Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Relationship between exhaled nitric oxide and pulmonary function test in children with asthma

소아 천식에서 호기산화질소와 폐기능 검사의 관계

  • Ko, Han-Seok (Department of Pediatrics, College of Medicine, Kyung Hee University) ;
  • Chung, Sung-Hoon (Department of Pediatrics, College of Medicine, Kyung Hee University) ;
  • Choi, Yong-Sung (Department of Pediatrics, College of Medicine, Kyung Hee University) ;
  • Choi, Sun-Hee (Department of Pediatrics, East-West Neo-medical Center, Kyung Hee University) ;
  • Rha, Yeong-Ho (Department of Pediatrics, College of Medicine, Kyung Hee University)
  • 고한석 (경희대학교 의과대학 소아과학교실) ;
  • 정성훈 (경희대학교 의과대학 소아과학교실) ;
  • 최용성 (경희대학교 의과대학 소아과학교실) ;
  • 최선희 (경희대학교 동서신의학병원 소아청소년과) ;
  • 나영호 (경희대학교 의과대학 소아과학교실)
  • Received : 2007.10.10
  • Accepted : 2007.11.22
  • Published : 2008.02.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : Asthma is characterized by reversible airway obstruction and bronchial hyperresponsiveness result from airway inflammation. Fraction of nitric oxide in expired air (FeNO) has recently been investigated as a noninvasive measure of airway inflammation. FeNO has been reported to correlate with induced sputum eosinophilia and methacholine challenge test that it is represent severity of asthma. The purpose of this study was to analyze the relationship of FeNO with pulmonary function tests in patients with intermittent asthma. Methods : Eighty children included in this study were diagnosed as asthma from April through August, 2005 in Department of Pediatrics, College of Medicine, Kyunghee University. They aged from 4 to 15 years who were able to conduct spirometry and FeNO monitoring. They did not have upper respiratory tract infection and did not use an asthma controller which contain corticosteroids within 4 weeks. Pulmonary function test was done and FeNO was measured with online tidal breathing method using a chemiluminescence NO analyzer (CLD 88 sp, Eco Medics, Duernten, Switzerland). The correlations between pulmonary function test and FeNO were analyzed using Spearman correlation coefficient method. Results : The mean of FeNO of subject was 16.88 parts per billion (ppb). The mean of forced expiratory volume in 1 second ($FEV_1$) was $0.890{\pm}0.455L$ and forced vital capacity (FVC) was $1.071{\pm}0.630L$. The mean of predicted $FEV_1%$ ($FEV_1%pred$) was $98.39{\pm}34.27%$ and $FEV_1/FVC$ was $88.53{\pm}19.49$. FeNO was significantly correlate with $FEV_1$ (r=0.345, P<0.01) and FVC (r=0.244, P<0.05). FeNO did not correlate with $FEV_1%pred$ or $FEV_1/FVC$. Conclusion : The measurement of FeNO could be a useful marker in the management of childhood asthma and it is evolving to provide a complementary role alongside existing pulmonary function test. We propose that measuring technique and establishment of normal reference range are important area for future research.

목 적 : 천식의 특징은 기도염증의 결과인 가역적인 기류제한과 기관지과반응성이다. 최근에 호기산화질소(exhaled nitric oxide; FeNO)이 비침습적으로 기도염증을 알 수 있는 지표로서 이에 대한 많은 연구가 있었다. 또한 FeNO는 천식의 중증도를 나타내는 데 이용되는 객담내 호산구수나 메타콜린 기도유발시험과 관련이 있다고 보고되었다. 이에 저자들은 간헐성 천식환자에서 폐기능검사와 호기산화질소와의 관계를 알아보고자 본 연구를 시행하였다. 방 법 : 2005년 4월부터 8월까지 경희의대부속병원 소아과에서 천식으로 진단되어 폐기능검사와 호기산화질소 측정이 가능하였던 5세부터 15세의 80명의 환자를 대상으로 하였다. 최근 4주내에 상기도 감염이 없었고, 부신피질스테로이드를 포함한 조절약물을 사용하지 않은 경우에 연구 대상에 포함하였다. 폐기능검사는 Microspirometer를 사용하였다. Eco Medics사의 Chemiluminescence NO-analyzer(CLD 88 sp, Duernten, Switzerland)를 사용하여 FeNO를 측정하였으며 폐기능 검사와 FeNO와의 상관관계 분석은 Spearman correlation coefficient를 사용 하였다. 결 과 : 1초간 강제호기량(forced expiratory volume in 1 second, $FEV_1$)의 평균은 $0.890{\pm}0.455L$이었으며 강제폐활량 (forced vital capacity; FVC)의 평균은 $1.071{\pm}0.630L$이었다. $FEV_1%pred$의 평균은 $98.39{\pm}34.27%$였으며 $FEV_1/FVC$의 평균은 $88.53{\pm}19.49$이었다. FeNO의 평균치는 16.88 parts per billion(ppb)이었다. FeNO 측정치는 $FEV_1$(r=0.345, P<0.01), FVC(r=0.244, P<0.05)와 유의한 상관관계를 보였으나 $FEV_1%pred$와 $FEV_1/FVC$는 FeNO와 유의한 상관관계를 나타내지 않았다. 결 론 : FeNO의 측정은 폐기능 검사와 함께 소아천식 환자의 관리에 유용하게 사용될 수 있는 신빙성있는 검사로 생각되며 측정 방법이나 측정치의 참고치 설정에 앞으로 많은 연구가 필요할 것으로 생각된다.

Keywords

References

  1. Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, Silkoff PE, Murphy J, et al. Relations between exhaled nitric oxide and measures of disease activity among children with mildto-moderate asthma. J Pediatr 2003;142:469-75 https://doi.org/10.1067/mpd.2003.187
  2. Djukanovic R, Roche WR, Wilson JW, Beasley CR, Twentyman OP, Howarth RH, et al. Mucosal inflammation in asthma. Am Rev Respir Dis 1990;142:434-57 https://doi.org/10.1164/ajrccm/142.2.434
  3. Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG. Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide. J Allergy Clin Immunol 2006;118:1218-25 https://doi.org/10.1016/j.jaci.2006.08.019
  4. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniak RM, Chinchilli VM, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 2002;109:410-8 https://doi.org/10.1067/mai.2002.122635
  5. Boskababy MH, Fasihfar M, Maemoori GA. Correlation between symptom score, wheeze, reversibility of pulmonary function tests and treatment response in asthma. Iran J Allergy Asthma Immunol 2003;2:61-7
  6. de Blic J, Tillie-Leblond I, Tonnel A, Jaubert F, Scheinmann P, Gosset P. Difficult asthma in children: an analysis of airway inflammation. J Allergy Clin Immunol 2004;113:94-100
  7. Payne DN, Adcock IM, Wilson NM, Oates T, Scallan M, Bush A. Relationship between exhaled nitric oxide and mucosal eosinophillic inflammation in children with difficult asthma, after treatment with oral prednisolone. Am J Respir Crit Care Med 2001;164:1376-81 https://doi.org/10.1164/ajrccm.164.8.2101145
  8. Gibson PG, Henry RL, Thomas P. Noninvasive assessment of airway inflammation in children: induced sputum, exhaled nitric oxide, and breath condensate. Eur Respir J 2000;16:1008-15
  9. Nightingale JA, Rogers DF, Barnes PJ. Effect of repeated sputum induction on cell counts in normal volunteers. Thorax 1998;53:87-90 https://doi.org/10.1136/thx.53.2.87
  10. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium derived relaxing factor. Nature 1987;327:524-6 https://doi.org/10.1038/327524a0
  11. Gustafsson LE, Leone AM, Persson MG, Wiklund NP, Moncada S. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochem Biophys Res Commun 1991;181:852-7 https://doi.org/10.1016/0006-291X(91)91268-H
  12. Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 1993;6:1368-70
  13. Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, et al; Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. J Allergy Clin Immunol 2003;112:883-92 https://doi.org/10.1016/j.jaci.2003.08.014
  14. Harkins MS, Fiato KL, Iwamoto GK. Exhaled nitric oxide predicts asthma exacerbation. J Asthma 2004;41:471-6 https://doi.org/10.1081/JAS-120033990
  15. 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
  16. Taylor DR. Nitric oxide as a clinical guide for asthma management. J Allergy Clin Immunol 2006;117:259-62 https://doi.org/10.1016/j.jaci.2005.11.010
  17. Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 1998;53:91-5 https://doi.org/10.1136/thx.53.2.91
  18. Mattes J, Storm vans GK, Reining U, Alving K, Ihorst G, Henschen M, et al. NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma. Eur Respir J 1999;13:1391-5
  19. Stirling RG, Kharitonov SA, Campbell D, Robinson DS, Durham SR, Chung KF, et al. Increase in exhaled nitric oxide levels in patients with difficult asthma and correlation with symptoms and disease severity despite treatment with oral and inhaled corticosteroids, asthma and allergy group. Thorax 1998;53:1030-4 https://doi.org/10.1136/thx.53.12.1030
  20. Yates DH, Kharitonov SA, Barnes PJ. Effect of short and long acting inhaled beta 2 agonists on exhaled nitric oxide in asthmatic patients. Eur Respir J 1997;10:1483-8 https://doi.org/10.1183/09031936.97.10071483
  21. Sistek D, Tschopp JM, Schindler C, Brutsche M, Ackermann-Liebrich U, Perruchoud AP, et al. Clinical diagnosis of current asthma: predictive value of respiratory symptoms in the SAPALDIA study. Eur Respir J 2001;17:214-9 https://doi.org/10.1183/09031936.01.17202140
  22. American Thoracic society. Recommendation for standardized procedure for the on-line and off-line measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. Am J Respir Crit Care Med 1999;160:2104-17 https://doi.org/10.1164/ajrccm.160.6.ats8-99
  23. 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
  24. Gibson PG, Simpson JL, Chalmers AC, Toneguzzi RC, Wark PA, Wilson AJ, et al. Airway eosinophilia is associated with wheeze but is uncommon in children with persistent cough and frequent chest colds. Am J Respir Crit Care Med 2001;164:977-81 https://doi.org/10.1164/ajrccm.164.6.9910053
  25. Stevenson EC, Turner G, Heaney LG, Schock BC, Taylor R, Gallagher T, et al. Bronchoalveolar lavage findings suggest two different forms of childhood asthma. Clin Exp Allergy 1997;27:1027-35 https://doi.org/10.1111/j.1365-2222.1997.tb01254.x
  26. Saito J, Inoue K, Sugawara A, Yoshikawa M, Watanabe K, Ishida T, et al. Exhaled nitric oxide as a marker of airway inflammation for an epidemiologic study in schoolchildren. J Allergy Clin Immunol 2004;114:512-6 https://doi.org/10.1016/j.jaci.2004.05.033
  27. Tsujino I, Nishimura M, Kamachi A, Makita H, Munakata M, Miyamoto K, et al. Exhaled nitric oxide-is it really a good marker of airway inflammation in bronchial asthma? Respiration 2000;67:645-51 https://doi.org/10.1159/000056294
  28. Langley SJ, Goldthorpe S, Custovic A, Woodcock A. Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large group of asthmatic patients. Ann Allergy Asthma Immunol 2003;91:398-404 https://doi.org/10.1016/S1081-1206(10)61688-2
  29. Spergel JM, Fogg MI, Bokszczanin-Knosala A. Correlation of exhaled nitric oxide, spirometry and asthma symptoms. J Asthma 2005;42:879-83 https://doi.org/10.1080/02770900500371344
  30. del Giudice MM, Brunese FP, Piacentini GL, Pedulla M, Capristo C, Decimo F, et al. Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naive atopic asthmatic children. J Asthma 2004;41:759-65 https://doi.org/10.1081/JAS-200027862
  31. Colon-Semidey AJ, Marshik P, Crowley M, Katz R, Kelly HW. Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma. Pediatr Pulmonol 2000;30:385-92 https://doi.org/10.1002/1099-0496(200011)30:5<385::AID-PPUL4>3.0.CO;2-#
  32. Flanklin 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
  33. Beasley R, Roche WR, Roberts JA, Holgate ST. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis 1989;139:806-17 https://doi.org/10.1164/ajrccm/139.3.806
  34. Laitenen LA, Laitenen A, Haahtela T. Airway mucosal inflammation even in patients with newly diagnosed asthma. Am Rev Respir Dis 1993;147:697-704 https://doi.org/10.1164/ajrccm/147.3.697
  35. Ulrik CS, Backer V. Nonreversible airflow obstruction in life-long nonsmokers with moderate to severe asthma. Eur Respir J 1999;14:892-6 https://doi.org/10.1034/j.1399-3003.1999.14d27.x
  36. 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
  37. Redington AE, Meng QH, Springall DR, Evans TJ, Creminon C, Maclouf J, et al. Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment. Thorax 2001;56:351-7 https://doi.org/10.1136/thorax.56.5.351
  38. Kharitonov SA, Yetes D, Barnes PJ. Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. Eur Respir J 1995;8:295-7 https://doi.org/10.1183/09031936.95.08020295
  39. Kharitonov S, Yates DH, Chung KF, Barnes PJ. Changes in the dose of inhaled steroid affect exhaled nitric oxide levels in asthmatic patients. Eur Respir J 1996;9:196-201 https://doi.org/10.1183/09031936.96.09020196
  40. van Rensen E, Straathof K, Veselic-Charvat M, Zwinderman A, Bel E, Sterk P. Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma. Thorax 2002;57:586-9 https://doi.org/10.1136/thorax.57.7.586

Cited by

  1. Spirometric Pulmonary Function Test in Preschool Children vol.53, pp.5, 2008, https://doi.org/10.5124/jkma.2010.53.5.417
  2. Comparison of Exhaled Nitric Oxide Analyzers in Childhood Asthma vol.21, pp.1, 2011, https://doi.org/10.7581/pard.2011.21.1.17
  3. Relevance of Exhaled Nitric Oxide Levels to Asthma Control Test Scores and Spirometry Values in Children with Atopic Asthma vol.21, pp.1, 2008, https://doi.org/10.7581/pard.2011.21.1.24
  4. Relationships between Fraction of Nitric Oxide, Airway Hyperresponsiveness, Blood Eoshinophil Counts and Serum Eosinophil Cationic Protein in Asthmatic Children vol.22, pp.3, 2008, https://doi.org/10.7581/pard.2012.22.3.282
  5. Relationship between exhaled nitric oxide and small-airway dysfunction in children with asthma using spirometry and the impulse oscillometry system vol.3, pp.4, 2015, https://doi.org/10.4168/aard.2015.3.4.267
  6. Relationships between fractional exhaled nitric oxide levels and FEF25%-75% in children with asthma vol.4, pp.1, 2008, https://doi.org/10.4168/aard.2016.4.1.14
  7. Relationship between Bronchodilator Response, Airway Hyperresponsiveness, and Exhaled Nitric Oxide Levels in Patients with Suspected Bronchial Asthma vol.92, pp.5, 2008, https://doi.org/10.3904/kjm.2017.92.5.458