Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols

Overview

Journal Ann Am Thorac Soc

Specialty Pulmonary Medicine

Date 2019 Nov 27

PMID 31770003

Citations 37

Authors

Adam J Shapiro

Sharon D Dell

Benjamin Gaston

Michael OConnor

Nadzeya Marozkina

Michele Manion

Milan J Hazucha

Margaret W Leigh

Affiliations

Soon will be listed here.

Abstract

Nasal nitric oxide concentrations are extremely low in primary ciliary dyskinesia (PCD), and measurement of this nasal gas is recommended as a PCD diagnostic test in cooperative patients aged 5 years and older. However, nasal nitric oxide measurements must be performed with chemiluminescence analyzers using a standardized protocol to ensure proper results, because nasal nitric oxide values can be influenced by various internal and external factors. Repeat nasal nitric oxide testing on separate visits is required to ensure that low diagnostic values are persistent and consistent with PCD. This technical paper presents the standard operating procedures for nasal nitric oxide measurement used by the PCD Foundation Clinical and Research Centers Network at various specialty centers across North America. Adherence to this document ensures reliable nasal nitric oxide testing and high diagnostic accuracy when employed in a population with appropriate clinical phenotypes for PCD.

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References

Boon M, Meyts I, Proesmans M, Vermeulen F, Jorissen M, De Boeck K . Diagnostic accuracy of nitric oxide measurements to detect primary ciliary dyskinesia. Eur J Clin Invest. 2014; 44(5):477-85. DOI: 10.1111/eci.12254. View

Olin A, Hellgren J, Karlsson G, Ljungkvist G, Nolkrantz K, Toren K . Nasal nitric oxide and its relationship to nasal symptoms, smoking and nasal nitrate. Rhinology. 1998; 36(3):117-21. View

Kouis P, Papatheodorou S, Yiallouros P . Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: a meta-analysis. BMC Pulm Med. 2015; 15:153. PMC: 4669667. DOI: 10.1186/s12890-015-0147-3. View

Beydon N, Chambellan A, Alberti C, De Blic J, Clement A, Escudier E . Technical and practical issues for tidal breathing measurements of nasal nitric oxide in children. Pediatr Pulmonol. 2015; 50(12):1374-82. DOI: 10.1002/ppul.23167. View

Marthin J, Philipsen M, Rosthoj S, Nielsen K . Infant nasal nitric oxide over time: natural evolution and impact of respiratory tract infection. Eur Respir J. 2018; 51(6). DOI: 10.1183/13993003.02503-2017. View

Imada M, Nonaka S, Kobayashi Y, Iwamoto J . Functional roles of nasal nitric oxide in nasal patency and mucociliary function. Acta Otolaryngol. 2002; 122(5):513-9. DOI: 10.1080/00016480260092327. View

Liu C, Zheng M, He F, Wang X, Zhang L . Role of exhaled nasal nitric oxide in distinguishing between chronic rhinosinusitis with and without nasal polyps. Am J Rhinol Allergy. 2017; 31(6):389-394. DOI: 10.2500/ajra.2017.31.4480. View

Boerwinkle C, Marshall J, Bryant J, Gahl W, Olivier K, Gunay-Aygun M . Respiratory manifestations in 38 patients with Alström syndrome. Pediatr Pulmonol. 2016; 52(4):487-493. PMC: 7171443. DOI: 10.1002/ppul.23607. View

Walker W, Jackson C, Lackie P, Hogg C, Lucas J . Nitric oxide in primary ciliary dyskinesia. Eur Respir J. 2012; 40(4):1024-32. DOI: 10.1183/09031936.00176111. View

10.

Zysman-Colman Z, Kaspy K, Alizadehfar R, NyKamp K, Zariwala M, Knowles M . Nasal Nitric Oxide in Primary Immunodeficiency and Primary Ciliary Dyskinesia: Helping to Distinguish Between Clinically Similar Diseases. J Clin Immunol. 2019; 39(2):216-224. PMC: 6870987. DOI: 10.1007/s10875-019-00613-8. View

11.

Hoffmeyer F, Sucker K, Berresheim H, Monse C, Jettkant B, Beine A . Methodological Implications and Repeatability of Nasal Nitric Oxide: Relevance for Challenge Studies. Adv Exp Med Biol. 2018; 1113:1-10. DOI: 10.1007/5584_2018_166. View

12.

Imada M, Iwamoto J, Nonaka S, Kobayashi Y, Unno T . Measurement of nitric oxide in human nasal airway. Eur Respir J. 1996; 9(3):556-9. DOI: 10.1183/09031936.96.09030556. View

13.

Marthin J, Nielsen K . Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia. Eur Respir J. 2010; 37(3):559-65. DOI: 10.1183/09031936.00032610. View

14.

Struben V, Wieringa M, Mantingh C, Bommelje C, Don M, Feenstra L . Nasal NO: normal values in children age 6 through to 17 years. Eur Respir J. 2005; 26(3):453-7. DOI: 10.1183/09031936.05.00015205. View

15.

Fu C, Huang C, Chen Y, Chang P, Lee T . Nasal nitric oxide in relation to quality-of-life improvements after endoscopic sinus surgery. Am J Rhinol Allergy. 2015; 29(6):e187-91. DOI: 10.2500/ajra.2015.29.4249. View

16.

Lundberg J, Weitzberg E, Nordvall S, Kuylenstierna R, Lundberg J, Alving K . Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome. Eur Respir J. 1994; 7(8):1501-4. DOI: 10.1183/09031936.94.07081501. View

17.

Shapiro A, Davis S, Polineni D, Manion M, Rosenfeld M, Dell S . Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2018; 197(12):e24-e39. PMC: 6006411. DOI: 10.1164/rccm.201805-0819ST. View

18.

Everard M, Donnelly D . A pilot study of oral L-arginine in cystic fibrosis. J Cyst Fibros. 2005; 4(1):67-9. DOI: 10.1016/j.jcf.2004.10.001. View

19.

Leigh M, Hazucha M, Chawla K, Baker B, Shapiro A, Brown D . Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc. 2013; 10(6):574-81. PMC: 3960971. DOI: 10.1513/AnnalsATS.201305-110OC. View

20.

de Winter-de Groot K, van der Ent C . Measurement of nasal nitric oxide: evaluation of six different sampling methods. Eur J Clin Invest. 2008; 39(1):72-7. DOI: 10.1111/j.1365-2362.2008.02064.x. View