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1 pissn: eissn: (1):35-39, January ORIGINAL ARTICLE 정상성인에서 Vitamin D 결핍과폐기능과의연관성에관한연구 김영욱 1, 류동수 2, 이주석 3 성균관대학교의과대학삼성창원병원 1 직업환경의학과, 2 비뇨기과, 3 소아청소년과 Relationship between serum 25-hydroxyvitamin D and lung function among Korean adults Young Wook Kim 1, Dong Soo Ryu 2, Ju Suk Lee 3 Departments of 1 Occupational and Environmental Medicine, 2 Urology, and 3 Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea Purpose: The relationship between vitamin D status and pulmonary function has been investigated in several studies. But previous study results are controversial. We want to know the relationship between vitamin D status and pulmonary function in Korean adults in small regional area. Methods: The medical records of 3,253 subjects were reviewed retrospectively, those visited for routine health examination in Samsung Changwon Hospital between January and December All of them were workers in one company and lived in one island ( Geojedo ). Results: Vitamin D deficiency group (serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/ml) showed lowed % forced vital capacity in one second (%FEV1; P< 0.01), forced vital capacity (FVC; P< 0.01) and higher FEV1/FVC (P< 0.01). Serum 25(OH)D was positively correlated with %FEV1 (R= 0.035, P< 0.05), %FVC (R= 0.081, P< 0.01), FVC (R= 0.125, P< 0.01) and negatively with FEV1/FVC (R= 0.083, P < 0.01). After adjustment for smoking history, we found serum 25(OH)D level was positively correlated with %FVC (R = 0.058, P< 0.01), FVC (R= 0.093, P< 0.01) and negatively with FEV1/FVC (R= 0.055, P< 0.01). After adjustment for smoking and asthma history, we found serum 25(OH)D level was positive correlated with %FVC (R= 0.103, P< 0.01) and negatively with FEV1/FVC (R= 0.119, P< 0.01). Conclusion: Serum 25(OH)D level was associated with pulmonary function. ( 2015;3:35-39) Keywords: Vitamin D, Respiratory function tests, Forced expiratory volume 서론비타민 D의결핍은전세계적으로증가하는추세이며 1,2) 한국성인남자 49.9% 에서비타민 D 결핍이동반된다. 3) 비타민 D는뼈의대사작용과의연관성은널리알려져있으며, 4) 최근에는심혈관계질환, 자가면역질환등과같은질환과의연관성에대해서도많은보고가이루어지고있다. 5-7) 천식, 결핵과같은폐질환과비타민 D 의연관성에대해서는널리알려져있으나 8,9) 폐기능과의연관성에 대해서는일관된보고가이루어지고있지않다 ) 현재보고된대규모연구의결과를보면비타민 D 농도와폐기능이연관성이있다는기존의보고들은여러지역에거주하는대상자로하는연구인반면, 10-12) 한지역에거주하는대상자로실시한연구에서는상반된결과가보고되었다. 13) 국내보고의경우에도대규모이기는하지만연구대상자들의거주가한지역으로국한되어있지않으며 12) 비타민 D 농도는위도, 생활습관에영향을받는것으로알려져있다. 이에연구자들은이전연구에서보인폐기능과비타민 D농도와의관 Correspondence to: Ju Suk Lee Department of Pediatrics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, 158 Paryong-ro, Masanhoewon-gu, Changwon , Korea Tel: , Fax: , ljs @lycos.co.kr Received: June 26, 2014 Revised: October 5, 2014 Accepted: October 18, The Korean Academy of Pediatric Allergy and Respiratory Disease The Korean Academy of Asthma, Allergy and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( 35

2 Kim YW, et al. Relationship between serum 25-hydroxyvitamin D and lung function 계에의한결과차이가연구참여자들의거주지의차이때문에일어난선택삐뚤림의영향을배제할수없으리라는의문으로한지역에거주하며동일직장인으로실외활동이유사하리라생각되는군에서비타민 D와폐기능사이에연관성을알아본다면이전연구결과의선택삐뚤림에의한영향을배제할수있으리라추론하였다. 따라서본연구자들은거제한지역에거주하고동일직장에근무하며동일실외활동을하게되는성인을대상으로비타민 D와폐기능과의관계에대한연구를시행하였다대상및방법 1. 연구대상본연구는검진자료를이용한후향적단면연구로 2013년거제지역일개조선소에서사무직으로근무하면서 2013년 1월 1일부터 12월 31일까지삼성창원병원에서건강검진을받았던 19세이상의성인을연구대상으로선정하였다. 총건강진단수진자 4,187명중흉부방사선및폐활량검사를받지않은경우 (52명 ), 흉부방사선검사상활동성폐결핵, 만성기관지염, 무기폐등폐질환이의심되는경우 (21명 ), 설문에충실히대답하지않아연구에필요한기록이미비하거나연구에필요한혈액검사결과가누락된경우 (861명 ) 를제외한 3,253명을최종연구대상자로선정하였다. Japan) 을이용하여 American thoracic society/european respiratory society 지침에따라 2명의기사에의해수행되었다. 16) 4. 다른변수정의체질량지수는 <23, 23 25, 25 kg/m 2 을기준으로세군으로나누었고이는정상, 과체중, 비만으로정의하였다. 흡연의경우는흡연을한번도하지않았던군, 이전에흡연을하였지만현재금연을한군, 현재도흡연을하고있는군으로나누었으며금연군은금연시행후흡연을한번도하지않은군으로정의하였고간헐적흡연이있었던군은흡연군으로분류하였다. 계절은 3월에서 5월까지를봄으로, 6월에서 8월까지를여름으로, 9월에서 11월까지를가을로, 11월에서 2월까지를겨울로정의하였다. 5. 통계방법자료분석은 PASW Statistics ver (SPSS Inc., Chicago, IL, USA) 프로그램을사용하였고 2군에서빈도, 평균비교는 chi-square, t-test를사용하였고비타민 D와폐기능과의상관관계는 Pearson correlation analysis 를사용하였다. P값이 0.05 미만인경우를통계적으로의미있다고판단하였다. 결과 2. 비타민 D 농도의측정비타민 D의농도는혈중 25-hydroxyvitamin D (25(OH)D) 를측정하였고검체는측정전까지냉동보관하여 Modular E (Hitachi Co., Tokyo, Japan) 장비를이용하여전기적화학발광면역측정법 (electrochemiluminescence immunoassay) 으로측정하였다. 25(OH)D 농도가 20 ng/ml 이하인경우를비타민 D 결핍으로정의하였고 10 ng/ml 이하인경우를중증비타민 D 결핍으로정의하였다. 3,14) 3. 폐기능측정정상폐활량예측치는 Knudson 등 15) 의폐활량예측식을사용하여나이, 신장, 성별, 인종등과같은폐활량에영향을미치는요인을보정하였다. 폐활량검사실시전호흡기질환, 근무경력, 업무내용등에대한설문조사를시행하였으며, 폐활량검사에결격사유가있는경우에는 ( 감기, 검사전흡연, 호흡기질환, 약물복용, 수술, 심한피로감 ) 검사가능한상태가될때까지연기하여검사를실시하였다. 폐활량검사는폐활량검사정도관리교육을이수한숙련자를통해실시하였으며, 하루 2회보정을시행하였고센서를교체할경우다시보정하였다. 보정은 3 L 보정용시린지로 L 이내의범위에들도록하였다. 검사시온도와습도를기록하여입력하였으며폐활량측정기는 HI-801 (CHEST.M.I. Inc., Tokyo, 1. 대상자들의특성본연구대상자중혈중농도 20 ng/ml 이하를보인비타민 D 결핍군은 2,212명 (68.0%) 이었고정상군은 1,041명 (32.0%) 이었으며남성은 2,796명 (86.0%) 이었다 (P < 0.01). 비타민 D 결핍군에서정상군에비해유의하게여성이많았고체질량지수가낮았으며비흡연경우가많았다 (P<0.01). 비타민 D 결핍군의빈도는겨울철에높았고여름철에가장낮았으며나이분포에있어서 40세이전의경우에는비타민 D 결핍군의빈도가높았으나이후에는정상군의빈도가높았다 (P<0.01). 천식유무를확인할수있었던 1,332명중천식환자는 16명으로천식빈도는 1.2% 였고비타민결핍유무에따른천식빈도의차이는없었다 (Table 1). 2. 비타민 D 결핍과폐기능과의연관성비타민 D 결핍군은정상군에비해 1초간강제호기량비 (% forced vital capacity in one second, %FEV 1), 노력성폐활량 (functional vital capacity, FVC) 이낮게측정되었으나 FEV 1/FVC는높게측정되었다 (P<0.01) (Table 2). 3. 비타민 D와폐활량상관관계비타민농도와 %FVC의상관계수는 (P<0.01), FVC 와의상관계수는 (P < 0.01), %FEV 1 와의상관계수는 (P < 36

3 김영욱외 Vitamin D 결핍과폐기능과의연관성에관한연구 Table 1. Clinical characteristics of vitamin D deficiency subjects 0.05) 로통계학적으로유의한양의상관관계를보였으나비타민 D 와 FEV 1/FVC 의상관계수는 (P<0.01) 으로유의한음의상 관관계를보였다. 흡연유무를보정후비타민 D 농도와 %FVC (R= 0.058, P<0.01), FVC (R= 0.093, P<0.01) 는유의한양의상관 관계를보였고 FEV 1/FVC (R= 0.055, P<0.01) 은유의한음의상관 관계를보였다. 천식유무를확인할수있었던 1,332 명에서흡연과 천식유무를보정한후비타민 D 농도와 %FVC (R= 0.103, P<0.01) 는유의한양의상관관계를보였고 FEV 1/FVC (R= 0.119, P<0.01) 는유의한음의상관관계를보였다 (Table 3). 고 25(OH)D (ng/ml) < 20 (n= 2,212) 20 (n= 1,041) 본연구는비타민 D 결핍과폐기능의연관성이거주지역범위에 영향을받는지알아보고자실시하였다. 이전연구에서한지역에 국한된거주자를대상으로하였던 Shaheen 등 13) 은비타민 D 와폐 기능사이에유의한통계적관계는없었다고하였고여러지역거주 자를대상으로하였던 Black 등 11) 과 Choi 등 12) 은비타민 D 농도가 찰 P-value Sex < 0.01 Male 1,828 (82.7) 968 (93.0) Female 384 (17.3) 73 (7.0) Age (yr) < 0.01 < (30.4) 273 (26.2) ,066 (48.2) 471 (45.2) (16.0) 196 (18.8) (5.4) 101 (9.7) Body mass index (kg/m 2 ) < 0.01 < (39.3) 339 (32.6) (26.3) 300 (28.8) (34.4) 402 (38.6) Smoking < 0.01 Never 1,174 (53.1) 415 (39.9) Ex-smoker 420 (19.0) 240 (23.1) Current 618 (27.9) 386 (37.1) Season < 0.01 Spring 199 (9.0) 35 (3.4) Summer 639 (28.9) 447 (42.9) Fall 1,173 (53.0) 528 (50.7) Winter 201 (9.1) 31 (3.0) Asthma (n= 1,332) n= 902 n= 430 > 0.60 Yes 12 (1.3) 4 (0.9) No 890 (98.7) 426 (99.1) Values are presented as number (%). 25(OH)D, 25-hydroxyvitamin D. Table 2. Lung function by serum 25(OH)D deficiency in subjects 25(OH)D (ng/ml) < 낮은경우에 FEV 1, FVC 이낮다고보고하여이러한차이가거주지 역범위차이에따른결과인지를알아보고자본연구를실시하였 다. 본연구에서비타민 D 결핍군은정상군에비해 %FEV 1, FVC 가 낮게측정되어비타민 D 결핍과폐기능의관계는거주지역범위차 이에따른영향을받지않았다. 본연구에서비타민 D 농도가증가 함에따라 %FVC 는증가하고 FEV 1/FVC 는감소하는경향을보였 는데이러한이유는혈중비타민 D 가증가에따른폐기능증가에 있어서 FEV 가 FEV 1 보다가파르게증가하기때문으로생각되며다 른연구에서도비타민 D 증가에따른폐기능증가에있어서 FVC 가 FEV 1 보다가파르게증가하는경향을보인다. 10,11,13) P-value %FEV1 94.6± ± 12.2 < 0.01 FVC (L) 4.38± ± 0.71 < 0.01 %FVC 94.7± ± FEV1/FVC 83.3± ± 6.7 < 0.01 Values are presented as mean± standard deviation. 25(OH)D, 25-hydroxyvitamin D; %FEV1, % forced vital capacity in one second; %FVC, % forced vital capacity. Table 3. Relationship of serum vitamin D and lung function 25(OH)D, correlation coefficient Model 1 (n= 3,253) Model 2 (n= 3,253) Model 3 (n= 1,332) %FVC 0.081** 0.058** 0.103** %FEV * FEV1/FVC 0.083** 0.055** 0.119** FVC 0.125** 0.093** (OH)D, 25-hydroxyvitamin D; model 1, unadjusted; model 2, adjusted by smoking; model 3, adjusted by smoking and asthma; %FVC, % forced vital capacity; %FEV1, % forced vital capacity in one second. *P< **P< 이전많은연구에서비타민 D 의천식, 폐질환에서의연관성, 기 전은알려져있으나폐기능과의연관성에대해서는명확한기전이 알려져있지않다. 8,9) 그러나최근에비타민 D 가항염증효과와폐 기능에영향을미치는유전자발현에관여한다는보고가있어비 타민 D 의폐기능에대한영향이유전자발현에의하여발생할가 능성이제안되고있다. 17) 또한비타민 D 는선천, 후천면역모두에 영향을미치는것으로알려져있는데 cathelicidin 과같은항균펩 티드 (antimicropeptide) 의발생에영향을미치며, 또한 T 세포의활 성화과정, 항원표출세포 (antigen presenting cell) 의기능에영향 을미쳐후천면역반응을조절하기도한다 ) 비타민 D 가결핍되 면면역기능장애에의해발생하는반복되는호흡기감염에의해 폐기능감소가발생할가능성도있어 FEV 1 보다 FVC 가더욱비타 민 D 의농도에영향을받으리라생각된다. 최근흡연과비타민 D 와 37

4 Kim YW, et al. Relationship between serum 25-hydroxyvitamin D and lung function 의관계에대한연구에서흡연이일으키는폐기능감소를비타민 D 가줄인다는보고가있는데이는비타민 D 의항염증작용과항산 화작용에의한것으로알려져있으며 22) 본연구에서도흡연을보정 한이후에비타민 D 의증감에따른폐기능변화가감소하는경향 을보였다. 성인천식환자의 60% 에서는천식이충분히조절되지 않고정상인에비해낮은폐기능을보이는것으로알려져있다. 23) 국내성인환자의유병률은약 2% 로보고되고있으나 24,25) 본연구 에서는천식유병률이 1.2% 로국내다른연구에비해낮게측정되 었고조절되지않은천식이폐기능에영향을미칠수있으나본연 구에서는천식중등도와조절유무에대해서는조사하지못하였 다. 비타민 D 와폐기능의관계에대한다른견해로는비타민 D 가 섬유아세포의증식과기도콜라겐형성에영향을미쳐기도개형 에관계함으로써폐기능에영향을준다는보고도있다. 26,27) 본연구의단점은첫째후향적단면연구로비타민 D 농도와폐 기능사이의인과관계를밝히기어렵고대상자선정에서선택삐뚤 림이발생할수있다. 둘째연구참여자의기록에의하므로회상삐 뚤림이발생할수있으며비록동일직장인들로연구대상자를정 하였지만이들각각의실외근무시간을조사하지못하였고비타민 D 보조제섭취와같은식생활습관도조사하지못하였다. 그럼에 도불구하고이연구의장점은단일기관연구이므로검사자, 검사 시설이동일하였고동일한방법으로모든검사가시행되었다. 또한 연구대상자를한지역거주자로국한하여위도와날씨의비타민 D 에대한영향을줄이려고하였고동일사업장에서실내근무를 하는사무직직장인들을대상으로함으로써실외활동에따른영 향을줄이려고노력하였다. 결론적으로비타민 D 결핍군에서정상군에비해 FEV 1, FVC 의 감소를발견할수있었으며이전연구결과의차이가거주지역범위 에의한영향은아닌것으로생각된다. 비타민 D 농도와각폐기능 단위검사인 FEV 1, FVC 에있어서앞으로보다많은연구가필요하 리라생각되며이에대한연구결과가비타민 D 의폐기능에미치는 영향에대해보다많은정보를제공하리라생각된다. REFERENCES 1. 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5 김영욱외 Vitamin D 결핍과폐기능과의연관성에관한연구 25. Kim SY, Jung JY, Park MS, Kang YA, Kim EY, Kim SK, et al. Increased prevalence of self-reported asthma among Korean adults: an analysis of KNHANES I and IV data. Lung 2013;191: Dobak J, Grzybowski J, Liu FT, Landon B, Dobke M. 1,25-Dihydroxyvitamin D3 increases collagen production in dermal fibroblasts. J Dermatol Sci 1994;8: Koli K, Keski-Oja J. 1alpha,25-dihydroxyvitamin D3 and its analogues down-regulate cell invasion-associated proteases in cultured malignant cells. Cell Growth Differ 2000;11:

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II)

전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) 전립선암발생률추정과관련요인분석 : The Korean Cancer Prevention Study-II (KCPS-II) - i - - ii - - iii - - iv - - v - - vi - - vii - - viii - - ix - -