title: Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia.
abstract: BACKGROUND
  Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized.
  
  
  OBJECTIVE
  To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites.
  
  
  METHODS
  At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD.
  
  
  RESULTS
  At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD.
  
  
  CONCLUSIONS
  Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.
authors.affiliation: 1 Department of Pediatrics.
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Leigh
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Hazucha
authors.forename: Kunal K
authors.initials: KK
authors.lastname: Chawla
authors.forename: Brock R
authors.initials: BR
authors.lastname: Baker
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shapiro
authors.forename: David E
authors.initials: DE
authors.lastname: Brown
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Lavange
authors.forename: Bethany J
authors.initials: BJ
authors.lastname: Horton
authors.forename: Bahjat
authors.initials: B
authors.lastname: Qaqish
authors.forename: Johnny L
authors.initials: JL
authors.lastname: Carson
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Davis
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Dell
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Ferkol
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Atkinson
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.forename: Scott D
authors.initials: SD
authors.lastname: Sagel
authors.forename: Margaret
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Carlos
authors.initials: C
authors.lastname: Milla
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.forename: Maimoona A
authors.initials: MA
authors.lastname: Zariwala
authors.forename: Michael R
authors.initials: MR
authors.lastname: Knowles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis; D056444:Axonemal Dyneins / Q000235:genetics; D001944:Breath Tests / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002923:Cilia / Q000648:ultrastructure; D003550:Cystic Fibrosis / Q000175:diagnosis; D005260:Female; D006801:Humans; D007619:Kartagener Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000648:ultrastructure; D009569:Nitric Oxide / Q000032:analysis*; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D009569:Nitric Oxide; D056444:Axonemal Dyneins; C465433:DNAH11 protein, human
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