The Value of Nasal Nitric Oxide Measurement in the Diagnosis of Primary Ciliary Dyskinesia.

Nasal nitric oxide (nNO) is widely used as a first-line test in the diagnostic evaluation of primary ciliary dyskinesia (PCD). Although low nNO is characteristic of classic PCD forms, its diagnostic performance varies across age groups, measurement techniques, and genetic subtypes. This review summarizes current evidence on the diagnostic accuracy of nNO and its evolving position within PCD guidelines. In recent prospective referral cohorts using comprehensive diagnostic work-ups, pooled sensitivity and specificity remain high, though slightly lower than in earlier, more selected cohorts. Previous European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines took different positions on the role of nNO, but the newly published joint ERS-ATS guideline harmonizes these approaches and recommends nNO as an important, though not stand-alone, component of the diagnostic pathway. Growing recognition of PCD genotypes with preserved ultrastructure and relatively normal nNO values has broadened the clinical spectrum. In these individuals, as well as in patients classified as "probable PCD" (no genetic or electron microscopic confirmation), diagnostic performance is reduced, with greater overlap between PCD and non-PCD populations. Age-adjusted reference values improve discrimination but do not eliminate this overlap. Additional factors, including technique, cooperation, ambient NO, and infection status, further influence interpretation. In conclusion, PCD represents a heterogeneous spectrum of motile ciliopathies with substantial variation in ultrastructure, ciliary function, symptoms, and nNO. Given this heterogeneity, no single biomarker can be expected to perform uniformly across all subtypes. nNO should therefore be interpreted in conjunction with clinical features and complementary diagnostic tests.