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1 DOI: /trd ISSN: (Print)/ (Online) Tuberc Respir Dis 2011;71:24-29 CopyrightC2011. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved. Original Article 만성기침환자에서기관지과민성, 아토피와비만의상관관계 : 두기관연구 1 한림대학교의과대학내과학교실, 2 울산대학교의과대학서울아산병원내과학교실, 3 전북대학교의과대학내과학교실, 4 순천향대학교의과대학내과학교실, 5 성균관대학교의과대학강북삼성병원내과학교실박소영 1, 박종원 1, 오연목 2, 이양근 3, 이영목 4, 박용범 1 *, 임성용 5 *, 천식연구회 The Association of Obesity, Airway Hyperresponsiveness and Atopy in Chronic Cough Patients: Results of a Two-Center Study So Yong Park, M.D. 1, Jong Won Park, M.D. 1, Yeon Mok Oh, M.D., Ph.D. 2, Yang Keun Rhee, M.D., Ph.D. 3, Young Mok Lee, M.D. 4, Yong Bum Park, M.D. 1 *, Seong Yong Lim, M.D., Ph.D. 5 *, Korean Asthma Study Group 1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Hallym University College of Medicine, Seoul, 2 Department of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 3 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, 4 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, 5 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Korea Background: The rising prevalence of asthma worldwide may be associated with the rising prevalence of obesity in developed nations. Although several studies have suggested a relationship between asthma and obesity, controversy still remains. The aim of this study was to examine the relationship between obesity and asthmatic factors such as atopy, eosinophilia, serum total Ig E and bronchial hyperresponsiveness in chronic cough patients. Methods: This study was a retrospective, observational study in two centers done between January 2007 and June The subjects included individuals who had a chronic cough. We examined body mass index (BMI) to measure obesity and pulmonary function. We did a metacholine provocation test for airway hyperresponsiveness (AHR), a skin prick test for atopy, and tests for blood eosinophils and serum IgE. Results: A total of 1022 subjects were included. Airway hyperresponsiveness was not related with obesity (p=0.06), and atopy incidence was significant higher in non obese patients (p=0.00). There was no significant difference in serum IgE and blood eosinophil counts between obese and non obese patients. Forced expiratory volue in one second (FEV 1 )/forced vital capacity (FVC) was significantly reduced in obese patients (p=0.03), but FEV 1 and FVC were no significant difference between obese and non obese patients. Conclusion: There is no relationship between obesity and bronchial hyperresponsiveness. The nonobese group appears to have more atopy. The relationship between obesity and bronchial hyperresponsiveness and atopy need further investigation. Key Words: Obesity; Bronchial Hyperresponsiveness; Dermatitis, Atopic Address for correspondence: Yong Bum Park, M.D. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, 445, Gil-dong, Gangdong-gu, Seoul , Korea Phone: , Fax: , bfspark@medimail.co.kr Co-correspondence: Seong Yong Lim, M.D., Ph.D. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Pyeong-dong, Jongno-gu, Seoul , Korea Phone: , Fax: , mdlimsy@skku.edu *These two authors equally contributed to this article. Received: Apr. 28, 2011 Accepted: Jun. 24,

2 서 론 Tuberculosis and Respiratory Diseases Vol. 71. No. 1, Jul 방법 만성기침의중요한원인중하나인천식은자연적또는치료에의해크게변화하는호흡기류의폐쇄에의해나타나는특징적인증후군이다 1. 전세계적으로천식의유병률은지속적인증가추세를보이고있으며, 여기에는대기오염, 흡연, 알레르기항원에의노출, 식이등의환경적인요인이다양한기전을통해천식의발생과악화에영향을미치는것으로알려져있다 2-4. 최근에는여러연구에서이러한요소중비만이천식의발생률과유병률, 천식의중증도와관련이있다는보고가있었다 지난수십년간비만의유병률은시간이지날수록전세계적으로증가하는추세를보이고있으며, 우리나라에서도비만인구가증가함에따라비만은천식환자에있어중요하게고려할만한인자로주목받고있다 12. 일반성인을대상으로한연구에서비만한경우기관지폐쇄증상과천식의유병률이증가함을보고하였으며 13,14, 비만한천식환자에서체중감량으로폐기능향상과천식증상이호전됨이보고되었다 15. 그러나, 이러한결과들은서양에서의연구가대부분이었고천식과비만의상관관계에있어우리나라성인인구를대표할수있는연구가미비한상태이다. 이에본연구에서는비만을정량적으로나타낼수있는체질량지수와천식의관련인자인기관지과민성, 아토피의임상적척도를분석함으로써천식과비만의상관관계를알아보고자하였다. 대상및방법 1. 연구대상본연구는 2007년 1월부터 2008년 6월까지 18개월동안한림대학교강동성심병원과성균관대학교강북삼성병원호흡기알레르기내과외래에만성기침을주소로내원한비흡연또는 10갑년이하의흡연력을가진환자 1,022 명을대상으로후향적관찰연구를진행하였다. 단, 최근수개월내에심근경색이나뇌경색이진단된환자, 조절되지않는고혈압환자, 임신중인환자는대상군에서제외하였으며, 최근 6개월이내에전신적스테로이드투여를받은환자나종양환자, 호흡기결핵이나만성폐쇄성폐질환등의호흡기질환을진단받은과거력이있는환자도제외하였다. 1) 비만도 : 비만도는체질량지수 (body mass index, BMI) 로결정하였다. 체질량지수는체중과신장을이용한 Queterelets index 를이용하여모든환자들의체중및키를측정하여체질량지수를계산하였다. 체질량지수 25 kg/m 2 를기준으로비만환자군과일반환자군으로구분하였다. 2) 메타콜린기관지유발시험 : 비특이적기도과민성을평가하기위해메타콜린으로기관지유발시험을시행하였다. PC 20 methacholine (1초간노력성호기량 [forced expiratory volume in one second, FEV 1 ] 을 20% 감소시키는메타콜린농도 mg/ml) 을구하여기도과민성을정량화하였고 PC 20 methacholine 이 25 mg/ml 이하인경우를기관지과민성에대한양성반응으로판정하였다. 3) 아토피 : 12종류의 allergen (Dermatophagoides pteronyssinus, Dermatophagoides farine, Tree mix, Grass mix, birch, Mugwort, Ragweed, Cat, Dog, Cockroach, Alternaria, Aspergillus) 에대한 skin prick test를시행하여 A/H ratio 가 1 이상인경우또는 MAST 검사에서 12종의알레르겐중한개이상에서 class 2 이상의반응을보이는경우아토피로판정하였다. 또한혈액검사를시행하여각환자의혈중호산구수와혈청 IgE 농도를확인하였다. 3. 통계분석대상군의성별에따른연령과 FEV 1 의차이는 t-test 로검정하였고기관지과민성여부와성별, 연령, 비만도와의관계는 Chi-square 검정을이용하여비교하였다. 통계처리는 SPSS version 15.0 (SPSS Inc, Chicago, IL, USA) 프로그램을사용하였으며, p값이 0.05보다작은경우통계적으로유의한차이가있다고판단하였다. 결과 1. 대상환자의특성연구에참여한환자는총 1,022 명으로대상자의일반적인특징은 Table 1과같다. 연령의중간값은 44.2±15.6 세였고 40세이하가 443명 (43.3%), 61세이상이 190명 (18.6%) 이었다. 대상자의성별은남자가 454명 (43.3%), 여자가 568명 (56.7%) 이었다. 대상환자중체질량지수가 25 kg/m 2 이상인환자는 328명 (32.1%) 이었는데, 남자가 25

3 SY Park et al: The association of obesity and asthmatic parameters in chronic cough 157명 (34.6%) 으로여자 171명 (30.1%) 보다많았으나통계학적인차이는보이지않았다. 1초간노력성호기량 (FEV 1 ) 은추정정상치의평균 91.8±25.5% 이었고노력성폐활량 (forced vital capacity, FVC) 은추정정상치의평균 88.6±13.8% 였으며 1초간노력성호기량의노력성폐활량에대한비 (FEV 1 /FVC) 는평균 80.5±11.7% 였다 (Table 1). 2. 체질량지수와천식의지표와의관계 체질량지수가 25 kg/m 2 이상인환자는 40세미만에서 24% 였으나 61세이상환자군에서는 40.5% 로체질량지수는나이가많을수록유의하게증가하는양상을보였다 (p=0.00). 대상자의성별에따라서는체질량지수의차이를보이지않았다. 폐기능검사에서는 1초간노력성호기량 (FEV 1 ) 과노력성폐활량 (FVC) 은체질량지수에따른차이를보이지않았으나 1초간노력성호기량의노력성폐활량에대한비 (FEV 1 /FVC) 는체질량지수가 25 kg/m 2 이상인환자에서 79.5±7.3, 체질량지수가 25 kg/m 2 미만인군 81.0±13.3으로체질량지수가 25 kg/m 2 이상인환자에서의미있게낮았다 (p=0.025). 혈중호산구수와혈청 IgE 농도는체질량지수에따른차이를보이지않았다 (Table 2). 체질량지수가 25 kg/m 2 이상인군에서기관지과민성양성인환자는 90명 (27.4%), 체질량지수가 25 kg/m 2 미만인군에서기관지과민성양성인환자는 231명 (33.3%) 으 Table 1. Clinical characteristics of study population Male (n=454) Female (n=568) Total (n=1,022) Age, yr 41.6± ± ± (49.6%) 218 (38.4%) 443 (43.3%) (33.5%) 237 (41.7%) 389 (38.1%) (16.9%) 113 (19.9%) 190 (18.6%) BMI, kg/m ± ± ±10.9 < (65.4%) 397 (69.9%) 694 (67.9%) (34.6%) 171 (30.1%) 328 (32.1%) FEV 1, % pred* 90.5± ± ±25.5 FVC, % pred* 87.3± ± ±13.8 FEV 1/FVC 80.2± ± ±11.7 IgE, KU/L* 317.4± ± ±46.5 Eosinophil, /ml* 269.0± ± ±55.2 Data were calculated by t-test. *Mean±2 SD. BMI: body mass index; FEV 1: forced expiratory volume in one second; FVC: forced vital capacity; SD: standard deviation. 로체질량지수에따른기관지과민성의차이는보이지않았다 (p=0.06) (Table 3). 아토피의발현양상을시험한환자 308 명 (30.1%) 중체질량지수가 25kg/m 2 미만인군에서아토피가양성인군은 99명 (32.1%) 으로체질량지수가 25 kg/m 2 이상인군 24명 (7.8%) 보다통계적으로유의하게많았다 (p=0.00) (Table 4). Table 2. Characteristics according to BMI BMI <25 kg/m 2 (n=694) Table 3. Difference of AHR according to BMI BMI <25 kg/m 2 BMI 25 kg/m 2 p-value AHR ( ) 463 (45.3%) 238 (23.3%) 0.06 AHR (+) 231 (22.6%) 90 (8.8%) Data were calculated by chi-squire test. AHR: airway hyperresponsiveness; BMI: body mass index. Table 4. Difference of atopy according to BMI Atopy (n=308) BMI <25 kg/m 2 BMI 25 kg/m 2 p-value Atopy ( ) 116 (37.7%) 69 (22.4%) 0.00 Atopy (+) 99 (32.1%) 24 (7.8%) Data were calculated by chi-square test. BMI: body mass index. BMI 25 kg/m 2 (n=328) p-value Age, yr (76.0) 106 (24.0) (62.7) 145 (37.3) (59.5) 77 (40.5) Gender 0.12 Male 297 (65.4) 157 (34.6) Female 397 (69.9) 171 (30.1) FEV 1, % pred* 91.3± ± FVC, % pred* 89.1± ± FEV 1/FVC 81.0± ± IgE, KU/L* 286.0± ± Eosinophil, /ml* 266.7± ± Values are presented number (%) unless otherwise indicated. Data were calculated by t-test. *Mean±2 SD, p<0.05. BMI: body mass index; FEV 1: forced expiratory volume in one second; FVC: forced vital capacity. 26

4 Tuberculosis and Respiratory Diseases Vol. 71. No. 1, Jul 기관지과민성을기준으로한대상자의특징 1,022명의환자중에서 321명 (31.4%) 이기관지과민성유발시험양성소견을보였다. 연령별기관지과민성의유병률은 40세미만에서 32.5%, 41 60세에서 26.5%, 61 세이상에서 38.9% 로 60세이상에서기관지과민성의유병률이증가하는소견을보였다 (p=0.008). 성별로는남자 33.7%, 여자 29.6% 에서기관지유발시험양성소견을보여두군간의의미있는차이는없었다 (p=0.15). 기관지과민성양성은체질량지수가 25 kg/m 2 미만인군은 33.3%, 25 kg/m 2 이상인군은 27.4% 로두군간통계학적차이는없었다 (p=0.06). 기관지과민성양성군과음성군사이에는통계적으로유의한 FEV 1, FVC, FEV 1 /FVC의차이를확인할수있었다 (p=0.00). 혈중호산구수와혈청 Table 5. Characteristics according to AHR Negative (n=701) Positive (n=321) p-value Age, yr (67.5%) 144 (32.5%) (73.5%) 103 (26.5%) (61.1%) 74 (38.9%) Gender 0.15 Male 301 (66.3%) 153 (33.7%) Female 400 (70.4%) 168 (29.6%) BMI, kg/m < (66.7%) 231 (33.3%) (72.6%) 90 (27.4%) FEV 1, % pred* 95.2± ± FVC, % pred* 89.6± ± FEV 1/FVC 82.9± ± IgE, KU/L* 214.3± ± Eosinophil, /ml* 174.6± ± Data were calculated by t-test. *Mean±2 SD, p<0.05. AHR: airway hyperresponsiveness; BMI: body mass index; FEV 1: forced expiratory volume in one second; FVC: forced vital capacity. IgE 농도는기관지과민성양성군에서통계적으로유의하게많았다 (p=0.00) (Table 5). 아토피와기관지과민성은통계적으로유의한상관관계를나타냈으며 (p=0.00) 기관지과민성을가진환자군에서는음성군에비해 2.89배의아토피양성률을보였다 (Table 6). 고찰본연구에서는만성기침으로호흡기내과외래에내원한환자들을대상으로하여체질량지수와천식과관계된요소인기관지과민성, 아토피및이와관련있는요소들에대해연관성을밝히고자하였다. 본연구에서는비만과기관지과민성간의유의한연관성은찾을수없었으며아토피는체질량지수가 25 kg/m 2 미만인군에서의미있게증가하여아토피와체질량지수는역상관관계를보였다. 지난수십년간비만은전세계적으로도매우빠르게증가하고있다 12. 우리나라에서도체질량지수 25 kg/m 2 이상인경우를기준으로하였을때 19세이상성인에서비만유병률은 2007년 31.7% 로파악되고있으며 1998년에비하여지난 10년간 5.7% 가증가하였다 16. 전체인구에서와같이기침이나호흡곤란을동반한환자에서도비만이동반된환자들의비율이증가하고있으며, 특히비만과천식에대해서발생및유병률에유의한상관관계를보이는연구결과가다수보고된바있다 5,10,14,17,18. 비만과천식과의관련성을설명할수있는가설로는첫째, 비만환자에서나타나는폐생리의변화를그원인으로고려할수있다. 비만환자에서는기능적잔기용량 (Functional residual capacity) 과호기예비기량 (expiratory reserve volume, ERV), 그리고폐활량 (vital capacity) 이감소함에따라흉곽유순도가감소하며, 이로인해흡기근육에탄성부하가걸리고호흡일이증가하게된다 둘째, 비만환자에서보이는전신적염증소견이천식환자에 Table 6. Difference of atopy according to AHR Atopy ( ) Atopy (+) p-value OR (95% CI) AHR ( ) 138 (44.8%) 62 (20.1%) ( ) AHR (+) 47 (15.3%) 61 (19.8%) Data were calculated by chi-squire test. AHR: airway hyperresponsiveness; OR: odd ratio; CI: confidence interval. 27

5 SY Park et al: The association of obesity and asthmatic parameters in chronic cough 서의전신및기도염증과관련이있을가능성이제기된바있다. 비만한경우혈중에사이토카인, 사이토카인수용체, 케모카인, 급성반응단백의농도가증가되어있는데 22,23 이로인해기도평활근에만성적인염증반응이진행되며특히환자의지방조직에서분비되는 leptin, adponectin 등의사이토카인으로인한면역반응으로인해기도과민성이증가된다는것이다. 셋째, 비만과천식의발생에각각유의한영향을미치는동반질환의존재가능성이다. 비만환자에서정상체중의환자에비해역류성식도염또는수면무호흡증등의질환이동반될가능성이높은것으로알려져있으며, 이러한동반질환을가진환자에서정상환자군과비교했을때난치성천식환자의비율이더높음을보고한예가있다 천식의여러지표중기관지과민성은여러자극물질에대한기도의수축능력을나타내고일반인에서기관지천식의발생을예측하게하며, 천식의중등도와밀접한연관성이있다 27. 기관지과민성의발현에는유전적인소인과함께아토피, 흡연력도관여하는것으로알려져있다 28. 그러나, 최근까지비만과천식간의관계를설명하기위해기관지과민성의연관관계에대한연구가이루어졌으나일관되는상관관계를밝혀내지는못했다 29. 국내에서 Kim 등 30 이연구한바에따르면비만이기관지과민성의발생위험을통계적으로유의하게증가시키는것으로나타났다. 그러나 Schachter 등 31 이백인성인을대상으로한연구에서는심한비만군에서쌕쌕거리는증상으로천식이진단되고천식치료를받는빈도가높았지만기도폐쇄의증거나히스타민기도과민성의증거는없었다고보고하였다. 이는비만자체가천식의특징인기도과민성이나아토피와상관없이천식과비슷한증상을일으킬수있음을시사하고천식의정의에기도염증을포함시킨다면비만과기도염증의연관성에대한증거가없기때문에비만군에서천식의유병률이실제로는높지않을수있다는가능성을생각할수있게한연구결과이다. Bai 등 32 의연구에서도비만할수록천식증상은호소하지만기관지과민성이나아토피의증거는높지않다고하였는데이는해부학적변화가발생하여도기도반응의변화없이천명이나호흡곤란이일어날수있음을시사한다고할수있다. 본연구에서기관지과민성은아토피, 혈중호산구수와혈청 IgE 농도같은천식관련인자와유의한상관관계를보였으나, 체질량지수와는연관관계를보이지않았다. 이는비만이천식발생이나중증도에미치는기전과기관 지과민성의기전이독립적임을시사한다. 또한본연구에서아토피가비만과역연관성을보이고있는점도기관지과민성과비만의관련가능성을배제하는데도움을줄수있다. 그러나본연구는만성기침환자를대상으로이루어졌다는점, 천식의중증도와비만도사이의연관성을조사할수없었던점, 호흡기증상이없는정상대조군과비교연구를하지않았다는점에서연구의제한점이있을수있다. 또한천식이가진다양하고복합적인발생기전을고려할때연구대상군의연령, 성별의분포, 흡연유무에따라비만이기관지과민성에미치는상이한결과를보일수있어, 정확한인과관계의확인을위해서는더많은연구가필요할것으로생각된다. 결론적으로비만과기관지과민성, 그리고아토피와천식의상관관계에대해더많은환자군을대상으로한연구가필요하며, 이를위해비만을동반한천식환자의표현형을확인하는다양한천식의발생기전에대한체계적이고개별적인접근이요구된다. 또한비만이천식의생리학적양상과염증성질환으로서미치는영향에대한연구가필요할것으로생각된다. 참고문헌 1. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31: Gershon AS, Guan J, Wang C, To T. Trends in asthma prevalence and incidence in Ontario, Canada, : a population study. Am J Epidemiol 2010;172: Gibson PG, McDonald VM, Marks GB. Asthma in older adults. Lancet 2010;376: Pearce N, Aït-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, et al. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2007;62: Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 2007; 175: Camargo CA Jr, Weiss ST, Zhang S, Willett WC, Speizer FE. Prospective study of body mass index, weight change, and risk of adult-onset asthma in women. Arch Intern Med 1999;159:

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한국성인에서초기황반변성질환과 연관된위험요인연구

한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 - - i - - i - - ii - - iii - - iv - χ - v - - vi - - 1 - - 2 - - 3 - - 4 - 그림 1. 연구대상자선정도표 - 5 - - 6 - - 7 - - 8 - 그림 2. 연구의틀 χ - 9 - - 10 - - 11 -