만성 기침에서 스테로이드 흡입제의 역할

The Role of Inhaled Corticosteroid in the Management of Chronic Cough

  • 이경훈 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 장승훈 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 이정화 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 엄광석 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 반준우 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 김동규 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 신태림 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 박상면 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 이명구 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 김철홍 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 현인규 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과) ;
  • 정기석 (한림대학교 의과대학 내과학교실, 한림대학교성심병원 호흡기 알레르기내과)
  • Lee, Kyung-Hun (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Jang, Seung Hun (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Lee, Jung-Hwa (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Eom, Kwang-Seok (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Bahn, Joon-Woo (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Kim, Dong-Gyu (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Shin, Tae Rim (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Park, Sang Myon (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Lee, Myung-Gu (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Kim, Chul-Hong (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Hyun, In-Gyu (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine) ;
  • Jung, Ki-Suck (Division of Pulmonary, Allergy and Critical Care Medicine of Hallym University Medical Center, Hallym University College of Medicine)
  • 투고 : 2005.08.31
  • 심사 : 2006.01.23
  • 발행 : 2006.02.28

초록

연구배경 : 만성 기침은 정밀 검사를 추가하여도 진단율을 향상시키는데 한계가 있고, 확진은 특이적 치료에 반응할 때에만 가능하다. 스테로이드는 비특이적 항염증 작용을 가지므로 만성 기침에 효과적일 수 있다. 본 연구에서는 원인 진단에 대한 진료 한계를 극복하기 위한 방법으로서, 만성 기침에 대한 흡입 스테로이드의 반응률을 알아보기 위하여 시행되었다. 방 법 : 3주 이상의 만성 기침 환자를 대상으로 처음 내원하였을 때 객담 호산구, 메타콜린 기관지 유발검사, 부비동 방사선촬영 등의 기본적인 객관적 검사를 시행하고, 동시에 budesonide turbuhaler $800{\mu}g/day$를 10일간 투여하고 추적 방문토록 하였다. 추적 방문일에 환자 증상의 개선도에 따라 흡입 스테로이드 반응군과 불응군으로 분류하였고 검사의 진단 성적을 조사하였으며, 각 진단에 따른 스테로이드 반응률을 알아보았다. 결 과 : 총 69명의 만성 기침 환자가 최종 분석되었고, 흡입 스테로이드의 투여로 증상의 호전이 있었던 경우는 79.7%였다. 진단된 질환에 따른 흡입 스테로이드의 반응률은 차이가 없었다. 투여 기간 동안 부작용은 거의 관찰되지 않아서 우수한 내약성을 보였다. 결 론 : 만성 기침 환자를 진료할 때 기본 검사를 시행하는 동시에 흡입 스테로이드를 단기간 투여하는 것은 매우 안전하며, 검사의 진단적 한계를 극복하고 초기에 진료 지침을 세우는 방법이 될 수 있다.

Background : Cough may be a consequence of bronchial hyperresponsiveness or inflammation. Empirical treatment is important in this context because it difficult to verify the obvious cause of cough using laboratory tests, Corticosteroid has a nonspecific anti-inflammatory effect, and can be used for cough management. However, its response rate has not yet been fully elucidated. This study investigated the short- term effects of inhaled corticosteroid on chronic cough Methods : Patients with chronic cough with a normal chest radiograph and a pulmonary function test were enrolled. Cases with a prior respiratory infection within 8 weeks, a history of bronchial asthma, objective wheezing on examination, subjective symptoms of gastroesophageal reflux or taking an ACE inhibitor were excluded. On the first visit, a methacholine bronchial provocation test, spontaneous sputum eosinophil count performed twice and a paranasal sinus radiograph were checked, and the patients were treated with budesonide turbuhaler $800{\mu}g/day$ for ten days. The primary outcome measure was a decrease in the cough score after treatment. Results : Sixty nine chronic coughers were finally analyzed. The final diagnoses by the routine tests were as follows: bronchial asthma 13.0%, eosinophilic bronchitis 18.8%, paranasal sinusitis 23.2% and non-diagnostic cases 53.6%. The following responses to the inhaled corticosteroid were observed: definite responders, 76.8%, possible responders, 2.9% and non-responders, 20.3%. The response rate was not affected by the final diagnosis even in the non-diagnostic cases. There were minimal adverse drug related effects during the empirical treatment. Conclusion : Routine objective tests such as methacholine provocation, sputum eosinophil count and simple radiographs were notare not suitable for diagnosing chronic cough Therefore, empirical treatment is important. Short term inhaled corticosteroid is effective and can guide a further treatment plan for chronic cough.

키워드

참고문헌

  1. Irwin RS, Rosen MJ, Braman SS. Cough. A comprehensive review. Arch Intern Med 1977;137:1186-91 https://doi.org/10.1001/archinte.137.9.1186
  2. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis 1981;123:413-7
  3. Irwin RS, Curley FJ, French CL. Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 1990;141:640-7 https://doi.org/10.1164/ajrccm/141.3.640
  4. Brightling CE, Ward R, Goh KL, Wardlaw AJ, Pavord ID. Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med 1999;160:406-10 https://doi.org/10.1164/ajrccm.160.2.9810100
  5. Irwin RS, Madison JM. The diagnosis and treatment of cough. N Engl J Med 2000;343:1715-21 https://doi.org/10.1056/NEJM200012073432308
  6. Mello CJ, Irwin RS, Curley FJ. Predictive values of the character, timing, and complications of chronic cough in diagnosing its cause. Arch Intern Med 1996;156:997-1003 https://doi.org/10.1001/archinte.156.9.997
  7. McGarvey LP, Heaney LG, Lawson JT, Johnston BT, Scally CM, Ennis M, et al. Evaluation and outcome of patients with chronic non-productive cough using a comprehensive diagnostic protocol. Thorax 1998;53:738-43 https://doi.org/10.1136/thx.53.9.738
  8. Jatakanon A, Lalloo UG, Lim S, Chung KF, Barnes PJ. Increased neutrophils and cytokines, TNF-alpha and IL-8, in induced sputum of non-asthmatic patients with chronic dry cough. Thorax 199954:234-7 https://doi.org/10.1136/thx.54.3.234
  9. Lee SY, Cho JY, Shim JJ, Kim HK, Kang KH, Yoo SH, et al. Airway inflammation as an assessment of chronic nonproductive cough. Chest 2001;120:1114-20 https://doi.org/10.1378/chest.120.4.1114
  10. Jeon G, Jang SH, Song HG, Ha JW, Eom KS, Bahn JW, et al. Diagnostic performance of routine objective tests and cost-effective approach for chronic cough. Tuberc Respir Dis 2004;57:535-42 https://doi.org/10.4046/trd.2004.57.6.535
  11. Boulet LP, Milot J, Boutet M, St Georges F, Laviolette M. Airway inflammation in nonasthmatic subjects with chronic cough. Am J Respir Crit Care Med 1994;149:482-9 https://doi.org/10.1164/ajrccm.149.2.8306050
  12. Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave FE. Chronic cough: eosinophilic bronchitis without asthma. Lancet 1989;17:1346-8
  13. Lundgren R, Soderberg M, Horstedt P, Stenling R. Morphological studies of bronchial mucosal biopsies from asthmatics before and after ten years of treatment with inhaled steroids. Eur Respir J 1988;1:883-9
  14. Jeffery PK, Godfrey RW, Adelroth E, Nelson F, Rogers A, Johansson SA. Effects of treatmenton airway inflammation and thickening of basement membrane reticular collagen in asthma. Am Rev Respir Dis 1992;145:890-9 https://doi.org/10.1164/ajrccm/145.4_Pt_1.890
  15. Heino M, Karjalainen J, Ylikoski J, Laitinen A, Laitinen LA. Bronchial ciliogenesis and oral steroid treatment in patients with asthma. Br J Dis Chest 1988;82:175-8 https://doi.org/10.1016/0007-0971(88)90040-X
  16. Ponsioen BP, Hop WC, Vermue NA, Dekhuijzen PN, Bohnen AM. Efficacy of fluticasone on cough. Eur Respir J 2005;25:147-52 https://doi.org/10.1183/09031936.04.00053604
  17. Barnes TW, Afessa B, Swanson KL, Lim KG. The clinical utility of flexible bronchoscopy in the evaluation of chronic cough. Chest 2004;126:268-72 https://doi.org/10.1378/chest.126.1.268
  18. McGarvey LP, Heaney LG, MacMahon J. A retrospective survey of diagnosis and management of patients presenting with chronic cough to a general chest clinic. Int J Clin Pract. 1998;52:158-61
  19. Tomlinson JE, McMahon AD, Chaudhuri R, Thompson JM. Efficacy of low and high dose inhaled corticosteroid in smokers versus non-smokers with mild asthma. Thorax 2005;60:282-7 https://doi.org/10.1136/thx.2004.033688
  20. Chalmers GW, Macleod KJ, Little SA, Thomson LJ, McSharry CP. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax 2002;57:226-3 https://doi.org/10.1136/thorax.57.3.226
  21. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 200115:1110-2 https://doi.org/10.1096/fj.00-0432fje
  22. Livingston E, Thomson NC, Chalmers GW. Impact of smoking on asthma therapy. Drugs 2005;65:1521-36 https://doi.org/10.2165/00003495-200565110-00005
  23. Dicpinigaitis PV. Cough reflex sensitivity in cigarette smokers. Chest 2003;123:685-8 https://doi.org/10.1378/chest.123.3.685