Abstract / Summary
Rationale: Nasal nitric oxide (nNO) measurement is a recommended noninvasive screening tool for primary ciliary dyskinesia (PCD), but studies examining its real-world performance are limited, and integration of PCD diagnostic pathways varies across centers. Objective: The objective of this study was to evaluate the diagnostic utility of nNO, describe phenotypic profiles of patients with low and normal NO levels, and highlight the existing challenges in diagnosing PCD. Methods: We assessed the diagnostic performance of nNO testing in patients with suspected PCD, known PCD, or bronchiectasis/bronchiolitis with no known etiology who underwent nNO measurement using the velum closure technique between January 2023 and May 2025. We recorded and analyzed baseline clinical features, pulmonary function testing values, microbiologic data, and available genetic and other PCD diagnostic testing results. Results: Among 86 patients (mean age 30.4 ± 18.96 years; 61.6% female), 24 (27.9%) had low nNO (<77 nL/min) and 62 (72.1%) had normal nNO (≥77 nL/min). Of the 24 individuals with low nNO, 17 (70.8%) were confirmed to have PCD through genetic and/or electron microscopy testing. Of the 62 with normal nNO, 2 were confirmed to have PCD via genetic analysis; both had nNO < 100 nL/min. nNO testing supported the diagnosis of PCD in 6 of 19 cases (31.6%) with newly diagnosed PCD. Patients with low nNO had lower Forced Expiratory Volume in 1 s (FEV1) percent predicted (72.2 ± 23.0% vs. 84.5 ± 22.0%, p = 0.04) and had higher rates of Pseudomonas aeruginosa (54.2% vs. 25.8%, p = 0.02) compared with those with normal nNO. Conclusions: nNO testing performs well in the diagnostic evaluation of PCD among patients with clinical phenotypes suspicious for PCD. Substantial heterogeneity in the extent of PCD genetic testing was observed, underscoring the need to better define which patients may benefit from expanded PCD diagnostic evaluation or whole-genome sequencing (WGS). As there is no gold-standard diagnostic test for PCD, there is a need for further studies to refine diagnostic algorithms.