The Korean Journal of Pathology 2006; 40: 소기도질환의임상특성및병리학적판독 권건영 최원일 1 고성민 2 계명대학교의과대학병리학교실 1 내과학교실, 2 진단방사선학교실 Small Airway Diseases: Clinical

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1 The Korean Journal of Pathology 2006; 40: 소기도질환의임상특성및병리학적판독 권건영 최원일 1 고성민 2 계명대학교의과대학병리학교실 1 내과학교실, 2 진단방사선학교실 Small irway Diseases: Clinical Characteristics and Pathological Interpretation Kun Young Kwon, Won Il Choi 1 and Sung Min Ko 2 Departments of Pathology, 1 Internal Medicine and 2 Diagnostic Radiology, Keimyung University School of Medicine, Daegu, Korea 책임저자 : 권건영우 대구광역시중구동산동 194 계명대학교의과대학병리학교실전화 : Fax: k19156ky@dsmc.or.kr Small airway diseases are seen in many clinical conditions. The locations of small airway diseases are small bronchioles including terminal and respiratory bronchioles, and alveolar duct. The histopathologic features of bronchiolar injury have been described variously and have led to confusing and overlapping terms. The purpose of this article is to describe the clinical characteristics and histopathologic interpretation of small airway diseases. We classify the small airway diseases as primary bronchiolar diseases, and secondary bronchiolar diseases including pulmonary parenchymal diseases, and large airway diseases with prominent bronchiolar involvement. Primary bronchiolar diseases include respiratory bronchiolitis, acute bronchiolitis, constrictive bronchiolitis, follicular bronchiolitis, diffuse panbronchiolitis, mineral dust airway diseases, and a few other variants. Pulmonary parenchymal diseases with bronchiolar involvement include respiratory bronchiolitis-associated interstitial lung disease, organizing pneumonia, hypersensitivity pneumonitis, pulmonary Langerhans cell histiocytosis, sarcoidosis and idiopathic pulmonary fibrosis. ronchiolar changes can also be seen in large airway diseases such as chronic bronchitis, bronchiectasis, cystic fibrosis and asthma. The patterns of bronchiolar response to various injuries are relatively limited and these patterns are generally non-specific in regard to the etiology. ppropriate interpretation and diagnosis of small airway diseases depend on judicious correlation of clinical, radiologic, and histopathologic characteristics. Key Words : Small airway disease; Primary bronchiolar disease; Secondary bronchiolar disease; Tobacco-related disease 소기도 (small airways) 의병변은다양한임상조건에서흔하게볼수있다. 폐이식환자에서폐쇄세기관지염 (bronchiolitis obliterans, O) 이발생하며, 인접한기관지에기관지확장증이있거나폐실질에기관지폐렴또는만성호산구폐렴이있을때소기도에병변이확장될수있다. 1-3 만성폐쇄폐질환이나천식이있을때소기도에염증성병변을동반하기도하며, 4 감염, 흡연, 약물, 흡입성손상및결합조직질환등에서도소기도에염증을볼수있다. 1 그러나다양한원인에의해소기도질환이초래되지만병리조직학적으로는그변화의양상이제한적이며, 비특이적이므로정확한판독과진단을위해서임상, 방사선및병리조직학적소견을종합하여평가하는것이필요하다. 2,5 본론소기도의정상구조소기도는내경 2 mm 이하의작은세기관지와종말세기관지 (terminal bronchiole), 호흡세기관지 (respiratory bronchiole) 및폐포관 (alveolar duct) 으로구성된다. 6 여기에병변이있을경우소기도질환이라고하며대부분세기관지에염증-섬유성변화를보여준다. 1 기관지와달리세기관지벽에는연골이없어서외부압력에의해서허탈 (collapse) 되기쉬우며, 분비샘이존재하지않는다. 2,6 내경 1 mm 이내의종말세기관지는대체로 3개의호흡세기관지로분지하여폐포관과폐포로연결되며가스교환을담당하는단위인세엽 (acinus) 을이룬다. 2,6 기도점막의상피세 389

2 390 권건영 최원일 고성민 포는위치에따라서다양한광학현미경적소견을보인다. 기관및기관지에는위중층섬모원주상피세포가풍부하나세기관지에이르면섬모원주상피세포의수가감소하고기저세포가사라진다. 종말세기관지에는클라라세포가출현하며, 호흡세기관지에이르면서그수가현저히증가한다. 3,6 소기도의기능과임상적의의내경이 2 mm보다큰기도에서는와류 (turbulent) 가형성되나 2 mm 이하의소기도에서는대기도에비해서단면적이매우넓어지면서결흐름 (laminar) 의기류가주로이루어진다. 8 종말세기관지와호흡세기관지에많이분포하는클라라세포는표면활성제를분비하여소기도점막면의표면장력을낮춘다. 특히호기때에표면장력이많이낮아져서폐용적이매우작아질때에도소기도의폐색이발생하지않는다. 9 소기도에정상적으로표면활성제가존재하는경우표면장력이 5 dynes/cm가된다. 염증에의해소기도상피세포의표면에혈장으로덮이면 40 dynes/ cm으로상승하고, 점액으로덮이면 25 dynes/cm이된다. 따라서표면활성제이외의성분으로점막상피세포표면이덮이게되면소기도가불안정해지고쉽게폐색이일어난다. 만일표면활성제의결핍에의해서소기도의폐색이광범위하게진행하면공기가폐포에갇히게되며, 결과적으로잔기량을증가시킨다. 10 정상적인경우소기도는잔기량까지폐용적이감소하면닫히게된다. 잔기량은나이가많아지면서증가하며이로인해종말세기관지가젊은사람에비해서쉽게닫히게된다. 성인천식에서는기도내강이협소해지며점액에의한기도폐색과함께소기도의염증으로인해세기관지가기류폐색을일으키는주요지점으로인식되고있다. 10,11 정상성인의폐에서소기도의저항은전체기도저항의 10% 정도로매우낮다. 12 소아에서는성인에비해서소기도의저항이상대적으로크므로소아에서세기관지염이발생할경우성인보다기류폐색의증상이심하게나타난다. 13 성인의경우소기도에장애가생겨서기도저항이 2배가증가하더라도전체기도저항은약 10% 만상승하므로폐기능검사에서이상소견을발견하기가어렵고임상증상도경미한경우가많다. 13 실험적으로크기가다른구슬을사용하여소기도와대기도를각각막은후측정한폐의압력-용적곡선을그리면소기도를막은경우에는변화가없으며, 총기도저항은약 10% 만상승한다. 14 특히곁환기 (collateral ventilation) 가발달되어있는사람과개에서는소기도폐색에따른기도저항으로인한영향과환기분포의변화가뚜렷하지않다. 14 소기도폐색의임상적진단기준호기시공기는기도에서부터폐포순으로나온다. 기도용적곡선에서폐활량이중간 (maximal mid-expiratory flow rate) 혹 은끝에서측정한기류는말초기도의공기흐름을반영하므로, 소기도저항을반영한다고할수있다. 그러나이러한말초기도의기류도소기도저항과폐의복원력에의해결정이되므로소기도저항을민감하게반영하지않을수있다. 또한기류의측정은모든소기도의평균치만반영하므로, 국소적으로세기관지염이있는상황에서기류의측정만으로소기도저항의변화를정확하게판단하기는매우어렵다. 기류의측정이외에도잔기량, 폐쇄용적 (closing volume), 그리고주파수의존형유순도 (frequency dependence of compliance) 등을소기도폐색의진단에사용하나임상적유용성은적은편이다. 11 소기도질환의분류 소기도질환의주류가되는세기관지의염증은소기도를침범하는가장흔한병변이나세기관지염자체로서임상증상을가지는경우는흔하지않다. 2 소기도질환을진단하고분류하는데있어서임상의사와병리의사가진단용어를달리사용하거나중복또는혼선을보이는경우가많다. 3,7 실제로소기도질환은병변의원인별스펙트럼이넓고다양하여적절한분류와정확한진단을하기가쉽지않은편이다. 임상적으로기도에진행성공기흐름의장애를보이며세기관지에염증, 섬유화및폐쇄를야기하는세기관지염 (obliterative bronchiolitis) 은폐쇄세기관지염 (O), 협착세기관지염 (constrictive bronchiolitis, C) 또는폐실질의침윤성진행을보이는폐쇄세기관지-기질화폐렴 (bronchiolitis obliterans organizing pneumonia, OOP) 으로혼용되어왔다. 5,15 그러나임상특성과조직학적소견의특징으로이들폐쇄성세기관지염을다음과같이구분할수있다. 폐쇄세기관지염은주로폐이식후이식폐에대한만성거부반응이있는환자 Table 1. Causes and underlying disorders associated with organizing pneumonia (OOP pattern) Diffuse alveolar damage Infection (bacteria, mycoplasma, cryptococcus, nocardia, viruses) Distal to bronchial obstruction spiration pneumonia Inhalation injury (e.g., silo filler s disease, paint aerosols, paraquat) Radiation injury Drug reactions (e.g., amiodarone, nitrofurantoin, bleomycin, gold, amphotericin, mesalamine, methotrexate, naproxen sodium, cephalosporin, busulfan, sulfasalazine, cocaine, etc.) Systemic connective tissue diseases Hypersensitivity pneumonitis Eosinophilic pneumonia Chronic bronchiolitis or diffuse panbronchiolitis Inflammatory bowel diseases Wegener s granulomatosis, abscess, necrosis, tumor, and infarct llograft recipients (heart-lung, lung and bone marrow) Cryptogenic organizing pneumonia (idiopathic OOP) Source, modified from Ryu JH et al. 7

3 소기도질환의임상및병리판독 391 에서종말세기관지강에섬유모세포증식을가지는폴립양상의병변이관찰될때진단할수있다. 폐쇄세기관지-기질화폐렴 (O- OP) 은종말세기관지강, 폐포관과주위의폐포내에다수의섬유모세포증식을가지는폴립양상의병변이관찰되며, OOP 형태의기질폐렴 (organizing pneumonia, OP) 으로불리기도하고, 다양한원인에의해서초래된다 (Table 1). 만일임상적으로특이한원인없이병리조직학적으로 OOP 소견을보이면특발성기질폐렴 (cryptogenic organizing pneumonia, COP) 으로진단한다. 기질폐렴은폐실질의폐포관과폐포내에폴립양상의섬유모세포증식이많이관찰되며, 비특이적인병변으로기도내의기질화 (airspace organization) 로서여러임상원인에의한 폐손상후수복반응으로해석하고있다. 협착세기관지염 (C) 은세기관지벽에염증-섬유화로인해서세기관지내강이좁아지거나협착을초래하는질환이다 (Fig. 1). 협착세기관지염은골수이식환자에서볼수있으며, 특발성또는여러임상원인에의해서초래될수있다. 1,3,5,7 세기관지에발생하는질환은여러가지원인, 선행질환과병리조직학적소견에따라서다음과같이세분할수있다. 세기관지에주로병변을보이는일차세기관지질환 (primary bronchiolar diseases) 과인근폐실질또는대기도에주병변이있으며세기관지를침범하는이차세기관지질환 (secondary bronchiolar diseases) 으로나눌수있다 (Table 2). 2,3,5,16 O R T D T OP OOP/COP C Fig. 1. Schematic drawing and light micrographs of bronchiolitis obliterans (O), organizing pneumonia (OP), bronchiolitis obliterans organizing pneumonia/cryptogenic organizing pneumonia (OOP/COP) and constrictive bronchiolitis (C). O shows fibroblastic proliferated polypoid lesion in the terminal bronchiole. OP shows multiple foci of fibroblastic proliferated polypoid lesions in the alveolar ducts and alveoli. OOP shows combined histologic features of O and OP. C shows peribronchiolar fibrotic scarring with luminal narrowing of the bronchiole., bronchiole; T, terminal bronchiole; R, respiratory bronchiole; D, alveolar duct;, alveolus.

4 392 권건영 최원일 고성민 일차세기관지질환 임상원인은다양하며, 조직학적으로주로세기관지에국한하여현저한염증성병변을가진다. 일차세기관지질환에포함하는예로호흡세기관지염 (respiratory bronchiolitis, R) 와급성세기관지염, 협착세기관지염, 소포세기관지염 (follicular bronchiolitis), 미만성범세기관지염 (diffuse panbronchiolitis), 무기질분진에의한기도질환 (mineral dust airway disease) 과미만성흡입세기관지염 (diffuse aspiration bronchiolitis) 등을들수있다. 7 일차세기관지질환을가진환자에서공통적으로소기도의공기흐름장애또는폐쇄를보이는데, 협착세기관지염의경우에가장현저하다. 7 호흡세기관지염 Table 2. Classification of bronchiolar diseases Primary bronchiolar diseases Respiratory bronchiolitis cute bronchiolitis Constrictive bronchiolitis ronchiolitis obliterans Follicular bronchiolitis Diffuse panbronchiolitis Mineral dust airway disease Others (e.g., diffuse aspiration bronchiolitis, lymphocytic bronchiolitis) Secondary bronchiolar diseases Parenchymal diseases with prominent bronchiolar involvement Respiratory bronchiolitis-associated interstitial lung disease Organizing pneumonia (ronchiolitis obliterans organizing pneumonia) Hypersensitivity pneumonitis Pulmonary Langerhans cell histiocytosis Sarcoidosis Idiopathic pulmonary fibrosis Large airway diseases with bronchiolar involvement Chronic bronchitis ronchiectasis sthma Cystic fibrosis Source, modified from Ryu JH 1 and Ryu JH et al. 7 흡연과관련이있는소기도질환의특이한형태로 Niewoehner 등 17 이처음기술하였다. 임상적으로별다른증상이없으며, 고해상전산단층촬영 (CT) 에서양측폐의상엽과중엽에경계가불분명한소엽중심성소결절, 간유리음영, 공기가둠, 폐기종등의소견을관찰할수있다 (Fig. 2). 18 광학현미경소견으로호흡세기관지와주변폐포내에갈색먼지를탐식한대식세포가많이관찰된다 (Fig. 2). 2,7,18 만일호흡세기관지주위의폐포내로대식세포출현의범위가넓어지면서폐간질에염증을동반하며, 간질성폐질환의임상증상을보일때는호흡세기관지연관간질폐질환 (respiratory bronchiolitis-associated interstitial lung disease, R-ILD) 으로진단할수있다. 2,7,18,19 호흡세기관지염만있을경우에는특별한치료가없으며흡연을중단하면호전된다. 급성세기관지염 급성세기관지염은유아와어린이에서발생하는호흡기계의가장흔한질환으로바이러스감염에의해서주로초래된다. 20,21 흔히호흡합포체바이러스 (respiratory syncytial virus) 감염때발생하나, 아데노바이러스, 인플루엔자, 파라인플루엔자등의바이러스감염때와미코플라스마, 클라미디아등비바이러스병원체감염에의해서도초래될수있다. 1,20,21 성인에서는급성세기관지염이흔하지않으나호흡합포체바이러스감염이나, 독성물질흡입, 결합조직질환, 폐및골수이식그리고 Stevens- Johnson 증후군때초래될수있다. 7,22 고해상 CT에서소엽중심성의소결절이나분지성선상구조물을보이며, 공기가둠을동반한다. 그리고군데군데기관지폐렴의소견을동반할수있다. 병리조직학적으로작은세기관지에급성염증세포의현저한침윤을보이며, 상피세포의괴사와탈락을관찰할수있다 (Fig. 3). 7 세기관지강에는삼출액과점액을보이며폐실질의부종을동반한다. 협착세기관지염 협착세기관지염을초래하는원인이나동반하는질환에는선행된바이러스및미코플라스마감염, 흡입손상, 만성과민폐렴, 약물, 결합조직질환, 기관이식등을들수있다 (Table 3). 3,20,23,24 특히협착세기관지염은골수, 심폐또는폐이식후만성거부반응으로초래되며, 폐이식후후기사망의주요원인이될수있 Fig. 2. () High resolution computed tomographic (HRCT) image at the level of bronchus intermedius shows ill defined centrilobular nodules (arrow) with ground glass opacity. () Light micrograph of respiratory bronchiolitis shows lightly brown pigmented macrophages filling in the lumen of respiratory bronchiole and extending into the alveolar duct.

5 소기도질환의임상및병리판독 393 다. 3,25 임상에서폐이식을받은환자에서진행성기도폐쇄를보일때세기관지폐쇄증후군 (bronchiolitis obliterans syndrome) 으로진단하며, 이는병리학적으로폐쇄세기관지염또는협착세기관지염을뜻한다. 1,26 이외에도위식도역류, 카르시노이드소종양 (tumorlet), 광범위특발신경내분비세포증식, 염증장질환 (inflammatory bowel disease), 금치료, 페니실라민치료, HIV 감염, 그리고기도허혈같은경우에서도협착세기관지염이발생할수있다. 7,23,24,26,27 류마티스관절염과관련된협착세기관지염은주로 40-50대여성에서호발한다. 28 그러나임상에서원인을알수없는경우에는특발세기관지염으로진단한다. 29 기도의공기흐름폐쇄를가지는협착세기관지염은여러가지폐감염과흡입손상을초래한다. 3,30 고해상 CT에서협착세기관지염을야기하는원인질환에관계없이모자이크양상의저음영병소, 호기시의공기 가둠, 기관지확장증등소견이주로관찰되며, 소엽중심성결절이나분지성선상구조물이보인다 (Fig. 4). 광학현미경소견에서세기관지벽에염증세포침윤, 평활근섬유증식과섬유성비후, 세기관지강의반흔상협착소견등을볼수있다. 2,7 염증-섬유성변화는세기관지의벽과주위에현저하며, 기도강을압박하여폐쇄시킬수있다 (Fig. 4). 세기관지의조직변화의정도는생검의채취부위에따라서달리나타나기때문에작은생검이나조직채취가잘못되었을때는진단적인소견을얻을수없는경우도있다. 29 따라서협착세기관지염의정확한병리학적진단을위해서는작은생검보다는개방폐생검또는 Video-assisted thoracic surgery (VTS) 생검이필요하다. 2,3,5 특발협착세기관지염의경우스테로이드치료에잘반응하지않고임상경과가진행하여호흡부전또는사망을초래하기도한다. Table 3. Causes and underlying disorders associated with constrictive bronchiolitis Fig. 3. cute bronchiolitis. Light micrograph shows infiltration of many neutrophils and lymphocytes in the bronchiolar wall, desquamated mucosal epithelium, and inflammatory exudate in the dilated bronchiolar lumen. Infections (e.g., respiratory syncytial virus, cytomegalovirus, adenovirus, influenza and parainfluenza virus, varicella, mycoplasma, etc.) Inhalation injury (e.g., nitrogen oxide, sulfur dioxide, ammonia, phos gene, hot gases, fly ash, etc.) Chronic hypersensitivity pneumonitis Toxins (e.g., Sauropus androgynus) Drugs (e.g., penicillamine, lomustine, cocaine, gold, etc.) Systemic connective tissue diseases (e.g., rheumatoid arthritis) llograft recipients (heart-lung or lung transplant, bone marrow trans plant) Others (inflammatory bowel diseases, neuroendocrine cell hyperplasia, multiple carcinoid tumolets, gold, penicillamine, HIV infection, airway ischemia) Idiopathic (cryptogenic organizing pneumonia) Source, modified from arbareschi M and Leslie KO 6, and Ryu JH et al. 7 Fig. 4. () Postexpiratory HRCT image shows multifocal areas of air-trapping (arrows). () Light micrograph of constrictive bronchiolitis shows markedly peribronchiolar fibrous thickening with fibroblast and smooth muscle proliferation resulting in constriction of the bronchiolar lumen. Fig. 5. Light micrograph of follicular bronchiolitis shows prominent peribronchiolar and parenchymal lymphoid aggregates with germinal centers.

6 394 권건영 최원일 고성민 소포세기관지염소포세기관지염은특발성으로발생하거나낭섬유증, 기관지확장증, 만성흡인등기도의만성감염또는염증성질환을가진환자에서흔히볼수있다. 2,7 그외에도류마티스관절염을포함한결합조직질환이나후천성면역결핍증후군에서도소포세기관지염을동반할수있다. 7,31 그리고근위부의기관지확장증을가진환자에서이차적으로소포세기관지염이때때로관찰된다. 7 소포세기관지염은외부면역자극에대한림프구증식또는류마티스관절염에서와같이전신면역반응의변화로초래된다. 32 고해상 CT에서전형적으로직경 1-3 mm 내외의소엽중심성결절과더불어경계가불분명한기관지주위결절과반점상의젖빛유리음영을보인다. 7,33 육안검사에서기관지를중심으로직경 1-2 mm 의결절을볼수있으며, 광학현미경소견에서세기관지를중심으로주위에림프구침윤과더불어반응성배중심 (germinal center) 을가지는림프소포의증식을보일때진단할수있다 (Fig. 5). 2,4,31 일차성소포세기관지염에서세기관지주위의폐간질에림프구침윤이현저한증례에서림프간질폐렴 (lymphoid interstitial pneumonia) 과감별을요한다. 33 기존의다른질환을가지는소포세기관지염에서환자의예후를평가하기는쉽지않다. 미만성범세기관지염미만성범세기관지염은원인을잘알수없는질환으로일본, 한국등아시아지역의성인에서주로보고되며, 특징적으로세기관지염증과만성부비동염을가진다. 34 환자들은농성객담을동반한기침과호흡곤란을호소한다. 일본환자에서 HL-54 항원의관련성에대한보고가있으나그원인은확실히밝혀져있지않다. 34 호중구, T-림프구 ( 특히 CD8 양성세포 ), IL-8, 대식세포염증단백-1- 등이미만성범세기관지염의유발과관련있음이보고되어있다. 35 소기도에서활성화된호중구의침윤은이질환에서폐조직손상의기전에중요한역할을하는것으로알려져있다. 34 임상적으로진행성호흡기능장애를가지며, Pseudomonas aeruginosa와같은세균의중복감염을동반할수있다. 36 치료를하지않을경우환자는진단받은후 5년이내에약 50% 가사망한다. 36 고해상 CT에서급성세기관지염과유사한소견을볼수있다. 즉소엽중심성의결절이나분지성선상구조물, 공기가둠, 그리고기관지확장소견을폐의중하엽에서관찰할수있으며폐용적은증가한다 (Fig. 6). 조직학적으로호흡세기관지, 폐포관과폐포주위로림프구, 형질세포침윤과함께특징적인거품양대식세포의출현을보인다 (Fig. 6). 2,7 무기질분진에의한기도질환무기질분진의지속적인흡입으로폐실질에섬유화를초래하거나진폐증을만들어임상적으로폐쇄성폐기능장애를보인다. 3 또한소기도에도변화를야기하여공기흐름의장애나폐쇄를 초래할수있다. 37 소기도에침착하는분진은주로무기질먼지로서석면, 철산화물, 알루미늄산화물, 활석, 운모, 이산화규소 (silica), 규산염과석탄등을포함하며, 호흡세기관지주위로염증성섬유화를초래한다. 37 고해상 CT에서규폐증환자에서는소결절이폐소엽중심이거나흉막하에분포하며, 주로폐상엽의후부에위치한다 (Fig. 7). 석면폐증일경우불규칙한선상음영, 벌집모양음영등소견이양폐의하엽에서관찰된다. 광학 Fig. 6. () HRCT image obtained through the level of the lower lobe shows centrilobular nodular and branching opacities (arrows), and bronchiectasis. () Light micrograph of diffuse panbronchiolitis illustrates dense peribronchiolar infiltrate of mainly mononuclear cells and associated with many foamy macrophages in the peribronchiolar alveolar septa (arrow). Fig. 7. () HRCT at the level of the upper lobe shows subpleural and centrilobular distribution of micronodules (arrows), with predominant involvement of the posterior portion. () Mineral dust airway disease with anthraco-silicotic dust exposure. Light micrograph shows fibrotic nodule formation with centrally laminated collagen deposition and surrounding fibrotic thickening with anthracotic pigments. Inset illustrates many scattered silicotic particles in the nodular lesion on polaroid filter examination.

7 소기도질환의임상및병리판독 395 현미경소견에서흡입한분진이호흡세기관지를중심으로침착하며폐포관도침범한다. 세기관지를중심으로반 (macule) 또는소결절 (nodule) 을만들면서분진침착과섬유성비후를보이고소기도의내강은좁아진다 (Fig. 7). 2,3,37 미만성흡인세기관지염이물질의반복적인흡인에의해폐실질과세기관지에만성염증을초래한다. 38 미만성흡인세기관지염은주로병원의침대생활을오래하는노인에서호발하나, 위-식도역류를가지는성인에서볼수있다. 38 고해상 CT에서소엽중심성의결절이나분지성선상구조물을보이며, 광학현미경소견에서세기관지벽과주위폐실질에이물반응을가지는만성염증을볼수있다. 흡연과관련된폐질환에서볼수있는소기도병변흡연자에서세기관지특히호흡세기관지를중심으로염증과섬유화병변을흔히볼수있으며, 흡연자에서종양등으로절제한폐조직에서흔히호흡세기관지염이관찰된다. 17 임상적으로간질성폐질환의증상과방사선소견을보일경우호흡세기관지연관간질폐질환 (R-ILD) 으로진단할수있다. 2,7,18,19 광학현미경관찰에서호흡세기관지강과주위의폐포내에갈색먼지를포함한다수의폐포대식세포가출현하고폐포벽에염증과경한섬유성비후를동반한다. 병변은호흡세기관지를중심으로국소적이며폐실질에광범위한병변은보이지않는다. R-ILD 병변이진행하여미만성으로폐실질을침범하는경우탈락간질폐렴 (desquamative interstitial pneumonia, DIP) 으로진단한다. 2,5,39 이때갈색입자를탐식한폐포대식세포가광범위하게폐포내를채우며, 폐포벽은약간비후되고 II형폐포상피세포의증식을동반하는소견을볼수있다. DIP 환자에서흔히현저한호흡곤란과저산소혈증을가지며제한성폐기능장애를보이는데비하여 R-ILD 를가진환자에서는상대적으로경미한임상증상과제한성및폐쇄성의혼합양상의폐기능장애를보인다. 19,39 R, R-ILD 및 DIP는원인, 조직학적진단기준, 임상소견, 방사선소견및환자의예후에서서로연관성이있으며, 흡연과관련된간질성폐질환의한스펙트럼으로해석하는경향이다 (Fig. 8). 18 폐의랑게르한스세포조직구증 (Langerhans cell histiocytosis) 의초기에세기관지와폐포관을중심으로랑게르한스세포의증식과호산구가침윤하며, 폐포내에는갈색색소를탐식한대식세포출현을볼수있다. 간질성폐질환에서볼수있는소기도병변폐실질을침범하는많은질환에서소기도에다양하게염증과섬유성반흔을동반한다. 폐실질의변화와더불어세기관지의병변이현저할경우정확한진단을하기가어려울수있다. 여기에속하는질환으로흡연과관련된질환 (R-ILD, DIP), 기질폐렴 ( 또는세기관지폐쇄기질폐렴 ), 과민폐렴등을들수있다. C Fig. 8. Light micrograph of smoking related lung diseases. () Respiratory bronchiolitis. Many brown-pigmented macrophages are filled in the respiratory bronchiole and adjacent alveoli. () Respiratory bronchiolitis-associated interstitial lung disease. There is a patchy fibrotic thickening of the respiratory bronchiolar wall and alveolar walls associated with brown-pigmented macrophages in the airspaces. The changes are patchy and have a bronchiolocentric distribution. (C) Desquamative interstitial pneumonia is characterized by diffuse presence of brown-pigmented macrophages in the alveoli and mild interstitial fibrous thickening of the alveolar walls.

8 396 권건영 최원일 고성민 Fig. 9. () HRCT image at a level of the ventricle shows multiple patchy areas of consolidation, predominantly along the bronchovascular bundles and the subpleural portion. () Organizing pneumonia (OOP pattern). Low-magnification photomicrograph shows a zonal fibrotic lesion with multiple plugs of proliferating fibroblasts filling in the air spaces (arrows). Fig. 10. () HRCT image through the right upper lobe shows illdefined centrilobular nodules of ground glass opacity (arrows). () Hypersensitivity pneumonitis. Low-magnification photomicrograph shows a dense peribronchiolar and adjacent alveolar wall infiltrates of inflammatory cells mainly lymphocytes and plasma cells, and a focus of vague granuloma (arrow). 기질폐렴또는세기관지폐쇄기질폐렴기질폐렴은감염, 결합조직질환, 흡입손상, 과민폐렴, 약물, 방사선치료, 흡인폐렴등다양한원인과선행질환에서볼수있는비특이적인염증의수복반응으로해석한다. 2,7 만일원인을찾지못하는경우특발성기질폐렴또는특발성세기관지폐쇄기질폐렴 (idiopathic OOP) 이라고한다. 특발성기질폐렴의환자는주로경도또는중등도의제한성폐기능결함을보이며, 스테로이드요법에잘반응한다. 40 고해상 CT 소견은주로폐경화가양측흉막하혹은기관지혈관을따라분포하는경향이특징적이며, 경계가불분명한소결절들이기관지나세기관지주위에보이기도한다 (Fig. 9). 광학현미경소견에서폐포관, 호흡낭 (alveolar sac) 및폐포내에섬유모세포증식을보이는폴립양의초기섬유성병변을볼수있으며, 폐포구조의변형은동반되지않는다 (Fig. 9). 과민폐렴세기관지를중심으로하는염증성변화로호흡할때기도내에공기흐름이방해되거나차단되어환자는호흡곤란을호소한다. 고해상 CT에서급성기에는양측성폐경화를보이며, 미세결절이동반될수있다. 아급성기에는경계가불분명한소엽중심성결절들이젖빛유리음영과함께나타나며반점형의공기가둠이동반된다 (Fig. 10). 만성기에는불규칙한선상음영과폐구조왜곡소견이폐중하엽또는무작위로관찰된다. 광학현미경소견에서세기관지를중심으로하여림프구를주로하는단핵구침윤을보이며, 세기관지벽과주위폐실질에경계가불분명한육아종성병변을관찰할수있다 (Fig. 10). 병변이진행하는경우평활근비대와함께폐실질에섬유화를동반한다. 41 그외사르코이드증, 특발성폐섬유증 (idiopathic pulmonary fibrosis) 등에서도세기관지에염증-섬유성병변을동반한다. 사르코이드증에서는비건락육아종이소엽중심의기도주위, 소엽간중격및늑막하의림프관이위치한곳에서흔히관찰된다. 소기도와대기도에흔히침범하며, 기도내의공기흐름에장애를줄수있다. 7 특발성폐섬유증에서세기관지에염증과섬유화를관찰할수있으며, 때로는세기관지확장증도동반한다. 42 세기관지주위에현저한섬유화가있으면서간질폐질환의소견을함께보일때기도중심간질폐질환 (airway centered interstitial lung disease) 으로진단할수있다. 43,44 대기도질환에서동반되는소기도병변기관지확장증, 만성기관지염, 폐기종, 천식의만성폐쇄폐질환과낭섬유증 (cystic fibrosis) 등에서세기관지벽의섬유화, 평활근비대및세기관지강에점액저류등다양한염증성병변을동반한다. 1,2,7,45 세기관지벽에는케모카인수용체인 CXCR3 와리간드인 CXCL10에의해서 T 림프구 (CD4 및 CD8) 침윤이증가한다. 46,47 소기도에동반되는염증의정도는기도내의공기흐름장애와밀접한관련을가지면서만성폐쇄폐질환의진행에영향을끼친다. 46 결론소기도질환은대부분세기관지에염증성섬유화병변을보이며, 다양한질환에서볼수있는흔한변화이나임상적으로현저한소견을보이지않는특성이있다. 세기관지질환을판독하는

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