Diagnostic accuracy of nitric oxide measurements to detect primary ciliary dyskinesia

Background Primary Ciliary Dyskinesia (PCD) is an orphan disease characterized by recurrent respiratory infections and an increased prevalence of situs inversus and male infertility. Low nasal Nitric Oxide (nNO) is used as a new test to diagnose PCD. The test sensitivity is good, but specificity has not been studied widely. Therefore, we evaluated the diagnostic accuracy of low nNO to diagnose PCD in a large cohort, including healthy patients and different disease controls. Materials and methods Nasal nitric oxide was measured during plateau exhalation against resistance (nNO(plat)) and during tidal breathing (nNO(tid)). Moreover, we measured fractional exhaled NO (FENO). We included 226 patients: 38 with PCD, 49 healthy controls, and 139 disease controls (cystic fibrosis, humoral immunodeficiency, and asthma). Results The nNO(plat) cut-off value of 300ppb provided the best sensitivity (89.5%) and specificity (87.3%) to detect PCD. There was overlap between PCD and disease controls: 16.5% of disease controls had a false-positive result. nNO(tid) correlated with nNO(plat) (r=0.912), but values differed (P=0.0001). The nNO(tid) cut-off of 200ppb had a sensitivity of 89.5% and a specificity of 80.6% to detect PCD. The FENO cut-off of 10ppb had an acceptable sensitivity (89.5%), but a low specificity (58.3%). Positive and negative likelihood ratios were suboptimal for all tests. Conclusions nNO(plat), nNO(tid) and FENO measurements overlap between PCD and disease controls. Sensitivity is comparable for the three tests. Applying composite scores slightly improves diagnostic accuracy. Given the less than 90% test sensitivity, PCD should be considered in patients with intermediate results.