DOI: 10.4046/trd.2011.70.6.498 ISSN: 1738-3536(Print)/2005-6184(Online) Tuberc Respir Dis 2011;70:498-503 CopyrightC2011. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. 만성폐쇄성폐질환 (COPD) 환자에서운동시발생하는산소불포화반응과관련된인자 계명대학교의과대학 1 내과학교실, 2 예방의학교실, 3 영상의학교실심상우 1, 조준연 1, 권용식 1, 채진녕 1, 박지혜 1, 이미영 2, 노병학 3, 최원일 1 Original Article Factors Related to Exertional Oxygen Desaturation in Patients with COPD Sang Woo Shim, M.D. 1, Jun Yeon Jo, M.D. 1, Yong Sik Kwon, M.D. 1, Jin Nyeong Chae, M.D. 1, Jie Hae Park, M.D. 1, Mi-Young Lee, M.D. 2, Byung Hak Rho, M.D. 3, Won-Il Choi, M.D., Ph.D. 1 Departments of 1 Internal Medicine, 2 Preventive Medicine, and 3 Diagnostic Radiology, Keimyung University School of Medicine, Daegu, Korea Background: The causes of exertional desaturation in patients with COPD can be multifactorial. We aimed to investigate factors predict exertional desaturation in patients with moderate to severe COPD. Methods: We tested 51 consecutive patients with stable COPD (FEV 1 /FVC, 40±13% predicted). Patients performed a six minute walk test (6MWT). Pulse oxymetric saturation (SpO2) and pulse rate were recorded. Results: Oxygen desaturation was found in 15 subjects after 6MWT, while 36 subjects were not desaturated. Lung diffusing capacity was significantly lower in desaturation (DS) group (62±18% predicted) compared with not desaturated (ND) group (84±20, p<0.01). However there was no statistical difference of FEV 1/FVC ratio or residual volume between two groups. The pulse rate change was significantly higher in the desaturated compared with the not desaturated group. Six minute walking distance, subjective dyspnea scale, airflow obstruction, and residual volume did not predict exertional oxygen desaturation. Independent factors assessed by multiple logistic regression revealed that a pulse rate increment (odd ratio [OR], 1.19; 95% confidence interval [CI], 1.01 1.40; p=0.02), a decrease in baseline PaO 2 (OR, 1.105; 95% CI, 1.003 1.218; p=0.04) and a decrease in lung diffusing capacity (OR, 1.10; 95% CI, 1.01 1.19; p=0.01) were significantly associated with oxygen desaturation. Receiver operator characteristic (ROC) analysis showed that an absolute increment in pulse rate of 16/min gave optimal discrimination between desaturated and not desaturated patients after 6MWT. Conclusion: Pulse rate increment and diffusion capacity can predict exertional oxygen desaturation in stable COPD patients with moderate to severe airflow obstruction. Key Words: Pulmonary Disease, Chronic Obstructive; Heart Rate; Anoxia 서 론 Address for correspondence: Won-Il Choi, M.D., Ph.D. Department of Internal Medicine, Keimyung University School of Medicine, 216, Dalseong-ro, Jung-gu, Daegu 700-712, Korea Phone: 82-53-250-7572, Fax: 82-53-250-7434 E-mail: wichoi@dsmc.or.kr Received: Jan. 22, 2011 Accepted: May 21, 2011 만성폐쇄성폐질환 (chronic pulmonary obstructive disease, COPD) 환자에서발생하는호흡곤란은환자의건강상태에부정적인영향을주고, 사회적활동범위를결정하는중요한요소이다 1,2. COPD 환자에서활동시산소불포화 (oxygen desaturation) 반응이발생하면, 이로인해활동이제약된다 3,4. 저산소혈증이동반된 COPD 환자에산소치료를할경우사망률이감소되며 5,6, 국내에서도안 498
Tuberculosis and Respiratory Diseases Vol. 70. No. 6, Jun. 2011 정시저산소혈증이있는환자에서산소가널리처방되고있다. COPD 환자에서저산소혈증은기류제한과연관된환기관류장애에의하여주로발생한다고알려져있지만 7,8, COPD 환자에서쌕쌕거림이나가래가없는상황에서도산소포화도의차이가있는경우를고려하면, 기류제한에의한환기관류장애만으로는설명되지않는부분이있다. COPD 환자에서운동시발생하는산소불포화반응은환기관류장애 7, 폐확산능의제한 9,10, 혼합정맥혈의단락, 폐포저환기, 폐로회귀하는혼합정맥혈의감소된산소등다양한원인에의해발생할수있으며, 운동전산소포화도는운동후산소불포화반응과유의한상관관계가있다는보고도있다 9-12. COPD 환자에서 6분보행검사 (6-minute walk test, 6MWT) 는활동시산소불포화를발견하는데운동부하검사에비해더민감한것으로알려져있으며 13, 6분보행검사의운동거리와산소소모량은 COPD 환자의생존율과연관되어있다 4,14. 이에본연구는 COPD 환자에서 6분보행검사를시행하여, 산소불포화반응과관련된요인들을조사하고자한다. 대상및방법 1. 연구대상본연구는계명대학교동산병원의학연구윤리심의위원회 (Institutional Review Board) 의승인을받아시행되었다. 연구대상은 COPD 로진단받고최근 2개월간기침, 가래, 호흡곤란등호흡기증상의변화없이안정적으로외래에서추적관찰중인환자를대상으로하였다. 2006년 6월부터 2008년 12월사이에계명대학교동산의료원호흡기내과를방문한환자중 COPD 환자 51명이연구에참여하였다. 호흡기질환이외의장애로보행을하지못하는경우는대상에서제외하였다. 모든환자들은폐기능검사와 6분보행검사를하였다. 2. 폐기능검사폐활량은미국 SensorMedics사 (Sensormedics Corp., Anaheim, CA, USA) 의 6200 Autobox DL Pulmonary Function Laboratory를이용하였다. Plethysmographic 방법으로기능적잔기량 (functional residual capacity, FRC) 을측정하였다. 폐활량의추정정상치는한국인을대상으로제시한식으로계산하였다 15. 3. 6분보행검사 (6-Minute Walk Test) 6분보행검사는미국흉부학회 (American Thoracic Society, ATS) 에서제시하는방법을바탕으로 45 미터의거리, 직선으로된복도를반복하여시행하였다 16. 6MWT 전혈압측정과동맥혈가스분석을하였다. 6MWT 시행전과후에맥박수, 산소포화도, medical research council (MRC) 호흡곤란척도로호흡곤란정도를측정하였다. 산소포화도는손가락형맥박산소측정기 (Onyx 9,500, Nonin Finger Pulse Oximeter) 를이용하여측정하였다. 본연구에서는 6MWT 직후에측정한산소포화도가기저치에비해 2% 이상감소한경우를산소불포화군 (desaturated, DS) 으로, 기저치에비해감소하지않거나증가한경우를산소불포화가없는군 (not desaturated, ND) 으로정의하였다 17. 4. 통계분석결과값은평균값 ± 표준편차로나타내었다. DS와 ND, 두군사이의평균치비교는독립표본 t-검정, 그리고 6분보행검사시행전후의산소포화도감소에미치는인자는다중로지스틱회귀분석법을이용하였고, 이때단변량분석에서통계적인유의성이있거나, 중요한영향을미칠것으로여겨지는변수들 (Hct, FEV 1, residual volume, baseline PCO 2, baseline PaO 2, baseline O 2 saturation) 을함께투입하였다. 6분보행검사전후맥박수의변화및산소포화도는피어슨상관계수를구하여상관관계를분석하였다. 통계프로그램은 SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) 을이용하였고, 0.05 미만의 p값을통계적으로유의한것으로판단하였다. 결과 1. 환자특성연구대상자는모두 51명으로남자가 45명 (88%), 여자가 6명 (12%) 이었다. 전체환자의연령범위는 43세부터 82 세였으며평균연령은 66±9세였다 (Table 1). 흡연량은평균 39갑년이었다. 2. 폐기능검사대상자에서 1초간노력성호기량의노력성폐활량에대한비 (forced expiratory volume in 1 second/forced vital capacity, FEV 1 /FVC) 의평균은 49% 였으며, FEV 1 예측치 499
SW Shim et al: Exertional oxygen desaturation in patients with COPD Table 1. Patient characteristics and pulmonary function data Variables Total (n=51) COPD DS (n=15) COPD ND (n=36) p-value Sex, M/F 45/6 13/2 32/4 0.82 Age* (range), yr 66±9 (43 82) 65±11 ( 82) 67±9 (45 82) 0.49 BMI*, kg/m 2 21.7±2.8 21.3±3.0 21.9±2.7 0.43 FEV 1, % of predicted 40±13 36±12 42±13 0.13 FEV 1/FVC, % 49±9 47±7 49±9 0.53 RV, % of predicted 181±52 184±54 174±48 0.55 DLCO*, % of predicted 77±22 62±18 84±20 <0.001 *Mean±SD, Chi-square test for comparison. COPD: chronic pulmonary obstructive disease; DS: desaturated; ND: not desaturated; BMI: body mass index; FEV 1: forced expiratory volume in one second; FEV 1/FVC: forced expiratory volume to forced vital capacity ratio; RV: residual volume; DLCO: diffusing capacity of the lung for carbon monoxide; SD: standard deviation. 의평균은 40% 였다. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 진료지침에따라 COPD 의중증도를분류하면중등증 20명 (37%), 중증 25명 (46%), 고도중증 9명 (17%) 이었다. 폐확산능 (diffusing capacity of carbon monoxide, DLCO) 의예측치는산소불포화군에서산소불포화가발생하지않은군에비해 22% 정도낮았고, 통계적으로유의하였다 (Table 1). 그러나 FEV 1, FEV 1 /FVC과잔기량 (residual volume) 등은두군사이에유의한차이가관찰되지않았다. 3. 6분보행검사검사전후손가락형맥박산소측정기를사용하여산소포화도와맥박수를측정하였다. 15명 (29%) 에서산소포화도가감소하였고, 평균감소치는 6.4±5.7% 였다. 산소포화도가감소하지않은환자 36명은검사전보다평균 0.6±.6% 증가하였다. 산소포화도가감소되지않은군 7 명에서 2% 이상산소포화도가증가하였다. 51명의환자중 48명이검사후에맥박수가 1회 / 분이상증가하였고, 1명은변화가없었으며, 2명은검사전보다 1회 / 분이상감소하였다. 맥박수가 10회 / 분미만으로증가한환자는 10명 (19%), 10 19회 / 분증가한환자는 20명 (43%), 20 29회 / 분증가한환자는 12명 (23%), 30회 / 분이상증가한환자는 4명 (7%) 이었다. 산소불포화반응이발생한환자군 (DS) 에서검사후맥박수는평균 21회가증가하여, 평균맥박이 14회증가한 ND군에비해통계적으로유의한차이가관찰되었다 (p=0.019). 6분보행검사보행거리, MRC 호흡곤란척도, 적혈구용적률 (hematocrit), 운동전산소포화도, ph, HCO 3, PaCO 2 등은양군사이에유의한차이가관찰되지않았다. 기저동맥혈산소분압 (PaO 2 ) Table 2. Oxygen saturation and pulse rate of pre and post 6MWT Variables COPD (n=51) Desaturation No desaturation p-value Number 15 36 O 2 saturation, % Pre 94.0±3.9 95.2±1.9 0.13 Post 87.5±7.6 95.8±2.3 <0.001 Pulse, /min Pre 83±18 82±13 0.83 Post 104±22 98±14 0.12 Pulse difference 21±12 13±8 0.02 6MWD, m 326±80 339±93 0.65 Hct 41.3±4.5 40.5±4.2 0.51 Baseline blood gas ph 7.40±0.03 7.42±0.03 0.14 PCO 2, mm Hg 42.4±5.3 39.1±6.3 0.09 HCO 3, meq/l 26.2±2.4 25.0±3.6 0.28 PaO 2, mm Hg 70.5±13.6 85.7±17.5 0.03 Baseline MRC grade 3.6±0.8 3.1±0.7 0.08 Values are presented as Mean±SD unless otherwise indicated. COPD: chronic pulmonary obstructive disease; 6MWT: 6-minute walk test; 6MWD: 6-minute walk distance; MRC: medical research council; SD: standard deviation. 은산소포화도가감소한군에서감소하지않은군에비해유의하게낮았다 (p=0.03) (Table 2). 4. 산소포화도감소와관련된인자 산소포화도감소에영향을미칠수있는변수들을다중로지스틱회귀방법으로분석한결과에서맥박수증가와, 기저동맥혈산소분압, 그리고폐확산능감소만이유의한 500
Tuberculosis and Respiratory Diseases Vol. 70. No. 6, Jun. 2011 Table 3. Multiple logistic regression analysis for factors associated with oxygen desaturation in patients with COPD after 6-minute walk test Variable OR 95% CI Hct 0.908 0.702 1.175 FEV 1, % predicted 0.979 0.905 1.058 A decrease in DLCO, % predicted 1.101 1.011 1.198 RV, % predicted 0.988 0.966 1.010 Pulse rate difference 1.190 1.010 1.402 Baseline PaCO 2 1.028 0.844 1.253 A decrease in baseline PaO 2 1.105 1.003 1.218 Baseline O 2 sat 1.098 0.755 1.599 Table 4. Sensitivity, specificity of pulse rate increment after 6-minute walk test Pulse rate change, per min Sensitivity Specificity >5 93 0 >11 87 47.2 >16 67 61.1 >20 53 80.5 >24 33 83.3 Total number of patients is 51 and rates are represented as percent. COPD: chronic pulmonary obstructive disease; OR: odd ratio; CI: confidence interval; FEV 1: forced expiratory volume in 1 second; DLCO: diffusing capacity of the lung for carbon monoxide; RV: residual volume. Figure 2. ROC curve of pulse rate change. Area under the ROC curve=0.704 (95% CI, 0.56 to 0.82). ROC: receiver operating characteristic; CI: confidence interval. Figure 1. Correlation between the change in oxygen saturation and pulse rate before and after 6-minute walk test. 인자로관찰되었다 (Table 3). 6분보행검사전후의맥박수변화와산소포화도변화는상관계수는 0.53 (p< 0.001) 으로서로유의한상관관계가있었다 (Figure 1). 5. 산소포화도감소진단의민감도와특이도 맥박수가 16회이상증가한경우를기준으로했을때 15명의산소포화도감소환자중에서 10명을양성으로판정하여민감도 67%, 36명의산소포화도가변동이없거나증가한환자중에서는 22명에서음성으로판정하여특이도는 61% 로관찰되었고 (Table 4), 이때 receiver operating characteristic (ROC) 곡선의하부영역 (area under the ROC curve) 은 0.70으로중등도의정확한검사수준으로 관찰되었다 (Figure 2). 고찰 COPD 환자에게발생하는만성저산소혈증과고이산화탄소혈증은전신질환의발생위험도를증가시킨다 18. 안정시산소포화도는정상범위이나운동시발생하는저산소혈증이있는 COPD 환자에게이동용산소치료를하면운동능력이개선된다 19. 본연구는 COPD 환자에서운동시에발생하는산소포화도감소와연관된인자를분석하고자했다. 산소불포화반응이일어난환자군은산소포화도의변화가없는군에비하여폐확산능이통계적으로유의하게낮았으며이는이전의연구와잘일치하였다 9-12. 본연구에서 6MWT 후맥박수의변화정도는산소불포 501
SW Shim et al: Exertional oxygen desaturation in patients with COPD 화반응이일어난군이분당평균 21회가증가되었고, 산소포화도의변화가없었던군은분당평균 14회증가되었으며유의한차이가있었다 (p=0.02). 맥박수의증가폭이클수록산소불포화정도가심하여이들은음의상관관계 (R 2 =0.288) 로관찰되었다 (Figure 1). 운동후발생하는맥박수의변화는비교적간결하게측정할수있으며, 환자의생리적인상황을대변할수있는장점이있어서임상적인유용성이있으리라생각한다. 본연구에서는 6분보행검사후에맥박수가분당 16회이상증가할경우산소포화도감소를진단할수있는민감도가 67% 로, 맥박수증가의기준을 12회로할경우산소포화도감소를진단할수있는민감도가 87% 로증가하였다 (Table 4). 이에비해서 6분보행검사보행거리또는운동전호흡곤란의정도는산소포화도감소를예측하는데도움을주지않았다. 이전연구에서는운동후발생한산소불포화를기저치에비해 2 4% 감소한것으로정의하였다 9,20. 본연구에서사용한산소포화도측정기 (Onyx 9,500; Nonin Finger Pulse Oximeter, Nonin Medical, Inc., Minneapolis, MN, USA) 는평균오차가 0.3% 내외로낮은점을고려하여 17, 6분보행검사전후를비교하여산소포화도가 2% 이상감소된환자를산소불포화가있는군으로정의하였다. 산소불포화의기준을 2% 로했을때폐확산능과운동후산소포화도감소의정도및상관관계는이전의보고들과잘일치하였다 9-12. FEV 1, FEV 1 /FVC, 그리고잔기량등은 6분보행검사후산소포화도가감소한군과산소포화도가감소하지않은군사이에차이가없었다. FEV 1 /FVC과 FEV 1 이운동후산소포화도감소를예측할수있다는보고가있었지만 9,21, 본연구에서는두변수모두다중회귀분석에서유의한결과를보이지않았다. DS군과 ND군의잔기량 (RV) 과 FEV 1, FEV 1 /FVC 등의유의한차이가없고 (Table 1), 다중로지스틱회귀분석에서유의한결과를보이지않은점을고려한다면, 본연구에서기류제한으로인한산소포화도감소의정도는매우적었을것으로보인다. 운동전산소포화도가운동후산소포화도감소를예측할수있다는보고가있고 12, 본연구에서도운동전산소포화는운동후산소포화도감소와는통계적유의성이없었으나산소포화도감소군에서산소포화도감소가없는군에비해기저 PaO 2 가유의하게낮았다. 이는산소포화도보다는동맥혈산소분압이혈중산소농도를더민감하게반영해서생긴것으로보인다. 따라서기저동맥혈산소농도를통해서운동후산소포화도감소를예측할수 있다. COPD 환자에서안정시동맥혈산소분압이 55 mm Hg 이하인환자에게하루 18시간이상의산소치료는사망률을감소시킨다 6. 그러나, 안정시에는저산소혈증이없으나, 운동시에저산소혈증이발생하는 COPD 환자에서는산소치료가증상호전에명백한이득이없다는연구도있다 3,22. 따라서향후연구를통해산소포화도감소의원인이저산소혈증으로설명되는군과다른원인, 예를들면이산화탄소분압이증가해서생기는경우등으로나누어서, 평가할필요가있다. 7명의 COPD 환자에서는운동후산소포화도가 2% 이상증가하였다. 이는운동시에폐혈류관류불균형 (ventilation perfusion mismatch) 이호전되어발생하는현상으로보인다. 결론적으로, 폐확산능은 COPD 환자에서운동시산소포화도감소를예측할수있으며, 운동전후맥박수의증가폭은산소포화도감소를예측할수있다. 중등도이상의 COPD 환자에서 6분보행검사를기준으로검사전후에 16회이상맥박수가증가할경우산소포화도감소를진단하는민감도는 67% 이다. 참고문헌 1. Reardon JZ, Lareau SC, ZuWallack R. Functional status and quality of life in chronic obstructive pulmonary disease. Am J Med 2006;119(10 Suppl 1):32-7. 2. Weaver TE, Richmond TS, Narsavage GL. An explanatory model of functional status in chronic obstructive pulmonary disease. Nurs Res 1997;46:26-31. 3. Nonoyama ML, Brooks D, Guyatt GH, Goldstein RS. Effect of oxygen on health quality of life in patients with chronic obstructive pulmonary disease with transient exertional hypoxemia. Am J Respir Crit Care Med 2007;176:343-9. 4. Cote CG, Pinto-Plata V, Kasprzyk K, Dordelly LJ, Celli BR. The 6-min walk distance, peak oxygen uptake, and mortality in COPD. Chest 2007;132:1778-85. 5. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980;93:391-8. 6. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet 1981;1:681-6. 502
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