pissn: 2288-0402 eissn: 2288-0410 Allergy Asthma Respir Dis 5(5):287-293, September 2017 https://doi.org/10.4168/aard.2017.5.5.287 ORIGINAL ARTICLE 객담배출이어려운소아청소년결핵의심환자에서굴곡성기관지내시경검사의유용성 이혜진, 박유미, 양은애, 김환수, 전윤홍, 윤종서, 김현희, 김진택 가톨릭대학교의과대학소아과학교실 Usefulness of flexible bronchoscopy in children with suspected pulmonary tuberculosis who have difficulty in sputum expectoration Hye Jin Lee, Yumi Park, Eun Ae Yang, Hwan Soo Kim, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea Purpose: To assess the usefulness of flexible bronchoscopy in patients with suspected pulmonary tuberculosis (PTB) who have difficulty in sputum expectoration. Methods: The subjects of this study were patients who were suspected of PTB and visited the Division of Pediatric Pulmonology at a tertiary hospital from April 2006 to March 2016. PTB suspects were determined by clinical symptoms, radiologic findings, and immunologic studies. We aimed to examine the value and safety of bronchoscopy in diagnosis and differential diagnosis of PTB in PTBsuspected patients. The diagnostic criteria for PTB were defined when Mycobacterium tuberculosis was cultured in the sputum specimen or in the bronchial washing fluid. Results: A total of 19 PTB suspects were included. One patient was diagnosed with PTB by using the sputum study. However, the remaining 18 patients could not expectorate sputum or showed no evidence of Mycobacterium tuberculosis infection from the sputum study. Of the 18 patients, 15 underwent bronchoscopy. After bronchoscopy, 6 patients were diagnosed with PTB and 9 patients were diagnosed with Mycoplasma, viral, or fungal pneumonia, and tumors. For antituberculous drug resistance, there were 1 case of isoniazid (INH) resistance and 1 case of concurrent resistance to INH and prothionamide. There was no multidrug-resistant tuberculosis. None of the patients had significant complications due to bronchoscopy. Conclusion: Flexible bronchoscopy appears to be a definitive and safe procedure for the differential diagnosis of patients suspecting PTB in children who have difficulty expectorating sputum. (Allergy Asthma Respir Dis 2017;5:287-293) Keywords: Pulmonary tuberculosis, Bronchoscopy, Diagnosis, Diagnostic imaging 서론 2015년 World Health Organization (WHO) 보고서에따르면전세계적으로 960만명의결핵환자가발생하였고, 그중소아환자는 100만명정도로추정되고있다. 1 우리나라의경우, 2011년인구 10 만명당결핵환자수 78.9명으로최고치를기록한이후감소추세를보이고있으나결핵은아직까지중요한감염질환의하나이다. 결핵균의감염이후활동성결핵으로의진행여부는연령과체내의면역상태에의해결정되는데, 결핵균감염이후평생결핵질환 으로진행할확률은건강한정상면역상태의성인에서는 10% 정도인반면, 면역력이저하되어있는 5세미만소아에서는 25% 50% 정도로높기때문에, 소아에서의활동성결핵및잠복결핵의진단및조기치료는매우중요하다고할수있다. 2 그러나최근연구에따르면, WHO에서정한 0 14세를기준으로한소아결핵의진단율은전세계적으로약 70% 이하로낮게보고된바있다. 3,4 폐결핵의진단이소아청소년환자에서성인에비하여특히어려움을겪는이유는크게두가지이다. 첫번째로, 소아청소년환자는객담을배출하지못하는경우가많으며, 이를대체할수있는검사 Correspondence to: Jong-Seo Yoon https://orcid.org/0000-0002-5782-6175 Department of Pediatrics, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-7612, Fax: +82-2-537-4544, E-mail: pedjsyoon@catholic.ac.kr Received: February 3, 2017 Revised: June 24, 2017 Accepted: August 2, 2017 2017 The Korean Academy of Pediatric Allergy and Respiratory Disease The Korean Academy of Asthma, Allergy and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/). 287 http://www.aard.or.kr
Allergy Asthma Respir Dis Lee HJ, et al. Pulmonary tuberculosis and flexible bronchoscopy 인비위관을사용한위흡인액검사나유도객담검사의시행도어려운경우가많다. 두번째로, 소아청소년결핵의특성상, 균의배출이적어항산균도말검사및결핵균배양의위음성확률이높아미생물학적확진이불가능한경우가많다. 가장많이사용되는객담도말검사는특이도가높고결핵균을빠르게확인할수있다는장점이있으나, 민감도가 50% 60% 로낮고, 5 결핵균배양검사의경우는민감도가 80% 85% 정도로높으나, 기간이 3 8주정도로오래걸린다는단점이있다. 6 QuantiFERON-TB, T-SPOT 과같은면역학적검사및 MTB PCR, Xpert MTB/RIF 등과같은분자생물학적검사들이개발되어사용되고있으나소아에서의사용은연령에제한적이며, 각검사들의진단적유용성에대해서는보편적근거가부족하다. 7,8 이러한이유로폐결핵의심소아청소년환자에서는환자가호소하는증상이나징후, 영상학적소견등의임상적판단에의존하여항결핵치료를시작하거나, 진단이늦어지는경우가많다. 3 현재까지소아청소년폐결핵의진단에있어기관지내시경을일반적으로사용하지는않으며, 진단적가치는명확하게알려져있지않다. 이에저자들은소아청소년폐결핵의심환자를대상으로굴곡성기관지내시경을시행하여소아청소년폐결핵진단에있어기 관지내시경이가지는유용성에대하여알아보고자하였다. 대상및방법 1. 대상 2006년 4월 1일부터 2016년 3월 31일까지서울성모병원소아청소년과호흡기분과에폐결핵이의심되어내원한만 18세미만의환자들을대상으로의무기록, 실험실검사, 그리고방사선학적소견을검토하였다. 폐결핵의심여부는결핵의심증상 ( 항생제사용에도 2주이상지속되는기침, 발열, 호흡곤란, 객혈, 야간발한등 ), 영상의학검사상폐결핵의심소견, 결핵에대한면역학적검사 (tuberculin skin test [TST], interferon-γ release assays [IGRA]) 양성소견등을바탕으로하였다. 대상환자들중, 객담검사를통해결핵확진이가능하였던경우, 기관지내시경에협조가어렵다고판단된경우, 그리고결핵에대한검사권유를거절한경우를제외한모든결핵의심환자를대상으로굴곡성기관지내시경검사를시행하였다 (Fig. 1). 대상환자 16명의임상양상및과거력, 면역학적검사, 방사선학소견, 기관지세척 Pulmonary tuberculosis suspects (n=19) Is it possible for the patient to expectorate sputum? Yes (n=3) No (n=16) M. TB PCR (+) AFB smear (+) M. TB culture (+) Evidence of M. TB infection (n=1) Pulmonary tuberculosis (n=1) No evidence of M. TB infection (n=2) M. TB PCR (-) AFB smear (-) Sputum-scarce patient (n=16) Excluded (n=3) - Poor general condition (n=1) - Follow up loss (n=2) Bronchoscopy case included (n=15) Washing fluid M. TB culture (+) Pulmonary tuberculosis (n=6) Washing fluid M. TB culture (-) Nontuberculosis (n=9) Fig. 1. Flow diagram of patients included in the study. M. TB, Mycobacterium tuberculosis; PCR, polymerase chain reaction; AFB, acid fast bacilli. 288 https://doi.org/10.4168/aard.2017.5.5.287
이혜진외 폐결핵과굴곡성내시경 Allergy Asthma Respir Dis 액의미생물학검사, 내시경적조직학검사결과및최종진단을검토하였다. 2. 방법 1) 방법굴곡성기관지내시경은 Olympus BF-XP260F (Olympus Co., Tokyo, Japan; 말단부위외경 2.8 mm) 또는 Olympus BF-260 (Olympus Co.; 말단부위외경 4.9 mm) 을이용하였으며국소마취하에서진행하였다. 기관지세척액은기관지내분비물이있거나영상검사에서병변이의심되는부위에 10 ml의생리식염수를 3 5차례반복주입및흡인하여수집하였다. 얻어진검체를통하여항산균도말및배양검사, 결핵균중합효소연쇄반응 (M. Tuberculosis polymerase chain reaction, MTB PCR) 및세포진검사, 호흡기바이러스및마이코플라스마중합효소연쇄반응 (respiratory virus PCR, Mycoplasma pneumoniae PCR), 세균및진균배양검사결과와필요시조직검사를시행하였다. 2) 진단및정의의무기록을검토하여 (1) 결핵의과거력혹은폐결핵환자접촉력, (2) 임상증상, (3) 투베르쿨린검사혹은 IGRA와같은면역학적검사소견, (4) 방사선검사소견등을토대로폐결핵의심소견을분석하였고, 폐결핵의진단은객담검체혹은기관지세척액배양검사에서 M. tuberculosis가확인된경우로하였다. 투베르쿨린검사는 PPD 2 TU 0.1 ml를전박내측에피내주사하여 48 72시간이내에상완의장축과교차하는경결 (induration) 의길이를판독하였으며, 10 mm 이상일때양성으로판정하였다. 비결핵환자군의진단은기관지내시경검체의미생물학, 조직학적검사결과에근거하였으며, 두환자군모두치료경과를추적검토하였다. 3) 방사선학적소견흉부 X선사진및흉부전산화단층촬영을영상의학과전문의가판독하였다. 판독상폐결핵의심소견에대한언급이있었는지여부를조사하였으며, 폐결핵영상의학검사에서동반될수있는경화 (consolidation), 림프절병증 (lymphadenopathy) 결절 (nodule), 공동 (cavity), 흉수 (effusion), 무기폐, 젖빛유리혼탁 (groundglass opacity) 등을분석하였다. 결과 1. 환자의특성대상환자총 19명중, 1명은객담에서결핵균이배양되었다. 나머지 18명은객담에서결핵균을확인할수없었거나, 객담을뱉을수없는환자였다. 이 18명을대상으로기관지내시경술을권유하였으 나, 이중 1 명은정신지체로인하여기관지내시경술시에협조가안 될것으로판단되어서기관지내시경술시행없이항결핵치료를시 작하였고, 2 명은검사권유를거절후재방문하지않아더이상추 적이되지못하였다 (Fig. 1). 객담검사를통해폐결핵이진단된 1 명 과기관지내시경을시행한 15 명의진단, 임상양상, 검사실소견을 조사하였다. 연구기간동안실제폐결핵으로진단된환자는총 7 명으로, 1 명 은객담검사를통해진단되었으며 6 명은기관지내시경을통해진 단되었다. 객담검사를통해폐결핵이진단된환자의경우도말검사, 결핵균 PCR, 배양검사모두양성이확인되어폐결핵으로확진되었 으며기관지내시경을통해진단된환자중 1 명은객담검사는음성 이었으나기관지내시경을통해확진되었다. 총 15 명의결핵의심환 자를대상으로기관지내시경을시행하였다 (Fig. 1). 기관지내시경 을통해폐결핵이진단된환자는 6 명 (40%), 폐결핵이외의질환 ( 비 결핵군 ) 으로진단된환자가 9 명 (60%) 이었다. 총환자들의진단당 시나이의중앙값 (median age) 은 13 세였고, 남자, 여자가 8 명으로 같았다 (Table 1). 총 7 명의폐결핵환자중가족혹은학급내친구 와긴밀한결핵접촉력이있었던경우가 3 명 (42.9%) 이었고, 결핵과 거력이있었던환자는없었다 (Table 2). 폐결핵환자군의투베르쿨 Table 1. Demographic and clinical characteristics of all patients Characteristic All suspects (n= 16) TB (n= 7) Non-TB (n= 9) Age (yr) 13.6± 4.0 14.7± 2.0 12.8± 5.0 Male sex 8 (50.0) 1 (14.3) 7 (77.8) Previous TB history 4 (25.0) 0 (0) 4 (44.4) Contact TB history 5 (31.3) 3 (42.9) 2 (22.2) Immunologic test IGRA positivity 6/11 (54.5) 5/6 (83.3) 1/5 (20) TST positivity 5/10 (50) 4/6 (66.7) 1/4 (25) Symptom Cough 10 (62.5) 4 (57.1) 5 (55.6) Sputum 5 (31.3) 2 (28.6) 3 (33.3) Fever 5 (31.3) 2 (28.6) 3 (33.3) Hemoptysis 2 (12.5) 1 (14.3) 1 (11.1) Night sweats 1 (6.3) 1 (14.3) 0 (0) Dyspnea 1 (6.3) 1 (14.3) 0 (0) Radiologic findings Consolidation 11 (68.8) 4 (57.1) 7 (77.8) Lymphadenopathy 8 (50.0) 3 (42.9) 5 (55.6) Nodule 6 (37.5) 5 (71.4) 2 (22.2) Cavity 1 (6.3) 1 (14.3) 0 (0) Effusion 4 (25.0) 1 (14.3) 3 (33.3) GGO 6 (37.5) 2 (28.6) 4 (44.4) Tree in bud 2 (12.5) 2 (28.6) 0 (0) Atelectasis 1 (6.3) 0 (0) 1 (11.1) Values are presented as mean± standard deviation or number of patients (%) TB, tuberculosis, IGRA, interferon-γ release assays; TST, tuberculin skin test; GGO, ground-glass opacity. https://doi.org/10.4168/aard.2017.5.5.287 289
Allergy Asthma Respir Dis Lee HJ, et al. Pulmonary tuberculosis and flexible bronchoscopy Table 2. The results of laboratory tests for the 7 pulmonary TB patients Case Sex/age (yr) Previous TB Hx Contact TB Hx Symptom Radiologist reading suspecting TB Radiologic finding Bronchoscopic finding TST (mm) IGRA Washing fluid laboratory results M. TB PCR AFB smear M. TB Cx. Other result M. TB sensitivity Treatment Outcome A* 1 F/16 (-) (-) Cough (+) Nodule, cavity Not done 0 (+) Sputum (+) Sputum (+) Sputum (+) (-) All S HERZ+HER Improved B 1 F/15 (-) (+) Cough, sputum, hemoptysis (+) Consolidation, LAP, nodule, tree in bud 2 F/11 (-) (-) Cough, fever (+) Consolidation, nodule, GGO 3 F/14 (-) (-) Cough, sputum, fever, night sweats (+) Consolidation, LAP, GGO, effusion RLL bronchus RLL bronchus 0 NA (+) (+) (+) (-) INH R+ HERZ F/U loss 10 (-) (+) (+) (+) (-) All S HERZ+HER Improved N/S 25 (+) Sputum (-) Sputum (-) Sputum (+) Rhino virus All S HERZ+HR Improved (+) (-) (+) 4 F/14 (-) (+) Dyspnea (+) Nodular opacity RUL bronchus inflammation NA (+) (+) (-) (+) (-) All S HERZ+HR Improved 5 M/17 (-) (+) (-) (+) Nodule, tree in bud N/S 10 (+) (-) (-) (+) (-) INH R+, PTH R+ 6 F/16 (-) (-) Cough (+) Consolidation, LAP, nodule Right main bronchus narrowing ERZ(9) Improved 17 (+) (+) (+) (+) Influenza virus All S HERZ+HR Improved TB Hx, tuberculosis history; TST, tuberculin skin test; IGRA, interferon-γ release assays; M. TB, Mycobacterium tuberculosis; PCR, polymerase chain reaction; AFB, acid fast bacilli; Cx., culture; LAP, lymphadenopathy; RLL, right lower lobe; NA, not available; INH, isoniazid; HERZ, isoniazid+ethambutol+rifampicin+pyrazinamid; F/U, follow-up; GGO, ground-glass opacity; N/S, nonspecific; HR, isoniazid+rifampicin; RUL, right upper lobe; PTH, prothionamide. *A, pulmonary tuberculosis (PTB) patient confirmed by only sputum test; B, PTB patients confirmed by bronchoscopy. Table 3. The results of laboratory tests for the 9 nonpulmonary TB patients Case Sex/ age (yr) Previous TB Hx Contact TB Hx Symptom Radiologist reading suspecting TB Radiologic finding Bronchoscopic finding TST (mm) IGRA Washing fluid laboratory results M. TB PCR AFB smear M. TB Cx. Other result Diagnosis Treatment Outcome 1 F/13 (-) (+) Cough, sputum 2 M/17 (+) (-) Sputum, hemoptysis (+) Consolidation, nodule, GGO 3 M/12 (-) (-) Cough (+) Consolidation, effusion, GGO LLL bronchus (-) NA (-) (-) (-) Mycoplasma PCR (+) MPP Roxithromycin Improved (-) LAP, atelectasis N/S NA NA (-) (-) (-) (-) (-) Observation Improved RML bronchus NA NA (-) (-) (-) RSV Pneumonia AMX-CLA, prednisolone 4 M/0 (+) (+) Cough, fever (-) Consolidation N/S (+) (-) (-) (-) (-) Adenovirus, E. facium 5 M/14 (-) (-) Neck mass (+) Consolidation, LAP LUL bronchus 6 M/10 (+) (-) Cough, sputum, fever (-) Consolidation, LAP, effusion, GGO 7 M/15 (+) (-) Cough, fever (+) Consolidation, endobronchial TB 8 F/17 (-) (-) (-) (-) Consolidation, LAP, effusion, GGO LUL bronchus mucus plug RUL bronchus mass 9 M/16 (-) (-) (-) (+) LAP, nodule RUL bronchus mucus NA (-) (-) (-) (-) Hodgkin's lymphoma (-) (+) Sputum (-) Sputum (-) Sputum (-) P.aeruginosa, (-) (-) (-) Asp Ag (+) NA NA (-) (-) (-) Carcinoid tumor N/S NA (-) (-) (-) (-) Mycoplasma PCR (+) Pneumonia Cefotaxime, clindamycin, prednisolone Hodgkin's lymphoma Fungal pneumonia Carcinoid tumor Improved Improved Chemotherapy Improved Voriconazole Improved VATS lobectomy Improved MPP Roxithromycin Improved (-) (-) (-) (-) (-) (-) (-) Observation Improved TB Hx, tuberculosis history; TST, tuberculin skin test; IGRA, interferon-γ release assays; M. TB, Mycobacterium tuberculosis; PCR, polymerase chain reaction; AFB, acid fast bacilli; Cx., culture; LLL, left lower lobe; NA, not available; MPP, Mycoplasma pneumonia pneumonia; LAP, lymphadenopathy; GGO, ground-glass opacity; LUL, left upper lobe; RUL, right upper lobe; AMX-CLA, amoxicillin-clavulanate; N/S, nonspecific; E. facium, Enterococcus faecium; LUL, left upper lobe; RUL, right upper lobe; VATS, video associated thoracoscopy. 290 https://doi.org/10.4168/aard.2017.5.5.287
이혜진외 폐결핵과굴곡성내시경 Allergy Asthma Respir Dis 린피부반응검사와 IGRA 검사양성률은각각 66.7%, 83.3% 였으며, 비결핵환자군의경우투베르쿨린피부반응검사와 IGRA 검사가위양성으로나타난사례가각각한명있었다 (Table 3). 연구기간동안총 5 명에서객담도말검사와배양검사가가능하였고, 이중 2명은기관지내시경후객담검체로양성이확인된환자였다. 위흡인액도말검사와배양검사를실시한경우는없었다. 두그룹모두첫내원시주호소증상은기침이 5명 (57.1%, 55.6%) 으로가장많았으며, 폐결핵환자중특이증상없이학교건강검진에서우연히발견된폐경화소견으로진단된경우도 1명있었다. 대상환자들중기저에만성폐질환, 혹은악성혈액종양등의전신질환이있는경우는없었다. 2. 흉부방사선소견대상환자들은모두흉부 X선사진혹은흉부전산화단층촬영검사상이상소견이관찰되었다. 영상의학과전문의의흉부 X선사진혹은흉부전산화단층촬영검사판독상폐결핵의심소견이있었는지여부를조사한결과, 6명의폐결핵환자는모두영상의학검사상결핵의심소견이있었으며그중 1명은흉부 X선사진은정상소견이었으나흉부전산화단층촬영검사상폐결핵의심소견으로기관지내시경시행후폐결핵으로진단되었다. 9명의비결핵환자군중 5명의환자에서는영상의학검사상결핵의심소견이있었으나, 기관지내시경결과최종적으로결핵이아닌것으로진단되었다. 폐결핵환자군에서는영상의학검사상결절소견을보인경우가 6명 (85.7%) 으로가장많았고, 다음으로폐경화와림프절병증소견이각각 4명 (57.1%), 3명 (42.9%) 으로많았다 (Table 1). 폐결핵환자에서는특징적으로 tree in bud 소견이 2명관찰되었으며, cavity 가동반된경우가 1예있었다. 이에비하여비결핵군에서는폐경화가가장흔한영상의학적소견이었으며, 결절이동반된경우가 2명 (22.2%) 으로폐결핵환자군에비하여상대적으로낮았다. 3. 기관지내시경소견기관지내시경을통하여폐결핵으로진단된환자 6명중 4명에서기도내염증및분비물증가소견이관찰되었으며, 이중 3명에서우측기관지 ( 우상엽 1명, 우하엽 2명 ) 점막이상소견을보였다. 비결핵군 9명중기도내염증소견이관찰된경우는 5명이었으며, 좌, 우기관지이상소견은각각 2명, 3명으로차이는없었다. 항결핵제에대한감수성검사결과 2명에서 isoniazid (INH) 내성이확인되었다 (Table 2). 폐결핵환자들의기관지세척액검사결과항산균도말검사양성이었던환자는 3명 (50%) 이었으며, MTB PCR 양성소견을보인환자는 5명 (83.3%) 으로항산균도말검사에비하여높은양성률을보였다. 비결핵군에서는 MTB PCR, 항산균도말검사, 결핵균배양검사모두음성으로확인되었다. 비결핵환자 9명중 2명은기관지세척액마이코플라스마 PCR 검사양성으로마이코플라 스마폐렴으로진단되었고마크로라이드항생제투여후호전되었다. 기관지세척액호흡기바이러스 PCR 검사양성으로진단된바이러스폐렴 2명및아스페르길루스항원양성으로진단된진균성폐렴 1명에서는각각항생제및항진균제치료후호전되었다. 그밖에조직검사결과 Hodgkin s lymphoma와 carcinoid tumor로확인되어항암치료및수술적치료로호전된사례 2명이포함되었으며, 기관지내시경검사결과아무것도확인되지않은 2명에서는치료없이외래추적하였으며, 폐결핵의심증상및영상의학결과호전되었음을확인하였다. 기관지내시경시술이후에유의한부작용이발생한환자는없었다. 고찰이번연구에서는객담배출이어렵거나객담도말검사에서위음성이의심되는소아청소년결핵의심환자를대상으로굴곡성기관지내시경검사를시행하여, 폐결핵진단율및항산균도말양성률, 결핵균배양양성률, MTB PCR 양성률등을알아봄으로써기관지내시경이폐결핵의진단에가지는효용가치를알아보았다. 활동성폐결핵의심환자에서내시경을이용한기관지세척법에의한연구는현재까지객담배출이불가능하거나객담결핵균도말검사상음성소견을보인성인환자들을대상으로제한적으로시행되었다. 이번연구에서기관지내시경을시행한총 15명의소아폐결핵의심환자중활동성폐결핵확진환자는 6명 (40%) 으로, 국내및국외연구에서객담도말음성결핵의심성인환자를대상으로기관지내시경을시행하였을때결핵진단률 40% 57% 와비교하였을때다소낮은편이나 Le palud 등이보고한 18.5% 보다는높다. 6,9-11 위연구들에서내시경검체를이용한항산균도말검사와결핵균배양검사의민감도는각각 25% 59%, 51% 88% 로보고하였다. 전통적으로폐결핵의진단에있어단순흉부방사선검사의이상소견이강조되어왔으나, 단일검사로서의가치는미약하다. 이번연구에서 1명의폐결핵환자는흉부 X선사진은정상소견이었으나흉부전산화단층촬영검사상폐결핵의심소견으로기관지내시경시행후폐결핵으로진단되었고, 영상의학검사상결핵이의심되었던환자중 12명중 5명은비결핵환자로확인되었다. 이전의연구에서도단순흉부방사선검사상결핵이의심되었던환자의단지약 1/3에서만결핵으로진단되었고, 12 활동성폐결핵이의심되었던환자들에서영상의학검사의특이도는 52% 63% 정도로높지않은것으로나타났다. 13 이번연구에서폐결핵환자군의가장흔한영상의학소견은결절 (71.4%) 이었고그다음으로는폐경화 (57.1%) 가많았으며, 이는이전국내청소년폐결핵환자를대상으로시행된영상학적검사연구결과와일치한다. 14 기관지내시경검체의항산균도말검사, 결핵균 PCR, 병리학적소견및내시경후객담도말검사를종합하여폐결핵환자의 92% 를 https://doi.org/10.4168/aard.2017.5.5.287 291
Allergy Asthma Respir Dis Lee HJ, et al. Pulmonary tuberculosis and flexible bronchoscopy 최종배양검사확인전진단가능하며, 9 기관지세척액검사결과를토대로총 75.9% 의폐결핵환자를진단할수있다는보고가있다. 6 MTB PCR의경우도말음성검체의경우민감도가 50% 미만으로감소하며, 15 특히우리나라와같은결핵유병률이높은지역에서는위양성가능성이높아미생물학적근거없이단일검사로써폐결핵을진단하는검사로서는무리가있다. 8 그러나기관지세척액을통한 MTB PCR의민감도는항산균도말검사에비하여의미있게높게보고되고있으며 9,11 이번연구에서도객담검사는음성이었으나기관지세척액에서 MTB PCR 양성이확인된결핵환자가 1명있었다. 객담도말음성환자들을대상으로기관지내시경을시행한여러임상연구들에서, 기관지내시경이폐결핵을진단한유일한도구였으며, 유용한검사방법임을서술한바있다. 6,9 또한기관지내시경은이전에객담배출이불가능하였거나객담도말검사음성이었던환자들에서내시경시행이후객담배출을용이하게함으로써, 결핵균을검출하는데효과적임이밝혀졌으며, 내시경이후에시행한객담검사에서유일하게결핵균이동정되는사례들도보고되었다. 9 이연구에서비결핵환자군의진단명은바이러스, 세균성, 진균성폐렴 (5예), 종양 (2예), 기타감염의근거가확인되지않은사례 (2 예 ) 등이었으며, 관련질환에대한치료혹은경과관찰로결핵의심증상및방사선소견호전경과를보였다. 이연구의비결핵환자군에서검출되지않은결핵이있었을가능성을완전히배제할수는없으나, 모두항결핵치료없이호전되었으므로가능성은낮다. 비결핵 case 4번환자의경우, 과거폐결핵환자접촉력과 TST 양성으로잠복결핵치료를완료하였던영아에서이후에폐렴이발생한경우로, 재활성화결핵에대한감별이필요하였다. 환자의기관지세척액결핵균검사는모두음성으로확인되었으며, 잠복결핵환자에서발생한바이러스성폐렴으로진단및치료후호전된경과를보였다. 지금까지보고된연구들에서도잠복결핵환자의기관지세척액검사에서결핵균이확인된경우는없었다. 16 활동성폐결핵으로진단된 6명중 1명에서 INH 단독내성이확인되었고, 다른 1명은 INH와 prothionamide에대한동시내성이관찰되었으며다제내성환자는없었다. 2004년조사에따르면국내폐결핵환자에서 INH 단독내성률은초치료환자에서 5% 정도로보고되고있고, 다제내성률도의미있게증가하고있다고알려져있으나, 소아청소년에환자의내성에대한연구는더필요한상태이다. 17 단일병원의단일분과내에서소아청소년폐결핵의심환자를대상으로굴곡성기관지내시경을시행한이번연구는, 대상자수가적어폐결핵의진단에있어기관지내시경술의효용적가치를명확히제시하기에는한계가있다. 또한, 이연구에서는내시경시행이전에항결핵제치료를시작한환자군을제외하였으므로, 모든폐결핵의심환자를대상으로기관지내시경을시행하지않았다는 한계점이있다. 결론적으로, 굴곡기관지내시경술은소아청소년을대상으로국 소마취하에도시행이가능하고, 심각한합병증발생의가능성이 적으며, 18 또한폐결핵이외에도기관지내감염및기타악성종양 의감별에도유용하다는장점이있으므로, 객담배출이어렵거나 객담도말검사에서위음성이의심되는소아청소년폐결핵의심환 자를대상으로기관지내시경검사가적극적으로이루어져야할것 으로생각한다. REFERENCES 1. Global tuberculosis report 2015. 20th edition [Internet]. Geneva: World Health Organization; c2015 [cited 2016 Nov 23]. Available from: http:// apps.who.int/iris/bitstream/10665/191102/1/9789241565059_eng.pdf. 2. Steingart KR, Sohn H, Schiller I, Kloda LA, Boehme CC, Pai M, et al. Xpert MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 2013;(1):CD009593. 3. Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health 2014;2:e453-9. 4. Jenkins HE, Tolman AW, Yuen CM, Parr JB, Keshavjee S, Pérez-Vélez CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet 2014;383:1572-9. 5. Siddiqi K, Lambert ML, Walley J. Clinical diagnosis of smear-negative pulmonary tuberculosis in low-income countries: the current evidence. Lancet Infect Dis 2003;3:288-96. 6. Shin JA, Chang YS, Kim TH, Kim HJ, Ahn CM, Byun MK. Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative pulmonary tuberculosis. BMC Infect Dis 2012;12:141. 7. Yoo R, Kim JI, Kim S, Lee J. Discordance between tuberculin skin test and interferon-gamma release assays for diagnosis of tuberculosis infection in Korean children. Pediatr Infect Vaccine 2016;23:18-24. 8. Jo YS, Park JH, Lee JK, Heo EY, Chung HS, Kim DK. Discordance between MTB/RIF and real-time tuberculosis-specific polymerase chain reaction assay in bronchial washing specimen and its clinical implications. PLoS One 2016;11:e0164923. 9. Tamura A, Shimada M, Matsui Y, Kawashima M, Suzuki J, Ariga H, et al. The value of fiberoptic bronchoscopy in culture-positive pulmonary tuberculosis patients whose pre-bronchoscopic sputum specimens were negative both for smear and PCR analyses. Intern Med 2010;49:95-102. 10. Lee SJ, Yoon DK, Kim SH, Park IW, Choi BW, Hue SH, et al. Diagnosis of suspected active pulmonary tuberculosis by flexible fiberoptic bronchoscopy. Tuberc Respir Dis 1989;36:22-7. 11. Le Palud P, Cattoir V, Malbruny B, Magnier R, Campbell K, Oulkhouir Y, et al. Retrospective observational study of diagnostic accuracy of the Xpert MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis. BMC Pulm Med 2014;14:137. 12. Schoch OD, Rieder P, Tueller C, Altpeter E, Zellweger JP, Rieder HL, et al. Diagnostic yield of sputum, induced sputum, and bronchoscopy after radiologic tuberculosis screening. Am J Respir Crit Care Med 2007;175: 80-6. 13. Dasgupta K, Menzies D. Cost-effectiveness of tuberculosis control strategies among immigrants and refugees. Eur Respir J 2005;25:1107-16. 14. Kang SJ, Kim YH, Jung CY, Lee HJ, Hyun MC. Clinical characteristics 292 https://doi.org/10.4168/aard.2017.5.5.287
이혜진외 폐결핵과굴곡성내시경 Allergy Asthma Respir Dis and radiologic patterns of adelescents with pulmonary tuberculosis: relevance to the reactive tuberculosis. Pediatr Allergy Respir Dis 2012;22: 163-70. 15. Rapid diagnostic tests for tuberculosis: what is the appropriate use? American Thoracic Society Workshop. Am J Respir Crit Care Med 1997; 155:1804-14. 16. Iyer VN, Joshi AY, Boyce TG, Brutinel MW, Scalcini MC, Wilson JW, et al. Bronchoscopy in suspected pulmonary TB with negative inducedsputum smear and MTD( ) Gen-probe testing. Respir Med 2011;105: 1084-90. 17. Bai GH, Park YK, Choi YW, Bai JI, Kim HJ, Chang CL, et al. Trend of anti-tuberculosis drug resistance in Korea, 1994-2004. Int J Tuberc Lung Dis 2007;11:571-6. 18. Kahn MA, Whitcomb ME, Snider GL. Flexible fiberoptic bronchoscopy. Am J Med 1976;61:151-5. https://doi.org/10.4168/aard.2017.5.5.287 293