Tuberculosis and Respiratory Diseases

  • 제65권4호
  • /
  • Pages.301-307
  • /
  • 2008
  • /
  • 1738-3536(pISSN)
  • /
  • 2005-6184(eISSN)
대한결핵및호흡기학회 (The Korean Academy of Tuberculosis and Respiratory Diseases)
권호 표지

급성호흡곤란증후군 환자에서 Soluble Triggering Receptor Expressed on Myeloid Cells-1의 예후인자로서의 유용성

Prognostic Utility of the Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Patients with Acute Respiratory Distress Syndrome

  • 허진원 (인제대학교 의과대학 일산백병원 내과) ;
  • 정훈 (인제대학교 의과대학 일산백병원 내과) ;
  • 임채만 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 고윤석 (울산대학교 의과대학 서울아산병원 호흡기내과) ;
  • 홍상범 (울산대학교 의과대학 서울아산병원 호흡기내과)
  • Huh, Jin Won (Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Jung, Hoon (Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine) ;
  • Lim, Chae-Man (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Koh, Younsuck (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hong, Sang-Bum (Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine)
  • 투고 : 2008.08.29
  • 심사 : 2008.10.01
  • 발행 : 2008.10.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

연구배경: Triggering receptor expressed on myeloid cells-1 (TREM-1)은 호중구와 단핵구의 표면에 표현되는 수용체로 호중구가 자극되면 표면에서 떨어져 수용체인 sTREM-1으로 존재하며 염증반응을 증폭시킨다. 본 연구는 호중구의 활성화가 중요한 병인인 급성호흡곤란증후군 환자의 기관지폐포세척액과 혈청에서 측정한 sTREM-1의 농도가 예후인자로서 유용성이 있는지 확인하고자 시행되었다. 방 법: 32명의 급성호흡곤란증후군 환자가 포함되었고 이 중 15명이 생존군, 17명이 사망군으로 분류되었다. 중증도 지표로 APACHE II score, Clinical Pulmonary Infection Score (CPIS)를 측정하였고, 기관지폐포세척액과 혈청에서 sTREM-1 농도를 측정하였고 중환자실 사망여부를 확인하였다. 결 과: 진단 시 급성호흡곤란증후군 환자의 혈청 내 sTREM-1의 농도는 사망군에서 생존군 보다 유의하게 상승되어 있었으나 ($54.3{\pm}10.3pg/ml$ vs. $22.7{\pm}2.3pg/ml$, p<.05) 기관지폐포세척액 내의 sTREM-1의 농도는 차이가 없었다. 혈청 내 sTREM-1의 농도는 급성호흡곤란증후군 환자의 예후를 예측할 수 있는 독립적인 인자(OR: 22.051, 95% CI: 1.780~273.146, p=0.016)이었고, 33pg/ml 경계로 분류 시 중환자실 사망률을 예측하는데 71%의 민감도와 93%의 특이도를 보였다. 결 론: 급성호흡곤란증후군 환자의 진단 당시 측정한 혈청 sTREM-1의 농도는 중요한 예후 인자로서 유용성이 있을 것으로 생각된다.

Background: The triggering receptor expressed on myeloid cells-1 (TREM-1) is an activating receptor that is expressed on the surface of neutrophils and mature monocytes when stimulated with several microbial components, which can amplify the inflammatory response. This study analyzed the prognostic value of the sTREM-1 levels in patients with acute respiratory distress syndrome (ARDS). Methods: The bronchoalveolar lavage (BAL) fluid and blood was collected prospectively from 32 patients with ARDS, 15 survivors and 17 nonsurvivors. An enzyme-linked immunosorbent assay was performed to measure the sTREM-1. The following data was obtained: APACHE II score, Clinical Pulmonary Infection Score (CPIS), BAL fluid analysis, C-reative protein. Mortality in the ICU was defined as the end point. Results: The serum sTREM-1 level was significantly higher in the nonsurvivors than survivors ($54.3{\pm}10.3pg/ml$ vs. $22.7{\pm}2.3pg/ml$, p<0.05). The sTREM-1 level in the serum, but not in the BAL fluid, was an independent predictor of the ICU mortality (OR: 22.051, 95% CI: 1.780~273.148, p<0.016), and a cut-off value of ${\geq}33pg/ml$ yielded a diagnostic sensitivity of 71% and specificity of 93%. Conclusion: The serum sTREM-1 level may be a useful predictor of the outcome of ARDS patients.

키워드

참고문헌

  1. Abel SJ, Finney SJ, Brett SJ, Keogh BF, Morgan CJ, Evans TW. Reduced mortality in association with the acute respiratory distress syndrome (ARDS). Thorax 1998;53:292-4. https://doi.org/10.1136/thx.53.4.292
  2. Ware LB. Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design. Crit Care Med 2005;33:S217-22. https://doi.org/10.1097/01.CCM.0000155788.39101.7E
  3. Adamzik M, Frey U, Sixt S, Knemeyer L, Beiderlinden M, Peters J, et al. ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS. Eur Respir J 2007;29:482-8. https://doi.org/10.1183/09031936.00046106
  4. Zhang P, Summer WR, Bagby GJ, Nelson S. Innate immunity and pulmonary host defense. Immunol Rev 2000;173:39-51. https://doi.org/10.1034/j.1600-065X.2000.917306.x
  5. Bouchon A, Dietrich J, Colonna M. Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 2000;164:4991-5. https://doi.org/10.4049/jimmunol.164.10.4991
  6. Colonna M, Facchetti F. TREM-1 (triggering receptor expressed on myeloid cells): a new player in acute inflammatory responses. J Infect Dis 2003;187 Suppl 2:S397-401. https://doi.org/10.1086/374754
  7. Bleharski JR, Kiessler V, Buonsanti C, Sieling PA, Stenger S, Colonna M, et al. A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol 2003;170:3812-8. https://doi.org/10.4049/jimmunol.170.7.3812
  8. Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature 2001;410:1103-7. https://doi.org/10.1038/35074114
  9. Nathan C, Ding A. TREM-1: a new regulator of innate immunity in sepsis syndrome. Nat Med 2001;7:530-2. https://doi.org/10.1038/87846
  10. Cohen J. TREM-1 in sepsis. Lancet 2001;358:776-8. https://doi.org/10.1016/S0140-6736(01)06007-X
  11. Kollef MH, Bock KR, Richards RD, Hearns ML. The safety and diagnostic accuracy of minibronchoalveolar lavage in patients with suspected ventilator-associated pneumonia. Ann Intern Med 1995;122:743-8. https://doi.org/10.1001/archinte.122.1.43
  12. Souweine B, Veber B, Bedos JP, Gachot B, Dombret MC, Regnier B, et al. Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: impact of previous antimicrobial treatments. Crit Care Med 1998;26:236-44. https://doi.org/10.1097/00003246-199802000-00017
  13. Determann RM, Millo JL, Gibot S, Korevaar JC, Vroom MB, van der Poll T, et al. Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia. Intensive Care Med 2005;31:1495-500. https://doi.org/10.1007/s00134-005-2818-7
  14. Horonenko G, Hoyt JC, Robbins RA, Singarajah CU, Umar A, Pattengill J, et al. Soluble triggering receptor expressed on myeloid cell-1 is increased in patients with ventilator-associated pneumonia: a preliminary report. Chest 2007;132:58-63. https://doi.org/10.1378/chest.06-2731
  15. Tejera A, Santolaria F, Diez ML, Aleman-Valls MR, Gonzalez-Reimers E, Martinez-Riera A, et al. Prognosis of community acquired pneumonia (CAP): value of triggering receptor expressed on myeloid cells-1 (TREM-1) and other mediators of the inflammatory response. Cytokine 2007;38:117-23. https://doi.org/10.1016/j.cyto.2007.05.002
  16. Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, et al. The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome. Am J Respir Crit Care Med 1998;157:1332-47. https://doi.org/10.1164/ajrccm.157.4.ats2-98
  17. Michel F, Franceschini B, Berger P, Arnal JM, Gainnier M, Sainty JM, et al. Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures. Chest 2005;127:589-97. https://doi.org/10.1378/chest.127.2.589
  18. Bellingan GJ. The pulmonary physician in critical care * 6: the pathogenesis of ALI/ARDS. Thorax 2002;57:540-6. https://doi.org/10.1136/thorax.57.6.540
  19. Weiland JE, Davis WB, Holter JF, Mohammed JR, Dorinsky PM, Gadek JE. Lung neutrophils in the adult respiratory distress syndrome: clinical and pathophysiologic significance. Am Rev Respir Dis 1986;133:218-25.
  20. Chollet-Martin S, Jourdain B, Gibert C, Elbim C, Chastre J, Gougerot-Pocidalo MA. Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS. Am J Respir Crit Care Med 1996;154:594-601. https://doi.org/10.1164/ajrccm.154.3.8810592
  21. Kurt-Jones EA, Mandell L, Whitney C, Padgett A, Gosselin K, Newburger PE, et al. Role of toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils. Blood 2002;100:1860-8.
  22. Dibbert B, Weber M, Nikolaizik WH, Vogt P, Schoni MH, Blaser K, et al. Cytokine-mediated Bax deficiency and consequent delayed neutrophil apoptosis: a general mechanism to accumulate effector cells in inflammation. Proc Natl Acad Sci U S A 1999;96:13330-5. https://doi.org/10.1073/pnas.96.23.13330
  23. Gibot S, Kolopp-Sarda MN, Bene MC, Cravoisy A, Levy B, Faure GC, et al. Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis. Ann Intern Med 2004; 141:9-15. https://doi.org/10.7326/0003-4819-141-1-200407060-00009
  24. Gibot S, Cravoisy A, Levy B, Bene MC, Faure G, Bollaert PE. Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med 2004;350:451-8. https://doi.org/10.1056/NEJMoa031544
  25. Huh JW, Lim CM, Koh Y, Oh YM, Shim TS, Lee SD, et al. Diagnostic utility of the soluble triggering receptor expressed on myeloid cells-1 in bronchoalveolar lavage fluid from patients with bilateral lung infiltrates. Crit Care 2008;12:R6. https://doi.org/10.1186/cc6770
  26. Gibot S, Cravoisy A, Kolopp-Sarda MN, Bene MC, Faure G, Bollaert PE, et al. Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis. Crit Care Med 2005;33:792-6. https://doi.org/10.1097/01.CCM.0000159089.16462.4A
  27. Giamarellos-Bourboulis EJ, Zakynthinos S, Baziaka F, Papadomichelakis E, Virtzili S, Koutoukas P, et al. Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory mediator in sepsis. Intensive Care Med 2006;32:237-43. https://doi.org/10.1007/s00134-005-0017-1
  28. Routsi C, Giamarellos-Bourboulis EJ, Antonopoulou A, Kollias S, Siasiakou S, Koronaios A, et al. Does soluble triggering receptor expressed on myeloid cells-1 play any role in the pathogenesis of septic shock? Clin Exp Immunol 2005;142:62-7. https://doi.org/10.1111/j.1365-2249.2005.02887.x
  29. Pelosi P, D'Onofrio D, Chiumello D, Paolo S, Chiara G, Capelozzi VL, et al. Pulmonary and extrapulmonary acute respiratory distress syndrome are different. Eur Respir J Suppl 2003;42:48s-56s.