title: Diagnostic accuracy of nitric oxide measurements to detect primary ciliary dyskinesia.
abstract: 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.
  
  
  METHODS
  Nasal nitric oxide was measured during plateau exhalation against resistance (nNOplat) and during tidal breathing (nNOtid). 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 nNOplat cut-off value of 300 ppb 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. nNOtid correlated with nNOplat (r=0·912), but values differed (P=0·0001). The nNOtid cut-off of 200 ppb had a sensitivity of 89·5% and a specificity of 80·6% to detect PCD. The FENO cut-off of 10 ppb had an acceptable sensitivity (89·5%), but a low specificity (58·3%). Positive and negative likelihood ratios were suboptimal for all tests.
  
  
  CONCLUSIONS
  nNOplat, nNOtid 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.
authors.affiliation: Department of Pediatrics, Pediatric Pulmonology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Boon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meyts
authors.forename: Marijke
authors.initials: M
authors.lastname: Proesmans
authors.forename: Francois L
authors.initials: FL
authors.lastname: Vermeulen
authors.forename: Mark
authors.initials: M
authors.lastname: Jorissen
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
mesh_terms: D000293:Adolescent; D000328:Adult; D001944:Breath Tests / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007619:Kartagener Syndrome / Q000175:diagnosis*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D009569:Nitric Oxide
keywords: Cilia; diagnostic accuracy; fractional exhaled NO; nitric oxide; primary ciliary dyskinesia; sensitivity and specificity