Pulmonary diffusing capacity for nitric oxide in disease: a scoping review

This scoping review aims to map the available studies on single-breath pulmonary diffusing capacity for nitric oxide (D _LNO) in various clinical diseases and identify gaps for future research.

We followed the JBI methodology for scoping reviews. A systematic literature search was conducted in Embase, MEDLINE (EBSCOhost), PubMed, Scopus, Web of Science and the Cochrane Library to identify studies on D _LNO from 1983 to 2025. Two reviewers screened abstracts using Rayyan software and extracted data using standardised templates implemented into REDCap (Research Electronic Data Capture).

We identified 1638 studies, of which 69 met the eligibility criteria. These studies represented respiratory (n=22), immunological/genetic/systemic (n=14), post-COVID-19 sequelae (n=13), cardiovascular (n=9), metabolic/endocrine/renal (n=6), environmental-related (n=3) and other (n=2) conditions. There was substantial heterogeneity in disease categories, sample sizes and reporting methods. Nearly half of the studies (49.3%) used convenience sampling, where participant selection processes are often poorly described; 62.3% included <50 participants. Only 18.8% reported a sample size calculation, and 10.1% registered or published a study protocol. Disparate findings within disease categories were often difficult to interpret; and small sample sizes limited generalisability. In some specific conditions, D _LNO showed sensitivity in detecting interstitial and fibrotic changes compared to conventional single-breath pulmonary diffusing capacity for carbon monoxide (D _LCO) while simultaneous D _LNO-D _LCO measurements permitted the detection of pulmonary vascular-haematological perturbations.

Single-breath D _LNO-D _LCO may provide additional pathophysiological insight by assessing the relative contributions from membrane and blood resistance of diffusion. Larger studies are required to clarify its interpretation across disease states.