기류제한환자의일산화탄소확산능해석에서폐용적보정의의의 계명대학교의과대학내과학교실, 방사선과 1, 핵의학과 2, 흉부외과 3, 예방의학교실 4 서용우, 최원일, 이정은, 박훈표, 고성민 1, 원경숙 2, 금동윤 3, 이미영 4, 전영준 Importance of Carbon Monoxide Transfer Coefficient (KCO) Interpretation in Patients with Airflow Limitation Yong Woo Seo, M.D., Won-Il Choi, M.D., Jeong Eun Lee, M.D., Hun Pyo Park, M.D., Sung Min Ko, M.D. 1, Kyoung Sook Won, M.D. 2, Dong Yoon Keum, M.D. 3, Mi-Young Lee, M.D. 4, Young June Jeon, M.D. Departments of Medicine, Radiology 1, Nuclear Medicine 2, Thoracic Surgery 3, and Preventive Medicine 4, Keimyung University School of Medicine, Daegu, Korea Background : The single-breath carbon monoxide diffusion capacity (DLCO) and the per unit alveolar volume (KCO; D LCO/VA) gave discordant values when there was an abnormal alveolar volume (VA). However, the clinical significance of the discordant values in patients with airflow limitation has not been examined. This study investigated the D LCO and KCO changes after improving the airflow limitation. Methods : The baseline D LCO and KCO with lung volume were measured in patients with an airflow obstruction. The effective alveolar volume was measured using the single-breath CH 4 dilution method. The patients divided into two groups according to the baseline values: (1) increased KCO in comparison with the D LCO (high discordance) (2) decreased or not increased KCO in comparison with the D LCO (low discordance). The diffusion capacity and lung volume were measured after treatment. Results : There was no significant difference in the baseline lung volumes including the FEV 1 and FVC between the two groups. The FEV 1 and FVC were significantly increased in the high discordance group compared with the low discordance group after treating the airflow limitation. The D LCO and alveolar volume were significant higher in the high discordance group compared with the low discordance group while the TLC was not. Conclusion : The discordance between the D LCO and KCO could be translated into an airflow reversibility in patients with an airflow limitation. (Tuberc Respir Dis 2005; 59: 374-379) Key words : DLCO, KCO, Pulmonary function test, Obstructive lung disease 서 폐의가스교환장애를측정하는검사로는확산능검사가있다. 일산화탄소를이용한일회호흡 (single breath) 확산능검사는임상에서흔히사용하는검사이며이러한일산화탄소확산능은주로폐전체의값 (carbon monoxide diffusion capacity; D L CO) 또는이값을폐포용적 (alveolar volume; VA) 으로나눈확산계수 (carbon monoxide transfer coefficient; KCO; D L CO / VA) 로표현한다 1. Address for correspondence : Won-Il Choi, M.D. Department of Medicine, Keimyung University School of Medicine 194 Dongsan-Dong, Jung-Gu, Daegu, 700-712, Korea Phone : 82-53-250-7572 Fax : 82-53-250-7434 E-mail : wichoi@dsmc.or.kr Received : Apr. 27. 2005 Accepted : Sep. 5. 2005 론 확산능은일반적으로빈혈 2-4 인경우에는감소하고운동시 5,6 및폐출혈 7 의경우에는증가한다. 그리고폐기종과세포외바탕질의변화를초래하는간질성폐질환의경우에도감소한다 8. 임상에서는기류제한이있는환자에서확산능과확산계수가같이감소되어있을경우폐기종을시사하는소견으로볼수있으며 9, 기류제한이있다고해도경증의천식환자에서확산능은오히려증가하기도한다. 그러나기류제한이있는환자에서확산능은감소하였으나확산계수는정상범위를유지하는경우를임상에서흔히볼수있다. 즉기류제한이있는환자에서확산능과확산계수가차이를보이는경우어떠한의미를지니는지에대해서는아직잘연구되지않았다. 확산능해석에서폐포용적의보정을사용하지않거나 10, 폐포용적을전폐용적으로보정하여확산계수와확산능의차이를줄이자는주장도있고 9 확산계수와 374
Tuberculosis and Respiratory Diseases Vol. 59. No. 4, Oct. 2005 확산능의차이에대한의미를밝히려는노력도있어왔다 11. 이에본연구에서는기류제한환자에서확산능과확산계수의차이가가지는의미를조사하고자한다. 대상및방법 국 SensorMedics 사의 6200 Autobox DL Pulmonary Function Laboratory를이용하였다. Debuois 등 12 이제시한방법에의거하여체적변동기록법 (plethysmo graphy) 으로기능적잔기량 (functional residual cap acity; FRC) 을측정하였다. 폐활량과폐용적의추정정상치는유럽흉부학회에서제시한식으로계산하였다 13. 1. 대상군본연구는호흡곤란, 기침을주소로내원하여청진에서천명음이들려임상적으로기류폐색이있는환자를대상으로하였다. 폐결핵및근육질환의병력있거나늑막비후또는흉곽변형이있는자는대상에서제외하였다. 기저폐기능검사를기준으로 D L CO / VA (% 예측치 ) 에대한 D L CO (% 예측치 ) 의비가 115% 를넘는경우를고차이군 (high discordance gr oup) 으로 D L CO / VA (% 예측치 ) 와 D L CO(% 예측치 ) 의비가 115% 미만인경우를저차이군 (low dis cordance group) 으로정하였다. D L CO / VA (% 예측치 ) 와 D L CO(% 예측치 ) 차이의절대값이 15 이상인경우를고차이군으로, 그렇지않은경우를저차이군으로나눈경우에도환자군의구성에는차이가없었다. 조사대상자는모두 31명으로고차이군 (high disco rdance group) 이 16명이었고저차이군 (low discor dance group) 은 15명이었다. 모든환자에서베타-2 교감신경작용제와스테로이드흡입제를사용하였고만성폐쇄성폐질환으로진단한 8명의환자들은 ipra tropium bromide 흡입제를추가하였다. 내원시폐확산능을포함한폐기능검사를같이측정하였고, 추적중폐기능검사를반복하였다. 2. 검사장비및방법첫번째폐기능검사에서는검사 12시간전부터는기관지확장제를사용하지않은상태에서검사를시행하였고, 추적중에시행한두번째폐기능검사에서는약물사용시간에제한을두지않았다. 폐활량은미 3. 폐확산능 (diffusion capacity; DLco) 과폐포용적 (alveolar volume) 의측정폐확산능은상용화된기계 (Sensor Medics Autobox 6200, USA) 로측정하였으며모든환자에서 5분간격으로 2회이상측정하였다. 환자의협조가잘된반복측정치에서두값의차이가 10% 미만이거나 3ml CO/min/mmHg 이내일때에첫번째또는협조가가장잘된하나를선택하여폐확산능치로정하였다. 대상자는잔기량까지호기를한상태에서총폐용량 (total lung capacity; TLC) 까지혼합기체 (0.3% CO, 0.3% CH 4, 0.3% C 2 H 2, 21% O 2, balance N 2 ) 를빨리흡입시켰다. 흡기시작시점부터최대 10초까지숨을멈추게하며이후호기를한다. 호기시먼저사강 (dead space) 내기체가빠지고폐포내기체가나올때호기시 CO의농도를계속측정하여 Krogh 공식을이용하여확산능을계산하였다 16. 폐확산능과폐확산능을폐용적으로나눈값의추정정상치는유럽흉부학회에서제시한식으로계산하였다 14,15. 폐포용적 (alveolar volume; V A ) 은일회호흡법 (single-breath) 으로계산하였고, 흡입한 CH 4 기체의호기시희석정도에따라폐포용적을측정하였다. 식은아래와같다. V A = V I (F ICH 4/F ECH 4) V I: inspired volume, liters (BTPS) F ICH 4 = (1-V D/V I) F ICH 4 F ICH 4 = concentration of CH 4 inspired V D = 0.15 liter F ECH 4 = concentration of CH 4 expired BTPS = body temperature and ambient pressure, and saturated with water vapor 375
YW Seo et al. : Lung diffusion capacity in patients with airflow limitation 3. 통계처리폐기능검사치의결과는평균 ± 표준편차로표현하였다. 데이터의비율비교는 Fisher s exact test, 치료전후의평균치비교는 Wilcoxon signed rank test, 치료전후의변화량비교에는 Pearson s correla tion을사용하였다. 통계패키지는 SPSS 11.0 version 을사용하였고유의수준 5% 이하로검증하였다. 결과 1. 대상군특성조사대상자는모두 31명으로, 확산계수 (D L CO/VA) 의예측치와확산능 (D L CO) 의예측치비가 115% 를넘는고차이군 (high discordance group) 이 16명이었고확산계수의예측치와확산능의예측치비가 115% 미만인저차이군 (low discordance group) 은 15명이었다. 고차이군과저차이군의기저특성의비교에서고차이군에서남성의비가저차이군에비해낮은점을제외하고는통계적으로유의한차이는없었다 (Table 1). 폐활량치및폐용적에서두군사이에유의한차이는관찰되지않았다. 그리고확산계수는양군에서유 의한차이가관찰되지않은반면확산능은고차이군에서저차이군에비해유의하게낮았다. 2. 폐활량, 폐용적및폐확산능의변화폐기능검사의평균추적기간은고차이군에서 96일, 저차이군에서 99일이었다. 추적후기저치에대한변화를분석한결과폐활량의변화 (FEV 1, FVC) 는고차이군에서저차이군에비해증가하였으나전폐용적과잔기량은통계적으로유의한차이가없었다 (Table 2). 추적폐확산능에서확산계수는두군에서유의한변화가없었으나확산능과폐포용적은고차이군에서는치료후기저치에비해증가하였으나저차이군에서는오히려감소하였다 (Table 2). 치료후메탄 (CH 4 ) 을이용하여측정한폐포용적 (VA) 의변화와 FEV 1 의변화사이에는유의한양의상관관계가관찰되었다 (Figure 1). 고찰본연구에서는고차이군과저차이군사이의기저확산능 (D L CO) 평균 (% 예측치 ) 은 69와 106으로유의한차이가있는데비해확산계수의평균 (% 예측치 ) 은 113과 100이었고통계적으로유의한차이는관찰 Table 1. Characteristics of the study subjects 376 Characteristic High discordance (n = 16) Low discordance ( n = 15) P value Age, year 63 ± 15 62 ± 13 0.91 Male gender No. (%) 6 (38%) 11 (73%) 0.04 Smoker No. (%) 5 (31%) 10 (67%) 0.53 Asthma No. (%) 13 (81%) 10 (67%) 0.37 FVC (% predicted) 69 ± 14 79 ± 16 0.09 FEV 1 (% predicted) 59 ± 22 64 ± 26 0.56 FEV 1/FVC 58 ± 14 56 ± 14 0.62 TLC (% predicted) 122 ± 28 127 ± 21 0.35 RV (% predicted) 200 ± 65 182 ± 65 0.55 DLCO (% predicted) 69 ± 16 106 ± 28 < 0.01 DLCO/VA (% predicted) 113 ± 30 100 ± 28 0.29 Values are patient number or means with standard deviation (percentage) FEV 1 = forced expiratory volume in one second FVC = forced vital capacity TLC = total lung capacity RV = residual volume DLCO = carbon monoxide diffusion capacity VA = alveolar volume
Tuberculosis and Respiratory Diseases Vol. 59. No. 4, Oct. 2005 Table 2. Lung function change after treatment High discordance (n = 16) Low discordance ( n = 15) P value FVC (% change) 25 ± 11 15 ± 7 < 0.01 FEV 1 (% change) 30 ± 10 20 ± 8 0.03 TLC (% change) -5.6 ± 13-4.4 ± 9 0.89 RV (% change) -29 ± 23-23 ± 11 0.62 DLCO (% change) 16±13-11±18 < 0.01 DLCO/VA (% change) 4 ± 9-0.6 ± 9 0.35 Values are means with standard deviation FEV 1 = forced expiratory volume in one second FVC = forced vital capacity TLC = total lung capacity RV = residual volume DLCO = carbon monoxide diffusion capacity VA = alveolar volume Figure 1. Correlation between FEV 1 and alveolar vol ume VA change from baseline 되지않았다 (Table 1). 따라서확산능과확산계수의차이는 CH 4 희석법으로측정한폐포용적의변화로기인한것임을알수있다. 기류제한이있는환자에서확산능 (% 예측치 ) 보다확산계수 (% 예측치 ) 가 15% 이상증가한고차이군의경우치료후추적 FEV 1 과 FVC가저차이군과비교해서기저치에비해의미있게증가하였다 (Table 2). 그러나기류가역성의유의한변화와는달리치료전후잔기량과전폐용적등의정적폐용적은두군사이에통계적으로유의한차이는없었다 (Table 2). FEV 1 의변화와 CH 4 기체를이용해측정한폐포용적의변화는유의한양의상관관계가있음을알수있다 (Figure 1). 이는기류의호전이, CH 4 기체의폐포혼합증가로이어짐을미루어짐작할수있다. 미국흉부학회에서는확산능측정시 helium (He), neon (Ne), argon (Ar), 그리고 methane (CH 4 ) 등의기체를이용하여폐포용적을측정할수있음을소개하고있으며 16, 유럽흉부학회에서는 He을이용한폐포용적측정법을추천하고있다 14. 기관지및폐포에서확산및대류등의 CH 4 기체특성은 He과거의동일하며 17, 확산능측정에서 CH4를이용한폐포용적측정이널리이용되고있다 18. 폐포용적 (alveolar volume) 을 Helium 또는 CH 4 등이포함된기체를사용해서일회호흡법 (single breath) 으로측정할경우, 기류폐색이있는경우에는잔기량이하의폐용적에서기체의혼합이충분히이루어지지않기때문에측정된폐포용적은실제전폐용적보다작아진다. Helium 희석일회호흡법으로폐포용적을측정한경우정상인에서는전폐용적의 90-95% 에이르지만 19, 기류폐색이있는경우폐포용적은전폐용적의 80% 미만으로감소할수있다 11. 본연구에서는체적변동기록법 (plethysmography) 으로측정한잔기량의평균예측치는고차이군 (200%) 이저차이군 (182%) 보다높았으나통계적으로유의하지않았다. 따라서세기관지의폐쇄와기체의혼합이잘이루어지지않는잔기량용적의차이등으로인해고차이군에서폐포용적 (VA) 측정치가저차이군보다감소한것으로보인다. 치료후추적폐기능에서잔기량, 전폐용적등의정적인폐용적변화는두군사이에서통계적유의성이관찰되지않았으나 FEV 1 과 FVC 등의동적인폐용적변화는고차이군에서높았다. 이는치료전고차 377
YW Seo et al. : Lung diffusion capacity in patients with airflow limitation 이군에서는소기관지또는세기관지에서의가역적인기류폐색으로인해기체의혼합을방해하여폐포용적 (VA) 감소를일으키고, 치료후가역적인기류폐색이호전되어 CH 4 희석법으로측정한폐포용적의증가와함께 FEV 1 및 FVC의추가상승을가져왔을것으로추측할수있다. CH 4 희석법으로측정한폐포용적의변화와 FEV 1 의변화사이에유의한양의상관관계가있음은위의가설을뒷받침한다고볼수있다. 추적폐기능검사에서고차이군의경우확산능이증가하였는데이는폐포용적의감소와밀접한연관을가질것으로생각한다. 폐용적은막전도도 (mem brane conductance) 와모세혈관의혈액량에도영향을미쳐서확산능을변화시킨다 20-22. 그리고 Stam등은폐포용적과확산능사이에역상관관계가있음을보고하였다 23. 본연구에서도고차이군에서확산능이증가된것은폐포용적과밀접한관련이있을것으로미루어짐작할수있다. 제한성폐질환으로인해서폐포용적이감소하는경우에도확산계수는증가한다. 전폐절제술 24, 늑막질환 25, 근육질환 26, 그리고흉곽변형 27 등의질환에서확산계수가정상범위보다증가한다. 결핵의유병율이높은우리나라에서는기류제한이있는환자에서도결핵으로인한제한성환기장애를흔히볼수있다. 따라서확산계수와확산능사이의예측치차이를설명할때제한성환기장애에대한평가가필요하다. 본연구에서는전폐용적과잔기량등폐용적에서고차이군과저차이군사이에유의한차이는관찰되지않았고, 모든대상환자에서병력및흉부방사선검사를통해제한성환기장애가의심되는환자는제외하였으므로제한성환기장애로인한확산계수차이가능성을배제할수있다. 결론적으로, 기류제한이있는환자에서확산계수는정상범위에있지만확산능이감소한경우확산능이감소하지않은환자에비해가역적인기류폐색이클것으로예측할수있다. 요약배경 : 폐확산능 (D L CO) 과폐용적을보정한확산계수 (D L CO/VA; KCO) 는폐포용적이비정상적인경우차이가생긴다. 그러나, 기류제한으로비정상적인폐포용적을가지는환자에서이러한차이의의미는연구되지않았다. 본연구는기류제한이있는환자에서기류제한의호전에따른폐확산능과확산계수의변화를연구하고자한다. 방법 : 기류제한이있는환자에서기저폐기능과더불어폐확산능을측정하고, 일회호흡 CH 4 희석법으로폐포용적을측정하였다. 기저치에따라서환자는다음의두군으로나누었다. 확산계수 ( 예측치에대한백분율 ) 와확산능 ( 예측치에대한백분율 ) 의비가 115% 를넘는경우를고차이군으로하였고, 115% 미만인경우를저차이군으로하였다. 기류제한을치료한후폐기능검사와폐확산능을반복해서측정하였다. 결과 : 고차이군과저차이군의기저폐기능은유의한차이가관찰되지않았다. 두군모두확산계수의예측치에대한백분율은평균 113% 와 100% 로정상범위였다. 치료후추적폐기능에서 FEV 1 과 FVC는저차이군에비해고차이군에서증가하였다. 고차이군에서치료후측정한폐기능은기저치에비해폐확산능과폐포용적은증가하였으나저차이군에서는유의한차이는관찰되지않았다. 전폐용적과잔기량은치료전후에양군모두에서유의한차이가관찰되지않았다. 결론 : 기류제한이있는환자에서확산계수는정상범위에있지만확산능이감소한경우확산능이감소하지않은환자에비해가역적인기류폐색이클것으로예측할수있다. 참고문헌 1. Ogilvie CM, Forster RE, Blakemore WS, Morton JW. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest 1957;36:1-17. 2. Clark EH, Woods RL, Hughes JM. Effect of blood transfusion on the carbon monoxide transfer factor of the lung in man. Clin Sci Mol Med 1978;54:627-31. 3. Cotes JE, Dabbs JM, Elwood PC, Hall AM, McDonald 378
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