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Exhaled nitric oxide: A test for diagnosis and control of asthma?

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Abstract

The fractional concentration of nitric oxide (FENO) in exhaled breath is a noninvasive marker of airway inflammation in asthma. The precise role of FENO in the asthma management algorithm has not been defined. However, there are compelling data for use of FENO for diagnosing asthma, assessing control and severity, titrating inhaled corticosteroids, and detecting ongoing airway inflammation. This article reviews the biology of nitric oxide in airway pathology and its role in asthma.

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References and Recommended Reading

  1. Palmer RM, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987, 327:524–526.

    Article  PubMed  CAS  Google Scholar 

  2. Gustafsson LE, Leone AM, Persson MG, et al.: Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun 1991, 181:852–857.

    Article  PubMed  CAS  Google Scholar 

  3. Alving K, Weitzberg E, Lundberg JM: Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 1993, 6:1368–1370.

    PubMed  CAS  Google Scholar 

  4. Kharitonov SA, Yates D, Robbins RA, et al.: Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994, 343:133–135.

    Article  PubMed  CAS  Google Scholar 

  5. Persson MG, Zetterstrom O, Agrenius V, et al.: Single-breath nitric oxide measurements in asthmatic patients and smokers. Lancet 1994, 343:146–147.

    Article  PubMed  CAS  Google Scholar 

  6. Yates DH, Kharitonov SA, Robbins RA, et al.: Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide. Am J Respir Crit Care Med 1995, 152:892–896.

    PubMed  CAS  Google Scholar 

  7. Kharitonov SA, Yates DH, Barnes PJ: Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 1996, 153:454–457.

    PubMed  CAS  Google Scholar 

  8. Massaro AF, Gaston B, Kita D, et al.: Expired nitric oxide levels during treatment of acute asthma. Am J Respir Crit Care Med 1995, 152:800–803.

    PubMed  CAS  Google Scholar 

  9. Ricciardolo FL: Multiple roles of nitric oxide in the airways. Thorax 2003, 58:175–182.

    Article  PubMed  CAS  Google Scholar 

  10. Yates DH: Role of exhaled nitric oxide in asthma. Immunol Cell Biol 2001, 79:178–190.

    Article  PubMed  CAS  Google Scholar 

  11. Bates CA, Silkoff PE: Exhaled nitric oxide in asthma: from bench to bedside. J Allergy Clin Immunol 2003, 111:256–262.

    Article  PubMed  CAS  Google Scholar 

  12. Silkoff PE, McClean PA, Slutsky AS, et al.: Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am J Respir Crit Care Med 1997, 155:260–267.

    PubMed  CAS  Google Scholar 

  13. Silkoff PE, Sylvester JT, Zamel N, Permutt S: Airway nitric oxide diffusion in asthma: Role in pulmonary function and bronchial responsiveness. Am J Respir Crit Care Med 2000, 161:1218–1228.

    PubMed  CAS  Google Scholar 

  14. ATS/ERS Recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide. Am J Respir Crit Care Med 2005, 171:912–930.

  15. George SC, Hogman M, Permutt S, Silkoff PE: Modeling pulmonary nitric oxide exchange. J Appl Physiol 2004, 96:831–839.

    Article  PubMed  CAS  Google Scholar 

  16. Tsoukias NM, George SC: A two-compartment model of pulmonary nitric oxide exchange dynamics [see comment]. J Appl Physiol 1998, 85:653–666.

    PubMed  CAS  Google Scholar 

  17. Paraskakis E, Brindicci C, Fleming L, et al.: Measurement of bronchial and alveolar nitric oxide production in normal children and children with asthma. Am J Respir Crit Care Med 2006, 174:260–267.

    Article  PubMed  CAS  Google Scholar 

  18. Lehtimaki L, Kankaanranta H, Saarelainen S, et al.: Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation. Am J Respir Crit Care Med 2001, 163:1557–1561.

    PubMed  CAS  Google Scholar 

  19. Franklin PJ, Taplin R, Stick SM: A community study of exhaled nitric oxide in healthy children. Am J Respir Crit Care Med 1999, 159:69–73.

    PubMed  CAS  Google Scholar 

  20. Kissoon N, Duckworth LJ, Blake KV, et al.: Exhaled nitric oxide concentrations: online versus offline values in healthy children. Pediatr Pulmonol 2002, 33:283–292.

    Article  PubMed  Google Scholar 

  21. Tsang KW, Ip SK, Leung R, et al.: Exhaled nitric oxide: the effects of age, gender and body size. Lung 2001, 179:83–91.

    Article  PubMed  CAS  Google Scholar 

  22. Chambers DC, Tunnicliffe WS, Ayres JG: Acute inhalation of cigarette smoke increases lower respiratory tract nitric oxide concentrations. Thorax 1998, 53:677–679.

    PubMed  CAS  Google Scholar 

  23. Horvath I, Donnelly LE, Kiss A, et al.: Exhaled nitric oxide and hydrogen peroxide concentrations in asthmatic smokers. Respiration 2004, 71:463–468.

    Article  PubMed  CAS  Google Scholar 

  24. Berlyne GS, Parameswaran K, Kamada D, et al.: A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation. J Allergy Clin Immunol 2000, 106:638–644.

    Article  PubMed  CAS  Google Scholar 

  25. Jatakanon A, Lim S, Kharitonov SA, et al.: Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 1998, 53:91–95.

    Article  PubMed  CAS  Google Scholar 

  26. Warke TJ, Fitch PS, Brown V, et al.: Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax 2002, 57:383–387.

    Article  PubMed  CAS  Google Scholar 

  27. Brightling CE, Symon FA, Birring SS, et al.: Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Thorax 2003, 58:528–532.

    Article  PubMed  CAS  Google Scholar 

  28. Payne DN, Adcock IM, Wilson NM, et al.: Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone [see comment]. Am J Respir Crit Care Med 2001, 164:1376–1381.

    PubMed  CAS  Google Scholar 

  29. van den Toorn LM, Overbeek SE, de Jongste JC, et al.: Airway inflammation is present during clinical remission of atopic asthma. Am J Respir Crit Care Med 2001, 164:2107–2113. [Published erratum appears in Am J Respir Crit Care Med 2002, 166:1143.]

    PubMed  Google Scholar 

  30. Silkoff PE, Lent AM, Busacker AA, et al.: Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma. J Allergy Clin Immunol 2005, 116:1249–1255.

    Article  PubMed  CAS  Google Scholar 

  31. Sont JK, Han J, van Krieken JM, et al.: Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids. Thorax 1996, 51:496–502.

    Article  PubMed  CAS  Google Scholar 

  32. Dupont LJ, Demedts MG, Verleden GM: Prospective evaluation of the validity of exhaled nitric oxide for the diagnosis of asthma. Chest 2003, 123:751–756.

    Article  PubMed  CAS  Google Scholar 

  33. Smith AD, Cowan JO, Filsell S, et al.: Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med 2004, 169:473–478.

    Article  PubMed  Google Scholar 

  34. Smith AD, Taylor DR: Is exhaled nitric oxide measurement a useful clinical test in asthma? Curr Opin Allergy Clin Immunol 2005, 5:49–56.

    Article  PubMed  CAS  Google Scholar 

  35. Zietkowski Z, Bodzenta-Lukaszyk A, Tomasiak MM, et al.: Comparison of exhaled nitric oxide measurement with conventional tests in steroid-naive asthma patients. J Investig Allergol Clin Immunol 2006, 16:239–246.

    PubMed  CAS  Google Scholar 

  36. Delgado-Corcoran C, Kissoon N, Murphy SP, Duckworth LJ: Exhaled nitric oxide reflects asthma severity and asthma control. Pediatr Crit Care Med 2004, 5:48–52.

    Article  PubMed  Google Scholar 

  37. Jatakanon A, Lim S, Barnes PJ: Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med 2000, 161:64–72.

    PubMed  CAS  Google Scholar 

  38. Sont JK, Willems LN, Bel EH, et al.: Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med 1999, 159:1043–1051.

    PubMed  CAS  Google Scholar 

  39. Green RH, Brightling CE, Woltmann G, et al.: Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 2002, 57:875–879.

    Article  PubMed  CAS  Google Scholar 

  40. Meyts I, Proesmans M, De Boeck K: Exhaled nitric oxide corresponds with office evaluation of asthma control. Pediatr Pulmonol 2003, 36:283–289.

    Article  PubMed  Google Scholar 

  41. Smith AD, Cowan JO, Brassett KP, et al.: Use of exhaled nitric oxide measurements to guide treatment in chronic asthma [see comment]. N Engl J Med 2005, 352:2163–2173.

    Article  PubMed  CAS  Google Scholar 

  42. Little SA, Chalmers GW, MacLeod KJ, et al.: Non-invasive markers of airway inflammation as predictors of oral steroid responsiveness in asthma. Thorax 2000, 55:232–234.

    Article  PubMed  CAS  Google Scholar 

  43. Smith AD, Cowan JO, Brassett KP, et al.: Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med 2005, 172:453–459.

    Article  PubMed  Google Scholar 

  44. Szefler SJ, Phillips BR, Martinez FD, et al.: Characterization of within-subject responses to fluticasone and montelukast in childhood asthma [see comment]. J Allergy Clin Immunol 2005, 115:233–242.

    Article  PubMed  CAS  Google Scholar 

  45. Pijnenburg MW, Bakker EM, Hop WC, De Jongste JC: Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. Am J Respir Crit Care Med 2005, 172:831–836.

    Article  PubMed  Google Scholar 

  46. Katsara M, Donnelly D, Iqbal S, et al.: Relationship between exhaled nitric oxide levels and compliance with inhaled corticosteroids in asthmatic children. Respir Med 2006, 100:1512–1517.

    Article  PubMed  Google Scholar 

  47. Olivieri M, Talamini G, Corradi M, et al.: Reference values for exhaled nitric oxide (reveno) study. Respir Res 2006, 7:94.

    Article  PubMed  CAS  Google Scholar 

  48. Olin AC, Alving K, Toren K: Exhaled nitric oxide: relation to sensitization and respiratory symptoms. Clin Exp Allergy 2004, 34:221–226.

    Article  PubMed  CAS  Google Scholar 

  49. Buchvald F, Baraldi E, Carraro S, et al.: Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years. J Allergy Clin Immunol 2005, 115:1130–1136.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO, 80206, USA

    Rohit Katial

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  1. Rohit Katial
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  2. Lora Stewart
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Correspondence to Rohit Katial.

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Katial, R., Stewart, L. Exhaled nitric oxide: A test for diagnosis and control of asthma?. Curr Allergy Asthma Rep 7, 459–463 (2007). https://doi.org/10.1007/s11882-007-0070-7

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  • DOI: https://doi.org/10.1007/s11882-007-0070-7

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