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1 기관지탄분섬유화증에서동반된기관지협착에따른환기역학 대구파티마병원내과정승욱, 김연재, 김건현, 김민선, 손혁수, 김준철, 류현욱, 이수옥, 정치영, 이병기 Ventilatory Dynamics According to Bronchial Stenosis in Bronchial Anthracofibrosis Seung Wook Jung, M.D., Yeon Jae Kim, M.D., Gun Hyun Kim, M.D., Min Seon Kim, M.D., Hyuk Soo Son, M.D., Jun Chul Kim, M.D., Hyon Uk Ryu, M.D., Soo Ok Lee, M.D., Chi Young Jung, M.D., Byung Ki Lee, M.D. Departments of Internal Medicine, Fatima Hospital, Daegu, Korea Background : Bronchial anthracofibrosis usually manifest as a form of obstructive airway disease, and can be accompanied by parenchymal diseases such as pneumonia, and pulmonary tuberculosis. This study investigated the ventilatory dynamics according to the severity of bronchial stenosis in patients with bronchial anthracofibrosis. Method : One hundred and thirteen patients with bronchial anthracofibrosis that was confirmed by bronchoscopy and who had undergone a pulmonary function test were enrolled in this study group. The correlation coefficients between the pulmonary functional parameters and the number of lobes with bronchial stenosis were investigated. Results : The incidence of ventilatory dysfunction was 56(49.6%) for obstructive, 8(7.1%) for restrictive, 2(1.8%) for mixed, and 47(41.6%) for a normal pattern. The FEV 1/FVC, FEF 25 75%, FEF 25%, FEF 50%, FEF 75%, and PEF showed a significant negative correlation (p<0.05) and the Raw had a significant positive correlation with the number of lobes with bronchial stenosis(p<0.001). Conclusion : These findings suggest that the most common abnormality of the ventilatory function in bronchial an thracofibrosis is an obstructive pattern with a small airway dysfunction according to the severity of bronchial stenosis. (Tuberc Respir Dis 2005; 59: ) Key words : Bronchial anthracofibrosis, Ventilatory dynamics, Obstructive, Airway resistance 서 기관지탄분섬유화증은주로나무연기와같은생물자원연료의연기에대한장기적인노출로인하여기관지내다발성색소침착과이와동반하여엽또는구역기관지에협착이보이는경우로무증상에서심한호흡곤란까지다양한호흡기증상을유발할수있으며 1-5, 주로만성폐쇄성기도질환의형태로발현된다 1,2,4,5. 장기적인나무연기흡입은폐쇄성기도질환의독립적인위험인자이고, 만성폐질환의발생과밀접한상관이있다고한다 그러나이와같은보고 6-11 들은 론 Address for correspondence : Yeon Jae Kim, M.D. Departments of Internal Medicine, Fatima Hospital, , Shinam Dong, Dong-Gu, Daegu, , Korea Phone : Fax : persimmonkim@lycos.co.kr Received : Apr Accepted : Sep 나무연기와폐쇄성기도질환과의인과관계를단지역학적으로규명한연구들이며, 나무연기흡입으로인한기도내병태생리의한형태인기관지탄분섬유화증과폐기능과의관계를본경우는거의없는것같다 12. 기관지점막에침착된입자들로인한주위기도벽또는간질의섬유화, 상부기도벽의비후및협착, 그리고대부분석회화가동반된림프절종창으로설명되는기관지탄분섬유화증의병태생리가일반적인만성폐쇄성기도질환과는크게차이가있음을알수있고 5, 또한경과중에폐쇄성폐렴또는폐결핵과같은폐실질병변이동반되는경우가흔히있어나타나는폐기능도다양할것으로생각된다. 저자들은기관지탄분섬유화증의환기역학을알아보기위한일환으로노력성호기곡선, 기류-용량곡선, 폐용량및기도저항을분석하여환기장애의병형별빈도및동반된기관지협착과기도의환기기능과의관계를조사하여그성적을보고하는바이다. 368
2 Tuberculosis and Respiratory Diseases Vol. 59. No. 4, Oct 대상 대상및방법 1997년 1월부터 2002년 5월까지호흡기증상이나흉부방사선사진의이상소견으로내원하여기관지내시경검사상기관지탄분섬유화증으로진단받은환자가운데폐기능검사를실시한 113례의환자를대상으로하였다. 이들의신체적조건및임상적특징은 Table 1과같이대부분고령의여자가많았으며, 36예 (31.8%) 에서폐결핵의과거력이있었다. 그리고기관지협착이동반되어있는폐엽의수는 2.7 ± 1.50 이었다. 2. 방법 1) 기관지내시경검사기관지내시경검사전처치로 atropine 0.5mg을검사 30분전에근육주사하였으며, 국소마취는 4% lidocaine 5ml(200mg) 를분무기 (Pulmo aide R ) 를통해 분동안흡입시킨후구강을통하여기관지경을삽입하여검사를실시하였다. 기관지내시경검사상기관지점막에다발성의흑청색의색소침착이있거나엽또는구역기관지에색소침착과동반된섬유화성협착이관찰되는경우를기관지탄분섬유화증으로진단하였다. 기관지의협착은색소침착이있는엽기관지또는구역기관지의내경이정상기관지에비해좁아져있거나완전폐색을보이는경우로하였으며, 협착을보인기관지의수는엽또는구역기관지의협착이동반되어있는폐엽의수로하였다 5. Table 1. Clinical and physical characteristics in patients with bronchial anthracofibrosis (N=113) 2) 폐기능검사모든폐기능검사는급성기의호흡기증상이호전된후안정상태에서실시하였다. 폐활량측정법을이용하여 (Sensoromedics, Vmax 229, Yorba Linda, California, U.S.A.) 노력성호기곡선에서노력성폐활량 (FVC), 노력성호기량의 1초치 (FEV 1 ) 및최대중간호기류속도 (FEF 25 75% ) 를구하였으며, 기류용량곡선에서최고호기류속도 (PEF) 와 FVC의 25, 50 및 75% 수준에서의최대호기류속도즉 FEF 25%, FEF 50%, FEF 75% 를구하였다. 최대자발성호흡량 (MVV) 은환자로하여금 10초간최대한빠르고깊게호흡을시켜호흡량을 1분간의양으로환산하였다. 잔기량및기도저항의측정은체적기록법 (body plethysmography) 을이용하였으며 (Jaeger, GmbH & CoKG, German), 잔기량 (RV), 전폐기량 (TLC), RV/TLC, 기도저항 (Raw) 및기도유순도 (Gaw) 를분석하였다. FEV 1 /FVC를제외한모든폐기능성적은추정정상치의백분율 (%) 로표시하였으며, FEV 1 /FVC가 70% 미만인경우를폐쇄성환기장애, FEV 1 /FVC가 70% 이상이고 FVC가추정정상치의 80% 미만인경우를제한성환기장애, 그리고 FEV 1 /FVC가 70% 이상이고 FVC 및 FEV 1 이추정정상치의 80% 이상인경우를정상으로하였다. 대상환자들의폐기능검사에서구한여러계측치들에서환기장애의병형별분포를구하였으며, 이들계측치들과기관지내시경검사상협착을보인기관지의수와의상관관계를구하였다. 3) 통계처리협착을보인기관지의수와폐기능계측치들간의상관관계는 Pearson 상관계수를측정하였으며, 모든통계학적유의성은 p<0.05( 유의수준 ) 를기준으로하였다. Characteristics Sex (n, M/F) Age (yr) Height (cm) Weight (kg) History of tuberculosis (n, %) Numbers of lobe with bronchial stenosis *Mean ± S.D. Value 18 / ± 5.66* ± 8.80* 53.4 ± 9.73* 36 (31.8) 2.7 ± 1.50* 결과환기장애의병형별분포는 Table 2와같이폐쇄성환기장애가 56례 (49.6%), 제한성환기장애가 8례 (7.1%), 혼합성환기장애가 2례 (1.8%) 로폐쇄성환기장애가 369
3 SW Jung et al. : Ventilatory dynamics according to bronchial stenosis in bronchial anthracofibrosis Table 2. Patterns of ventilatory dysfunction in patients with bronchial anthracofibrosis Patterns Obstructive Restrictive Mixed Normal Number(%) 56 (49.6) 8 (7.1) 2 (1.8) 47 (41.5) Total 113 (100) Obstructive = FEV 1/FVC<70% Restrictive = FEV 1/FVC 70% and FVC<80% predicted Normal = FEV 1/FVC 70% and FVC 80% predicted and FEV 1 80% predicted 많았으며, 47례 (41.6%) 에서정상환기소견을보였다. 노력성호기곡선에서구한여러지표의성적과이들지표들과협착을보인기관지의수와의상관계수는 Table 3과같다. FVC의추정정상치의백분율의평균 은 94.3±24.76% 였으며, 상관계수는 0.023으로협착을보인기관지의수와는유의하지는않았다. 반면에기도폐쇄를반영하는 FEV 1 /FVC은 69.9±13.14% 로감소되었으며, 상관계수가 로협착을보인기관지의수와유의한음의상관관계를보였다 (p<0.05). FEV 1 의추정정상치의백분율의평균은정상범위였으며, 상관계수는 로협착을보인기관지의수에따라감소되는경향이나유의하지는않았다. FEF 25 75% 및 MVV은 41.1±21.47%, 58.9±20.40% 로모두낮게관찰되었으며, FEF 25 75% 의상관계수는 으로협착을보인기관지의수와유의한음의상관관계를보였으나 (p<0.005), MVV은 으로뚜렷한상관관계는없었다. 기류용량곡선에서구한여러계측치의추정정상 Table 3. Correlation coefficients between parameters derived from forced expiratory volume curve and numbers of lobe with bronchial stenosis Parameters Value Coefficient FVC, %pred. FEV 1, %pred. FEV 1/FVC, % FEF 25-75, %pred. MVV, %pred. Values are mean ± S.D. *<0.05*, p<0.005, n= ± ± ± ± ± * Table 4. Correlation coefficients between parameters derived from flow-volume curve and numbers of lobe with bronchial stenosis Parameter Value Coefficient PEF, %pred. FEF 25, %pred. FEF 50, %pred. FEF 75, %pred. Values are mean ± S.D. * p<0.005, p< ± ± ± ± * * * Table 5. Correlation coefficients between parameters derived from body plethysmography and numbers of lobe with bronchial stenosis Parameter Value (N=55) Coefficient RV, %pred. TLC, %pred. RV/TLC, %pred. Raw %pred. Gaw %pred. Values are mean ± S.D. * p<0.001, p< ± ± ± ± ± *
4 Tuberculosis and Respiratory Diseases Vol. 59. No. 4, Oct 치에대한백분율의성적과협착을보인기관지의수와의상관계수는 Table 4와같다. 대기도및소기도의기능을반영하는 PEF, FEF 25%, FEF 50% 및 FEF 75% 는모두낮게관찰되었으며, 상관계수도각각 , , , 그리고 로협착을보인기관지의수와유의한음의상관관계를보였다 (p<0.005). 폐용량을반영하는지표및기도저항에대한성적은 Table 5와같다. TLC는 94.6±13.39% 로정상범위였으며, RV 및 RV/TLC는 119.7±39.01%, 130.3±28.80% 로대체적으로증가되어있었으나, 협착을보인기관지의수와는뚜렷한상관은없었다. Raw는 345.5±194.42% 로협착을보인기관지의수에따라유의하게증가하였으며 (p<0.001), Gaw는유의하게감소하였다 (p<0.005). 고찰저자들의성적에서 FVC 및 FEV 1 은정상범위였으나, 기도폐쇄를반영하는 FEV 1 /FVC 및전기도기능을반영하는 FEF 25 75% 은 70% 이하로감소되었다. 특히 FEV 1 은협착을보인기관지의수에따라유의하지는않았으나감소되는경향이었으며, FEV 1 /FVC, FEF 25 75% 은협착을보인기관지의수에따라유의하게감소되는소견이었다. 이러한성적은기관지탄분섬유화증에서는기관지의협착과연관되어전기도저항의증가에의한폐쇄성환기장애가있으되제한성환기장애는뚜렷하지않음을시사한다고할수있다. Sandoval 등 12 은장기간의나무연기흡입과관련된만성폐질환에서의환기장애의병형은저자들과는달리대부분제한성과폐쇄성이같이있는혼합성환기장애였다고하였다. 이와같은성적은순수한기관지탄분섬유화증만을대상으로한경우가아니라기관지탄분섬유화증을포함한모든나무연기흡입관련폐질환을대상으로하였고, 또한나무연기로인한폐질환의가장심한단계인폐성심환자만을대상으로하였기때문이며, 폐성심이전단계의질환에있어서폐기능손상의정도및각환기장애의정확한기여유무는향후연구가필요할것이라고언급하였다. 국내의기관지탄분섬유화증에대한김등 2, 이등 4, 한등 13 의연구에서환기장애의병형은폐쇄성환기 장애가각각 40.7%, 44%, 50% 로저자들의경우에서처럼많은비율을차지하였으며, 제한성환기장애는각각 18.6%, 28%, 0%, 혼합성환기장애는 25.4%, 14%, 0% 로연구자들사이에상당한차이를나타내었다. 저자들의경우에서도제한성및혼합성장애는각각 7.1%, 1.8% 로이들과차이를보였는데, 이와같은소견은대상환자들의수, 나이, 결핵과같은폐실질파괴성병변의동반정도가서로달랐기때문으로생각된다. 즉이들에서는 2,4,13 비교적소규모의환자들을대상으로하였으며저자들의환자에비해평균나이가적었고, 김등 2 및한등 13 에서는결핵성병변이동반되었던경우가각각 52.6%, 50% 로저자들의 32% 보다많았으며, 제한성및혼합성장애가관찰되지않았던이등 4 에서는결핵또는간질성폐질환이동반되었던경우를제외하였기때문이다. 이와같이기관지탄분섬유화증에서는주로폐쇄성환기장애가관찰되며, 주위폐실질의섬유화, 폐허탈, 그리고협착된기관지이하부위의반복적인폐감염또는결핵과같은파괴성폐질환의동반등에의한이차적인폐실질의변화로제한성환기장애가일부동반될수있을것으로생각된다 5. 그리고저자들의성적에서정상환기가비교적많았던것은폐쇄성및제한성환기장애에속하지않는세소기도의기능장애가많이포함되었기때문으로생각된다. 한편기류-용량곡선은그모양으로써피검자의검사에대한협조상태 14, 기도폐쇄의부위 14,15 및환기장애의병형 15 등을알수있고, 계측치의분석을통하여폐쇄성폐질환의진단에예민하고편리하여널리이용되고있다. 즉이곡선에서구하는여러지표들가운데 PEF 및 FEF 25% 는 FEV 1 처럼주로대기도기능을반영하고 FEF 50% 는주로세소기도기능을반영하나중기도내지대기도기능도포함되며 FEF 75% 는세소기도기능을반영한다고한다 저자들의성적에서호기류속도를반영하는 PEF, FEF 25%, FEF 50%, FEF 75% 는모두추정정상치의 60% 미만으로감소되었으며, 협착을보인기관지의수에따라유의하게감소하였다. 이러한성적은기관지탄분섬유화증에서세소기도를포함한전기도의폐쇄가관찰되며, 특히협착을보이는기관지의수가많을수록기능도심하게감소 371
5 SW Jung et al. : Ventilatory dynamics according to bronchial stenosis in bronchial anthracofibrosis 된다는것을나타낸다. 또한폐용량을나타내는지표들가운데 TLC는정상범위였으나, RV 및 RV/TLC 가추정정상치의 100% 이상으로증가되었으며협착을보인기관지의수에따라유의하지는않았으나증가되는경향으로기도폐쇄로인한 air trapping을반영한다고할수있다. 한편기도내강이좁아질수있는기전으로첫째, 점막의충혈, 부종또는염증, 둘째, 점액, 삼출액또는이물질에의한내강의완전혹은부분폐쇄, 셋째, 표면장력에의한점막표면의응집 (cohesion), 넷째, 침윤, 압박또는섬유화, 다섯째, 증가된흉강내압 (in trapleural pressure) 및경폐압 (transpulmonary pre ssure) 에의한압박또는폐쇄, 여섯째, 기관지, 세기관지벽의지지구조물또는정상적인폐탄성조직의소실로인한기도의허탈또는뒤틀림 (kinking) 을들수있다 20. 이와같이기도내강이좁아지면호기시기류제한과함께기도저항이증가하게되며, 대표적인질환으로만성폐쇄성폐질환과기관지천식이있으나그발병기전에는차이가있다 21,22. 즉만성기관지염은점막의비후및점액의과분비, 폐기종은폐의탄성반동압 (elastic recoil pressure) 의감소, 그리고기관지천식은기관지점막의과민반응에의한일시적인기관지경련이주로관여하는것으로되어있다 21,23,24. 저자들의성적에서기도폐쇄및호기류속도를반영하는지표들과기도저항을나타내는지표들이협착을보인기관지의수와유의한상관관계가있어기도벽의비후및섬유화와기관지의왜곡으로인한다발성의엽또는구역기관지의비가역적인협착및이로인한기관지의폐쇄가이들지표들의변화에주로관여하는것으로볼수있다. 그리고기도저항 (Raw) 은전반적으로증가되어있었는데, 기관지탄분섬유화증이호기류의제한및폐쇄성환기장애를보이는것으로보아이러한소견은당연한결과라할수있으며, 세소기도폐쇄및폐탄성도를반영하는지표인 Raw 및 Gaw는협착을보인기관지의수와유의한상관관계를보인반면 TLC 및 RV는유의한상관관계가없는것으로보아본환자들에서관찰된 Raw의증가는세소기도의폐쇄가주된기전인것으로생각된다 22. 결론적으로기관지탄분섬유화증은협착을보인기관지의수가많을수록세소기도병변과더불어주로폐쇄성환기장애를나타내며, 임상적으로는만성폐쇄성폐질환, 천식과같은폐쇄성기도질환의형태로발현되는것으로이해할수있다. 요약연구배경 : 기관지탄분섬유화증은주로만성기관지염, 만성폐쇄성폐질환, 또는천식등과같은만성기도질환의형태로발현되며, 질환의경과중에폐렴, 폐결핵과같은실질성병변들이동반될수있다. 저자들은기관지탄분섬유화증에서환기장애의병형별빈도및동반된기관지협착에따른기도의환기기능및역학을알아보고자하였다. 방법 : 기관지내시경검사상기관지탄분섬유화증으로진단받은환자가운데폐기능검사를실시한 113례의환자를대상으로폐기능검사에서구한여러계측치들과협착을보인기관지의수와의상관관계를구하였다. 결과 : 폐쇄성환기장애가 56례 (49.6%), 제한성환기장애가 8례 (7.1%), 혼합성환기장애가 2례 (1.8%), 그리고정상환기가 47례 (41.6%) 였다. 노력성호기곡선에서구한계측치가운데 FEV 1 /FVC 및 FEF 25 75% 은상관계수가각각 , 으로협착을보인기관지의수에따라유의하게감소하였다 (p<0.05, p<0.005). 기류-용량곡선에서구한 PEF, FEF 25%, FEF 50% 및 FEF 75% 는모두낮게관찰되었으며, 상관계수가각각 , , , 그리고 로협착을보인기관지의수에따라유의하게감소하였다 (p<0.05). Raw도 0.477로협착을보인기관지의수에따라유의하게증가하였다 (p<0.001). 결론 : 기관지탄분섬유화증은협착을보인기관지의수가많을수록세소기도병변과함께주로폐쇄성환기장애를나타내는것으로생각된다. 372
6 Tuberculosis and Respiratory Diseases Vol. 59. No. 4, Oct 참고문헌 1. Park IW, Yoo CG, Kwon OJ, Kim YW, Han SK, Shim YS, et al. Clinical study of dark-blue pigmentation in the bronchial mucosa. Tuberc Respir Dis 1991;38: Kim JY, Park JS, Kang MJ, Yoo CG, Kim YW, Han SK, et al. Endobronchial anthracofibrosis is causally associated with tuberculosis. Korean J Intern Med 1996;51: Chung MP, Lee KS, Han J, Kim H, Rhee CH, Han YC, et al. Bronchial stenosis due to anthracofibrosis. Chest 1998;113: Lee HS, Maeng JH, Park PG, Jang JG, Park W, Ryu DS, et al. Clinical features of simple bronchial an thracofibrosis which is not associated with tuberculo sis. Tuberc Respir Dis 2002;53: No TM, Kim IS, Kim SW, Park DH, Joeng JK, Ju DW, et al. The clinical investigation for determining the etiology of bronchial anthracofibrosis. Korean J Med 2003;65: Perez-Padilla R, Regalado J, Vedal S, Pare P, Chapela R, Sansores R, et al. Exposure to biomass smoke and chronic airway disease in Mexican women: a case-co ntrol study. Am J Respir Crit Care Med 1996;154: Woolcock AJ, Blackburn CR, Freeman MH, Zylstra W, Spring SR. Studies of chronic (nontuberculous) lung disease in New Guinea populations. Am Rev Respir Dis 1970;102: Anderson HR. Chronic lung disease in the Papua New Guinea Highlands. Thorax 1979;34: Albalak R, Frisancho AR, Keeler GJ. Domestic biomass fuel combustion and chronic bronchitis in two rural Bolivian villages. Thorax 1999;54: Pandey MR. Prevalence of chronic bronchitis in a rural community of the Hill Region of Nepal. Thorax 1984;39: Pandey MR. Domestic smoke pollution and chronic bronchitis in a rural community of the Hill Region of Nepal. Thorax 1984;39: Sandoval J, Salas J, Martinez-Guerra ML, Gomez A, Martinez C, Portales A, et al. Pulmonary arterial hypertension and cor pulmonale associated with chr onic domestic woodsmoke inhalation. Chest 1993;103: Han SH, Cha GY, Lee YM, Kim KU, Uh ST, Kim YH, et al. Study of antituberculous medications in anthr acofibrosis. Tuberc Respir Dis 2001;51: Hyatt RE, Black LF. The flow-volume curve: a current perspective. Am Rev Respir Dis 1973;107: Lord GP, Gazioglu K, Kaltreider N. The maximum expiratory flow-volume in the evaluation of patients with lung disease. Am J Med 1969;46: Bass H. The flow volume loop: normal standards and abnormalities in chronic obstructive pulmonary dise ase. Chest 1973;63: Kryger M, Bode F, Antic R, Anthonisen N. Diagnosis of obstruction of the upper and central airways. Am J Med 1976;61: Takishima T, Sasaki T, Takahahi K, Sasaki H, Na kamura T. Direct-writing recorder of the flow volume curve and its clinical application. Chest 1972;61: Kim YJ, Park JY, Jung TH. Ventilatory dynamics in bronchiectasis. Tuberc Respir Dis 1993;40: Comroe JH Jr. Physiology of respiration. 2nd ed. Chi cago: Year book medical publishers; p Snider GL. Distinguishing among asthma, chronic bronchitis and emphysema. Chest 1985;87:35S-9S. 22. Macklem PT. The pathophysiology of chronic bronchi tis and emphysema. Med Clin North Am 1973;57: Dayman H. Mechanics of airflow in health and in emphysema. J Clin Invest 1951;30: Wells RE Jr. Mechanics of respiration in bronchial asthma. Am J Med 1959;26:
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