Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia

Margaret W. Leigh, Milan J. Hazucha, Kunal K. Chawla, Brock R. Baker, Adam J. Shapiro, David E. Brown, Lisa M. Lavange, Bethany J. Horton, Bahjat Qaqish, Johnny L. Carson, Stephanie D. Davis, Sharon D. Dell, Thomas W. Ferkol, Jeffrey J. Atkinson, Kenneth N. Olivier, Scott D. Sagel, Margaret Rosenfeld, Carlos Milla, Hye Seung Lee, Jeffrey KrischerMaimoona A. Zariwala, Michael R. Knowles

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211 Scopus citations


Rationale: 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. Objectives: Touse a standard protocol formeasuringnNOtoestablishadiseasespecific 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. Measurements and Main Results: At the lead site, nNO values in PCD (mean6standard deviation, 20.7624.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 6 118.8; 125.5-867.0 nl/min), asthma (267.8 6 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 6 87.1; 109.7-449.1 nl/min); however, therewas overlapwith cystic fibrosis (134.0673.5; 15.6-386.1 nl/min). The disease-specific nNOcutoff valuewas 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.

Original languageEnglish
Pages (from-to)574-581
Number of pages8
JournalAnnals of the American Thoracic Society
Issue number6
StatePublished - Dec 2013


  • Axoneme
  • Ciliopathy
  • Kartagener syndrome
  • Primary ciliary dyskinesia


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