Otology Korean J Otorhinolaryngol-Head Neck Surg 2018;62(1):15-22 / pissn / eissn Ana

Otology Korean J Otorhinolaryngol-Head Neck Surg 2018;62(1):15-22 / pissn 2092-5859 / eissn 2092-6529 https://doi.org/10.3342/kjorl-hns.2017.00899 Analysis of Risk Factors for Recurrence of Benign Paroxysmal Positional Vertigo: An 11-Year Nationwide Population-Based Study Su-Jin Han 1*, Chang Yong Kim 1, Dae Bo Shim 2, and Mee Hyun Song 2 1 Department of Otorhinolaryngology-Head and Neck Surgery, National Health Insurance Service Ilsan Hospital, Goyang; and 2 Department of Otorhinolaryngology-Head and Neck Surgery, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea 양성돌발두위현훈의재발요인분석 : 11 년간의국민건강보험공단표본코호트연구 한수진 1 * 김창용 1 심대보 2 송미현 2 국민건강보험일산병원이비인후과, 1 한양대학교의과대학명지병원이비인후과 2 Received September 19, 2017 Revised January 4, 2018 Accepted January 18, 2018 Address for correspondence Mee Hyun Song, MD, PhD Department of Otorhinolaryngology- Head and Neck Surgery, Myongji Hospital, Hanyang University College of Medicine, 55 Hwasu-ro 14beon-gil, Deogyang-gu, Goyang 10475, Korea Tel +82-31-810-5406 Fax +82-31-969-0500 E-mail meehyun924@hanmail.net *Current address: Soree Ear Clinic Current address: Gochang Hospital Background and Objectives Benign paroxysmal positional vertigo (BPPV) is one of the most common causes of dizziness with a high recurrence rate. This study aimed to analyze the recurrence rate and the risk factors for recurrence using the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC 2002-2013) data. Subjects and Method Patients aged 20 years or older who were diagnosed with BPPV in the period of 2002-2012 and had at least 1 year of monitoring period were included in this study. The diagnosis of BPPV was made when the code for BPPV (KCD-6 code H811) was used or when canalith reposition therapy (EDI code MX035) was entered even in cases with different diagnoses. The risk factors of BPPV recurrence were analyzed. Results Of the total of 21355 patients diagnosed with BPPV, 5876 patients (28%) demonstrated recurrence. Multiple recurrences were common. When using the univariate regression analysis, age, sex, vestibular disease, headache, osteoporosis, and ischemic heart disease were found significant. When the patients were classified into 4 groups according to age and sex, vestibular diseases were found as a common risk factor for recurrence in all groups, while headache, osteoporosis, hypertension, and ischemic heart disease were significant in females. Conclusion The recurrence rate of BPPV in the Korean adult population was approximately 28% and recurrences were more common in patients aged over 65 and in females. Patients with vestibular diseases were at a higher risk of recurrence regardless of age or sex, while headache, osteoporosis, hypertension and ischemic heart disease increased the risk of recurrence in females. Korean J Otorhinolaryngol-Head Neck Surg 2019;62(1):15-22 Key Words Benign paroxysmal positional vertigo ㆍ Cohort ㆍ Recurrence ㆍ Risk factors. 서 론 양성돌발두위현훈 (benign paroxysmal positional vertigo, This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. BPPV) 은말초성현훈의가장흔한원인으로두위변화에의해짧은회전성어지럼이반복적으로나타나고특정자세에서특징적인안진이관찰되면진단이가능하다. 1) BPPV는약 50~70% 에서특발성으로발생하지만, 내이손상을유발하는여러원인에의해이차적으로유발될수있다. 2) 알려진이차적원인으로는머리외상이가장흔하며, 그외전정신경염, 미 Copyright 2019 Korean Society of Otorhinolaryngology-Head and Neck Surgery 15

Korean J Otorhinolaryngol-Head Neck Surg 2019;62(1):15-22 로염, 메니에르병과같은내이질환과두통등이있다. 3) BPPV 의치료는이석정복술이권장되고있고, 발생한반고리관에따라 Epley 수기, Semont 수기, 바비큐회전수기, Gufoni 수기, 팽대부마루이석정복술 (cupulolith repositioning maneuver) 등다양한방법이개발되어있다. 1,4) BPPV의치료로서이석정복술의치료효과는대략 60~90% 정도로비교적높은편이다. 그러나 BPPV의재발률역시높아경과관찰기간에따라차이가있지만약 15~50% 정도에서재발하는것으로보고되고있다. 1,3,5-7) BPPV 재발의위험인자로는연구에따라차이를보이는데성별, 나이, 증상의기간이나유발원인등이 BPPV의재발과연관이없다는보고도있는반면여성, 골다공증, 내림프수종이동반된경우, 두가지이상의전신적인동반질환이있는경우, 처음발병당시여러번의이석정복술이시행된경우등에서 BPPV의재발위험성이높아진다는결과도제시된바있다. 3,7-12) 이에본저자들은국민건강보험공단표본코호트자료를이용하여 BPPV의재발및그양상을분석하고 BPPV 재발의위험인자를확인하고자하였다. 대상및방법 본연구는국민건강보험공단표본코호트 [Korean National Health Insurance Service(NHIS) National Sample Cohort 2002~2013] 자료를이용하였고, 이는국민건강보험공단의윤리위원회로부터승인된자료 (NHIS-2016-2-253) 이며, 연구의진행은보험공단일산병원윤리위원회의심의 (NHIMC 2016-01-024) 를받은후이루어졌다. 연구데이터베이스 2013년을기준으로하였을때우리나라국민 51448491 명 ( 남자 : 25780383명, 여자 : 25668348명 ) 중 97.1% 가건강보험제도에가입되어있는데, 본연구는이중약 2% 에해당하는 1025340명을표본으로추출한국민건강보험공단표본코호트 (NHIS-NSC 2002-2013) 자료를이용하여이자료에포함된외래진료기록과약국청구자료를참고하여분석하였다. 13) 표본코호트자료의진단명은국제질병분류 (ICD-10) 를수정한한국표준질병사인분류 (KCD-6) 에기초하고있다. 대상 2002년부터 2012 년까지의기간동안 20세이상의성인을대상으로최소 1년이상의추적관찰기간을확보하여연구를진행하였다. BPPV 환자의정의는국내이비인후과병원에서양성발작성두위현훈 (KCD-6 H811) 의진단명이발생하였거 나타진단명인경우에도이석정복술 (EDI code MX035) 을시행받은경우로정의하였다. BPPV의재발은양성돌발두위현훈 (H811) 의진단명이나이석정복술 (MX035) 이최초진단시점부터최소 1개월이상없어졌다가다시발생한경우로정의하였다. 상기진단명이나처치가 1개월이상의공백기를가지지않고계속발생한경우는제외하였다. 방법 BPPV의재발에연령이영향을미치는지분석하였고, 기준으로한연령은정부에서정한노인의연령기준이며기존여러연구에서기준연령으로사용한 65세를기준으로 65세이상과 65세미만의두군으로나누어분석하였다. 11,12,14) BPPV의재발요인으로고려할수있는동반질환으로는당뇨 (E10.0-14.9), 고혈압 (I10-13, I15-I15), 골다공증 (M80-82) 을진단받고그치료약제를복용하고있는경우와그외신장질환 (N18), 허혈성심장질환 (I20-25), 뇌혈관질환 (I60-67), 두통 (R51, G43-44), 결합조직침범자가면역질환 (M30-36, M05-09, M45) 을분석하였으며, 상기진단명이 BPPV의진단전에발생한경우만을포함하여분석하였다. BPPV의재발에영향을줄수있는두부외상 (S02, S06, S07) 이나전정기능장애 (H80, H81.0, H81.2, H83.0, H83.2) 는 BPPV의진단이전 6개월이내에발생한경우로제한하였다. 또한, 유양동삭개술 (S5671, S5672), 등골수술 (S5690, S5695), 이소골재건술 (S5791) 과같은이과수술이 BPPV의진단이전 6개월이내에시행된경우도분석하였다. 상기요인들이재발의위험인자로작용하는지확인하기위하여, 상기요인들이동반되는경우와상기요인들이없는대조군을비교하여 BPPV의재발률에차이가있는지를확인하였다. 통계재발요인이없는대조군에비교하여재발요인이있는군에서 BPPV가 1회발생한경우와 2회이상발생한경우사이의차이를확인하고, 각연령대에발생한전체 BPPV 환자중재발한환자비율이연령대별로의미있는차이가있는지확인하기위해 chi-square 분석을이용하였다. 연령과성별에따른재발률의차이를분석하기위하여여러질환이같이이환되어있는특성을보정한다변량 Cox 비례위험모형 (multivariate Cox proportional hazard regression) 을사용하였다. 모든분석에서 p값이 0.05 미만인경우를통계학적으로유의한것으로하였으며, 통계패키지는윈도우용 SAS 9.4 version(sas Inc., Cary, NC, USA) 을이용하였다. 16

Risk Factors for Recurrence of BPPV Han SJ, et al. 결 과 본연구에서정의된 BPPV 환자총 21355 명중남자가 6383 명, 여자가 14972 명으로여성이남성보다 2.3 배많았으며, 평 균연령은 54.4±15.5 세였다. 이중 BPPV 가재발한환자는총 5876 명으로전체 BPPV 환자의 28% 에해당되었다. 환자들 이추적관찰된기간은평균 48.2±37.2 개월로, 상기기간동안 3 회와 4 회재발한경우가각각 43% 와 25% 로가장많았고, 5 회재발률이 13%, 6 회재발률이 7% 로확인되었다. 재발한 환자 5876 명중에 BPPV 의초기진단후 12 개월이내에재발 한경우가 3373 명으로재발한전체환자의 57% 에해당하였 으며, 24 개월이내에재발한경우는 4348 명으로재발한전체 환자의 74% 를차지하였다 (Fig. 1). BPPV 가한번만발생한 경우와재발한경우를모두포함하여전체발생률을연령별 로분석해보면, 40 대이후에 BPPV 의전체발생률이증가하 여 BPPV 가발생한총연구대상자 21355 명중 40 대에발생 한경우가 4205 명 (20%), 50 대에발생한경우가 4838 명 (23%), 그리고 60 대에발생한경우가 4276 명 (20%) 이었다 (Fig. 2). 초 회진단연령대별로재발률을비교해보면통계적으로유의하 게재발률에차이가있었으며 (p<0.001), 50 대이상에서는각 연령대에발생한전체 BPPV 환자중재발한환자비율이약 30~35% 로 20 대나 30 대에비하여높게나타났다 (Fig. 2). BPPV 의재발요인으로고려할수있는인자들에대하여 BPPV 의재발률에영향을미치는지단변량분석을시행하였을 때, BPPV 의재발위험성이전정질환이동반되는경우 34%, 65 세이상에서 31%, 두통이동반되는경우 15%, 허혈성심장 질환이동반되는경우와여성의경우각각 10%, 고혈압과골 다공증이있는경우각각 8% 증가하였다 (Table 1). 성별과연령요인을배제하고다른질환에의한재발의증 가여부를분석하기위하여, 65 세를기준으로남녀성별에따 Survival probability 1.0 0.8 0.6 0.4 0.2 0.0 0 12 24 36 48 50 72 84 96 108 120 132 144 Month censored Recurrence 28% Fig. 1. The Kaplan-Meier estimation for recurrence of BPPV. The recurrence rate was 28%. Of the patients with BPPV recurrence, 57% and 74% recurred within 12 months and 24 months of initial diagnosis (vertical dashed lines), respectively. BPPV: benign paroxysmal positional vertigo. 라 4 개의군으로나누어재발요인을분석하였다. 65 세이상 남자의경우, 총 1820 명중 594 명 (33%) 에서재발하였고, 전 정질환이동반되는경우 BPPV 재발의위험이 62% 증가하 였으나다른동반질환은통계학적으로의미가없었다 (Table 2). 65 세미만남자의경우, 총 4563 명중재발한환자는 995 명으로전체의약 22% 에해당하였고역시이경우에도전정 질환이동반되면 BPPV 의재발위험이약 38% 증가하였다 (Table 2). 65 세이상여자의경우, 4049 명중전체의 35% 인 1403 명에서재발하였고 BPPV 의재발위험성은전정질환이 동반될경우 33%, 허혈성심장질환이동반될경우 19% 증가 하였다 (Table 3). 65 세미만여자의경우, 총 10923 명중 26% 인 2884 명에서재발하였고, BPPV 의재발위험성은전정질 환이동반될경우 29%, 두통이동반될경우 20%, 고혈압이 동반될경우 19%, 그리고골다공증이동반될경우 17% 증가 하였다 (Table 3). 고 찰 BPPV 는전체어지럼증환자의약 20% 를차지할정도로 매우흔한질환으로그유병률은계속증가하고있으며, 이는 BPPV 진단의정확도향상과더불어사회의고령화와연관 이있을것으로생각된다. 11) BPPV 의재발에대한기존연구 들에서는여러위험인자가재발률에미치는영향에대하여 다양한결과를보이는데, 동일한위험인자에대하여상반된 결과를보이기도한다. 3,7-12) 따라서이러한재발의위험인자를 확인하기위해본연구에서는대단위의코호트자료를이용하 Number of patients 4000 3500 3000 2500 2000 1500 1000 500 0 87.5% 12.5% 80.7% 19.3% 75.7% 24.3% 69.9% 30.1% 68.2% 31.8% 65.2% 34.8% 65.5% * 34.5% 20 29 30 39 40 49 50 59 60 69 70 79 80 89 Age Fig. 2. Distribution of age at initial diagnosis of benign paroxysmal positional vertigo in cases with or without recurrences. The proportion of recurrent cases within each age group rose above 30% for patients above and including the 6th decade. The numbers marked on the top of each bar represent the percentage of cases with or without recurrences within each age group. The percentage was marked with an asterisk (*) when it was above 30%. The difference of recurrence rates among the age groups was statistically significant (χ 2 =431.866, df=6, p<0.001). * * * www.kjorl.org 17

Korean J Otorhinolaryngol-Head Neck Surg 2019;62(1):15-22 여국내에서의 BPPV 유병률과재발률을분석하고자하였다. 우선본연구에서 BPPV의발생양상을보면, 50~60대에서발생률이가장높고여성에서남성에비하여 2.3배발생률이높아기존에보고된연구결과와비슷한양상을보였다. 2) 장기재발률에대한연구들을살펴보면, Brandt 등 8) 은 125명의 BPPV 환자를 10년간추적관찰하였을때, 재발률이 50% 이고재발한환자중 80% 가 1년이내에재발하였다고보고하였다. 그러나, 추적관찰기간이 4~6년사이인연구들은재발률이 25~40% 로보고하였으며, 이는본연구에서의재발률 28% 와비슷한결과를보였다. 3,10,15) 본연구에서단변량분석을시행하였을때연령과성별에따라재발률에의미있는차이를보였고그외에전정질환, Table 1. Univariate Cox regression analyses of the overall HR related to the recurrence of benign paroxysmal positional vertigo over an eleven-year follow-up period 18 Variable No recurrence Recurrence n (%) n (%) HR (95% CI) Gender 0.001* Age Male 4794 (75.1) 1589 (24.9) 0.904 (0.850-0.960) Female 10685 (71.4) 4287 (28.6) 1 65 years 3872 (66.0) 1997 (34.0) 1.312 (1.232-1.397) <65 years 11607 (75.0) 3879 (25.0) 1 <0.001* Hypertension 0.019* Yes 4820 (69.3) 2135 (30.7) 1.079 (1.013-1.150) No 10659 (74.0) 3741 (26.0) 1 Diabetes mellitus 0.874 Yes 1219 (70.6) 508 (29.4) 0.992 (0.902-1.091) No 14260 (72.7) 5368 (27.3) 1 Osteoporosis 0.021* Yes 2539 (67.2) 1239 (32.8) 1.086 (1.012-1.165) No 12940 (99.8) 4637 (0.2) 1 Chronic renal disease 0.160 Yes 100 (74.6) 34 (25.4) 1.276 (0.908-1.792) No 15379 (72.5) 5842 (27.5) 1 Ischemic heart disease 0.016* Yes 1933 (68.6) 885 (31.4) 1.099 (1.018-1.186) No 13546 (73.1) 4991 (26.9) 1 Stroke 0.880 Yes 2165 (69.3) 961 (30.7) 1.006 (0.934-1.083) No 13314 (73.0) 4915 (27.0) 1 Head trauma 0.374 Yes 256 (75.7) 82 (24.3) 1.104 (0.888-1.373) No 15223 (72.4) 5794 (27.6) 1 Ear surgery 0.156 Yes 49 (66.2) 25 (33.8) 0.753 (0.508~1.115) No 15430 (72.5) 5851 (27.5) 1 Vestibular disease Yes 2944 (67.1) 1445 (32.9) 1.344 (1.266-1.427) No 12535 (73.9) 4431 (26.1) 1 Headache Yes 7330 (70.8) 3017 (29.2) 1.155 (1.096-1.217) No 8149 (74.0) 2859 (26.0) 1 <0.001* <0.001* Autoimmune disease 0.120 Yes 2139 (69.6) 933 (30.4) 1.059 (0.985-1.139) No 13340 (73.0) 4943 (27.0) 1 *significant s. HR: hazard ratio, CI: confidence interval

Risk Factors for Recurrence of BPPV Han SJ, et al. 두통, 허혈성심장질환, 고혈압, 그리고골다공증이통계적으로유의한인자들로분석되었다. 연령의경우 65세이상일때가 65세미만일때보다재발의위험이약 31% 증가하는것으로분석되었는데, 연령에따른 BPPV의재발증가요인으로는노화에따른칼슘대사의변화로인한칼슘농도저하와이석농도의감소, 이석막의퇴화, 미세혈관장애로인한허혈등이연관이있을것으로추정되고있다. 16) 또한, 동물실험에의하면연령이증가할수록이석의형태가갈라지고조각나게되며연결섬유들도약해지는것으로확인되었다. 17) 기존의연구들에서성별에의한재발률의영향에대해상반된연구결과를보이나, 다수의연구들이여성에서 BPPV의발생률 과재발률이더높다고보고하고있는데, 이는여성에서의호르몬변화와연관성이높을것으로추정된다. 3,7,8,14,18) 특히많은연구가폐경기여성에서 BPPV의발생및재발률이높은것은골밀도감소와같은신체대사의변화뿐만아니라여성호르몬의변동에따른심리적인변화도영향을줄수있다고보고하고있다. 14,18-21) 성별과연령에따라 4개의군으로나누어다변량분석을하였을때, 남성에서는 65세이상일때와 65세미만일때모두전정질환만이의미있는재발인자로분석되었고여성의경우 65세이상에서는전정질환과허혈성심장질환, 65세미만에서는전정질환, 두통, 골다공증, 고혈압이의미있는인자로 Table 2. Multivariate Cox regression analyses of overall HR related to the recurrence of BPPV in males Variable 65 years <65 years n HR (95% CI) n HR (95% CI) Hypertension 0.360 0.128 Yes 1148 0.920 (0.769-1.100) 1146 1.126 (0.966-1.313) No 672 1 3417 1 Diabetes Mellitus 0.542 0.424 Yes 345 0.936 (0.756-1.158) 306 0.903 (0.702-1.160) No 1475 1 4257 1 Osteoporosis 0.542 0.681 Yes 151 0.909 (0.669-1.235) 56 0.882 (0.486-1.602) No 1669 1 4507 1 Chronic renal disease 0.490 0.466 Yes 32 1.266 (0.648-2.475) 25 1.445 (0.537-3.884) No 1788 1 4538 1 Ischemic heart disease 0.062 0.846 Yes 483 1.199 (0.991-1.452) 484 0.979 (0.794-1.208) No 1337 1 4079 1 Stroke 0.978 0.353 Yes 594 0.998 (0.833-1.194) 474 0.904 (0.731-1.118) No 1226 1 4089 1 Head trauma 0.066 0.603 Yes 47 1.925 (0.957-3.871) 92 0.889 (0.570-1.386) No 1773 1 4471 1 Ear surgery 0.952 0.048* Yes 5-21 0.495 (0.247-0.993) No 1815 4542 1 Vestibular disease <0.001* <0.001* Yes 360 1.622 (1.346-1.954) 855 1.378 (1.189-1.596) No 1460 1 3708 1 Headache 0.384 0.055 Yes 801 1.076 (0.912-1.270) 1725 1.135 (0.997-1.292) No 1019 1 2838 1 Autoimmune disease 0.345 0.675 Yes 281 1.113 (0.891-1.391) 319 1.053 (0.826-1.344) No 1539 1 4244 1 *significant s, none of the 5 patients with previous ear surgery showed recurrence of BPPV. HR: hazard ratio, CI: confidence interval, BPPV: benign paroxysmal positional vertigo www.kjorl.org 19

Korean J Otorhinolaryngol-Head Neck Surg 2019;62(1):15-22 분석되었다. 모든군에서공통적으로전정질환이재발인자로나타났는데, 기존연구들도전정신경염, 돌발성난청, 메니에르병등의내이질환의과거력이있는경우재발률이증가한다고보고하고있다. 11,12,22) 고혈압이나허혈성심장질환이동반되는경우에도 BPPV의재발률이증가하였는데이러한전신질환은내이의허혈성손상을초래하여이석막으로부터이석의탈락을유발하는것으로생각된다. 9,14) 두통이동반되는경우, BPPV는미로동맥의혈관경련에의한이석의탈락으로발생할수있다. 23) BPPV가두통과동반되는경우이석의비정상적흥분신호로인한감각자극의변화때문에두통이발생한다고생각할수도있으나, 혈관경 련으로인한내이의손상이전정상피세포의손상을초래하여이석이탈락할수있다. 14,23) 또한편두통동물실험모델에의하면반복되는신경성염증이이석기관의손상을초래하는것으로관찰되어이또한두통과동반된 BPPV의발생기전으로생각될수있겠다. 24) 본연구결과에서도두통이동반되는경우전체환자의 15%, 65세미만여성에서는약 20% 에서 BPPV의재발률이증가하였다. 골다공증이동반되는경우재발의위험이전체 BPPV 환자에서는 9%, 65세미만젊은여성에서는 17% 증가하였는데, 기존연구에따르면 BPPV 환자에서골밀도가정상인보다감소하여있고골다공증이동반된 BPPV 환자의경우재발 Table 3. Multivariate Cox regression analyses of overall HR related to the recurrence of benign paroxysmal positional vertigo in females Variable 65 years <65 years n HR (95% CI) n HR (95% CI) Hypertension 0.839 <0.001* Yes 2615 0.988 (0.880-1.109) 2046 1.194 (1.083-1.316) No 1434 1 8877 1 Diabetes Mellitus 0.627 0.167 Yes 655 0.964 (0.833-1.117) 421 1.151 (0.943-1.405) No 3394 1 10502 1 Osteoporosis 0.149 0.002* Yes 1998 1.083 (0.972-1.206) 1573 1.172 (1.059-1.296) No 2051 1 9350 1 Chronic renal disease 0.062 0.339 Yes 47 1.815 (0.972-3.392) 30 0.748 (0.412-1.356) No 4002 1 10893 1 Ischemic heart disease 0.006* 0.706 Yes 972 1.193 (1.053-1.352) 879 1.026 (0.896-1.176) No 3077 1 10044 1 Stroke 0.875 0.306 Yes 1167 1.010 (0.895-1.139) 891 1.071 (0.939-1.220) No 2882 1 10032 1 Head trauma 0.616 0.901 Yes 63 1.127 (0.707-1.794) 136 1.021 (0.735-1.419) No 3986 1 10787 1 Ear surgery 0.333 0.600 Yes 14 0.693 (0.329-1.457) 34 0.847 (0.455-1.576) No 4035 1 10889 1 Vestibular disease <0.001* <0.001* Yes 890 1.333 (1.182-1.505) 2284 1.292 (1.186-1.407) No 3159 1 8639 1 Headache 0.065 <0.001* Yes 2315 1.108 (0.994-1.234) 5506 1.200 (1.114-1.293) No 1734 1 5417 1 Autoimmune disease 0.672 0.233 Yes 997 1.027 (0.908-1.162) 1475 1.067 (0.959-1.186) No 3052 1 9448 1 *significant s. HR: hazard ratio, CI: confidence interval 20

Risk Factors for Recurrence of BPPV Han SJ, et al. 의위험성이유의하게높다고보고하고있다. 25) Yamanaka 등 20) 은골다공증이있는 50세이상의 BPPV 여성환자중 56% 에서 BPPV가재발하였고 44% 에서 2회이상재발하였다고보고하였다. 이석은탄산칼슘으로이루어져있는데이석의유지에중요한칼슘이온의흡수가잘되지않거나골기질단백질로알려진 osteopontin이골다공증환자에서부족하게되면이석의형성이불완전할수있다고한다. 20,26) 골다공증은갱년기여성에서에스트로겐의급격한감소와연관이많은것으로알려져있으며이는칼슘과골대사에중요한역할을하는에스트로겐의결핍으로인하여이석의내부구조에변형을유발하고이석간혹은이석과주변조직간의결합에영향을주기때문일것으로생각되고있다. 20,25) 또한, 에스트로겐결핍으로인하여유리칼슘이온이증가하면분리된이석잔해의흡수가떨어져 BPPV 의유발요인으로작용할수있다. 25) 기존에알려진재발요인인두부외상은본연구에서는통계학적의미가없었으며, 특히최근 6개월이내의귀수술시행여부는 BPPV의재발에의미가있을것으로의심하였지만총 21355 명환자중귀수술을받은경우는모두 74명으로환자수가너무작아통계학적으로의의가나타나지않은것으로생각되었다. 본연구는국민건강보험공단의빅데이터를이용한연구로방대한양의자료라는점은의의가있지만, 진단명만을기초로한자료분석에따른한계점이있을수있다. 우선 BPPV 로정의된환자에서양성돌발두위현훈 (KCD-6 H811) 의특징적인안진이관찰되지않은경우 의증 으로진단명을입력한경우가포함되어있을수있다. 이러한오류를최대한줄이기위하여양성돌발두위현훈 (KCD-6 H811) 이국내이비인후과병원에서발생한경우만을연구대상으로하였으며내과나신경과등타과의진단인경우를배제하여최대한양성돌발두위현훈진단의전문성을확보하고자하였다. 반대로어지럼증 (R42) 의진단명으로진료가지속되어양성돌발두위현훈 (KCD-6 H811) 의진단명이누락된경우도존재할수있으므로본연구에서는이를보완하기위해이석정복술 (EDI code MX035) 을시행한환자들을포함하여정확성을높이고자하였다. 또한, 진단코드 (KCD-6 H811) 나처치코드 (EDI code MX035) 를이용하여정의된 BPPV 환자에서병의경과와예후에영향을줄수있는침범반고리관의위치나향지성혹은원지성아형여부등이재발의위험인자분석에있어서반영되지못한아쉬움이있다. 하지만, 실제로우리나라에서최근 10년동안이루어진 BPPV의진단및발생빈도와재발률을분석하고재발과관련된동반질환과의경향성을평가한데에그의의가있다고생각된다. 결론적으로 65세이상의고령이거나여성인경우, 기저전정 질환이동반된경우 BPPV 의재발위험성이높아질수있다. 특히 65 세미만의젊은여성에서는두통, 허혈성심장질환, 고 혈압및골다공증이동반될때재발률이증가한다. 본연구 결과를통하여 BPPV 환자들에게더욱정확한정보의제공 과상담이가능할것으로보이며나아가이를바탕으로한 추가적인연구를통하여 BPPV 의예방및치료에도움이될 것으로생각된다. Acknowledgments This research was supported by the Basic Science Research Program (2015R1A1A1A05001472) of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning. REFERENCES 1) Bhattacharyya N, Baugh RF, Orvidas L, Barrs D, Bronston LJ, Cass S, et al. Clinical practice guideline: benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 2008;139(5 Suppl 4):S47-81. 2) Kim JS, Zee DS. Clinical practice. benign paroxysmal positional vertigo. N Engl J Med 2014;370(12):1138-47. 3) Pérez P, Franco V, Cuesta P, Aldama P, Alvarez MJ, Méndez JC. Recurrence of benign paroxysmal positional vertigo. Otol Neurotol 2012;33(3):437-43. 4) Kim SH, Jo SW, Chung WK, Byeon HK, Lee WS. A cupulolith repositioning maneuver in the treatment of horizontal canal cupulolithiasis. Auris Nasus Larynx 2012;39(2):163-8. 5) Choi SJ, Lee JB, Lim HJ, Park HY, Park K, In SM, et al. Clinical features of recurrent or persistent benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 2012;147(5):919-24. 6) Simhadri S, Panda N, Raghunathan M. Efficacy of particle repositioning maneuver in BPPV: a prospective study. Am J Otolaryngol 2003;24(6):355-60. 7) Nunez RA, Cass SP, Furman JM. Short- and long-term outcomes of canalith repositioning for benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg 2000;122(5):647-52. 8) Brandt T, Huppert D, Hecht J, Karch C, Strupp M. Benign paroxysmal positioning vertigo: a long-term follow-up (6-17 years) of 125 patients. Acta Otolaryngol 2006;126(2):160-3. 9) De Stefano A, Dispenza F, Suarez H, Perez-Fernandez N, Manrique- Huarte R, Ban JH, et al. A multicenter observational study on the role of comorbidities in the recurrent episodes of benign paroxysmal positional vertigo. Auris Nasus Larynx 2014;41(1):31-6. 10) Sakaida M, Takeuchi K, Ishinaga H, Adachi M, Majima Y. Longterm outcome of benign paroxysmal positional vertigo. Neurology 2003; 60(9):1532-4. 11) Su P, Liu YC, Lin HC. Risk factors for the recurrence of post-semicircular canal benign paroxysmal positional vertigo after canalith repositioning. J Neurol 2016;263(1):45-51. 12) Tanimoto H, Doi K, Nishikawa T, Nibu K. Risk factors for recurrence of benign paroxysmal positional vertigo. J Otolaryngol Head Neck Surg 2008;37(6):832-5. 13) National Health Insurance Service. National health insurance statistical yearbook. Seoul: Health Insurance Review and Assessment Service and National Health Insurance Service;2014. 14) Picciotti PM, Lucidi D, De Corso E, Meucci D, Sergi B, Paludetti G. Comorbidities and recurrence of benign paroxysmal positional vertigo: personal experience. Int J Audiol 2016;55(5):279-84. 15) Kansu L, Avci S, Yilmaz I, Ozluoglu LN. Long-term follow-up of patients with posterior canal benign paroxysmal positional vertigo. Acta Otolaryngol 2010;130(9):1009-12. 16) Ishiyama G. Imbalance and vertigo: the aging human vestibular periphery. Semin Neurol 2009;29(5):491-9. www.kjorl.org 21

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