood pressure. Our study provides the most comprehensive summary of randomized clinical trial evidence available to date. By showing that iNO did not produce clinically meaningful improvements in exercise capacity or physical activity, while maintaining a similar safety profile to placebo, our findings help clinicians and researchers better understand the current evidence. They also highlight the need for larger, well-designed studies to identify which patients, if any, may benefit from this therapy.
Perspectives
As both a clinician and researcher, I am interested in identifying treatments that can meaningfully improve the daily lives of patients with chronic lung disease. Although it is always encouraging to find effective new therapies, it is equally important to recognize when the current evidence does not support routine use. I hope this work helps clinicians make evidence-based decisions and provides a clearer direction for future research on pulmonary vascular therapies in interstitial lung disease.
Shun Nakahara
University of Hawaii System
Read the Original
This page is a summary of: Inhaled nitric oxide in fibrotic and advanced interstitial lung disease: A systematic review and meta-analysis of randomized controlled trials, PLOS One, June 2026, PLOS,
DOI: 10.1371/journal.pone.0351862.
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