ABSTRACT

The measurement of nasal nitric oxide (nNO) has been a very useful tool for the diagnosis of primary ciliary dyskinesia (PCD). Compared with healthy subjects or affected by others respiratory diseases, PCD patients show low concentrations of nNO. nNO is a simple test that requires minimal cooperation from the subject. The aim of this document is to review technical aspects for calibration, preparation and measurement of nNO.

KEYWORDS

Nitric oxide, nasal nitric oxide, primary ciliary dyskinesia.

REFERENCES

1. Davis SD, Eber E, Koumbourlis AC, American Thoracic Society, editors. Diagnostic tests in pediatric pulmonology: applications and interpretation. New York: Humana Press; 2015.p. 321.

2. Cantú-González G, Fernández-Figueroa F, Gochicoa-Rangel L, et al. Fracción exhalada de óxido nítrico. Recomendaciones clínicas y procedimiento. Neumol Cir Torax 2013;72(1):43-51.

3. Lane C, Knight D, Burgess S, et al. Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath. Thorax 2004;59(9):757-760. https://doi.org/10.1136/thx.2003.014894.

4. Ricciardolo FL. Multiple roles of nitric oxide in the airways. Thorax 2003;58(2):175-182. https://doi.org/10.1136/thorax.58.2.175.

5. de Diego Damiá A. Nitric oxide in asthma: what good does it do? Arch Bronconeumol 2010;46(4):157-159. https://doi.org/10.1016/j.arbres.2009.12.010.

6. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994;78(6):915-918. https://doi.org/10.1016/0092-8674(94)90266-6.

7. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987;84(24):9265-9269. https://doi.org/10.1073/pnas.84.24.9265.

8. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988;333(6174):664-666. https://doi.org/10.1038/333664a0.

9. Lundberg JO. Nitric oxide and the paranasal sinuses. Anat Rec 2008;291(11):1479-1484. https://doi.org/10.1002/ar.20782.

10. Narang I, Ersu R, Wilson NM, Bush A. Nitric oxide in chronic airway inflammation in children: diagnostic use and pathophysiological significance. Thorax 2002;57(7):586-589. https://doi.org/10.1136/thorax.57.7.586.

11. Manna A, Montella S, Maniscalco M, Maglione M, Santamaria F. Clinical application of nasal nitric oxide measurement in pediatric airway diseases. Pediatr Pulmonol 2015;50(1):85-99. https://doi.org/10.1002/ppul.23094.

12. Arnal JF, Flores P, Rami J, et al. Nasal nitric oxide concentration in paranasal sinus inflammatory diseases. Eur Respir J 1999;13(2):307-712. https://doi.org/10.1034/j.1399-3003.1999.13b15.x.

13. Bommarito L, Guida G, Heffler E, et al. Nasal nitric oxide concentration in suspected chronic rhinosinusitis. Ann Allergy Asthma Immunol 2008;101(4):358-362. https://doi.org/10.1016/S1081-1206(10)60310-9

14. Balfour-Lynn IM, Laverty A, Dinwiddie R. Reduced upper airway nitric oxide in cystic fibrosis. Arch Dis Child 1996;75(4):319-322. https://doi.org/10.1136/adc.75.4.319.

15. Collins SA, Gove K, Walker W, Lucas JSA. Nasal nitric oxide screening for primary ciliary dyskinesia: systematic review and meta-analysis. Eur Respir J 2014;44(6):1589-1599. https://doi.org/10.1183/09031936.00088614.

16. Katsuhara K, Kawamoto S, Wakabayashi T, Belsky JL. Situs inversus totalis and Kartagener’s syndrome in a Japanese population. Chest 1972;61(1):56-61. https://doi.org/10.1378/chest.61.1.56.

17. Chilvers MA, Rutman A, O’Callaghan C. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J Allergy Clin Immunol 2003;112(3):518-524. https://doi.org/10.1016/s0091-6749(03)01799-8.

18. Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med 2013;188(8):913-922. https://doi.org/10.1164/rccm.201301-0059CI.

19. Knowles MR, Leigh MW, Carson JL, et al.; Genetic Disorders of Mucociliary Clearance Consortium. Mutations of DNAH11 in primary ciliary dyskinesia with normal ciliary ultrastructure. Thorax 2012;67(5):433-441. https://doi.org/10.1136/thoraxjnl-2011-200301.

20. Leigh MW, Hazucha MJ, Chawla KK, et al. Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Ann Am Thorac Soc 2013;10(6):574-581.https://doi.org/10.1513/AnnalsATS.201305-110OC.

21. Shapiro AJ, Davis SD, Polineni D, et al.; American Thoracic Society Assembly on Pediatrics. Diagnosis of primary ciliary dyskinesia. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2018;197(12):e24-e39. https://doi.org/10.1164/rccm.201805-0819ST.

22. Karadag B, James AJ, Gültekin E, Wilson NM, Bush A. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J 1999;13(6):1402-1405.

23. Lundberg JO, Weitzberg E, Nordvall SL, Kuylenstierna R, Lundberg JM, Alving K. Primarily nasal origin of exhaled nitric oxide and absence in Kartagener’s syndrome. Eur Respir J 1994;7(8):1501-1504. https://doi.org/10.1183/09031936.94.07081501.

24. GE Analytical Instruments ©2006. Sievers® NOA 280i. Operation and Maintenance Manual. Firmware version 3.00 and later.

25. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 2005;171(8):912-930. https://doi.org/10.1164/rccm.200406-710ST.