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

Abstract

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:

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.

MEASUREMENTS AND MAIN 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: 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 Krischer, Maimoona A Zariwala, Michael R Knowles
• Journal: Annals of the American Thoracic Society (Ann Am Thorac Soc) Vol. 10 Issue 6 Pg. 574-81 (Dec 2013) ISSN: 2325-6621 [Electronic] United States
• PMID: 24024753 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Nitric Oxide
• Axonemal Dyneins
• DNAH11 protein, human

Topics

• Adolescent
• Adult
• Aged
• Asthma (diagnosis)
• Axonemal Dyneins (genetics)
• Breath Tests (methods)
• Case-Control Studies
• Child
• Child, Preschool
• Cilia (ultrastructure)
• Cystic Fibrosis (diagnosis)
• Female
• Humans
• Kartagener Syndrome (diagnosis, genetics, pathology)
• Male
• Microscopy, Electron, Transmission
• Middle Aged
• Nasal Mucosa (cytology, ultrastructure)
• Nitric Oxide (analysis)
• Prospective Studies
• Pulmonary Disease, Chronic Obstructive (diagnosis)
• Reference Values
• Sensitivity and Specificity
• Young Adult