Asthma exhaled nitric oxide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]


Measurement of fractional nitric oxide concentration in exhaled breath (FeNO) is a non-invasive method of assessing underlying airway inflammation.[1][2] However, due to technical complexities associated with the procedure, it is not routinely used.[3][4]

Exhaled Nitric Oxide

Asthma is a chronic inflammatory disease with hyper-responsive airways. As a part of the inflammatory process, there is an associated up-regulation in the nitric oxide synthase observed in the respiratory mucosal epithelium, which contributes to the increased concentrations of nitric oxide released in exhaled breath.

Benefits of Measurement of Exhaled Nitric Oxide in Asthmatics

  • Asthmatics are associated with higher concentrations of expired nitric oxide and hence expired nitric oxide evaluation may be a useful index to assess the disease severity.[5]
  • Exhaled NO has also shown to be associated with other asthmatic clinical parameters such as airway inflammation, sputum eosinophilia and viral infection.[6][7][8][9][10]
  • Exhaled nitric oxide closely correlates with the percentage of eosinophils in induced sputum and therefore may be a useful non-invasive marker to assess airway inflammation.[11][12]
  • Exhaled nitric oxide levels reduced with the administration of steroids and leukotriene receptor blockers suggesting that exhaled nitric oxide measurement may be a beneficial marker for assessing the airway inflammation in asthmatics.[5][8][9]

Supportive Trial Data

The role of monitoring exhaled nitric oxide levels is not established according to a meta-analysis of randomized controlled trials by the Cochrane Collaboration.[13]

  • An initial trial showed benefit[14]. The study further reported a significant reduction in the cumulative maintenance dose of inhaled steroid without worsening asthmatic symptoms.
  • However, two subsequent studies did not demonstrate any beneficial effect with the use of eNO- guided therapy in comparison to conventional-based therapy. One of the studies, involving 546 patients demonstrated good symptomatic control with conventional management; however, the use of fraction of exhaled NO as an indicator of asthmatic control, resulted in higher doses of inhaled steroids, without clinically improving symptomatic control.[15] Another randomized trial that assessed 118 asthmatics, demonstrated that the measurement of exhaled nitric oxide did not cause a significant reduction in the frequency of exacerbations or in the total amount of inhaled corticosteroid therapy used over 12-month period when compared to the current asthma guidelines.[16]


  1. Silkoff PE, Carlson M, Bourke T, Katial R, Ogren E, Szefler SJ (2004) The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma. J Allergy Clin Immunol 114 (5):1241-56. DOI:10.1016/j.jaci.2004.08.042 PMID: 15536442
  2. Sippel JM, Holden WE, Tilles SA, O'Hollaren M, Cook J, Thukkani N et al. (2000) Exhaled nitric oxide levels correlate with measures of disease control in asthma. J Allergy Clin Immunol 106 (4):645-50. DOI:10.1067/mai.2000.109618 PMID: 11031334
  3. Bates CA, Silkoff PE (2003) Exhaled nitric oxide in asthma: from bench to bedside. J Allergy Clin Immunol 111 (2):256-62. PMID: 12589342
  4. Smith AD, Taylor DR (2005) Is exhaled nitric oxide measurement a useful clinical test in asthma? Curr Opin Allergy Clin Immunol 5 (1):49-56. PMID: 15643344
  5. 5.0 5.1 Massaro AF, Gaston B, Kita D, Fanta C, Stamler JS, Drazen JM (1995) Expired nitric oxide levels during treatment of acute asthma. Am J Respir Crit Care Med 152 (2):800-3. PMID: 7633745
  6. Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G et al. (2003) Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol 112 (5):883-92. DOI:10.1016/j.jaci.2003.08.014 PMID: 14610474
  7. Kharitonov SA, Yates DH, Barnes PJ (1996) Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 153 (1):454-7. PMID: 8542158
  8. 8.0 8.1 Sandrini A, Ferreira IM, Gutierrez C, Jardim JR, Zamel N, Chapman KR (2003) Effect of montelukast on exhaled nitric oxide and nonvolatile markers of inflammation in mild asthma. Chest 124 (4):1334-40. PMID: 14555563
  9. 9.0 9.1 Tsujino I, Nishimura M, Kamachi A, Makita H, Munakata M, Miyamoto K et al. (2000) Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma? Respiration 67 (6):645-51. PMID: 11124647
  10. Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett D, Comhair SA et al. (2010) Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit Care Med 181 (10):1033-41. DOI:10.1164/rccm.200905-0695OC PMID: 20133930
  11. Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ (1998) Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 53 (2):91-5. PMID: 9624291
  12. Warke TJ, Fitch PS, Brown V, Taylor R, Lyons JD, Ennis M et al. (2002) Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax 57 (5):383-7. PMID: 11978911
  13. Petsky HL, Kew KM, Turner C, Chang AB (2016). "Exhaled nitric oxide levels to guide treatment for adults with asthma". Cochrane Database Syst Rev. 9: CD011440. doi:10.1002/14651858.CD011440.pub2. PMID 27580628.
  14. Smith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR (2005). "Use of exhaled nitric oxide measurements to guide treatment in chronic asthma". N Engl J Med. 352 (21): 2163–73. doi:10.1056/NEJMoa043596. PMID 15914548. Review in: Evid Based Med. 2006 Feb;11(1):20
  15. Szefler SJ, Mitchell H, Sorkness CA, Gergen PJ, O'Connor GT, Morgan WJ et al. (2008) Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. Lancet 372 (9643):1065-72. DOI:10.1016/S0140-6736(08)61448-8 PMID: 18805335
  16. Shaw DE, Berry MA, Thomas M, Green RH, Brightling CE, Wardlaw AJ et al. (2007) The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial. Am J Respir Crit Care Med 176 (3):231-7. DOI:10.1164/rccm.200610-1427OC PMID: 17496226

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