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 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

Research output: Contribution to journalArticle

115 Citations (Scopus)

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: 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
Volume10
Issue number6
DOIs
StatePublished - Dec 2013

Fingerprint

Kartagener Syndrome
Nose
Nitric Oxide
Cystic Fibrosis
Chronic Obstructive Pulmonary Disease
Asthma
Multicenter Studies
Healthy Volunteers
Sensitivity and Specificity
Mutation

Keywords

  • Axoneme
  • Ciliopathy
  • Kartagener syndrome
  • Primary ciliary dyskinesia

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Leigh, M. W., Hazucha, M. J., Chawla, K. K., Baker, B. R., Shapiro, A. J., Brown, D. E., ... Knowles, M. R. (2013). Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Annals of the American Thoracic Society, 10(6), 574-581. https://doi.org/10.1513/AnnalsATS.201305-110OC

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. / Leigh, Margaret W.; Hazucha, Milan J.; Chawla, Kunal K.; Baker, Brock R.; Shapiro, Adam J.; Brown, David E.; Lavange, Lisa M.; Horton, Bethany J.; Qaqish, Bahjat; Carson, Johnny L.; Davis, Stephanie; Dell, Sharon D.; Ferkol, Thomas W.; Atkinson, Jeffrey J.; Olivier, Kenneth N.; Sagel, Scott D.; Rosenfeld, Margaret; Milla, Carlos; Lee, Hye Seung; Krischer, Jeffrey; Zariwala, Maimoona A.; Knowles, Michael R.

In: Annals of the American Thoracic Society, Vol. 10, No. 6, 12.2013, p. 574-581.

Research output: Contribution to journalArticle

Leigh, MW, Hazucha, MJ, Chawla, KK, Baker, BR, Shapiro, AJ, Brown, DE, Lavange, LM, Horton, BJ, Qaqish, B, Carson, JL, Davis, S, Dell, SD, Ferkol, TW, Atkinson, JJ, Olivier, KN, Sagel, SD, Rosenfeld, M, Milla, C, Lee, HS, Krischer, J, Zariwala, MA & Knowles, MR 2013, 'Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia', Annals of the American Thoracic Society, vol. 10, no. 6, pp. 574-581. https://doi.org/10.1513/AnnalsATS.201305-110OC
Leigh, Margaret W. ; Hazucha, Milan J. ; Chawla, Kunal K. ; Baker, Brock R. ; Shapiro, Adam J. ; Brown, David E. ; Lavange, Lisa M. ; Horton, Bethany J. ; Qaqish, Bahjat ; Carson, Johnny L. ; Davis, Stephanie ; Dell, Sharon D. ; Ferkol, Thomas W. ; Atkinson, Jeffrey J. ; Olivier, Kenneth N. ; Sagel, Scott D. ; Rosenfeld, Margaret ; Milla, Carlos ; Lee, Hye Seung ; Krischer, Jeffrey ; Zariwala, Maimoona A. ; Knowles, Michael R. / Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. In: Annals of the American Thoracic Society. 2013 ; Vol. 10, No. 6. pp. 574-581.
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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: 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.",
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T1 - Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia

AU - Leigh, Margaret W.

AU - Hazucha, Milan J.

AU - Chawla, Kunal K.

AU - Baker, Brock R.

AU - Shapiro, Adam J.

AU - Brown, David E.

AU - Lavange, Lisa M.

AU - Horton, Bethany J.

AU - Qaqish, Bahjat

AU - Carson, Johnny L.

AU - Davis, Stephanie

AU - Dell, Sharon D.

AU - Ferkol, Thomas W.

AU - Atkinson, Jeffrey J.

AU - Olivier, Kenneth N.

AU - Sagel, Scott D.

AU - Rosenfeld, Margaret

AU - Milla, Carlos

AU - Lee, Hye Seung

AU - Krischer, Jeffrey

AU - Zariwala, Maimoona A.

AU - Knowles, Michael R.

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N2 - 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.

AB - 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.

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