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1 안정된만성폐쇄성폐질환환자에서신체질량지수와전신염증인자, 산화스트레스와의관련성 경상대학교의과대학 1 내과학교실, 2 소아과학교실, 3 건강과학연구원, 4 충북대학교의과대학해부학교실함현석 1, 이해영 1, 이승준 1, 조유지 1, 정이영 1,3, 김호철 1,3, 함종렬 1,3, 박찬후 2,3, 이종덕 1,3, 손현준 4, 윤희상 2,3, 황영실 1,3 Relationship between Systemic Inflammatory Marker, Oxidative Stress and Body Mass Index in Stable COPD Patient Hyun Seok Ham, M.D. 1, Hae Young Lee, M.D. 1, Seung Jun Lee, M.D. 1, Yu Ji Cho, M.D. 1, Yi Young Jung, M.D. 1, Ho Cheol Kim, M.D. 1,3, Jong Ryeal Hahm, M.D. 1,3, Chan Hoo Park, M.D. 2,3, Jong Deok Lee, M.D. 1,3, Hyun Joon Sohn, M.D. 4, Hee Shang Youn, M.D. 2,3, Young Sil Hwang, M.D. 1,3 1 Department of Internal Medicine, 2 Department of Pediatrics, College of Medicine, 3 Gyeongsang Institute of Health Sciences, Gyeongsang National University, Jinju, Korea, 4 Department of Anatomy, Medical School of Chungbuk National University, Chungju, Korea Background: The main factors associated with weight loss in patients with COPD are not well known. Since chronic inflammation and oxidative stress play a major pathogenic role in COPD, these factors may be responsible for the patients weight loss. Therefore, this study measured the body mass index (BMI) in COPD patients and evaluated the variables, such as systemic inflammatory marker, oxidative stress and lung function, that correlate with the BMI. Method: The stable COPD patients (M:F=49:4, mean age=68.25±6.32) were divided into the lower (<18.5), normal ( ) and higher (>25) BMI group. The severity of the airway obstruction was evaluated by measuring the FEV 1. The serum IL-6 and TNF-α levels were measured to determine the degree of systemic inflammation, and the carbonyl protein and 8-iso-prostaglandin F 2α level was measured to determine the level of oxidative stress. Each value in the COPD patients and normal control was compared with the BMI. Results: 1) Serum 8-iso-prostaglandin F 2α in COPD patients was significantly higher (456.08± pg/ml) than that in normal control (264.74± pg/ml) (p<0.05). However, there were no significant differences in the serum IL-6, TNFα, carbonyl protein between the COPD patients and normal controls. 2). In the COPD patients, the FEV 1 of the lower BMI group was significantly lower (0.93±0.25L) than that of the normal BMI (1.34±0.52L) and higher BMI groups (1.72±0.41L) (p<0.05). The lower FEV 1 was significantly associated with a lower BMI in COPD patients (p=0.002, r=0.42). The BMI of very severe COPD patients was significantly lower (19.8±2.57) than that of the patients with moderate COPD (22.6±3.14) (p<0.05). 3). There were no significant differences in the serum IL-6, TNF-α, carbonyl protein and 8-iso-prostaglandin F 2α according to the BMI in the COPD patients. Conclusion: The severity of the airway obstruction, not the systemic inflammatory markers and oxidative stress, might be associated with the BMI in stable COPD patients. Further study will be needed to determine the factors associated with the decrease in the BMI of COPD patients. (Tuberc Respir Dis 2006; 61: ) Keywords: COPD, Oxidative stress, Systemic inflammatory marker, BMI 서 론 만성폐쇄성폐질환은비가역적인기류제한을특징으로하는질환으로기류제한은유해한입자나가스의흡입에의해발생한비정상적인염증반응에동반 Acknowledgement: This study was supported by 되며점차진행하게된다 1. 이러한만성폐쇄성폐질환 Gyeongsang National University Hospital Research Funds in 의병인에서중요한역할을하는인자들로는크게만 Address for correspondence: Ho Cheol Kim, M.D. 성염증, proteinases와 anti-proteinases의불균형, 산 Department of Internal Medicine, Gyeongsang National University Hospital 90, Chilam-dong, Jinju, Gyeongnam, 화스트레스 (oxidative stress) 등을들수있다 1, , Korea. 만성폐쇄성폐질환에서만성염증반응은기도와폐 Phone: Fax: hochkim@gshp.gsnu.ac.kr 실질, 폐혈관등에서발생하며이러한염증반응에관 Received: Jul 여하는세포는주로대식세포, T 림프구 ( 특히 CD8+), Accepted: Sep 호중구등이다. 이들염증세포들이활성화되면여러 330

2 Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct 매개물질들이분비되는데특히 LTB4, IL-8, TNF-α 등이대표적이며이들이폐조직을손상시킬뿐만아니라호중구성염증을더욱증가시킨다고알려져있다 2,3. 만성폐쇄성폐질환에서산화스트레스는직접적으로폐를손상시킬뿐아니라항단백분해효소를불활성화시키고, 염증반응을항진시켜폐손상을더욱가중시킨다 4. 산화스트레스의측정은산화스트레스전체부하나산화스트레스에의한반응으로측정할수있지만단백질이나지질등의표적물질에대한산화스트레스의영향을측정하는것이더중요하다고할수있다 4. 단백질의산화반응의정도는카르보닐단백질 (carbonyl protein) 부산물, nitrotyrosine 등으로측정할수있고, 지질과산화 (lipid peroxidation) 의지표로는 F 2 -isoprostane, 4-hydroxynonenal(4-HNE), 탄화수소 (hydrocarbon) 등이있다 4. 만성폐쇄성폐질환환자에서는이러한만성염증과산화스트레스의증가로인해전신염증과골격근기능장애와같은전신적인영향을줄수있다 5,6. 상당수의만성폐쇄성폐질환환자는골격근육의감소와에너지장애로체중감소가일어나게되며 7 신체질량지수 (body mass index, BMI) 의감소는나쁜예후를시사하는인자임이밝혀졌다 8,9. 예전의연구들에서는신체질량지수의감소와만성폐쇄성폐질환의관계를에너지균형과연관하여생각하였으며신체질량지수의감소는대사과다증 (hypermetabolism) 이관여를하리라여겼다 10. 그러나, 영양섭취를증가시킴에도체중감소가지속적으로발생하는것이밝혀졌으며이러한에너지불균형이외에도만성폐쇄성폐질환환자에서체중감소를일으키는다른요인들이있음이고려되었다. 현재까지이런다른요인들에대한많은연구가이루어지고있으며이중하나가 TNF-α를포함한염증성 cytokine들이며만성폐쇄성폐질환환자에서이러한 TNF-α 및수용성 TNF 수용체가증가되어있음이여러논문에서보고되었다 11,12. 염증인자의하나인 IL-6의경우도 Song 등 13 의연구에의하면폐기종을유발하며, 폐질환의중증도에관여하고 TNF-α 와함께만성폐쇄성폐질환환자에있어서근육의위축과소실에관여한다고보고되고있다 14. 이러한여러사실로미루어볼때, 아마도신체질량지수의지속적인감소는만성폐쇄성폐질환환자에있어서보다심한전신염증과산화스트레스의증가와관련이있을것으로추측할수있다. 따라서연구자등은전신염증인자로서혈청에서 IL-6 및 TNF-α를측정하고, 산화스트레스인자로 8-iso-prostaglandin F 2 α, carbonyl protein을측정하여신체질량지수와관련이있는지알아보고자하였다. 앞서이루어진대부분의연구결과가정상대조군과만성폐쇄성폐질환의급성악화시를비교한것과는달리본연구는안정된만성폐쇄성폐질환환자를대상으로하였다. 대상및방법 1. 연구대상 2004년 12월부터 2005년 3월까지경상대학병원호흡기내과외래를방문한안정된만성폐쇄성폐질환환자를대상으로하였으며대조군으로는임상적으로만성폐쇄성폐질환의증거가없는정상인을대상으로하였다. 안정된만성폐쇄성폐질환환자의기준으로흉부방사선학적소견상급성감염의증거가없고, 가택산소요법을받지않으며, 최근 3개월이내에만성폐쇄성폐질환의악화 15 로외래나응급실을방문한과거력이없는경우로한정하였다. 2. 연구방법먼저신체질량지수를 Centers for Disease Control (CDC) 기준 16 에따라저체중 (<18.5), 정상체중 ( ), 고체중 ( 25) 세군으로나누었으며폐기능검사로폐활량측정법을사용하여 FEV 1 을구하고예측치를 % 로나타내었다. 환자의혈청에서전신염증인자로서 IL-6, TNF-α는 ELISA(R & D Systems, Abington, UK) 를이용하여측정하였고산화스트레스인자로 carbonyl protein은고작위액체크로마토그래피 (high-performance liquid chromatography, HPLC) (Bio-laboratories, USA) 방법 17 ( 혈청에서 carbonyl protein을분리한후이를펌프에넣고 331

3 HS Ham et al: Relationship between systemic inflammatory marker, oxidative stress and body mass index in stable COPD patient 410nm의파장에서측정기를적용시켜표본을통합시킨후그래프로표시하여측정 ) 을이용하여측정하였고 8-iso-prostaglandin F 2 α는 ELISA(StressXpress, Canada) 를이용하여측정하였다. 측정된 IL-6, TNF-α, carbonyl protein, 8-isoprostaglandin F 2 α의값은만성폐쇄성폐질환환자와정상대조군에서각각비교하였다. 또한만성폐쇄성폐질환환자를신체질량지수에따라세군으로나눈후각각의군에서측정된 IL-6, TNF-α, carbonyl protein, 8-iso-prostaglandin F 2 α, FEV 1 과 FEV 1 (%) 의값을비교하였고, 만성폐쇄성폐질환의중증도를 FEV 1 의예측치에따라경증, 증등증, 중증, 최중증으로구분하여신체질량지수의차이를비교하였다. 만성폐쇄성폐질환의중증도는 Global Initiative for Chronic Obstructive Lung Disease(GOLD) 진단기준을이용하였다 통계적분석방법 결과는평균 ± 표준편차로표시하였으며정상대조 Table 1. Clinical characteristics in COPD patients and normal control COPD (n=53) Normal Control (n=33) M:F 49:4 30:3 Age 68.25± ±5.07 FEV 1(L) 1.33± ±0.66 FEV 1(%) 52.1± ±19.31 FEV 1/FVC(%) 53.42± ±15.05 Weight(kg) 57.82± ±7.44 BMI(kg/m2) 21.31± ±2.83 No. of current smoker (%) 17(32%) 11(33%) p<0.05 compared with normal control Table 2. Clinical characteristics in COPD patients according to body mass index(bmi) Lower BMI(n=11) Normal BMI(n=32) Higher BMI(n=10) M:F 9:2 30:2 10:0 Age 70.27± ± ±5.07 PaO 2(mmHg) 80.09± ± ±7.06 PaCO 2(mmHg) 39.63± ± ±2.42 Weight(kg) 45.65± ± ±3.49 BMI(kg/m2) 16.74± ± ±0.79 No. of current smoker (%) 3(27.2%) 11(31.2%) 3(30%) p<0.05 compared with lower and normal BMI Figure 1. Serum IL-6 and TNF-α in normal control and COPD patients. p value>0.05 compared with normal control. 332

Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct. 2006 Figure 2. Serum 8-iso-prostaglandin F2α and carbonyl protein in normal control and COPD patients. p value<0.

p value<0.05 compared with normal and higher BMI. 군과만성폐쇄성폐질환환자의 IL-6, TNF-α, carbonyl protein, 8-iso-prostaglandin F 2 α 값의비교는 paired t-test 를이용하였다.

4 Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct Figure 2. Serum 8-iso-prostaglandin F2α and carbonyl protein in normal control and COPD patients. p value<0.05 compared with normal control. Figure 3. FEV1(L) value according to BMI and its relation with BMI in COPD patients. There was significant correlation between FEV1 and BMI (p<0.05, r=0.42). p value<0.05 compared with normal and higher BMI. 군과만성폐쇄성폐질환환자의 IL-6, TNF-α, carbonyl protein, 8-iso-prostaglandin F 2 α 값의비교는 paired t-test 를이용하였다. 신체질량지수에따른각측정값의비교와만성폐쇄성폐질환의중증도에따른신체질량지수의차이는일원배치변량분석을이용해서비교하였고신체질량지수와 FEV 1 값의상관관계는 Pearson s 상관계수를이용하였다. 통계처리는 SPSS 12.00(SPSS inc; Chicago, IL, USA) 프로그램을이용하였고 p 값이 0.05 미만인경우통계적으로유의한것으로판정하였다. 결과 1. 만성폐쇄성폐질환환자와정상대조군의임상적특징만성폐쇄성폐질환환자와정상대조군은각각 53 명, 33명이었고임상적특성은다음과같다 (table 1). 안정된만성폐쇄성폐질환환자에서 FEV 1 값과 FEV 1 예측치 (%), 신체질량지수는정상대조군에비해통계적으로유의하게낮았다 (p<0.05). 만성폐쇄성폐질환환자에서신체질량지수에따라임상적특징은다음과 333

HS Ham et al: Relationship between systemic inflammatory marker, oxidative stress and body mass index in stable COPD patient 로측정되었으며 TNF-α는각각 108.68±157.08 pg/ ml, 128.77±137.

5 HS Ham et al: Relationship between systemic inflammatory marker, oxidative stress and body mass index in stable COPD patient 로측정되었으며 TNF-α는각각 ± pg/ ml, ±137.5 pg/ml으로차이는없었다 (Figure 1). 8-iso-prostaglandin F 2 α 는각각 ± pg/ml, ± pg/ml로만성폐쇄성폐질환환자에서높았으나 (p<0.05), carbonyl protein은두군간의차이를나타내지않았다 (Figure 2). 3. 만성폐쇄성폐질환환자에서신체질량지수에따른 FEV 1 (%) 값의차이 Figure 4. Difference of BMI according to severity of COPD. P value<0.05 compared with moderate COPD. 같다 (table 2). 신체질량지수에따라환자의나이, 성별, 흡연의여부, PaO 2, PaCO 2 등은차이가없었으나체중과신체질량지수는세군간에유의한차이를보였다 (p<0.01) 2. 만성폐쇄성폐질환환자와정상대조군에서전신염증인자와산화스트레스의차이 만성폐쇄성폐질환환자와정상대조군에서 IL-6 값은각각 ± pg/ml, 86.42±38.16 pg/ml으 저신체질량지수환자의 FEV 1 은 0.93±0.25L으로정상및고신체질량지수환자의 FEV 1 인 1.34±0.52L, 1.72±0.41L에비해유의하게낮았고 (p<0.01), 신체질량지수가감소함에따라 FEV 1 값도감소하는양상을보였다 (p=0.002, r=0.42)(figure 3). 4. 만성폐쇄성폐질환의중증도에따른신체질량지수의차이만성폐쇄성폐질환환자를경증 (n=4), 중등증 (n=24), 중증 (n=17), 최중증 (n=8) 으로구별하여신체질량지수를비교하였을때신체질량지수의값은각각 21.8±2.07, 22.6±3.14, 20.2±3.26, 19.8±2.57로중등증환자에비해최중증환자가유의하게신체질량지수가낮았다 (p<0.05)(figure 4). Figure 5. Serum IL-6 and TNF- α according to BMI in COPD patients. p value>0.05 compared with lower and higher BMI. 334

Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct. 2006 Figure 6. Serum 8-iso-prostaglandin F2α and carbonyl protein according to BMI in stable COPD patients. p value>0.

6 Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct Figure 6. Serum 8-iso-prostaglandin F2α and carbonyl protein according to BMI in stable COPD patients. p value>0.05 compared with normal and higher BMI. 5. 만성폐쇄성폐질환환자에서신체질량지수에따른전신염증인자와산화스트레스의차이신체질량지수에따른 TNF-α, IL-6, carbonyl protein은유의한차이를보이지않았으며 (Figure 5), 8-iso-prostaglandin F 2 α는신체질량지수에따라각각 ± pg/ml, ± pg/ml, 353.7± pg/ml 로신체질량지수가높을수록낮은경향이있었으나통계적인유의성은없었다 (p<0.05) (Figure 6). 고찰 8-iso-prostaglandin F 2 α는지질과산화 (lipid peroxidation) 의표식자로 18 만성폐쇄성폐질환의급성악화시에호기호흡농축물 (exhaled breath concentrate) 19 과소변 20 에서증가하고회복시에는감소하는것으로보고되고있으나혈청에서증가한다는보고는아직까지없는실정이다. 본연구에서는급성악화가아닌안정된만성폐쇄성폐질환환자의혈청에서정상인에비해 8-iso-prostaglandin F 2 α가증가되어있는양상을보였는데이는안정된만성폐쇄성폐질환환자에서도전신적인산화스트레스가증가되어있다는것을시사하는소견이라고하겠다. 또한통계적유의 성은없지만신체질량지수의감소에따라혈청 8- iso-prostaglandin F 2 α가증가하는경향을보여신체질량지수와관련이있을것으로추측할수있다. 그러나혈청 8-iso-prostaglandin F 2 α의값은여러가지인자가영향을미치는것으로보고되고있고 18 측정한환자들사이에도상당한차이를보여신체질량지수와의관련성은좀더연구가필요할것으로사료된다. IL-6와 TNF-α는일반적으로만성폐쇄성폐질환환자의객담또는호기농축물에서증가하며질환의중등도와기도폐쇄의정도, 기도내균의집락형성과도관련이있는것으로알려져있다 21. 전신적으로는급성악화시나체중감소가심한환자에서증가하는것으로보고 11,22 되어있으나본연구에서는만성폐쇄성폐질환과정상대조군에서유의한차이가없었다. 그이유로첫번째는본연구의대상환자는급성악화가없는안정된상태이었으며약 70% 정도의환자가흡입성스테로이드또는간헐적경구스테로이드를복용중이었으며이것이전신염증의정도에영향을미쳤을가능성이있다. 두번째는만성폐쇄성폐질환에서전신염증의정도는저산소증과관련이있는것으로보고되고있으나 23 본연구의대상환자는대부분이저산소증이없는특징을가지고있었다. 세번째는만성폐쇄성폐질환환자에서체중감소와전신 TNF-α의증가는일정기간동안의미있는체중감소 335

7 HS Ham et al: Relationship between systemic inflammatory marker, oxidative stress and body mass index in stable COPD patient 가있었던환자에국한된연구 11 이며본연구에서는한시점에서의신체질량지수와관련성에대해알아본것으로그전연구와는다르다고판단된다. 또한 cytokine은일중변동을보이는것으로알려져있으며 24 본연구에서는대상환자의채혈시간이일정하지않아일중변동에의해영향을받았을가능성도있다. 본연구에서는단백질산화스트레스의지표로 protein carbonyl 부산물을측정하였는데이것은다른산화스트레스지표에비해혈액내에서비교적안정적이고, 산화과정중에생기는공통적인현상이므로산화스트레스의정도를유용하게측정할수있는것으로알려져있다 17. 만성신부전, 당료, Alzeimer s 질환등의질환에서는 protein carbonyl 부산물이질병의병인과관련이있는것으로연구되고있고급성호흡곤란증후군, 기관지폐형성이상 (bronchopulmonary dysplasia) 등의폐질환에서도증가를관찰할수있다 25. 그러나산화스트레스가병인에중요한역할을하는것으로알려진만성폐쇄성폐질환에서단백질산화스트레스의지표인 protein carbonyl 부산물이전신에서증가되어있다는연구결과는아직까지발표되지않았으며최근에는만성폐쇄성폐질환환자의횡격막및하지근육에서근육내단백질산화스트레스가증가되어있다고보고되었다 26,27. 본연구에서는정상인에비해만성폐쇄성폐질환환자에서높지않았는데이것은급성악화가없는안정된환자에서는그값이증가되지않는다는것을의미할수도있으며, 호흡근육과말초근육에서는증가되지만전신에서는증가되지않을수있다는것을의미할수있겠다. 신체질량지수와 FEV 1 과관계에대해서는이견이있지만 28 본연구에서는 FEV 1 값이낮을수록신체질량지수가낮은경향을보였고최중증만성폐쇄성폐질환환자의신체질량지수가중등증환자에비해유의하게낮았다. 이것은만성폐쇄성폐질환이진행되어기도폐쇄의정도가심할수록신체질량지수의더많은감소를일으킬수있다고추측할수있다. 그러나신체질량지수가낮을수록 FEV 1 의값이낮게측정될수있으므로폐기능의감소와신체질량지수의관계를규명하기위해서는한시점에서의관계보다는일정기간이지난시점에서폐기능의변화와함께신체질량지 수의변화를관찰하는것이더유용하다고할수있다. 본연구의결과로는만성폐쇄성폐질환환자에서전신염증인자와산화스트레스는신체질량지수와관련성은없을것으로생각되나기도폐쇄의정도와는관련이있을것으로사료된다. 만성폐쇄성폐질환환자에서신체질량지수의감소와관련된인자에대해서는더많은연구가필요할것으로사료된다. 요약연구배경 : 만성폐쇄성폐질환은기도염증으로인한기도폐쇄를특징으로하는질환이지만, 질병의경과중에체중감소나근위축같은전신증상을동반하게된다. 만성염증과산화스트레스가만성폐쇄성폐질환의병인에중요한역할을하므로신체질량지수의감소와관련이있을것으로추측할수있다. 연구자등은안정된만성폐쇄성폐질환환자에서신체질량지수와관련된인자를알아보기위해다음과같은연구를시행하였다. 방법 : 안정된만성폐쇄성폐질환환자 53명 ( 남 : 여 =49:4, 평균나이 =68.25±6.32) 과정상대조군 33명을대상으로폐기능검사를실시하고전신염증인자로혈청 IL-6, TNF-α를측정하고산화스트레스인자로혈청 8-iso-prostaglandin F 2 α와 carbonyl protein을측정하여비교하였다. 또한만성폐쇄성폐질환환자를신체질량지수에따라다시 3군 (<18.5, , >25) 으로나누어각각의수치들을비교하였고만성폐쇄성폐질환의중증도에따라신체질량지수를비교하였다. 결과 : 만성폐쇄성폐질환환자와정상대조군의혈청에서 IL-6, TNF-α, carbonyl protein은유의한차이가없었으며 8-iso-prostaglandin F 2 α은각각 ± pg/ml, ± pg/ml로만성폐쇄성폐질환환자에서유의하게높았다 (p<0.05). 만성폐쇄성폐질환에서신체질량지수의차이에따라혈청 IL-6, TNF-α, carbonyl protein과 8-iso-prostaglandin F 2 α은유의한차이를보이지않았다. 신체질량지수에따른환자의 FEV 1 은각각 0.93±0.25L, 1.34± 0.52L, 1.72±0.41L로신체질량지수가낮을수록 FEV 1 336

8 Tuberculosis and Respiratory Diseases Vol. 61. No.4, Oct 값도감소하는경향을보였고 (p=0.002, r=0.42), 최중증만성폐쇄성폐질환환자의신체질량지수는 19.8± 2.57로중등증의환자의 22.6±3.14에비해유의하게낮았다 (p<0.05). 결론 : 본연구에서안정된만성폐쇄성폐질환환자의신체질량지수는전신염증인자와산화스트레스의정도와는관련을보이지않았으나기도폐쇄의정도와는관련이있을것으로사료된다. 만성폐쇄성폐질환환자에서신체질량지수의감소와관련된인자에대해서는추가적인연구가필요할것으로사료된다. 참고문헌 1. Global Initiative for Chronic Obstructive Lung Disease. NHLBI/WHO, Workshop report. National Institutes of Health Publication Number 2701, MacNee W. Pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005;2: Spurzem JR, Rennard SI. Pathogenesis of COPD. Semin Respir Crit Care Med 2005;26: MacNee W. Pulmonary and systemic oxidant/antioxidant imbalance in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005;2: Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2003;21: Couillard A, Prefaut C. From muscle disuse to myopathy in COPD: potential contribution of oxidative stress. Eur Respir J 2005;26: Agust AG, Gari PG, Sauleda J, Busquets X. Weight loss in chronic obstructive pulmonary disease: mechanisms and implications. Pulm Pharmacol Ther 2002; 15: Dolan S, Varkey B. Prognostic factors in chronic obstructive pulmonary disease. Curr Opin Pulm Med 2005;11: Celli BR, Cote CG, Martin 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: Schols AM, Soeters PB, Dingemans AM, Mostert R, Frantzen PJ, Wouters EF. Prevalence and characteristics of nutritional depletion in patients with stable COPD; eligible for pulmonary rehabilitation. Am Rev Respir Dis 1993;147: di Francia M, Barbier D, Mege JL, Orehek J. Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994;150: de Godoy I, Donahoe M, Calhoun WJ, Mancino J, Rogers RM. Elevated TNF-a production by peripheral blood monocytes of weight-losing COPD patients. Am J Respir Crit Care Med 1996;153: Song W, Zhao Z, Li Z. Interleukin-6 in bronchoalveolar lavage fluid from patients with COPD. Chin Med J 2001;114: Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, et al. Relationship of interleukin-6 and tumor necrosis factor- with muscle mass and muscle strength in elderly men and women. J Gerontol A Biol Sci Med Sci 2002;57: M Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications. Eur Respir J Suppl 2003;41:46s-53s. 16. Expert Panel on the Identification, Evaluation and Treatment of Overweight in Adults. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Am J Clin Nutr : Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003;329: Janssen LJ. Isoprostanes: an overview and putative roles in pulmonary pathophysiology. Am J Physiol Lung Cell Mol Physiol 2001;280:L Biernacki WA, Kharitonov SA, Barnes PJ. Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD. Thorax 2003;58: PraticòD, Basili S, Vieri M, Cordova C, Violi F, Fitzgerald GA. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F 2a-III, an index of oxidant stress. Am J Respir Crit Care Med 1998;158: Wouters EF. Local and systemic inflammation in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005;2: Malo O, Sauleda J, Busquets X, Miralles C, Agusti AG, Noguera A. Systemic inflammation during exacerbations of chronic obstructive pulmonary disease. Arch Bronconeumol 2002;38: Takabatake N, Nakamura H, Abe S, Inoue S, Hino T, Saito H, et al. The relationship between chronic hypoxemia and activation of the tumor necrosis factorα system in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 161:

9 HS Ham et al: Relationship between systemic inflammatory marker, oxidative stress and body mass index in stable COPD patient 24.Petrovsky N, Harrison LC. The chronobiology of human cytokine production. Int Rev Immunol 1998; 16: Dalle-Donne I, Giustarini D, Colombo R, Rossi R, Milzani A. Protein carbonylation in human diseases. Trends Mol Med 2003;9: Barreiro E, de la Puente B, Minguella J, Corominas JM, Serrano S, Hussain SN, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;171: Barreiro E, Gea J, Corominas JM, Hussain SN. Nitric oxide synthases and protein oxidation in the quadriceps femoris of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2003; 29: Karadag F, Karul AB, Cildag O, Altun C, Gurgey O. Determinants of BMI in patients with COPD. Respirology 2004;9:

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar