흉수의 감별 진단 시 Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)의 유용성

Soluble Triggering Receptor Expressed on Myeloid cells-1: Role in the Diagnosis of Pleural Effusions

  • 김정현 (포천중문 의과대학교 분당차병원 내과학교실) ;
  • 박은영 (아산생명과학연구소) ;
  • 김원희 (포천중문 의과대학교 분당차병원 내과학교실) ;
  • 박웅 (포천중문 의과대학교 분당차병원 내과학교실) ;
  • 정혜철 (포천중문 의과대학교 분당차병원 내과학교실) ;
  • 이지현 (포천중문 의과대학교 분당차병원 내과학교실) ;
  • 김은경 (포천중문 의과대학교 분당차병원 내과학교실)
  • Kim, Jung-Hyun (Departments of Internal Medicine, College of Medicine, Pochon CHA University) ;
  • Park, Eun-Young (Asan Life Science Institute, Asan Medical Center) ;
  • Kim, Won-Hee (Departments of Internal Medicine, College of Medicine, Pochon CHA University) ;
  • Park, Woong (Departments of Internal Medicine, College of Medicine, Pochon CHA University) ;
  • Jeong, Hye-Cheol (Departments of Internal Medicine, College of Medicine, Pochon CHA University) ;
  • Lee, Ji-Hyun (Departments of Internal Medicine, College of Medicine, Pochon CHA University) ;
  • Kim, Eun-Kyung (Departments of Internal Medicine, College of Medicine, Pochon CHA University)
  • 투고 : 2007.03.09
  • 심사 : 2007.04.17
  • 발행 : 2007.04.30

초록

연구배경: 흉수는 다양한 원인에 의하여 생성되며 임상적으로 여출액과 삼출액으로 구분하게 되며 삼출액일 경우에는 그 원인 질환들을 감별해야 하나 적용할 만한 표지자가 많지 않다. Soluble Triggering Receptor Expressed on Myeloid cells(sTREM-1)는 면역글로블린의 일종으로 세균이나 진균 감염에서 증가된다고 보고되어 있으며 활성화된 탐식세포에서 떨어져 나와 체액에서도 수용성 상태로 발견될 수 있다. 저자들은 흉수에서 sTREM-1의 측정이 흉수의 감별 진단에 유용한지와 감염성 질환에 의한 흉수에 대한 표지자로서 유용한지에 대한 가능성을 알아보고자 하였다. 대상 및 방법: 2004년 3월부터 2005년 12월까지 흉수를 주소로 내원한 환자들에서 흉수의 세포 수 및 백혈구 분획, 생화학적 검사(pH, protein, LDH, glucose), 세포진 검사, ADA, 미생물학적 검사 결과 이외에 sTREM-1을 측정하였다. 대상환자는 48명으로 남:여 각각 27:21명이었고, 평균 연령은 59세였다. 최종 진단은 암성 흉수는 13명, 결핵성 흉수는 14명, 부폐렴성 흉수는 17명, 여출성 흉수는 4명이었다. 결과: 흉수의 sTREM-1은 부폐렴성 흉수에서 $344.0{\pm}488.7pg/mL$로 결핵성 흉수($81.7{\pm}56.6pg/mL$)와 악성 흉수($39.3{\pm}19.6pg/mL$)보다 높게 측정되었다. 부폐렴성 흉수에 대한 sTREM-1의 ROC 곡선 결과 55.4 pg/mL에서 민감도와 특이도가 각각 70.6%와 74.1%로 측정되었다. 또한 흉수 sTREM-1은 흉수의 호중구수, 흉수 LDH, 흉수/혈청 LDH, 흉수 ADA와 유의한 상관관계를 보였다. 결론: 흉수의 sTREM-1은 부폐렴성 흉수에서 다른 원인의 흉수에서보다 유의하게 상승되어 부폐렴성 흉수의 표지자로서 유용하였으며 기존의 진단 표지자에 더하여 흉수의 감별진단에 유용할 것으로 생각된다.

Background: The currently available diagnostic markers for pleural effusion have a limited role. The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a molecule recently reported to play an important role in the myeloid cell mediated inflammatory response, and is up regulated in the body fluid by bacterial or fungal products. This study examined the expression of sTREM-1 in pleural effusion. Methods: Between April 2004 and December 2005, 48 patients with pleural effusions were enrolled in this study. The pleural fluids were taken and analyzed for the total protein, glucose, lactate dehydrogenase (LDH), adenosine deaminase (ADA), and sTREM-1. Bacterial cultures and cytology tests were also performed. Results: The clinical diagnoses were 17 parapneumonic, 14 tuberculous, and 13 malignant effusions. Four patients presented with transudates. The mean ages of the parapneumonic, tuberculous and malignant effusion groups were $57.1{\pm}19.7$, $49.5{\pm}18.6$, $66.9{\pm}15.5$, and $76.0{\pm}18.1$. respectively. The level of sTREM-1 expression was significantly higher in the parapneumonic effusions ($344.0{\pm}488.7$) than in the tuberculous effusions ($81.7{\pm}56.6$) and malignant effusions ($39.3{\pm}19.6$). With a cut-off value of 55.4pg/ml, the sensitivity and specificity for a parapneumonic effusion was 70.6% and 74.1%. Conclusion: sTREM-1 expression is significantly higher in parapneumonic effusions, suggesting its potential role as an additional diagnostic marker for pleural effusions.

키워드

참고문헌

  1. Marel M. Zrustova M. Stasny B. Light RW. The incidence of pleural effusion in a well-defined region. Epidemiologic study in central Bohemia. Chest 1993; 104:1486-9 https://doi.org/10.1378/chest.104.5.1486
  2. Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusion: the diagnostic separation of transudates and exudates. Ann Intern Med 1972;77:507-13 https://doi.org/10.7326/0003-4819-77-4-507
  3. Romero S, Fernandez C, Arriero JM, Espasa A, Candela A, Martin C, et al. CEA, CA 15-3 and CYFRA 21-1 in serum and pleural fluid of patients with pleural effusions. Eur Respir J 1996;9:17-23
  4. Villena V, Lopez-Encuentra A, Echave-Sustaeta J, Martin-Escribano P, Ortuno-de-Solo B, Estenoz-Alfaro J. Diagnostic value of CA 72-4, carcinoembryonic antigen, CA 15-3, and CA 19-9 assay in pleural fluid. A study of 207 patients. Cancer 1996;78:736-40 https://doi.org/10.1002/(SICI)1097-0142(19960815)78:4<736::AID-CNCR7>3.0.CO;2-C
  5. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448-54 https://doi.org/10.1056/NEJM199902113400607
  6. Mackiewicz A, Speroff T, Ganapathi MK, Kushner I. Effect of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol 1991;146:3032-7
  7. Grove CS, Lee YC. Vascular endothelial growth factor: the key mediator in pleural effusion formation. Curr Opin Pulm Med 2002;8:294-301 https://doi.org/10.1097/00063198-200207000-00009
  8. Brown LF, Detmar M, Claffey K, Nagy JA, Feng D, Dvorak AM, et al. Vascular permeability factor/ vascular endothelial growth factor: a multifunctional angiogenic cytokine. EXS 1997;79:233-69
  9. Bouchon A, Dietrich J, Colonna M. 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
  10. 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
  11. 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
  12. Richeldi L, Mariani M, Losi M, Maselli F, Corbetta L, Buonsanti C, et al. Triggering receptor expressed on myeloid cells: role in the diagnosis of lung infections. Eur Respir J 2004;24:247-50 https://doi.org/10.1183/09031936.04.00014204
  13. Gibot S, Massin F, Le Renard P, Bene MC, Faure GC, Bollaert PE, et al. Surface and soluble triggering receptor expressed on myeloid cells-1: expression patterns in murine sepsis. Crit Care Med 2005; 33:1787-93 https://doi.org/10.1097/01.CCM.0000172614.36571.75
  14. 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
  15. 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
  16. Gibot S, Le Renard PE, Bollaert PE, Kolopp-Sarda MN, Bene MC, Faure GC, et al. Surface triggering receptor expressed on myeloid cells 1 expression patterns in septic shock. Intensive Care Med 2005; 31:594-7 https://doi.org/10.1007/s00134-005-2572-x
  17. Valdes L, San Jose E, Alvarez D, Sarandeses A, Pose A, Chomon B, et al. Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma. Chest 1993;103: 458-65 https://doi.org/10.1378/chest.103.2.458
  18. Light RW. Pleural diseases. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2001
  19. Maskell NA, Butland RJ. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 2003;58 Suppl 2:ii8-17 https://doi.org/10.1136/thx.58.suppl_2.ii8
  20. Kim SH, Lee WY, Park JY, Park HS, Han HK, Ju HS, et al. Diagnostic value of C-reactive protein and vascular endothelial growth factor in differentiation of pleural effusions. Tuberc Respir Dis 2003;55:467-77 https://doi.org/10.4046/trd.2003.55.5.467
  21. 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
  22. Meisner M. Biomarkers of sepsis: clinically useful? Curr Opin Crit Care 2005;11:473-80 https://doi.org/10.1097/01.ccx.0000176694.92883.ce
  23. Romero-Candeira S, Hernandez L, Romero-Brufao S, Orts D, Fernandez C, Martin C. Is it meaningful to use biochemical parameters to discriminate between transudative and exudative pleural effusions? Chest 2002;122:1524-9 https://doi.org/10.1378/chest.122.5.1524
  24. Shin MK, Ham HS, Lee WD, Cho YJ, Jeong YY, Kim HC, et al. The diagnostic usefulness of pleural fluid adenosine deaminase with lymphocyte/neutrophil ratio in tuberculous pleural effusion. Tuberc Respir Dis 2004;57:132-7 https://doi.org/10.4046/trd.2004.57.2.132
  25. Light RW, Girard WM, Jenkinson SG, George RB. Parapneumonic effusions. Am J Med 1980;69:507-12 https://doi.org/10.1016/0002-9343(80)90460-X
  26. Hamm H, Light RW. Parapneumonic effusion and empyema. Eur Respir J 1997;10:1150-6 https://doi.org/10.1183/09031936.97.10051150
  27. Rahman NM, Chapman SJ, Davies RJ. The approach to the patient with a parapneumonic effusion. Clin Chest Med 2006;27:253-66 https://doi.org/10.1016/j.ccm.2005.12.005
  28. Phua J, Koay ES, Zhang D, Tai LK, Boo XL, Lim KC, et al. Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections. Eur Respir J 2006;28:695-702 https://doi.org/10.1183/09031936.06.00005606