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1 Tuberculosis and Respiratory Diseases 원저 결핵및호흡기질환,Vol.55,No.4,Oct,2003 심한흉막비후로진행하여흉막박피술을시행받은결핵성흉막염환자들의흉막액분석 연세대학교의과대학내과학교실 1, 흉부외과학교실 2, 폐질환연구소 3, BK21 의과학사업단 4 정재호 1, 박무석 1, 김세규 1,3,4, 장준 1,3, 정경영 2,3, 김성규 1,3, 김영삼 1,3 =Abstract= Pleural Fluid Analysis in Tuberculous Pleurisy Progressing into Severe Pleural Thickening Underwent Pleural Decortication Jae Ho Chung, M.D. 1, Moo Suk Park, M.D. 1, Se Kyu Kim, M.D. 1,3,4, Joon Chang, M.D. 1,3, Kyung Young Chung, M.D. 2,3, Sung Kyu Kim, M.D. 1,3, Young Sam Kim, M.D. 1,3 Department of Internal Medicine 1, Cardiovascular and Thoracic Surgery 2, The Institute of Chest Diseases 3, and Brain Korea 21 Project for Medical Sciences 4, Yonsei University College of Medicine, Seoul, Korea Background :Although most patients with tuberculous pleurisy respond well to anti-tuberculous drugs, some are known to progress into severe pleural thickening which needs decortication despite adequate anti-tuberculous treatment. Therefore, the purpose of this study was to identify factors associated with the development of severe pleural thickening in patients who finally underwent pleural decortication in tuberculous pleurisy. Patients and Methods :From retrospective medical records review, 121 patients initially diagnosed as tuberculous pleurisy without initial pleural fluid loculation were enrolled between January 1998 and December They were separated into two groups: 85 patients in group 1 who improved by anti-tuberculous drugs only, and 36 patients in group 2 who had progressed into pleural adhesion and finally underwent pleural decortication despite adequate (more than 6 months) anti-tuberculous treatment. Results :Males were more common in group 2 (M/F=31/5) than in group 1 (M/F=53/32) (p=0.010). Group 2 patients tended to have lower pleural fluid glucose level (58±4 mg/dl) than group 1 (89±3 mg/dl) (p=0.001) and higher pleural fluid adenosine deaminase level (86±5 IU/L) than group 1 (76± Address for correspondence : Young Sam Kim, M.D. Department of Internal Medicine, Yonsei University College of Medicine, CPO Box 8044, Seoul, Korea. Phone : Fax : ysamkim@yumc.yonsei.ac.kr 353

2 C. H. Chung, et al 3 IU/L), (p=0.038). There were no significant differences in age, symptom duration, pleural fluid amount, or pleural fluid LDH level between groups 1 and 2. Conclusions :There was a relative risk of tuberculous pleurisy progression into severe pleural thickening which needed decortication in the case of male patients, low pleural fluid glucose or high adenosine deaminase level. But further, large-scale, prospective studies should be investigated. (Tuberculosis and Respiratory Diseases 2003, 55: ) Key words : Pleural thickening, Tuberculous pleurisy, Pleural Decortication. 서론결핵성흉막염은폐외결핵중결핵성임파선염다음으로빈도가높으며, 삼출성흉막염의주요원인중의하나이다. 흉막액은치료하지않아도대부분저절로흡수되지만치료하지않는경우 5 년내에약 50% 의환자에서폐결핵이발생하기때문에치료를필요로한다 1. 통상적으로항결핵제투여 2주이내에발열등증상이소실되고 6주이내에흉막액의완전한흡수가이루어지며흉막의비후가동반되더라도시간이경과함에따라감소하기때문에일반적으로흉막의비후나소방화 (loculation) 가발생하더라도항결핵제치료시작후 6개월까지는흉막박피술같은수술적치료는필요치않다 2. 그러나임상적으로는적절한항결핵제의투여에도불구하고흉막의소방화와섬유화, 석회화로심한흉막비후가발생하여흉막박피술같은수술적치료가필요한경우를종종경험하게된다. 지금까지항결핵제치료반응을예측할수있는인자에대한연구는다양한연구결과를보였으며 3-5, 어떤환자에서수술적처치가필요한경우로진행하는지에대한연구는많지않았다. 이에저자등은초기흉막액이소방화되어있지않은결핵성흉막염환자중항결핵제치료를 6개월이상받았으나심한흉막비후가발생하여흉막박피술을시행받은군과항결핵제만으로호 전된군간의임상적차이에대해알아보기위해후향적으로연구를시행하였다. 대상및방법 1998년 1월부터 2002년 12월까지연세대학교의과대학세브란스병원에서결핵성흉막염으로진단받고입원한환자 121명을대상으로의무기록을토대로후향적조사를하였다. 결핵성흉막염은 (1) 흉막액항산균배양검사상양성인경우, (2) 조직학적으로흉막생검상건락성괴사를동반한육아종소견을보이면서결핵이외의다른질환이배제된경우, (3) 흉막삼출액을동반한환자의객담항산균도말혹은배양양성이고다른원인에의한흉막염이배제된경우, (4) 림프구우세의삼출액으로 adenosine deaminase (ADA) 값이 45 IU/L이상이면서항결핵제치료후임상적인호전을보인경우로정의하였다. 흉막액의양은내원당시최초의단순흉부방사선촬영에서한쪽폐의늑골횡격막각 (costophrenic angle) 부위의반월화나횡격막각의둔화가있는경우를소량흉막액, 한쪽폐의 1/2 이하이면서소량흉수보다많은경우를중등도흉막액, 한쪽폐의 1/2 이상인경우를대량흉막액이라고정의하였다. 흉막액의소방화유무는단순흉부방사선촬영, 초음파검사또는흉부전산화단층촬영을통해서판단하였으며내원당시흉막액의소방화가있거나, 면역저하자는제 354

3 Pleural fluid analysis in tuberculous pleurisy progressing into severe pleural thickening Underwent Table 1. General characteristics of the study populations between group 1 (improved by anti-tuberculous drugs) and group 2 (progressing into severe pleural thickening which need pleural decortication). Sex (M/F) Age (yr) * Smoking Symptoms Cough Chest pain Fever Dyspnea Night sweat Weight loss Symptom duration (days) * Peripheral WBC (/mm 3 ) * Group 1 number (%) 53/32 39±2 35 (41%) 34 (40%) 24 (28%) 25 (29%) 35 (41%) 7 (8%) 13 (15%) 13±1 6300±123 * Datas are expressed as mean SE (standard error of mean) Group 2 number (%) 31/5 35±3 17 (47%) 20 (56%) 14 (39%) 10 (28%) 14 (39%) 5 (14%) 8 (22%) 17±2 6899±437 p-value 외하였고, 본원에내원하여처음흉막천자를시행받은환자들을대상으로하였다. 흉막비후는늑골횡격막각둔화부위상연의두께가 3mm 이상인경우로정의하였다. 항결핵제로치료받고흉막액이소량흉수이하로감소된군과항결핵제를 6개월이상투여받았으나폐의 1/4 이상의유착성흉막염이있거나, 기관지흉막루가동반되어흉막박피술을시행받은군간의임상적차이에대해서조사하였다. 자료분석과통계처리는 PC-SAS version 6.12 (SAS Institute Inc, Cary, NC) 를이용하였으며, 통계적유의수준은 p값을 0.05이하로하였다. 결과환자의성별, 연령및임상증상은 Table 1과같다. 두군모두남성이많았으며, 수술시행군에서호전군에비해유의하게남자가많았다. 두군간의평균연령은호전군에서 39세이었고수술시행군에서 35세로두군간에차이가없었다. 증상은기 침이제일많았고, 증상에따른두군간에차이는없었다. 증상발현에서부터치료시작까지의기간은수술시행군이호전군에비해길었으나 ( 호전군 : 13±1일, 수술시행군 : 17±2일 ) 유의한차이는없었다. 말초혈액의백혈구값은호전군에서 6300± 123 /mm 3, 수술시행군에서 6899±437 /mm 3 로두군사이에유의한차이는없었다. 방사선학적검사상폐실질에폐결핵병변이있었던경우는호전군에서 38예 (45%) 이며수술시행군에서 18예 (50%) 로양군간에유의한차이는없었으며, 초기의방사선학적검사에서대량흉막액을보였던경우가호전군에서 22예 (26%), 수술시행군에서 12예 (33%) 로두군간에차이가없었고, 흉막액의위치와도두군간에유의한차이는없었다 (Table 2). 흉막액에서의포도당값 (Fig. 1) 은호전군이 89 ±3 mg/dl, 수술시행군이 58±4 mg/dl 으로수술시행군에서유의하게낮았으며 (p=0.001), adenosine deaminase (ADA) (Fig. 2) 치도호전군이 76±3 IU/L, 수술시행군이 86±5 IU/L로수술시행군에서유의하게높았다 (p=0.038). 그러나흉막액 ph, 355

4 C. H. Chung, et al Table 2. Radiologic characteristics between group 1 (improved by anti-tuberculous drugs) and group 2 (progressing into severe pleural thickening which need pleural decortication). Site of effusion Right Left Both Size of effusion Small * Medium Massive Lung parenchymal tuberculosis Group 1 number (%) 56 (66%) 27 (32%) 2 (2%) 7 (8%) 56 (66%) 22 (26%) 38 (45%) * : CPA blunting, : <1/2 of chest PA, : >1/2 of chest PA Group 2 number (%) 19 (53%) 15 (42%) 2 (5%) 1 (3%) 23 (64%) 12 (33%) 18 (50%) p-value Fig. 1. Comparison of glucose levels in pleural fluid between group 1 (improved by anti-tuberculous drugs) and group 2 (progressing into severe pleural thickening which need pleural decortication). Hori zontal solid lines mean the mean value for each group. 단백질, LDH 및천자횟수는두군간에유의한차이가관찰되지않았다. 초기의흉막조직검사상건락성육아종은호전군에서 29예 (34%), 수술시행군에서 14예 (39%) 로두군간에유의한차이가없었으며흉막액항산균도말검사나배양도두 Fig. 2. Comparison of ADA levels in pleural fluid between group 1 (improved by anti-tuber culous drugs) and group 2 (progressing into severe pleural thickening which need pleural decortication). Horizontal solid lines mean the mean value for each group. 군간에유의한차이는없었다 (Table 3). 흉막박피술은평균항결핵제투여후 7.5개월에시행하였다. 고찰 결핵성흉막염은폐외결핵중비교적흔한질환 356

5 Pleural fluid analysis in tuberculous pleurisy progressing into severe pleural thickening Underwent Table 3. Pleural fluid characteristics between group 1 (improved by anti-tuberculous drugs) and group 2 (progressing into severe pleural thickening which need pleural decortication). Group 1 Group 2 p-value Thoracentesis Number ph WBC (/mm 3 ) Neutrophil (/mm 3 ) Lymphocyte (/mm 3 ) Glucose (mg/dl) Protein (g/dl) LDH * (IU/L) ADA (IU/L) Pleural fluid Positive AFB smear Positive AFB culture Pleural biopsy Caseating granuloma Noncaseating granuloma Chronic inflammation 1.3± ± ± ± ±36 89±3 5.3± ±62 76±3 0 (0%) 4 (5%) 29 (34%) 12 (14%) 20 (24%) * : lactate dehydrogenase, : adenosine deaminase. Datas are expressed as mean±se (standard error of mean) 1.3± ± ± ± ±32 58±4 5.4± ±110 86±5 0 (0%) 2 (6%) 14 (39%) 6 (17%) 2 (6%) 으로흉막강내에결핵균이침범하여발생하거나, 결핵균단백질에대한지연성과민반응으로발생하는것으로알려져있고 40% 의환자에서저절로흡수되지만치료를하지않은경우발병 5년내에약 50% 에서활동성폐결핵이발생하는것으로알려져있다 1. 대부분은항결핵제치료로호전되지만일부에서는항결핵제의투여에도불구하고흉막액의소방화나심한흉막비후로진행하여수술적처치를필요로하게된다. 결핵성흉막액에서흉막액포도당값은 Barber 등 6 은대부분낮다고하였으나, 최근의연구에서는대부분 60 mg/dl 이상이라고하였고 7, 흉막액 ph 는악성흉막액보다낮다고하였으나 8 최근보고에의하면악성흉막액과유사한분포를보인다고한다 9. 결핵성흉막염에서항결핵제치료이후흉막비후는약 50% 에서발생한다 4. 기전은혈액에의노출, 마찰, 이물질, 부분허혈등에의하여흉막의중피세포가손상을받게되고회복과정에서결핵성흉막염에서증가한 T-림프구나 interferon-γ 를포함한 cytokine 의증가에의해섬유모세포 (fibroblast) 가증가하면서섬유성조직화가발생하여폐와흉막사이에흉막섬유화나흉막비후가발생하며흉막의미세한손상조차도흉막비후를유발하는것으로알려져있다. 지금까지결핵성흉막염환자에서심한흉막비후로흉막박피술을시행받은환자들의유병율에대한연구는많지않았으며, Chan 등 10 은 83예의결핵성흉막염환자를추적관찰한결과그중 5예에서심한흉막비후가생겨서흉막박피술을시행하였다고보고하였다. 항결핵제치료반응에대한예측인자에대한연구는다양한연구결과를보였다 3-5. 흉막비후에대한임상적예측지표로는이등 3 에의하면흉막액의 357

6 C. H. Chung, et al 백혈구감별산정이나단백질값은영향이없고흉막액의포도당값이낮거나 LDH값이높은경우에흉막비후가남을가능성이유의하게많다고하였으나, Barbas 등 4 은흉막액의포도당값이나 LDH 값이두군사이에약간의차이는있었지만통계적으로는유의하지는않다고하였고, 이등 5 은흉막조직검사에서육아종이있는경우, 항산균염색검사에서결핵균이발견된경우, 흉막액 LDH가높은경우에흉막비후가더많이발생한다고하였다. 초기흉막액의양은지연성과민성반응에의하여혈관의투과성증가및흉막액의흡수장애로그양이결정된다는보고가있으며 11, 진단당시흉막액의양과흉막액천자횟수는흉막비후와는무관한것으로알려져있다 4. 흉막비후빈도를낮추기위해흉막삼출액의반복천자, 물리치료, 부신피질호르몬의투여등이시도되고있으나 Large 등 12 에의하면반복천자와단순천자간에임상적차이는없었으며, Lai 등 13 은 pigtail로흉막액을배액한군과항결핵제만으로치료한군사이에흉막비후의차이는관찰하지못하였다. 몇연구에서부신피질호르몬은흉막비후방지에는도움을주지못하고전신증상을줄여주는것에만도움을준다고하였다 14,15. 본연구에서는환자의발열유무나흉통, 호흡곤란, 기침, 흉막액의양, 위치, 흉막액천자횟수와심한흉막비후의발생과는관련성이없게나타났으며방사선학적으로폐실질에결핵이있는경우에도관련성이없었다. 이러한것은발열유무및말초혈액에서의백혈구수치가결핵성농흉과의진행과는무관함을볼때전신혹은폐의염증상태와관계없이흉막강내의국소적인요인에의하여발생함을시사한다. 강등 16 에따르면감염성흉막삼출액환자에서삼출액안에격막이많을수록흉막액단백질함량이많았으며, 보존적치료를하였을때흉막비후및유착의소견들을남기거나치료실패의경우가많다고하였다. 또한최근에 삼출성흉막질환에서 fibrin의대사에이상이있다는연구들이보고되었는데 17, 폐렴이나폐암, 또는세균성농흉등에의한흉막삼출액의경우에는응고기전의활성도가증가되었음에도불구하고높은농도의플라스미노겐활성억제제 (PAI-I) 등에의해섬유소해리기능은저하되어있다고하였고, Hua 등 18 은결핵성흉막염환자에서 TNF-α의증가에의한플라스미노겐활성억제제의증가와 tpa 의감소에의해 fibrin이침착하고흉막비후를일으킨다고하였으나이는결핵에특징적이라기보다는염증의정도를나타내는것으로항결핵제에반응을잘하는군과잘하지않는군사이에흉막액에서의응고및섬유소해리기능에차이가있다면결핵성흉막염환자등의치료방침결정에임상적으로중요한지표로사용될수있을것이므로앞으로이에대한추가적인연구는필요할것으로본다. 본연구에서흉막박피술을시행한군중남자에서유의하게많았는데이는여성에서미용적문제로수술을꺼려서생기는선택오류의문제가있을수있어남성에서유의한합병증이생긴다는결과에는조심스러운해석이필요할것으로생각되어진다. 또한흉막액 ADA 값이높을경우유의한합병증이발생하였는데이는결핵성흉막염에서증가한 T-림프구에서생성된 ADA와 interferonγ를포함한다른 cytokine 에의해섬유모세포 (fibroblast) 가증가하면서흉막비후가더욱생기는것이기때문인것으로생각되어진다. 흉막액에서진단당시의흉막에서의염증정도와흉막비후와관계가있어서, 흉막액포도당값이낮을수록흉막비후가잘생긴다는연구결과 3 가있어본연구와도일치하였으나이에상반되는결과 4 도있으며, 전신혹은폐의염증상태와관계없이흉막강내의국소적인요인에의하여흉막비후가발생한다는의견도있기때문에흉막비후의예측인자로서는조심스러운해석이필요할것으로생각되어진다. 358

7 Pleural fluid analysis in tuberculous pleurisy progressing into severe pleural thickening Underwent 본연구결과저자등은결핵성흉막염에서남자, 흉막액포도당값이낮거나 ADA 값이높은경우흉막박피술까지필요한심한흉막비후의위험성이커지는것으로관찰되었지만후향적연구결과이기때문에임상적으로신뢰할만한예측지표로서결론내리기에는아직부족하며, 향후대량의전향적연구가추가적으로진행되어야할것으로생각된다. 요약목적 : 결핵성흉막염의일부에서는항결핵제의투여에도불구하고흉막박피술이필요한심한흉막비후로진행되지만어떤인자들이이에관여하는지에대한연구는적다. 이에저자등은초기흉막액이소방화되어있지않은결핵성흉막염환자중에항결핵제를투여받았으나흉막비후가진행되어흉막박피술을시행받은군과항결핵제만으로유착없이호전된군간에임상적차이에대해알아보기위해연구를시행하였다. 방법 : 1998년 1월부터 2002년 12월까지내원한결핵성흉막염환자중에항결핵제를투여받았으나항결핵제만으로호전된 1군 (85명) 과심한흉막비후가진행되어흉막박피술을시행받은 2군 (36명) 간의임상적차이에대해후향적으로조사하였다. 결과 : 흉막박피술을시행한군중남자에서유의하게많았다 ( 호전군 : M/F=53/32, 심한흉막비후군 : M/F=31/5)(p=0.010). 수술시행군 (58±4 mg/dl) 에서흉막액포도당값이호전군 (89±3 mg/dl) 보다유의하게낮았으며 (p=0.001), ADA 값도수술시행군 (86±5 IU/L) 에서호전군 (76±3 IU/L) 보다높게나타났다 (p=0.038). 흉막액의 ph, 단백질, LDH 및천자횟수는두군간에유의한차이가없었다. 결론 : 남자, 흉막액포도당값이낮거나흉막액 ADA 값이높은경우에결핵성흉막염에서흉막박피술을시행한경우가많았지만임상적으로신뢰할만한예측지표로서결론내리기에는아직부족하며, 향후대량의전향적연구가추가적으로진행되어야할것으로생각된다. 참고문헌 1. Patiala J. Initial tuberculosis pleuritis in the Finnish Armed Forces in with special reference to eventual post pleuritic tuberculosis. Acta Tuberc Scand 1954;36: Light RW, Chapter 10, Tuberculous pleural effusions. In : Light RW. Pleural Diseases 4th ed. Baltimore : Williams & Wilkins,Inc ; p 이재호, 정희순, 이정상, 조상록, 윤혜경, 송치성. 결핵성늑막염에서삼출액의흡수에영향을미치는임상적지표. 결핵및호흡기질환 1995;42: Barbas CS, Cukier A, de Varvalho CR, Barbas Filho JV, Light RW. The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis. Chest 1991;100: 이기만, 이종준, 서광원, 박지현, 이미숙, 황재철. 결핵성흉막염에서항결핵제치료후의잔여흉막비후와관련된인자. 결핵및호흡기질환 2001;50: Barber LM, Mazzadi L, Deakins DD. Glucose level in pleural fluid as a diagnostic aid. Dis Chest 1957;31:

8 C. H. Chung, et al 7. Epstein DM, Kline LR, Albelda SM, Miller WT. Tuberculous pleural effusions. Chest 1987;91: Light RW, MacGregor MI, Ball WC Jr, Luchsinger PC. Diagnostic significance of pleural fluid ph and PCO2. Chest 1973;64: Good JT Jr, Taryle DA, Maulitz RM, Kaplan RL, Sahn SA. The diagnostic value of pleural fluid ph. Chest 1980;78: Chan CH, Arnold M, Chan CY, Mak TW, Hoheisel GB. Clinical and pathological featu res of tuberculous pleural effusion and its long-term consequences. Respiration 1991;58: picella MA, Allen JC. A physiologic differ entiation between delayed and imme diate hypersensitivity. J Clin Invest 1969;48: Large SE, Levic RK. Aspiration in the treatment of primary tuberculous effusion. Br Med J 1958;1: Lai YF, Chao TY, Wang YH, Lin AS. Pigtail drainage in the treatment of tuberculous ple ural effusions: a randomised study. Thorax 2003;58: Wyser C, Walzl G, Smedema JP, Swart F, van Schalkwyk EM, van de Wal BW. Corticosteroids in the treatment of tuber culous pleurisy. A double-blind, placebo-con trolled, randomized study. Chest 1996;110: Lee CH, Wang WJ, Lan RS, Tsai YH, Chiang YC. Corticosteroids in the treatment of tuberculous pleurisy. A double-blind, pl acebo-controlled, randomized study. Chest 1988;94: 강은영, 박철민, 차인호. 초음파검사상감염성 흉막삼출액내격막의임상적의미. 대한초음 파의학회지 1994;13: Idell S, Girard W, Koenig KB, McLarty J, Fair DS. Abnormalities of pathways of fibrin turnover in the human pleural space. Am Rev Respir Dis 1991;144: Hua CC, Chang LC, Chen YC, Chang SC. Proinflammatory cytokines and fibrinolytic enzymes in tuberculous and malignant pleural effusions. Chest 1999;116:

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar