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1 Korean J Fam Med. 2009;30: doi: /kjfm 기관지성폐렴환자에서경험한통상성간질성폐렴 1 예 증례 이정운 *, 신새론 1, 김휘정 2, 박정현 2 원광대학교산본병원가정의학과, 1 원광대학교병원가정의학과, 2 원광대학교산본병원호흡기내과 A Case Report of Usual Interstitial Pneumonia after Treatment of Bronchopneumonia Jung-Un Lee, MD*, Sae Ron Shin, MD 1, Hui Jung Kim, MD 2, Jeong Hyun Park, MD 2 Department of Family Medicine, Sanbon Medical Center, Wonkwang University, Gunpo, 1 Department of Family Medicine, Wonkwang University Hospital, Iksan, 2 Division of Pulmonology, Department of Internal Medicine, Sanbon Medical Center, Wonkwang University, Gunpo, Korea Usual interstitial pneumonia (UIP) is one type of idiopathic interstitial pneumonia, characterized by its poor prognosis and gradual deterioration of clinical course. So it is important to distinguish UIP from other interstitial pneumonia. Definitive histological diagnosis of UIP requires lung biopsy. The criteria for diagnosis of UIP in the absence of a surgical lung biopsy were recently defined. We report a case of 75-year-old man who was diagnosed as bronchopneumonia with chief complaint of fever, dyspnea on first visit, then finally diagnosed as UIP through the remaining of chest abnormality after treatment. Keywords: Usual Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Idiopathic Interstitial Pneumonia; Interstitial Pneumonia 서론 통상성간질성폐렴 (usual interstitial pneumonia, UIP) 은특발성폐섬유증 (idiopathic pulmonary fibrosis, IPF) 의병리학적소견으로내린진단명으로, 과거 Liebow와 Carrington 1) 이간질성폐렴을최초로조직학적으로분류하기시작한이래널리사용되었던진단명이다. 이후 2002년미국흉부학회와유 접수일 : 2009년 2월 4일, 승인일 : 2009년 4월 3일 * 교신저자 : 이정운 Tel: , Fax: tracheo@naver.com Korean Journal of Family Medicine Copyrights 2009 by The Korean Academy of Family Medicine 럽호흡기학회에서제시한진단기준에서는조직학적진단명 (histologic patterns) 으로는통상성간질성폐렴, 임상-방사선- 병리학적진단명 (clinical-radiological-pathological diagnosis) 으로는특발성폐섬유증 (IPF) 으로분류하였으며, 현재임상에서는기존의분류에따른통상성간질성폐렴과특발성폐섬유증이함께사용되고있다. 2) 통상성간질성폐렴은가장흔한형태의만성특발성간질성폐렴 (idiopathic interstitial pneumonias, IIP) 으로특징적으로 40-60세의연령분포를보이며점진적인호흡곤란, 마른기침, 피로감등을호소하며, 폐기능검사상대개제한성폐질환형태 (restrictive pattern) 와폐확산능 (diffusion lung capacity) 의감소소견을보이며특발성간질성폐렴중에서스테로이드치료에대한반응이없는것이특징이며예후는가장나쁜편으로진단후평균수명 (median survival) 은약 년이며사망률은약 44.6% 이다. 3-7) 가정의학회지 Vol. 30, No. 4 Apr

Jung-Un Lee, et al: A Case Report of Usual Interstitial Pneumonia After Treatment of Bronchopneumonia 통상성간질성폐렴의가장흔한방사선학적소견은양측성폐기저부의작거나중간크기의불규칙한선상음영또는간유리음영 (ground gland opacity) 을보이며더욱진행된병변의경우조잡한

8,9) 하지만저자들은우측폐에기관지폐렴을치료한후에도오른쪽폐에두드러지게 (dominant) 진행된망상형음영과간유리음영이벌집모양낭포가관찰되어통상성간질성폐렴환자로진단한 75세남자환자를경험하였기에문헌고찰과함께보고하는바이다. 증례 75세남자환자가 2일전부터시작된열감과왼쪽늑골부위통증을주소로외래를방문하였다.

과거력상환자는 1995년에뇌졸중으로왼쪽근력약화있으나거동에는불편함이없었고, 이후부터고혈압약물치료시작하였으며, 2000년췌장염합병증치료를위한부분췌장절제술을시행받은후당뇨병이발생하여자가인슐린주사로치료중이었다. 당시복용중인약물은 amlodipine besylate 10 mg, digoxin 0.

2 Jung-Un Lee, et al: A Case Report of Usual Interstitial Pneumonia After Treatment of Bronchopneumonia 통상성간질성폐렴의가장흔한방사선학적소견은양측성폐기저부의작거나중간크기의불규칙한선상음영또는간유리음영 (ground gland opacity) 을보이며더욱진행된병변의경우조잡한 (coarse) 망상형 (reticular) 또는망상결절 (reticulonodular) 음영의소견을보이며말기섬유화가동반되면약 1 cm 직경의뚜렷이구분되는벌집모양낭포 (honeycomb cyst) 와함께폐용적의점진적인감소소견을볼수있다. 8,9) 하지만저자들은우측폐에기관지폐렴을치료한후에도오른쪽폐에두드러지게 (dominant) 진행된망상형음영과간유리음영이벌집모양낭포가관찰되어통상성간질성폐렴환자로진단한 75세남자환자를경험하였기에문헌고찰과함께보고하는바이다. 증례 75세남자환자가 2일전부터시작된열감과왼쪽늑골부위통증을주소로외래를방문하였다. 환자는내원 5일전넘어지면서왼쪽늑골부위를다쳤고, 근처정형외과방문후왼쪽 7번늑골골절진단받은상태로집에서안정치료중에내원 2일전부터시작된열감과함께간헐적인호흡곤란증상을호소하여본원을방문하였다. 과거력상환자는 1995년에뇌졸중으로왼쪽근력약화있으나거동에는불편함이없었고, 이후부터고혈압약물치료시작하였으며, 2000년췌장염합병증치료를위한부분췌장절제술을시행받은후당뇨병이발생하여자가인슐린주사로치료중이었다. 당시복용중인약물은 amlodipine besylate 10 mg, digoxin mg, nifedipine 30 mg bid, gemfibrozil 30 mg bid, insulin 등이었다. 환자는 30년동 안군대에서근무하였는데그외의직업은가진적이없었다. 화약이나폭약을다루지않았으며, 전쟁에도참여하지않았으며군대에서도주로사무실근무를하였다. 내원당시생체징후는수축기혈압 130 mmhg, 이완기혈압 60 mmhg, 맥박 75회 / 분, 호흡 20회 / 분, 체온 37.5 o C였고, 흉부진찰소견에서우측폐야의호흡음감소와수포음관찰되었으며당일시행한흉부촬영결과오른쪽폐전장에걸친음영증가와양측폐하부의불규칙한선상음영이관찰되었다 ( 그림 1A). 기관지성폐렴의심하여입원후객담배양검사, 혈액배양검사후 ceftriaxone, isepamicin sulfate 정주로항생제치료시작하였다. 응급검사로시행한일반혈액검사에서는백혈구 9,800 mg/dl, 다핵구는 88.5% 로증가되었고, 동맥혈가스검사 ph 7.50, PCO mmhg, PO mmhg, HCO mmol/l, 공복혈당 124 mg/dl 측정되어 nasal prong으로 O2 2L 공급하면서산소포화도측정하였다. 입원 2일까지체온 37 o C로미열소견보이다가, 입원 3일부터체온정상으로떨어졌으며, 환자전신상태도호전되는양상관찰되었다. 왼쪽폐야의호흡음도정상이었고수포음도관찰되지않았다. 입원 3일째객담배양검사결과 Klebsiella Pneumoniae 균배양이관찰되었고균감수성결과에서도사용중인항생제감수성보여이후 2주간항생제치료하기로계획을세웠다. 입원 7일부터호흡곤란없어 O2 공급중지하였고, 입원 10일째실시한흉부촬영결과이전에비해오른쪽폐의음영은줄었지만, 불규칙한선상음영, 간유리음영 (ground gland opacity) 이오른쪽폐와양측폐기저부에서지속적으로관찰되었다 ( 그림 1B). 기관지성폐렴은임상적으로호전되었으나흉부촬영소견상간질성폐질환의심되어고해상도폐 Figure 1. (A) Chest PA on admission day shows that diffuse consolidation of whole right lung suggesting bronchopneumonia and reticular opacities in both lower lobes. (B) Follow up chest PA on 10th day of admission shows that improved opacities of right lung but still remained reticular opacities in both lower lobes (Right > Left). (C) Chest PA of 1 year ago was retrospectively reviewed, it showed that minimal reticular nodular opacities in both lower lung fields. 302 Vol. 30, No. 4 Apr 2009 Korean J Fam Med

이정운외 : 기관지성폐렴환자에서경험한통상성간질성폐렴 1 예 Figure 2. High resolution computed tomography shows reticular and ground-glass opacity with honeycombing cyst in both lungs especially both lower lobes and right lung.

HRCT 검사결과양측폐기저부에망상형음영 (reticular opacity) 이관찰되고, 우측폐전체에미만성간유리음영 (ground gland opacity) 이관찰되어통상성간질성폐렴이의심되었다.

3 이정운외 : 기관지성폐렴환자에서경험한통상성간질성폐렴 1 예 Figure 2. High resolution computed tomography shows reticular and ground-glass opacity with honeycombing cyst in both lungs especially both lower lobes and right lung. (A) sub-carinal level. (B) liver dome level. CT 검사 (high resolution computed tomography, HRCT) 를실시하였다 ( 그림 2). HRCT 검사결과양측폐기저부에망상형음영 (reticular opacity) 이관찰되고, 우측폐전체에미만성간유리음영 (ground gland opacity) 이관찰되어통상성간질성폐렴이의심되었다. 이에폐기능검사및기관지내시경검사를실시하였으며, 폐기능검사결과 FVC (forced vital capacity) 68% ( 정상 : 80% 이상 ), FEV1 (forced expiratory volume in 1 second) 82%, FEV1/FVC 119%, DL CO (diffusion lung capacity) 45% ( 정상 : 80% 이상 ) 로경도의제한성양상 (restrictive pattern) 과폐확산능력이저하되었고, 기관지내시경검사결과기도내부의이상소견은관찰되지않았으며기관지폐포세척술 (bronchoalveolar lavage, BAL) 결과백혈구 480/mm 3, 호중구 70%, 림프구 4% 였다 (BAL정상소견: 대식세포 80-85%, 호중구 1-2%, 림프구 10% 내외, 호산구 1% 미만 ). 류마티스양인자 (rheumatoid factor), 항핵항체 (antinuclear antibody), 항DNA항체 (anti double stranded DNA antibody) 검사모두음성이었다. 입원 14일째경구용항생제로바꾸었으며환자불편증상없어서퇴원하였고이후추적흉부촬영과 HRCT 검사를퇴원후실시하였으며, 현재기존질환에대한약물치료외에특별한치료없이외래추적관찰중이다. 고찰 통상성간질성폐렴의임상적증상은대부분만성적으로 1-2년에걸쳐서서히진행되는마른기침과, 노작성호흡곤란 (exertional dyspnea) 이주증상이고 10,11) 진찰상양폐저부에서흡기말수포음이들리고, 말단곤봉지가관찰되기도한다. 10) 교원성혈관질환의상관관계는복잡하며약 20% 의통상성간 질성폐렴환자가교원성혈관성또는기타면역학적질환의소견을보이는데류마티스관절염 (rheumatoid arthritis) 이가장흔히동반된다. 5) 또한임상적으로교원성혈관질환의증후를보이지않는통상성간질성폐렴환자에서류마티스인자또는항핵항체수치의단독상승소견이종종관찰되며교원성혈관질환과동반된경우좋지못한예후를보이는조직학적소견과동반된다는보고가있다. 12,13) 흉부 X선소견은양측폐기저부의불규칙적인선상음영, 간유리음영, 벌집모양변화및동반된폐용적의감소이다. 불규칙선상음영은모든예에서관찰되며폐하부주변부에가장흔하다. 8,9) 간유리음영은약 62% 정도에서보이며특히전형적으로폐기저부에위치한다. 폐용적은 45-75% 에서감소되며, 8,14) 74% 에서벌집모양변화 (honeycombing) 가유발된다. 8) HRCT는단순흉부 X선검사상정상인경우에도병변을발견할수있을뿐아니라, 다른간질성폐질환들과의감별진단에도도움이된다. 특징적인 HRCT 소견은망상음영으로주로양폐기저부, 특히흉막직하부위에서가장심하게나타나며, 주위의섬유화에의해세기관지들이확장된세기관지확장증 (traction bronchiectasis), 또는벌집모양현상에의한 2-4 mm의소낭포들이동반되기도한다 ) 폐기능검사소견은폐유순도 (compliance) 가감소하고, FVC와 TLC 등폐용적이감소하는제한성변화소견이며, FEV1도감소하나 FEV1/FVC와기도저항은정상이다. 대부분환자들에서폐확산능이저하되며, 이는가스교환에참여하는폐포-모세혈관자체가감소하는것에도기인하나, 환가 / 관료 (V/Q) 불균형이더중요한원인이다. 18) 안정기의동맥혈가스검사 (arterial blood gas analysis) 결과는정상, 또는환기 / 관류불균형에의한저산소혈증과호흡성알칼리혈증소견이나타날수있다. 기관지폐포세척술은발 가정의학회지 Vol. 30, No. 4 Apr

4 Jung-Un Lee, et al: A Case Report of Usual Interstitial Pneumonia After Treatment of Bronchopneumonia 병기전등을연구하는데큰역할을하였으나결과가비특이적이기때문에진단적가치는별로없어모든환자들에서시행할필요는없다. 통상성간질성폐렴에서는기관지폐포세척술액내총세포수와호중구의백분율이증가하는것이특징이며, 호산구와비반세포도약간의증가를보인다. 19) 통상성간질성폐렴은예후가나쁜병이므로최근에는엄격한진단기준을적용하는추세이며, 확진을위해서는개흉, 또는흉강경을통한수술적폐생검의병리조직학적검사가필수적이다. 특히임상소견과 HRCT 소견이전형적인통상성간질성폐렴의소견과일치하지않는경우에는반드시생검을권유하고있지만, 2) 미국흉부학회 (American Thoracic Society) 와유럽호흡기학회 (European Respiratory Society) 에서는다음의진단기준에적합하는경우에는조직검사없이통상성간질성폐렴진단이가능함을제시하였다. 2) 다음의주진단기준 (major criteria), 1) 약물, 독성물질, 환경적인노출이나결체조직질환과같은간질성폐렴의원인요인이없으면서, 2) 제한성폐질환형태의폐기능장애 (abnormal function studies) 와가스교환장애 (increased P (A-a) O 2, decreased Pa O2 with rest or exercise or decrease DL CO ) 가관찰되어야하며, 3) HRCT 검사결과양측폐하부의망상형음영이관찰되며, 4) 경기관지폐생검 (Trnasbronchial lung biopsy) 또는기관지폐포세척술 (bronchoalveolar lavage) 에서다른질환을의심할만한이상소견이없어야한다. 이모두해당되면서, 아래의부진단기준 4개중에서 3개이상에해당되어야한다. 1) 나이가 50세이상이면서, 2) 설명되지않는노작성호흡곤란이서서히진행되었으며, 3) 3개월이상의질환경과가있었으며, 4) 양측폐하부의수포음 (bibasilar inspiratory crackles) 이관찰된다 본증례의환자는갑작스런열과호흡곤란으로기관지폐렴치료를받았고, 치료후임상적인증상은호전되었으나흉부촬영에서오른쪽폐와양측폐기저부에지속되는망상형음영으로인해간질성폐렴의심하게되어, 추가검사및추가병력청취등을통해통상성간질성폐렴진단받았다. 환자는과거뇌졸중으로인해왼쪽편측마비로인해보행에장애가있었고, 활발한활동이어려워서호흡곤란을평소호소하지않았지만추가병력청취를통해확인한바로는노작성호흡곤란이있었으며, 1년전본원에서시행한흉부촬영검사에서도양측폐하부의미세한망상형음영이확인되었다 ( 그림 1C). 환자는 75세로이미뇌졸중, 당뇨, 고혈압등병력등으로정상적인활동에장애가있었던까닭에수술적인폐생검은시도하지않았으나임상증상과방사선학적인진단기준에따라통상성간질성폐렴으로진단할수있었다. 과거력상군대에서사무실근무를한것이외의직업력은없으며현재복용 중인약물중에서통상성간질성폐렴과관련이알려진것은없었다. 또한혈청학적검사결과도모두정상으로이차적인원인에의한간질성폐렴은의심되지않았다. 폐기능검사와 HRCT 검사결과, 그리고기관지폐포세척술과경기관지폐생검 (transbronchial lung biopsy, TBLB) 에서도모두진단기준에적합하였다. 국내에보고된통상성간질성폐렴증례를고찰해보면, 젊은환자에서폐암이병발되었거나, 20) 원발부위미상의암이동반되었던경우 21) 그리고통상성간질성폐렴환자에서원발성근결핵 (primary tuberculosis myositis) 이진단되었던경우 22) 등주로동반된질환에대한보고가대부분이었다. 하지만, 본증례는통상성간질성폐렴의전형적인 HRCT 소견을보이지만좌우대칭형이아니라, 우측폐를주로침범했다는 (right side dominant) 점에서흔히알려진통상성간질성폐렴증례와차별되며, 동시에노인환자에서기관지성폐렴을치료한후에도호흡곤란의해소여부에대한병력청취와추적방사선학적관찰이본증례와같은간질성폐렴의병발여부확인을위해매우중요함을보여준다. 특발성간질성폐렴은미만성폐실질질환 (diffuse prenchymal lung diseases) 의한그룹으로, 여러다른질환을배제하고호흡곤란이있으면서흉부방사선상미만성간질성폐침윤이관찰되고폐조직검사소견상폐실질의염증과섬유화등이나타나며특별한원인을찾을때를말한다. 2) 조직학적으로는폐간질의비후 (thickening) 와왜곡을특징으로하며전통적인특발성간질성폐렴의분류에는임상적, 병리학적으로많은혼동과변화가있어왔다. 18) 1960년대 Liebow와 Carrington 1) 은조직학적양상에따라최초로특발성간질성폐렴 (IIP) 을분류하였고, Katzenstein 와 Fiorelli 4) 는일부질환에서원인이밝혀지면서폐포성질환 (airspace pattern) 으로다시정리하였고, 최근만성특발성간질성폐렴의예중에서통상성간질성폐렴이나박리성간질성폐렴 (desquamative interstitial pneumonia, DIP) 으로분류할수없으나일정한병리학적소견을보이는예들을모아비특이적간질성폐렴 (nonspecific interstitial pneumonia, NIP) 이라칭하고, 이전에 Hamman-Rich 증후군으로기술된적이있는임상적으로급성호흡부전 (acute respiratory failure) 의증상을보이고빠른임상경과를보이며예후가나쁜간질성폐렴의종류를급성간질성폐렴 (acute interstitial pneumonia, AIP) 으로명명하면서현재의간질성폐렴의분류로자리잡았다. 18) 주요간질성폐렴의임상적인특징은다음과같다 ( 표 1). 특발성폐섬유증은예전에는특발성간질성폐렴과동일한의미로쓰이기도했으나, 최근에는특발성간질성폐렴중 304 Vol. 30, No. 4 Apr 2009 Korean J Fam Med

5 이정운외 : 기관지성폐렴환자에서경험한통상성간질성폐렴 1 예 Table 1. Clinical characteristics of interstitial pneumonia. 25) Clinical feature UIP (Usual interstitial pneumonia) DIP (Desquamative interstitial pneumonia) AIP (Acute interstitial pneumonia) Onset Chronic Chronic Acute or chronic Subacute Age 40-60th Younger than UIP 40-50th 30-50th NSIP (Nonspecific interstitial pneumonia) Course Several years Several years Several weeks-months Several months-years Prognosis Poor Good Poor Good Median survival 4 y 12 y A few days ~ months Variable Smoking correlation No Yes No No Association with cardiovascular disease Yes No No Yes Steroid response No Yes Yes Yes 에서가장흔한통상성간질성폐렴의병리소견을가진경우로제한되어사용되고있으며, 2) 영국및유럽에서는특발성섬유화성폐포염 (cryptogenic fibrosing alveolitis) 으로불리운다. 18) 통상성간질성폐렴의자연적인경과를아직정확히모르고, 현재사용되는약제들이부작용이심하고, 치료효과를확실하게증명할만한대조-연구가없기때문에환자를언제, 또어떻게치료해야되는지는정립되어있지못하다. 18) 그러나치료를하지않았을때계속적으로악화되어환자의약 50% 이상이 3-5년내에사망한다고알려져있고, 10,23,24) 또일단병이진행되어완전히섬유화로굳어진다음에는어떤치료를하더라도호전이되지않기때문에치료를한다면조기에치료할경우에효과가있을가능성이높을것으로예측하고있다. 치료제에는 steroid와 azathioprine, 또는 cyclophosphamide의병합요법을사용하는데동의하고있으나, steroid 치료에대해박리성간질성폐렴과폐쇄세기관지기질화폐렴 (bronchiolitis obliterans with organizing pneumonia, BOOP) 은반응이좋은반면통상성간질성폐렴은객관적으로호전을보이는경우는드물다. 보조적인치료로는 24시간지속적인산소투여와, 근력을유지하고, 심폐기능의효율을높이기위한지속적인재활치료가있다. 그러나말기 UIP 환자에서는폐이식외에는다른효과적인치료방법이없다. 18) 요약 통상성간질성폐렴은간질성폐렴의한종류로서, 조직병 리학적소견으로아직병의자연경과를정확히모르고치료법이정립되어있지않으며특히예후가나쁜병으로알려져있다. 원인모르게폐포벽에만성염증세포들의침윤과섬유모세포및교원질침착이증가되어심한폐조직의구조적변화를야기하는질환이다. 저자들은열감, 호흡곤란으로내원하여기관지성폐렴진단및치료후에도오른쪽폐에두드러지게진행된방사선학적이상소견으로통상성간질성폐렴으로진단된 75세남자환자를경험하였기에이를보고하는바이다. 중심단어 : 통상성간질성폐렴, 특발성폐섬유증, 특발성간질성폐렴, 간질성폐렴. 참고문헌 1. Liebow AA, Carrington CB. The interstitial pneumonias. In: Simon M, Potchen EJ, LeMay M, editors. Frontiers of pulmonary radiology. 1st ed. New York: Grune & Stratton; p American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 가정의학회지 Vol. 30, No. 4 Apr

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<313820C1F5B7CA B1E8B9CEC1A42DB1E8C0B1BCBA D E687770> 대한내과학회지 : 제 84 권제 1 호 2013 http://dx.doi.org/10.3904/kjm.2013.84.1.105 Bronchiolitis Interstitial Pneumonitis 1 예 1 좋은삼선병원내과, 양산부산대학교병원 2 내과, 3 흉부외과 김민정 1 김윤성 2 김도형 3 전태영 1 이수진 1 김양진 1 A Case of Bronchiolitis