DOI QR코드

DOI QR Code

Measurements of fractional exhaled nitric oxide in pediatric asthma

  • Hahn, Youn-Soo (Department of Pediatrics, Chungbuk National University College of Medicine)
  • 투고 : 2013.06.17
  • 심사 : 2013.08.27
  • 발행 : 2013.10.15

초록

Exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) measurements become an important adjunct for the evaluation of asthma. In addition, the availability of portable devices makes it possible to measure FeNO more easily and frequently in the routine pediatric practice. Despite various confounding factors affecting its levels, FeNO can be applicable in diagnosing asthma, monitoring treatment response, evaluating asthma control, and predicting asthma exacerbations. Thus, although pulmonary function tests are the standard tools for objective measurements of asthmatic control, FeNO can broaden the way of asthma monitoring and supplement standard clinical asthma care guidelines.

키워드

참고문헌

  1. Tattersfield AE, Postma DS, Barnes PJ, Svensson K, Bauer CA, O'Byrne PM, et al. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group. Am J Respir Crit Care Med 1999;160:594-9. https://doi.org/10.1164/ajrccm.160.2.9811100
  2. Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002;360:1715-21. https://doi.org/10.1016/S0140-6736(02)11679-5
  3. Crimi E, Spanevello A, Neri M, Ind PW, Rossi GA, Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med 1998; 157:4-9. https://doi.org/10.1164/ajrccm.157.1.9703002
  4. National Heart, Lung and Blood Institute. National Asthma Education and Prevention Program, Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full report 2007 [Internet]. Bethesda: National Heart, Lung and Blood Institute; [c2013] [cited 2013 Mar 26]. Available from: http://www.nhlbi.nih.gov/guidelines/ asthma.
  5. Gibson PG. Monitoring the patient with asthma: an evidence-based approach. J Allergy Clin Immunol 2000;106(1 Pt 1):17-26. https://doi.org/10.1067/mai.2000.108307
  6. Lundback B, Dahl R. Assessment of asthma control and its impact on optimal treatment strategy. Allergy 2007;62:611-9. https://doi.org/10.1111/j.1398-9995.2007.01399.x
  7. Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax 2006;61:817-27. https://doi.org/10.1136/thx.2005.056093
  8. Smith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. N Engl J Med 2005;352:2163-73. https://doi.org/10.1056/NEJMoa043596
  9. Shaw DE, Berry MA, Thomas M, Green RH, Brightling CE, Wardlaw AJ, et al. The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial. Am J Respir Crit Care Med 2007;176:231-7. https://doi.org/10.1164/rccm.200610-1427OC
  10. 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;172:831-6. https://doi.org/10.1164/rccm.200503-458OC
  11. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 1993;6:1368-70.
  12. Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001;163:1693-722. https://doi.org/10.1164/ajrccm.163.7.2009041
  13. Gaston B, Drazen JM, Loscalzo J, Stamler JS. The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med 1994;149(2 Pt 1): 538-51. https://doi.org/10.1164/ajrccm.149.2.7508323
  14. Ricciardolo FL, Sterk PJ, Gaston B, Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiol Rev 2004;84:731-65. https://doi.org/10.1152/physrev.00034.2003
  15. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002-12. https://doi.org/10.1056/NEJM199312303292706
  16. Maniscalco M, Sofia M, Pelaia G. Nitric oxide in upper airways inflammatory diseases. Inflamm Res 2007;56:58-69. https://doi.org/10.1007/s00011-006-6111-1
  17. Kleinert H, Pautz A, Linker K, Schwarz PM. Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 2004; 500:255-66. https://doi.org/10.1016/j.ejphar.2004.07.030
  18. Guo FH, Comhair SA, Zheng S, Dweik RA, Eissa NT, Thomassen MJ, et al. Molecular mechanisms of increased nitric oxide (NO) in asthma: evidence for transcriptional and post-translational regulation of NO synthesis. J Immunol 2000;164:5970-80. https://doi.org/10.4049/jimmunol.164.11.5970
  19. Lane C, Knight D, Burgess S, Franklin P, Horak F, Legg J, et al. Epithelial inducible nitric oxide synthase activity is the major determinant of nitric oxide concentration in exhaled breath. Thorax 2004;59:757-60. https://doi.org/10.1136/thx.2003.014894
  20. Woo SI, Lee JH, Kim H, Kang JW, Sun YH, Hahn YS. Utility of fractional exhaled nitric oxide (F(E)NO) measurements in diagnosing asthma. Respir Med 2012;106:1103-9. https://doi.org/10.1016/j.rmed.2012.03.022
  21. Janson C, Kalm-Stephens P, Foucard T, Norback D, Alving K, Nordvall SL. Exhaled nitric oxide levels in school children in relation to IgE sensitisation and window pane condensation. Respir Med 2005;99: 1015-21. https://doi.org/10.1016/j.rmed.2005.02.003
  22. Ihre E, Gyllfors P, Gustafsson LE, Kumlin M, Dahlen B. Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge. Eur Respir J 2006;27:1152-9. https://doi.org/10.1183/09031936.06.00142905
  23. Yao TC, Ou LS, Lee WI, Yeh KW, Chen LC, Huang JL, et al. Exhaled nitric oxide discriminates children with and without allergic sensitization in a population-based study. Clin Exp Allergy 2011; 41:556-64. https://doi.org/10.1111/j.1365-2222.2010.03687.x
  24. Sordillo JE, Webb T, Kwan D, Kamel J, Hoffman E, Milton DK, et al. Allergen exposure modifies the relation of sensitization to fraction of exhaled nitric oxide levels in children at risk for allergy and asthma. J Allergy Clin Immunol 2011;127:1165-72.e5. https://doi.org/10.1016/j.jaci.2011.01.066
  25. Scott M, Raza A, Karmaus W, Mitchell F, Grundy J, Kurukulaaratchy RJ, et al. Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study. Thorax 2010;65:258-62. https://doi.org/10.1136/thx.2009.125443
  26. Alving K, Malinovschi A. Basic aspects of exhaled nitric oxide: exhaled biomarkers. Eur Respir Monogr 2010;49:1-31.
  27. Vints AM, Oostveen E, Eeckhaut G, Smolders M, De Backer WA. Time-dependent effect of nitrate-rich meals on exhaled nitric oxide in healthy subjects. Chest 2005;128:2465-70. https://doi.org/10.1378/chest.128.4.2465
  28. American Thoracic Society; European Respiratory Society. 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;171:912-30. https://doi.org/10.1164/rccm.200406-710ST
  29. Dales R, Wheeler A, Mahmud M, Frescura AM, Smith-Doiron M, Nethery E, et al. The influence of living near roadways on spirometry and exhaled nitric oxide in elementary schoolchildren. Environ Health Perspect 2008;116:1423-7. https://doi.org/10.1289/ehp.10943
  30. Nickmilder M, de Burbure C, Carbonnelle S, Dumont X, Bernard A, Derouane A. Increase of exhaled nitric oxide in children exposed to low levels of ambient ozone. J Toxicol Environ Health A 2007; 70:270-4. https://doi.org/10.1080/15287390600884834
  31. Sanders SP, Proud D, Permutt S, Siekierski ES, Yachechko R, Liu MC. Role of nasal nitric oxide in the resolution of experimental rhinovirus infection. J Allergy Clin Immunol 2004;113:697-702. https://doi.org/10.1016/j.jaci.2004.01.755
  32. Leung TF, To MY, Yeung AC, Wong YS, Wong GW, Chan PK. Multiplex molecular detection of respiratory pathogens in children with asthma exacerbation. Chest 2010;137:348-54. https://doi.org/10.1378/chest.09-1250
  33. Barnes PJ. Role of GATA-3 in allergic diseases. Curr Mol Med 2008; 8:330-4. https://doi.org/10.2174/156652408785160952
  34. Heller NM, Matsukura S, Georas SN, Boothby MR, Stellato C, Schleimer RP. Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells. Clin Exp Allergy 2004;34:1690-700. https://doi.org/10.1111/j.1365-2222.2004.02091.x
  35. Bisgaard H, Loland L, Oj JA. NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast. Am J Respir Crit Care Med 1999;160:1227-31. https://doi.org/10.1164/ajrccm.160.4.9903004
  36. Lim S, Tomita K, Caramori G, Jatakanon A, Oliver B, Keller A, et al. Low-dose theophylline reduces eosinophilic inflammation but not exhaled nitric oxide in mild asthma. Am J Respir Crit Care Med 2001;164:273-6. https://doi.org/10.1164/ajrccm.164.2.2006043
  37. Carra S, Gagliardi L, Zanconato S, Scollo M, Azzolin N, Zacchello F, et al. Budesonide but not nedocromil sodium reduces exhaled nitric oxide levels in asthmatic children. Respir Med 2001;95:734-9. https://doi.org/10.1053/rmed.2001.1130
  38. Buchvald F, Bisgaard H. Comparisons of the complementary effect on exhaled nitric oxide of salmeterol vs montelukast in asthmatic children taking regular inhaled budesonide. Ann Allergy Asthma Immunol 2003;91:309-13. https://doi.org/10.1016/S1081-1206(10)63536-3
  39. Malmberg LP, Petays T, Haahtela T, Laatikainen T, Jousilahti P, Vartiainen E, et al. Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values. Pediatr Pulmonol 2006;41:635-42. https://doi.org/10.1002/ppul.20417
  40. Menzies D, Nair A, Lipworth BJ. Portable exhaled nitric oxide measurement: Comparison with the "gold standard" technique. Chest 2007;131:410-4. https://doi.org/10.1378/chest.06-1335
  41. Silkoff PE, McClean PA, Slutsky AS, Furlott HG, Hoffstein E, Wakita S, 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;155:260-7. https://doi.org/10.1164/ajrccm.155.1.9001322
  42. Buchvald F, Bisgaard H. FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yr. Am J Respir Crit Care Med 2001;163(3 Pt 1):699-704. https://doi.org/10.1164/ajrccm.163.3.2004233
  43. Dupont LJ, Rochette F, Demedts MG, Verleden GM. Exhaled nitric oxide correlates with airway hyperresponsiveness in steroid-naive patients with mild asthma. Am J Respir Crit Care Med 1998;157(3 Pt 1):894-8. https://doi.org/10.1164/ajrccm.157.3.9709064
  44. Smith AD, Cowan JO, Filsell S, McLachlan C, Monti-Sheehan G, Jackson P, et al. Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests. Am J Respir Crit Care Med 2004;169:473-8. https://doi.org/10.1164/rccm.200310-1376OC
  45. Deykin A, Massaro AF, Drazen JM, Israel E. Exhaled nitric oxide as a diagnostic test for asthma: online versus offline techniques and effect of flow rate. Am J Respir Crit Care Med 2002;165:1597-601. https://doi.org/10.1164/rccm.2201081
  46. Malmberg LP, Pelkonen AS, Haahtela T, Turpeinen M. Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma. Thorax 2003;58:494-9. https://doi.org/10.1136/thorax.58.6.494
  47. Henriksen AH, Lingaas-Holmen T, Sue-Chu M, Bjermer L. Combined use of exhaled nitric oxide and airway hyperresponsiveness in characterizing asthma in a large population survey. Eur Respir J 2000;15:849-55. https://doi.org/10.1034/j.1399-3003.2000.15e07.x
  48. 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. https://doi.org/10.1164/ajrccm.159.1.9804134
  49. Baraldi E, Azzolin NM, Cracco A, Zacchello F. Reference values of exhaled nitric oxide for healthy children 6-15 years old. Pediatr Pulmonol 1999;27:54-8.
  50. Buchvald F, Baraldi E, Carraro S, Gaston B, De Jongste J, Pijnenburg MW, et al. Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years. J Allergy Clin Immunol 2005;115:1130-6. https://doi.org/10.1016/j.jaci.2005.03.020
  51. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011;184:602-15. https://doi.org/10.1164/rccm.9120-11ST
  52. Kharitonov SA, Gonio F, Kelly C, Meah S, Barnes PJ. Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Eur Respir J 2003;21:433-8. https://doi.org/10.1183/09031936.03.00066903a
  53. Berlyne GS, Parameswaran K, Kamada D, Efthimiadis A, Hargreave FE. A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation. J Allergy Clin Immunol 2000; 106:638-44. https://doi.org/10.1067/mai.2000.109622
  54. Warke TJ, Fitch PS, Brown V, Taylor R, Lyons JD, Ennis M, et al. Exhaled nitric oxide correlates with airway eosinophils in childhood asthma. Thorax 2002;57:383-7. https://doi.org/10.1136/thorax.57.5.383
  55. Zacharasiewicz A, Wilson N, Lex C, Erin EM, Li AM, Hansel T, et al. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med 2005;171: 1077-82. https://doi.org/10.1164/rccm.200409-1242OC
  56. Pijnenburg MW, Hofhuis W, Hop WC, De Jongste JC. Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission. Thorax 2005;60:215-8. https://doi.org/10.1136/thx.2004.023374
  57. Silkoff PE, McClean P, Spino M, Erlich L, Slutsky AS, Zamel N. Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients. Chest 2001;119:1322-8. https://doi.org/10.1378/chest.119.5.1322
  58. Yoon JY, Woo SI, Kim H, Sun YH, Hahn YS. Fractional exhaled nitric oxide and forced expiratory flow between 25% and 75% of vital capacity in children with controlled asthma. Korean J Pediatr 2012;55:330-6. https://doi.org/10.3345/kjp.2012.55.9.330
  59. Szefler SJ, Mitchell H, Sorkness CA, Gergen PJ, O'Connor GT, Morgan WJ, et al. 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 2008;372:1065-72. https://doi.org/10.1016/S0140-6736(08)61448-8
  60. Leuppi JD, Salome CM, Jenkins CR, Anderson SD, Xuan W, Marks GB, et al. Predictive markers of asthma exacerbation during stepwise dose reduction of inhaled corticosteroids. Am J Respir Crit Care Med 2001;163:406-12. https://doi.org/10.1164/ajrccm.163.2.9912091
  61. Deykin A, Lazarus SC, Fahy JV, Wechsler ME, Boushey HA, Chinchilli VM, et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol 2005;115:720-7. https://doi.org/10.1016/j.jaci.2004.12.1129
  62. Jones SL, Kittelson J, Cowan JO, Flannery EM, Hancox RJ, McLachlan CR, et al. The predictive value of exhaled nitric oxide measurements in assessing changes in asthma control. Am J Respir Crit Care Med 2001;164:738-43. https://doi.org/10.1164/ajrccm.164.5.2012125
  63. Scichilone N, Battaglia S, Olivieri D, Bellia V. The role of small airways in monitoring the response to asthma treatment: what is beyond FEV1? Allergy 2009;64:1563-9. https://doi.org/10.1111/j.1398-9995.2009.02139.x
  64. Pijnenburg MW, De Jongste JC. Exhaled nitric oxide in childhood asthma: a review. Clin Exp Allergy 2008;38:246-59.

피인용 문헌

  1. Association of wheezing phenotypes with fractional exhaled nitric oxide in children vol.57, pp.5, 2013, https://doi.org/10.3345/kjp.2014.57.5.211
  2. Comparison between exhaled nitric oxide and bronchial challenge with methacholine or adenosine-5'-monophosphate in the diagnosis of childhood asthma vol.4, pp.2, 2016, https://doi.org/10.4168/aard.2016.4.2.100
  3. Evaluation of Fractional Exhaled Nitric Oxide in Pediatric Asthma and Allergic Rhinitis vol.8, pp.1, 2013, https://doi.org/10.3390/children8010003
  4. Determining the Best Tool Comparable with Global Initiative for Asthma Criteria for Assessing Pediatric Asthma Control vol.34, pp.3, 2013, https://doi.org/10.1089/ped.2020.1334