Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지

6-8세 천식 환아에서 △FVC(메타콜린 PC20에서의 강제폐활량의 감소율)와 혈청 호산구 양이온 단백의 관계

Relationship between △FVC(% fall in FVC at the PC20 Dose of Methacholine) and Serum Eosinophil Cationic Protein(ECP) in 6-8 Year Old Children with Asthma

  • 서동인 (서울대학교 의과대학 소아과학교실) ;
  • 유진호 (동국대학교 의과대학 소아과학교실) ;
  • 유영 (고려대학교 의과대학 소아과학교실) ;
  • 김도균 (서울대학교 의과대학 소아과학교실) ;
  • 강희 (고려대학교 의과대학 소아과학교실) ;
  • 고영률 (서울대학교 의과대학 소아과학교실)
  • Suh, Dong In (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Yu, Jinho (Department of Pediatrics, College of Medicine, Dongguk University) ;
  • Yoo Young (Department of Pediatrics, College of Medicine, Korea University) ;
  • Kim, Do Kyun (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Kang, Hee (Department of Pediatrics, College of Medicine, Korea University) ;
  • Koh, Young Yull (Department of Pediatrics, College of Medicine, Seoul National University)
  • 투고 : 2005.05.20
  • 심사 : 2005.08.05
  • 발행 : 2005.10.15
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초록

목 적 : 기관지 과반응성은 천식의 주된 특징이다. 또한 천식 환자에서 혈청 호산구 양이온 단백의 농도가 증가되어 있음이 잘 알려져 있다. 혈청 호산구 양이온 단백의 농도와, 기관지 과반응성의 대표적 지표인 메타콜린 $PC_{20}$과의 관계에 대해서 결과가 다소 상반되는 여러 보고가 있어왔다. 본 연구의 목적은 혈청 호산구 양이온 단백의 농도와 기관지 과반응성의 또다른 지표로서 최대 기도 반응을 반영하는 ${\Delta}FVC$와의 상관관계를 살펴보는 것이다. 방 법 : 6-8세 천식 환아 109명을 대상으로 폐기능 검사 및 메타콜린 기관지 흡입 유발 시험을 시행하였다. 개개의 환자로부터 메타콜린 용량 반응 곡선에서 ${\Delta}FVC$ 및 $PC_{20}$을 계산하였다. 이들의 혈액 내 총 호산구 수 및 혈청 ECP 농도를 측정하여 ${\Delta}FVC$ 및 $PC_{20}$과 상관관계를 분석하였다. 결 과 : 혈청 ECP는 ${\Delta}FVC$(r=0.217, P=0.023) 및 $PC_{20}$(r=-0.208, P=0.030)과 상관관계를 나타내었다. 반면 혈액 내 총 호산구 수는 ${\Delta}FVC$(r=0.085, P=0.378) 및 $PC_{20}$(r=-0.148, P=0.125)과 상관관계를 보이지 않았다. ${\Delta}FVC$는 $PC_{20}$과도 상관관계를 보이지 않았다(r=-0.079, P=0.417). 결 론 : 6-8세 천식 환아에서 기관지 과반응성이, 민감성 증가뿐만 아니라 최대반응의 증가라는 측면에서도 호산구성 염증의 활성화와 관련이 있다.

Purpose : Bronchial hyperresponsiveness(BHR) is considered a hallmark of asthma. Increased levels of eosinophil cationic protein(ECP) have been identified in serum of asthma patients. Several studies have examined the relationship between serum ECP and bronchial responsiveness, expressed as methacholine $PC_{20}$ in asthmatic patients, with conflicting results. The aims of this study were to examine the relationship between serum ECP and ${\Delta}FVC$, another index of bronchial responsiveness, which reflects increased maximal airway response. Methods : Six to 8-year-old children with asthma(n=109) underwent methacholine bronchoprovocation testing. The $PC_{20}$ dose of methacholine and ${\Delta}FVC$ were calculated for each individual from the methacholine dose response curves. Serum ECP levels and blood total eosinophil counts were also measured. Results : Serum ECP correlated with ${\Delta}FVC$(r=0.217, P=0.023), as well as $PC_{20}$(r=-0.208, P=0.030). However, blood eosinophil counts failed to show any correlations with ${\Delta}FVC$(r=0.085, P=0.378) or $PC_{20}$(r=-0.148, P=0.125). ${\Delta}FVC$ did not correlate with $PC_{20}$(r=-0.079, P=0.417). Conclusion : Blood eosinophil activation is associated with both components of BHR including increased sensitivity and increased maximal response in 6-8 year old children with asthma.

키워드

참고문헌

  1. Sheffer AL. Guidelines for the diagnosis and management of asthma. I. Definition and diagnosis. J Allergy Clin Immunol 1991;88:427-38 https://doi.org/10.1016/0091-6749(91)92137-P
  2. Woolcock CJ, Salome CM, Yan K. The shape of the dose-response curve to histamine in asthmatic and normal subjects. Am Rev Respir Dis 1984;130:71-5
  3. Sterk PH, Bel EH. Bronchial hyperresponsiveness : the need for a distinction between hypersensitivity and excessive narrowing. Eur Respir J 1989;2:267-74
  4. Cockcroft DW, Killian DN, Mellon JJ, Hargreave FE. Bronchial reactivity to inhaled histamine : a method and clinical survey. Clin Allergy 1977;7:235-43 https://doi.org/10.1111/j.1365-2222.1977.tb01448.x
  5. Josephs LK, Gregg I, Mullee MA, Holgate ST. Nonspecific bronchial reactivity and its relationship to the clinical expression of asthma. A longitudinal study. Am Rev Respir Dis 1989;140:350-7 https://doi.org/10.1164/ajrccm/140.2.350
  6. Gibbons WJ, Sharma A, Lougheed D, Macklem PT. Detection of excessive bronchoconstriction in asthma. Am J Respir Crit Care Med 1996;153:582-9 https://doi.org/10.1164/ajrccm.153.2.8564102
  7. Abisheganaden J, Chan CC, Chee CB, Wang YT. Methacholine-induced fall in forced vital capacity as a marker of asthma severity. Respir Med 1999;93:277-82 https://doi.org/10.1016/S0954-6111(99)90025-2
  8. Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033-9 https://doi.org/10.1056/NEJM199010113231505
  9. Ulrik CS. Peripheral eosnophil counts as a marker of disease activity in intrinsic and extrinsic asthma. Clin Exp Allergy 1995;25:820-7 https://doi.org/10.1111/j.1365-2222.1995.tb00024.x
  10. Venge P, Bystrom J, Carlson M, Hakansson L, Karawacjzyk M, Peterson C, et al. Eosinophil cationic protein(ECP) : molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease. Clin Exp Allergy 1999;29:1172-86. https://doi.org/10.1046/j.1365-2222.1999.00542.x
  11. Niimi A, Amitani R, Suzuki K, Tanaka E, Murayama T, Kuze F. Serum eosinophil cationic protein as a marker of eosinophilic inflammation in asthma. Clin Exp allergy 1998;28:233-40 https://doi.org/10.1046/j.1365-2222.1998.00217.x
  12. Prehn A, Seger RA, Faber J, Torresani T, Molinari L, Gerber A, et al. The relationship of serum-eosinophil cationic protein and eosinophil count to disease activity in children with bronchial asthma. Pediatr Allergy Immunol 1998;9:197-203 https://doi.org/10.1111/j.1399-3038.1998.tb00373.x
  13. Venge P. Monitoring of asthma inflammation by serum measurements of eosinophil cationic protein(ECP). A new clinical approach to asthma management. Respir Med 1995;89:1-2 https://doi.org/10.1016/0954-6111(95)90062-4
  14. Pizzichini E, Pizzichini MM, Efthimiadis A, Dolovich J, Hargreave FE. Measuring airway inflammation in asthma : eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood. J Allergy Clin Immunol 1997;99:539-44 https://doi.org/10.1016/S0091-6749(97)70082-4
  15. Fujimoto K, Kubo K, Matsuzawa Y, Sekiguchi M. Eosinophil cationic protein levels in induced sputum correlate with the severity of bronchial asthma. Chest 1997;112:1241-7 https://doi.org/10.1378/chest.112.5.1241
  16. Tarodo de la Fuente P, Romagnoli M, Carlsson L, Godard P, Bousquet J, Chanez P. Eosinophilic inflammation assessed by induced sputum in corticosteroid-dependent asthma. Respir Med 1999;93:183-9 https://doi.org/10.1016/S0954-6111(99)90006-9
  17. Ferguson AC, Whitelaw M, Brown H. Correlation of bronchial eosinophil and mast cell activation with bronchial hyperresponsiveness in children with asthma. J Allergy Clin Immunol 1992;90:609-13 https://doi.org/10.1016/0091-6749(92)90133-M
  18. Gruber W, Eber E, Pfleger A, Modl M, Meister I, Weinhandl E, et al. Serum eosinophil cationic protein and bronchial responsiveness in pediatric and adolescent asthma patients. Chest 1999;116:301-5 https://doi.org/10.1378/chest.116.2.301
  19. Rao R, Frederick JM, Enander I, Gregson RK, Warner JA, Warner JO. Airway function correlates with circulating eosinophil, but not mast cell, markers of inflammation in childhood asthma. Clin Exp Allergy 1996;26:789-93 https://doi.org/10.1111/j.1365-2222.1996.tb00609.x
  20. Piacentini GL, Bodini A, Costella S, Suzuki Y, Zerman L, Peterson CG, et al. Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children. Eur Respir J 2000;15:839-43 https://doi.org/10.1034/j.1399-3003.2000.15e05.x
  21. Alvarez MJ, Olaguibel JM, Garcia BE, Rodriquez A, Tabar AI, Urbiola E. Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing. Allergy 2000;55:355-62. https://doi.org/10.1034/j.1398-9995.2000.00312.x
  22. Yoo Y, Koh YY, Kang H, Yu J, Nah KM, Kim CK. Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma, and their relationships to airway hypersensitivity or maximal airway response to methacholine. Allergy 2004;59:1055-62 https://doi.org/10.1111/j.1398-9995.2004.00655.x
  23. Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 2000;161:309-29 https://doi.org/10.1164/ajrccm.161.1.ats11-99
  24. Yoon KA, Lim HS, Kim H, Koh YY. Normal predicted values of pulmonary function test in Korean school-aged children. J Korean Pediatr Soc 1993;36:25-37
  25. Chai H, Farr RS, Froehlich LA, Mathison DA, McLean JA, Rosenthal RR, et al. Standardization of bronchial inhalation challenge procedure. J Allergy Clin Immunol 1975;56:323-7 https://doi.org/10.1016/0091-6749(75)90107-4
  26. Venge P. Serum measurements of eosinophil cationic protein(ECP) in bronchial asthma. Clin Exp Allergy 1993;23Suppl 2:3-7
  27. Backman A. Skin tests for epidemiologic studies. Allergy 1994;49:493-4 https://doi.org/10.1111/j.1398-9995.1994.tb01118.x
  28. Brown WG, Halonen MJ, Kaltenborn WT, Barbee RA. The relationship of respiratory allergy, skin test reactivity, and serum IgE in a community population sample. J Allergy Clin Immunol 1979;63:328-35 https://doi.org/10.1016/0091-6749(79)90127-1
  29. Haley KJ, Drazen JM. Inflammation and airway function in asthma : what you see is not necessarily what you get. Am J Respir Crit Care Med 1998;157:1-3 https://doi.org/10.1164/ajrccm.157.1.ed-19
  30. Alvarez MJ, Castillo R, Rey A, Ortega N, Blanco C, Carrillo T. Sputum eosinophilia and maximal airway narrowing in Dermatophagoides pteronyssinus allergic rhinitis patients : only rhinitis or rhinitis plus mild asthma? Chest 2002;122:1560-65 https://doi.org/10.1378/chest.122.5.1560
  31. Yu J, Yoo Y, Kim DK, Koh YY. The relationship between ${\delta}$FVC%(%fall in FVC at the $PC_{20}$ dose of methacholine) and the maximal response in mild asthmatics. Allergy Asthma Proc. In press 2005
  32. Lacoste JY, Bousquet J, Chanez P, Van Vyve T, Simony-Lafontaine J, Lequeu N, et al. Eosinophilic and neutrophilic inflammation in asthma, chronic bronchitis, and chronic obstructive pulmonary disease. J Allergy Clin Immunol 1993;92:537-48 https://doi.org/10.1016/0091-6749(93)90078-T
  33. Wever AM, Wever-Hess J, Hensgens HE, Hermans J. Serum eosinophil cationic protein(ECP) in chronic asthma. Relationship to spirometry, flow-volume curves, $PC_{20}$, and exacerbations. Respir Med 1994;88:613-21 https://doi.org/10.1016/S0954-6111(05)80010-1
  34. Cuttitta G, Cibella F, Bellia V, Grassi V, Cossi S, Bucchieri S, et al. Changes in FVC during methacholine-induced bronchoconstriction in elderly patients with asthma : bronchial hyperresponsiveness and aging. Chest 2000;119:1685-90 https://doi.org/10.1378/chest.119.6.1685
  35. Macklem PT. Physiology of small airways. Am J Respir Crit Care Med 1998;157(5 Suppl):181S-183S https://doi.org/10.1164/ajrccm.157.5.rsaa-2
  36. Wiggs BR, Bosken C, Pare PD, James A, Hogg JC. A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992;145:1251-8 https://doi.org/10.1164/ajrccm/145.6.1251
  37. Carroll N, Elliot J, Morton A, James A. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993;147:405-10 https://doi.org/10.1164/ajrccm/147.2.405
  38. Hogg JC. Pathology of asthma : postmortem pathology in asthma. J Allergy Clin Immunol 1993;92:1-5 https://doi.org/10.1016/0091-6749(93)90029-F
  39. Macklem PT. A theoretical analysis of the effect of airway smooth muscle load on airway narrowing. Am J Respir Crit Care Med 1996;153:83-9 https://doi.org/10.1164/ajrccm.153.1.8542167