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1 만성폐쇄성폐질환환자의호흡곤란평가에서우심실박출계수의의의 계명대학교의과대학내과학교실 1, 예방의학교실 2, 핵의학교실 3 이정은 1, 민보람 1, 박재석 1, 박훈표 1, 전미정 2, 원경숙 3, 최원일 1 Right Ventricle Ejection Fraction Contributes Severity of Dyspnea in Chronic Obstructive Pulmonary Disease (COPD) Jung Eun Lee, M.D. 1, Bo Ram Min, M.D. 1, Jae Seok Park, M.D. 1, Hun Pyo Park, M.D. 1, Mi Jung Jun, M.S. 2, Kyung Sook Won, M.D. 3, Won Il Choi, M.D. 1 Departments of Medicine 1, Preventive Medicine 2, and Nuclear Medicine 3, Keimyung University School of Medicine, Daegu, Korea Background: Patients with COPD generally complain of very different degrees of dyspnea regardless of their pulmonary function. The study, we assessed the right ventricular ejection fraction in relation to dyspnea in COPD patient. Methods: The pulmonary function including the diffusion capacity was measured. The right ventricle ejection fraction (RVEF) was measured using a first-pass radionuclide scan by multigated acquisition (MUGA). Forty patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnea according to the Medical Research Council (MRC) scale. Moderate dyspnea and severe dyspnea is defined as MRC 2/3 (n = 16) and MRC 4/5 (n = 24) respectively. Results: The baseline pulmonary function tests including DLCO and the resting arterial blood gas were similar in the moderate and severe dyspnea group, with the exception of the residual volume (% predicted) (moderate 160 ± 27, severe 210 ± 87, p < 0.03). The right ventricle ejection fraction was significantly (p < 0.001) lower in the severe dyspnea group (25 ± 8) than in the moderate group (35 ± 6). The independent factor assessed by multiple logistic regression revealed only the severity of dyspnea to be significantly associated with RVEF (p < 0.02). Conclusion: This study showed that the right ventricle ejection fraction would contributes to severity of dyspnea in patients with a similar pulmonary function (Tuberc Respir Dis 2006; 60: ) Key Words: COPD, Ejection fraction, Dyspnea. 서 만성폐쇄성폐질환에서호흡곤란은매우중요한증상중의하나이며호흡곤란의정도는기류폐색의정도보다더의미있는생존율예측인자로알려져있다 1,2. 일반적으로폐기능이감소할수록호흡곤란이심해지지만, 비슷한정도로폐기능이감소한환자에서도호흡곤란의정도는다양하다 3,4. 만성폐쇄성폐질환에서호흡곤란을만드는중요한이유로는중추계에서일어나는호흡근육자극의증가에비해흡기근육의부적절한반응 5-8 과동적인폐 론 Address for correspondence : Won-Il Choi, M.D. Department of Medicine, Keimyung University School of Medicine 194 Dongsan-Dong, Jung-Gu, Daegu, , Korea Telephone : Fax : wichoi@dsmc.or.kr Received : Apr Accepted : Jun 과팽창에의해발생하는것으로알려져있다 9,10. 그러나임상에서는폐활량및폐용적그리고일산화탄소확산능등이매우유사함에도불구하고다양한정도의호흡곤란을호소하는환자를볼수있다. 만성폐쇄성폐질환은폐순환의혈류역학을변화시켜폐혈관저항을증가시키고궁극적으로는우심실기능부전을일으킬수있다. FEV 1 (forced expiratory volume in one second) 예측치의평균이 40% 이하인만성폐쇄성폐질환환자의혈류역학을조사한연구에서폐동맥압은정상범위에있었지만폐혈관저항은증가하였고폐혈관저항의증가는생존률과역상관관계가있음을보고한바있다. 11 우심실박출계수는우심실수축기능을반영하며우심실후부하, 즉폐혈관저항에의해서영향을받는다 그러므로폐혈관저항이증가하는만성폐쇄성폐질환에서는우심실박출계수가감소할수있다. 종합하면, 호흡곤란은만성폐쇄성폐질환의예후의중요한예측인자중의하나이며, 예후는폐혈관저항 631

2 JE Lee et al. : Right ventricle ejection fraction in COPD 과도밀접한연관이있으므로, 호흡곤란의정도와폐혈관저항을반영하는우심실박출계수와의관계를알아보고자본연구를계획하였다. 외래환자들을대상으로비침습적인방법을통해우심실기능을측정하고, 이것과호흡곤란과의연관이있는지를확인하고자한다. 대상및방법 1. 대상환자본연구는호흡곤란, 만성기침및객담을주소로내원한환자에서 20 갑-년이상의흡연력이있으면서, FEV 1 /FVC비가 70미만인만성폐쇄성폐질환환자중에서 3개월이상호흡곤란의증상의변화가없고, 과거심근경색의병력이없는자들을대상으로하였고, 2003년 12월부터 2005년 5월까지계명의대동산병원을방문한자를대상으로조사하였다. 흉부방사선에서간질성폐질환의음영이의심되는경우, 근육질환, 또는흉벽변형이있는경우에는대상자에서제 외하였다. 2. 검사장비및방법폐활량은미국 SensorMedics 사의 6200 Autobox DL Pulmonary Function Laboratory를이용하였다. Plethysmographic 방법으로기능적잔기량 (functional residual capacity; FRC) 을측정하였다 15. 폐활량과폐용적및폐확산능의추정정상치는유럽흉부학회에서제시한식으로계산하였다 16. 폐확산능은전술한바와같이측정하였다 우심실박출계수의측정우심실박출계수의측정은게이티드 (gated) 심장혈액풀스캔을이용하였다. 먼저 Tc-99m에환자의적혈구를표지하였는데이는간접법을이용하였고방법은아래와같다. 적혈구표지바이알 (RBC kit) 에생리식염수 3 ml를넣어희석시킨다음, 5분후에희석액 1 ml를뽑아환자에게정맥주사하였다. 다시 20 Table 1. Characteristics and Lung function of the study subjects 632 Characteristic Severe dyspnea (n = 24) Moderate dyspnea (n = 16) P value Age, year 64 ± ± Male gender No. (%) 20 (83%) 11 (63%) 0.29 Smoker (pack/year) 38 ± 5 37 ± BMI (kg/m2) 20 ± 2 21 ± FVC (% predicted) 64 ± ± FEV1 (% predicted) 43 ± ± FEV1/FVC (%) 47 ± 9 52 ± TLC (% predicted) 124 ± ± RV (% predicted) 210 ± ± DLCO (% predicted) 65 ± ± DLCO/VA (% predicted) 82 ± ± Values are patient number or means with standard deviation (percentage) BMI = body mass index FEV1 = 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

3 Tuberculosis and Respiratory Diseases Vol. 60. No.6, Jun 분을기다려 Tc-99m 20 mci를환자에게정맥주사하고, 5-10분후촬영을시작하였다. 스캔은환자를앙와위로놓고안정시킨후좌전사위로검출기가환자의심장부위에가깝게위치하도록한후전체 600개의심박수를얻었다. 저에너지일반목적용조준기를장착한감마카메라 (Vertex, ADAC Co., USA) 를사용하였으며매트릭스크기는 64 64, 줌 (zoom) 은 2.19, 심박주기당 16개의 frame을얻었으며허용변이범위는 20% 로얻었다. 얻어진영상에서우심실에반자동방법으로이완기말 (end diastolic) 과수축기말 (end systolic) 의관심영역을그려우심실박출계수를측정하였다 4. 통계처리폐기능검사치및우심실박출계수의결과는평균 ± 표준편차로표현하였다. 두집단의연관성분석은 Fisher s exact test, 두군사이의평균치비교는 Wilcoxon signed rank test, 그리고호흡곤란에미치는인자는다중회귀분석법을이용하였다. 통계패키지는 spss 11.0 version 을사용하였고유의수준 5% 이하로검증하였다. 결과 1. 대상군특성조사대상자는모두 40명으로, Medical Research Council (MRC) 호흡곤란등급을기준으로 4도와 5도의호흡곤란을호소하는경우중증군으로분류하였 고, MRC 2도와 3도의호흡곤란을호소하는경우를중등도군으로분류하였다. 중증군은 24명이었고중등도군은 16명이었다. 중증군과중등도군의기저특성의비교에서폐활량치및확산계수는두군사이에유의한차이는관찰되지않았으나, 중증군에서잔기량이중등도군에비해유의하게증가하였다 (Table 1). 2. 우심실박출계수와동맥혈가스소견우심실박출계수는중증군이중등도군에비해유의하게낮았다 (P < 0.001). 동맥혈가스분석에서는중증군이중등도군보다산소포화도가낮은경향을보였으나통계적으로유의하지않았다 (P = 0.07). 이산화탄소분압, 산소분압등은두군사이에유의한차이가관찰되지않았다. 3. 호흡곤란관련인자호흡곤란에영향을미칠수있는변수들을다중회귀분석방법으로분석한결과에서우심실박출계수만이 (P = 0.02) 유의한인자로관찰되었다 (Table 3). 고찰본연구에서는만성폐쇄성폐질환환자를중증호흡곤란군 (MRC 4/5도 ) 과중등증호흡곤란군 (MRC 2/3도 ) 으로나누어비교분석하였다. 우심실박출계수는중증군에서중등증군에비해유의하게낮았고, 잔기량은중증군에서유의하게증가되었으나폐활량은두군사이에유의한차이가관찰되지않았다 Table 2. Right ventricle ejection fraction (RVEF) and resting blood gas of the study subjects Severe dyspnea (n = 24) Moderate dyspnea (n = 16) P value RVEF 25 ± 8 36 ± 6 < PCO2, mmhg 43 ± ± PO2, mmhg 68 ± ± HCO3-, mmol/l 26 ± 4 27 ± O2 saturation (%) 91 ± 6 94 ± Values are means with standard deviation 633

4 JE Lee et al. : Right ventricle ejection fraction in COPD Table 3. Factors associated with dyspnea in patients with COPD B S.E. Sig. OR 95% CI Age ~ 1.28 Smoking ~ 1.28 FEV1 (% predicted) ~ 1.38 FEV1/FVC (%) ~ 1.15 TLC (% predicted) ~ 1.35 RV (% predicted) ~ 1.03 DLCO (% predicted) ~ 1.07 O2 Saturation (%) ~ 4.44 RVEF ~ 1.63 Abbreviations: B., regression coefficient; S.E., standard error; Sig., significance; OR, odd ratio; CI, confidence interval (Table 1, 2). 다중회귀분석을통해서우심실박출계수가호흡곤란에유의하게영향을미친독립적인인자로밝혀졌다 (Table 3). 우심실박출계수의정상치는 43-65% 정도이며, 좌심실박출계수의정상치는 60-70% 이며, 우심실박출계수가좌심실박출계수보다낮다 일반적으로우심실박출계수가 40-45% 이하이면감소된것으로평가한다. 만성폐쇄성폐질환에서우심실박출계수는 19-70% 로매우다양한정도로변화가있으며 21, 이러한차이는폐활량의감소정도와는연관성이적었다 22. 본연구에서도폐활량이유사한두군에서우심실박출계수는유의한차이가있었다. 중증폐기종환자의우심실박출계수의평균이 32% 였으며 23, 본연구에서도이와유사하게우심실박출계수의평균은 31% 였고범위는 11-63% 였다. 만성폐쇄성폐질환의폐혈관저항증가는혈류역학에서중요한변화로인식되고있으나폐혈관저항의증가가폐동맥고혈압으로바로이어지지는않는것으로보인다. 만성폐쇄성폐질환환자 1264명에서폐동맥압을조사한결과이중단지 11명의환자만이폐동맥고혈압이폐쇄성폐질환에의해발생한것으로추정되었다 24. 이러한결과미루어볼때만성폐쇄성폐질환환자에서폐동맥고혈압이있을경우다른병발질환을고려하여야함을알수있다. FEV 1 의예측치가 45% 정도인환자 131명을 7년간추적해서관찰한폐동맥압의변화를보면안정시폐동맥고혈압을보인환자가없다가 7년후 33명 (25%) 의환자에서경증의폐동맥고혈압이발생하였다 25. 이러한보고들로 판단해보면, 만성폐쇄성폐질환에서폐동맥고혈압의발생은빈도가낮고발생한다하더라도폐동맥혈압은정상에비해조금더상승한정도이다. 따라서만성폐쇄성폐질환에서는다른질환의감별이필요한경우에선택적으로침습적방법을사용하여폐동맥압을측정하는것이바람직할것으로보인다. 폐동맥압의측정은도플러심장초음파검사를이용해서도할수있는데, 이방법으로는이미많이진행한폐질환에서는폐동맥압을과대평가를할수있다 26. 이에만성폐쇄성폐질환에서비침습적인방법이면서우심실기능및폐순환의간접적인평가를할수있는우심실박출계수의임상적인유용성을확인하는노력이있어왔다 23, 만성폐쇄성폐질환에서호흡곤란의기전으로는동적인기도압박 (dynamic airway compression) 에의한기도의수용체자극에의해발생할수있으며 31, 저산소혈증, 그리고고탄산혈증을들수있다 32. 만성폐쇄성폐질환에서는흔히폐의과다팽창소견이관찰되며, 폐의과다팽창은횡격막을편평하게만들어서흡기시호흡일을증가시키게된다. 호흡일의증가또한호흡곤란을일으키는이유이며, 이에더해서폐의과다팽창은폐혈관저항을증가시켜서 33 호흡곤란을더악화시킬수있음을예상할수있다. 본연구에서는폐의동적과다팽창을조사하지못했지만, 안정시의폐활량과폐용적이유사하다할지라도동적과다팽창정도에따라활동시호흡곤란이다르게나타날수있을것임을예측할수있다. 폐용적감소술을통해서얻은결과에따르면, 우심 634

5 Tuberculosis and Respiratory Diseases Vol. 60. No.6, Jun 실기능의부전은과팽창에의해주로발생하는것으로볼수있다 23. 그러나과팽창이외에도혈관내피세포손상에의해서도혈류역학에문제를초래할수있음이알려져있다. 경증의만성폐쇄성폐질환에서부터중증의만성폐쇄성폐질환에까지모두폐동맥의혈관내피세포의기능부전이있으며 34,35, 이러한혈관내피세포의기능부전은 endothelial nitric oxide synthase (enos) 의발현감소와연관되어만성폐쇄성폐질환환자에서폐동맥고혈압을유발한다 36. 또한흡연에의해서도 enos의발현이감소될수있다 37. 결과에기술하지않았지만, 본연구에서는폐용적차이와우심실기능부전사이의유의한상관관계가관찰되지않았으며이러한점을고려해볼때, 흡연에대한폐용적반응과폐혈관반응이일치하지않을수있으리라추측할수있으며, 비슷한폐기능에도불구하고우심실박출계수가감소한것은혈관내피세포손상의정도의차이에따라서폐혈관저항이증가하여발생한것으로유추할수있겠다. 결론적으로, 만성폐쇄성폐질환에서안정시측정한우심실박출계수와호흡곤란은서로연관성이있으며, 특히폐기능에비해호흡곤란이심한환자에서우심실박출계수를측정하는것은호흡곤란의인자를감별하는데도움이되리라사료된다. 요약배경 : 만성폐쇄성폐질환환자의호흡곤란은일반적으로폐활량에반비례하나유사한폐기능에서도서로다른호흡곤란을호소한다. 본연구는만성폐쇄성폐질환환자에서우심실박출계수와호흡곤란의정도와연관관계가있는지를알아보고자한다. 방법 : 호흡곤란의정도는 Medical Research Council (MRC) 호흡곤란척도로분석하였고, MRC 4/5도인중증군 24명과, MRC 2/3도인중등증군 16명을비교분석하였다. 심전도게이트일회통과법을이용한방사성동위원소심조영술을이용하여우심실박출계수를구했으며, 안정시동맥가스분석및폐기능검사를시행하였다. 결과 : 기저폐기능에서잔기량의예측치평균이 (%) 중증군에서 (210 ± 87) 중등증군 (160 ± 27) 에비해유의하게증가되었으나 (P < 0.03), 폐활량및확산계수등에서는유의한차이가관찰되지않았다. 우심실박출계수 (%) 는중증군에서 (25 ± 8) 중등증군 (35 ± 6) 에비해유의하게감소되었으나 (P < 0.001), 동맥혈가스는두군사이에유의한차이가관찰되지않았다. 다중회귀분석을통해우심실박출계수가독립적으로호흡곤란에영향을미치는인자로밝혀졌다. 결론 : 만성폐쇄성폐질환에서우심실박출계수가호흡곤란의정도에영향을미치는것으로보인다. 참고문헌 1. Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al.the body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med 2004;350: Nishimura K, Izumi T, Tsukino M, Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest 2002;121: Mahler DA, Harver A. A factor analysis of dyspnea ratings, respiratory muscle strength, and lung function in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1992;145: Wegner RE, Jorres RA, Kirsten DK, Magnussen H. Factor analysis of exercise of exercise capacity, dyspnoea ratings and lung function in patients with severe COPD. Eur Respir J 1994;7: Dodd DS, Brancatisano T, Engel LA. Chest wall mechanics during exercise in patients with severe chronic air-flow obstruction. Am Rev Respir Dis 1984;129: Hamilton AL, Killian KJ, Summers E, Jones NL. Muscle strength, symptom intensity, and exercise capacity in patients with cardiorespiratory disorders. Am J Respir Crit Care Med 1995;152: Montes de Oca M, Rassulo J, Celli BR. Respiratory muscle and cardiopulmonary function during exercise in very severe COPD. Am J Respir Crit Care Med 1996;154: Marin JM, Montes de Oca M, Rassulo J, Celli BR. Ventilatory drive at rest and perception of exertional dyspnea in severe COPD. Chest 1999;115: Belman MJ, Botnick WC, Shin JW. Inhaledbronchodilators reduce dynamic hyperinflation during 635

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