ORIGINAL ARTICLE 한국인성인남성폐쇄성수면무호흡환자의 측모두부방사선계측학적비교 황상희 a ㆍ박인숙 b ㆍ남기영 a ㆍ김종배 c ㆍ조용원 d ㆍ서영성 e ㆍ안병훈 f ㆍ박신구 g ㆍ박효상 h 본연구는비만도에따른한국인남성폐쇄성수면무호흡환자의측모두부방사선계측학적특성을파악하기위하여시행되었다. 이를위하여계명대학교의과대학동산의료원수면클리닉에수면장애를주소로내원하여수면다원검사후치과에서측모두부방사선계측사진촬영을한 87 명의성인환자들을체질량지수 (BMI) 와수면무호흡지수 (AHI) 에따라비비만단순코골이군 (Non-obese, simple snorers), 비만단순코골이군 (Obese, simple snorers), 비비만수면무호흡군 (Non-obese, OSA patients), 비만수면무호흡군 (Obese, OSA patients) 의 4 군으로나누어비교하였다. 그결과, 4 군중비만수면무호흡군의수면무호흡지수가가장컸으며, 비만수면무호흡군보다비비만수면무호흡군의하악각이더크고혀길이는더작았다. 또한, 비비만수면무호흡군보다비만수면무호흡군의설골이더전하방에위치하였고, 수면무호흡지수에영향을미치는기여인자는비만수면무호흡군에서는혀길이, 비비만수면무호흡군에서는설골의후방위치였다. 이처럼비만수면무호흡환자와비비만수면무호흡환자의측모두부방사선계측학적특성과기여인자가다르게나타나므로, 치료방법도따라서다르게선택해야할것이다. 비만수면무호흡환자들에게는먼저체중감량이권고되어야할것이고, 비비만수면무호흡환자들은폐쇄부위에따라구강내장치나 Nasal CPAP (continuous positive airway pressure), UPPP (uvulopalatopharyngoplasty) 등이추천될수있을것이다. ( 대치교정지 2008;38(3):202-213) 주요단어 : 비만도, 폐쇄성수면무호흡, 측모두부방사선계측사진, 치료방법 서론 수면중간헐적인상기도폐쇄또는협착에의해공기의흐름이막혀반복적인무호흡또는저호흡이발생하는폐쇄성수면무호흡증 (obstructive sleep apnea, OSA) 은이로인해혈중산소포화도가떨어지고미세각성이일어나수면이분절되며대개심한코골이와주간졸음등의현상이동반된다. 1,2 수 a 조교수, b 임상전임강사, c 교수, 계명대학교의과대학치과학교실. d 부교수, 계명대학교의과대학신경과학교실. e 부교수, 계명대학교의과대학가정의학교실. f 부교수, 계명대학교의과대학이비인후과학교실. g 조교수, 인하대학교의과대학산업의학교실. h 부교수, 경북대학교치과대학교정학교실. 교신저자 : 황상희. 대구시중구동산동 194 계명대학교동산의료원치과. 053-250-7803; e-mail, hsh99@dsmc.or.kr. 원고접수일 : 2007 년 3 월 13 일 / 원고최종수정일 : 2007 년 6 월 20 일 / 원고채택일 : 2007 년 6 월 22 일. 면무호흡 (sleep apnea) 이란수면중호흡운동이유지된상태에서호흡이 10 초이상완전히멈춘경우이고, 수면저호흡 (sleep hypopnea) 은열전대로측정된호흡량진폭이 50% 이상감소하거나, 10 초이상명확한호흡량감소와동반하여뇌파상각성이있거나산소포화도가 4% 이상감소되는경우로, 수면 1 시간당발생하는무호흡과저호흡횟수의합의평균인무호흡 - 저호흡지수 (apnea-hypopnea index, AHI) 가 5 이상인경우폐쇄성수면무호흡증이있다고정의한다. 2 흔히사용되는용어인코골이 (primary snoring) 혹은상기도저항증후군 (upper airway resistance syndrome) 은현저한저호흡이나무호흡상태가동반되지않으면서상기도의기도저항이증가하여밤에자주깨어나게되는것을의미하며일반적으로수면무호흡지수 (AHI) 가 10 이하를나타낸다. 3,4 폐쇄성수면무호흡증은비교적흔한질환이지만, 5-8 진단에필수적인야간수면다원검사 (polysomnography) 9 의검사비용이비싸고, 시공간적제약이크 202
Vol. 38, No. 3, 2008. Korean J Orthod 한국인성인남성폐쇄성수면무호흡환자의측모두부방사선계측학적비교 며, 전문인력에의해서만수행이가능하다는점에서제약이있어많은환자들이상당히심각한상태가될때까지제대로진단받지못하고있는실정이다. 그러나폐쇄성수면무호흡환자는주간에심하게졸리는경향이있으며이는인지능력의결여나운전중혹은작업중집중력저하로이어지게되기도하고, 10,11 나아가폐쇄성수면무호흡은고혈압, 부정맥, 야간협심증등과도관련이있어서 12 적절히치료하지않을경우매우심각한결과를가져올수도있다. 교정학영역에서널리사용되어온측모두부방사선계측사진은폐쇄성수면무호흡의빠른진단을돕고원인을파악하기위한통상적인검사로추천되고 13,14 있는데, 여타의다른검사와는달리촬영이간단하고설치비용과촬영비용이저렴하며경조직뿐만아니라연조직의형태도어느정도파악할수있다는장점이있기때문이다. 15 물론, 3차원적인입체구조를측면에서촬영된 2차원적영상이모두반영할수없다는단점이있지만, 폐쇄성수면무호흡에있어서폐쇄가일어나는부위를어느정도파악할수있다는여러보고들 16-18 이있다. 특히, 연구개후방부위에서폐쇄가일어날경우 ( 상기도후방 ) 와설기저부후방 ( 하기도후방 ) 에서폐쇄가일어날경우를제대로파악하는것은진단뿐만아니라치료방법을결정하는데도중요한요소가된다. 그러나, 현재까지보고된여러문헌들은주로서양인을대상으로한분석이주를이루고있으며, 두부방사선학적계측치들은성별, 19 인종 20-22 등의요소에의해영향을받을수있으므로한국인폐쇄성수면무호흡환자들에대한기준자료로그대로받아들이기에는적합하지않다. 또한, 비만이폐쇄성수면무호흡에가장중요한기여인자라는사실은널리알려져있으며, 23-25 체중감소시수면무호흡의정도도역시감소된다는보고 26,27 가있으나백인과아시아인의비만기준은다르고 28 백인에비해아시아남성에서는비비만수면무호흡환자의비율이높다는보고 29 도있으므로아시아인에서비비만수면무호흡환자에대한연구가절실히요구된다. 또한, 원인에따른적절한치료방법의선택을위해서도비만한수면무호흡환자와비만하지않은수면무호흡환자를분리하여원인인자에대한형태학적및기능적연구가필요하다고볼수있겠다. 이에본연구에서는한국인성인남성을비만정도에따라구분하여수면다원검사치및측모두부방사선계측치를비교분석하고다중회귀분석등을 통해비만및비비만수면무호흡에미치는기여인자를각각파악하여적절한치료방법선택에도움이되고자한다. 연구방법 연구대상 2003 년 4 월부터 2006 년 3 월까지계명대학교의과대학동산의료원수면클리닉에수면장애를주소로내원하여수면다원검사후치과에서측모두부방사선계측사진촬영을한 135 명중심한골격적결함이나상하악총의치환자를제외한 87 명의남자환자만을대상으로하였다. 수면다원검사시행결과, 수면무호흡지수 (AHI) 가 10 이상인경우를폐쇄성수면무호흡증으로분류하여, 전체 87 명의환자중 44 명을수면무호흡군 (OSA patients) 으로, 43 명을대조군인단순코골이군 (simple snorers) 으로나누었다. 연구방법 수면무호흡지수와체질량지수신경과에서하룻밤사이의수면다원검사 (D/EEG- 32, Grass-telefactor, USA) 를통해수면무호흡지수 (AHI) 수치가시간당평균 10 회이상인경우를폐쇄성수면무호흡증으로진단하였으며신장과몸무게를측정한뒤단위체표면에대한체중을구하여체질량지수 (BMI, body mass index = kg/m 2 ) 가 25 이상인경우를비만으로분류 28 하였다. 비만도에따라단순코골이군 (simple snorers) 과수면무호흡군 (OSA patients) 을각각다시 2 군으로나누어모두 4 개군을서로비교하였다. 각군의체질량지수평균값과표준편차는비비만단순코골이군 (Non-obese, simple snorers) 이 23.06 ± 1.66, 비만단순코골이군 (Obese, simple snorers) 이 27.51 ± 2.06, 비비만수면무호흡군 (Nonobese, OSA patients) 은 23.45 ± 1.22, 비만수면무호흡군 (Obese, OSA patients) 은 28.25 ± 2.45 로나타났다. ANOVA test 로 4 군의체질량지수를비교하였을때비비만군과비만군의평균값은각각서로통계학적으로유의하게차이가있었으며 (p < 0.05), 비비만단순코골이군과비비만수면무호흡군사이, 비만단순코골이군과비만수면무호흡군사이에는각각유의한차이가없었다. 203
황상희, 박인숙, 남기영, 김종배, 조용원, 서영성, 안병훈, 박신구, 박효상 대치교정지 38 권 3 호, 2008 년 측모두부방사선계측사진의계측및분석중심교합상태에서상하순을이완시키고입술을가볍게다물게한다음 FH 평면과지면이평행하도록위치시킨후환자가한번침을삼키고멈춘상태에서통상적인방법으로측모두부방사선계측사진을촬영하였다 (Proline, Planmeca, Helsinki, Finland). 이렇게얻어진측모두부방사선계측사진을동일한계측자 1 인이묘사지 (acetate paper) 위에그린투사도상에서계측점과계측선을설정하고 V-ceph 4.0 program (CyberMed, Seoul, Korea) 에입력하였다 (Fig 1). 두개골기저부의굴절정도와상하악골의전방돌출정도를파악하기위해 N-S-Ba, SNA, SNB, ANB 각을측정하였고, 전안면의수직적길이평가를위해 N-ANS, ANS-Gn 길이를측정하였으며, 후안면고경은 S-Go 사이거리로측정하였다. 하악골전체의길이는 Cd-Gn 으로계측하였고, 하악골의전체적인형태를파악하기위해서 FH plane 에대한 Mn plane angle 과 Gonial angle 도측정하였다. 연구개조직의길이와두께, 경구개에대한기울기를측정하기위해각각 PNS-P, SPW, ANS-PNS-P angle 항목을계측하였으며, 상기도부위의전후적폭경을알아보기위해 Nph1 과 Nph2 를, 하기도부위의전후적폭경을알아보기위해 Oph1, Oph2, PAS 거리를계측하였다. 설골 (hyoid bone) 의수직적위치를파악하기위해 MP-Hyoid 거리를측정하였고, 전후적위치는 C3-Hyoid 거리로계측하였다. 혀의길이 (tongue length, TL) 와두께 (tongue thickness, TH) 도따로계측하였다. 각계측항목에대한자세한설명은다음과같다 (Table 1). Fig 1. Cephalometric landmarks. S (Sella), midpoint of the fossa hypophysealis; N (Nasion), anterior point at the frontonasal suture, Ba (Basion), most postero-inferior point on clivus; ANS (Anterior nasal spine), most anterior point of the nasal spine; PNS (Posterior nasal spine), most posterior point of the nasal spine; A, deepest anterior point in the concavity of the anterior maxilla; B, deepest anterior point in the concavity of the anterior mandible; Cd (Condylion), most postero-superior point of the condylar head; Gn (Gnathion), most antero-inferior point of the chin bone; Go (Gonion), a mid-point at the gonial angle located by bisecting the posterior and inferior borders of the mandible; Me (Menton), most inferior point of the chin bone; P, most inferior tip of soft palate; H, most antero-superior point of the hyoid bone; V, most antero-inferior point of the epiglottic fold; TT, most anterior point of the tip of the tongue; C3, most antero-inferior point of the third cervial vertebrae; MP (Mandibular plane), a tangent line constructed from Me to mandibular inferior border. 계측의신뢰도검사동일한계측자가 3주후, 20개의측모두부방사선계측사진을각각무작위로선택하여동일한방법으로재투사, 재입력, 재계측하여 paired t-test를시행하였다. 어떠한변수에서도첫번째계측치와두번째계측치사이에통계학적으로유의한차이가없었다 (p > 0.05). Dahlberg's formula (e = d: 두계측치간의차이, N: 두번계측한표본수 ) 를 d 2 /2N 이용한오차범위도측정하였는데, 각도계측치의경우 0.31-0.85 o 였으며, 선계측치의경우 0.01-0.76 mm의범위였다. 통계처리 SPSS 11.0 (SPSS, Chicago, IL, USA) 프로그램을이용하여, 비비만단순코골이군, 비만단순코골이군, 비비만수면무호흡군, 비만수면무호흡군의 4 개군을각각비교하기위해 ANOVA test 를시행하고, 사후검증방법으로 Scheffe's multiple comparison test 를이용하였다. 수면무호흡환자중에서비만도에따른측모두부방사선계측사진의각계측치들과수면무호흡지수 (AHI) 와의상관관계를파악하기위하여 Pearson correlation analysis 를시행하였고, 각계측항목중가장큰영향을미치는인자를확인하기위해다중회귀분석 (stepwise multiple regression test) 을시행하였다. 204
Vol. 38, No. 3, 2008. Korean J Orthod 한국인성인남성폐쇄성수면무호흡환자의측모두부방사선계측학적비교 Table 1. Cephalometric measurements Variable Definition SNA Angle from Sella (S) to Nasion (N) to A point ( o ) SNB Angle from Sella (S) to Nasion (N) to B point ( o ) ANB Angle from A point to Nasion (N) to B point ( o ) N-S-Ba Angle from Nasion (N) to Sella (S) to Basion (Ba) ( o ) N-ANS (upper ant. facial height) Distance from Nasion (N) to Anterior Nasal Spine (ANS) (mm) ANS-Gn (lower ant. facial height) Distance from Anterior Nasal Spine (ANS) to Gnathion (Gn) (mm) S-Go (post. facial height) Distance from Sella (S) to Gonion (Go) (mm) Cd-Gn (mandibular length) Distance from Condylion (Cd) to Gnathion (Gn) (mm) Mn plane angle Angle between Frankfurt horizontal plane and mandibular plane ( o ) Gonial angle Angle between mandibular plane and a tangent line to mandibular posterior border PNS-P (soft palate length) Distance from Posterior Nasal Spine (PNS) to tip of the soft palate (P) (mm) ANS-PNS-P angle Angle from Anterior Nasal Spine (ANS) to Posterior Nasal Spine (PNS) to tip of soft palate (P) ( o ) SPW (soft palatal width) Widest width along perpendicular line to Posterior Nasal Spine (PNS)-tip of soft palate (P) line (mm) Nph1 (nasopharyngeal airway width 1) Distance from posterior wall of soft palate to posterior pharyngeal wall at the level of Posterior Nasal Spine (PNS) along a line parallel to Anterior Nasal Spine (ANS)-Posterior Nasal Spine (PNS) (mm) Nph2 (nasopharyngeal airway width 2) Distance from posterior wall of soft palate to posterior pharyngeal wall at the widest level of soft palate along a line parallel to Anterior Nasal Spine (ANS)-Posterior Nasal Spine (PNS) (mm) Oph1 (oropharyngeal airway width 1) Distance from posterior wall of tongue base to posterior pharyngeal wall at tip of soft palate along a line parellel to Anterior Nasal Spine (ANS)-Posterior Nasal Spine (PNS) (mm) Oph2 (oropharyngeal airway width 2) Distance from tongue base to posterior pharyngeal wall along mandibular plane (mm) PAS (posterior airway space) Linear measurement between the base of tongue and posterior pharyngeal wall along the line B point (B)-Gonion (Go) (mm) MP-Hyoid Linear distance along the perpendicular plane from Hyoid (H) to mandibular plane (mm) C3-Hyoid Distance from C3 to Hyoid (H) (mm) TL (Tongue length) Distance from V to TT (mm) TH (Tongue thickness) Linear distance along the perpendicular bisector of the V-TT line to the tongue dorsum (mm) 연구성적 각군간특성비교단순코골이군 (simple snorers) 과수면무호흡군 (OSA patients) 사이에통계적으로유의한연령차이는없었고, 수면무호흡지수 (AHI) 는단순코골이군 (3.11 ± 3.25, 4.55 ± 3.36) 이나비비만수면무호흡군 (21.18 ± 7.56) 의평균치에비해비만수면무호흡군 (43.09 ± 205
황상희, 박인숙, 남기영, 김종배, 조용원, 서영성, 안병훈, 박신구, 박효상 대치교정지 38 권 3 호, 2008 년 Table 2. Characteristics of subjects Simple snorers OSA patients Non-obese Obese Non-obese Obese p value (n = 23) (n = 20) (n = 12) (n = 32) Age (years) 41.30 ± 15.2 40.80 ± 9.27 43.17 ± 9.91 43.69 ± 9.56 0.782 AHI (events/hr) 3.11 ± 3.25 a 4.55 ± 3.36 a 21.18 ± 7.56 b 43.09 ± 21.72 c 0.000 All data are presented as mean±sd; AHI, apnea-hypopnea index; a,b,c the same letters indicate non-significant difference between groups based on Scheffe's multiple comparison test. Table 3. Cephalometric measurements in simple snorers and OSA (obstructive sleep apnea syndrom) patients according to obesity Simple snorers OSA patients Parameters Non-obese Obese Non-obese Obese (n = 23) (n = 20) (n = 12) (n = 32) p value Bony structures SNA ( o ) 82.22 ± 4.03 81.80 ± 2.61 82.50 ± 3.59 83.33 ± 3.00 0.392 SNB ( o ) 76.78 ± 7.25 77.95 ± 3.12 77.33 ± 3.41 79.70 ± 3.29 0.124 ANB ( o ) 4.09 ± 2.27 3.85 ± 2.09 5.17 ± 2.29 3.63 ± 2.03 0.206 N-S-Ba ( o ) 128.07 ± 3.94 131.18 ± 4.68 129.04 ± 4.83 128.23 ± 4.27 0.079 N-ANS (mm) 62.63 ± 2.56 61.73 ± 3.76 62.42 ± 3.77 61.70 ± 3.46 0.719 ANS-Gn (mm) 78.61 ± 4.67 79.10 ± 4.97 83.42 ± 5.65 79.47 ± 5.41 0.063 S-Go (mm) 94.20 ± 7.37 93.85 ± 6.60 92.67 ± 7.42 97.17 ± 5.45 0.119 Cd-Gn (mm) 128.46 ± 7.61 131.07 ± 5.79 129.71 ± 3.66 130.48 ± 6.74 0.561 Mn plane angle ( o ) 27.28 ± 8.17 a,b 24.93 ± 6.91 a,b 29.54 ± 4.65 a 23.67 ± 4.68 b 0.028 Gonial angle ( o ) 120.37 ± 8.55 119.28 ± 9.53 123.46 ± 7.49 117.84 ± 6.78 0.218 Soft tissues PNS-P (mm) 45.35 ± 4.20 48.63 ± 4.48 46.08 ± 3.90 47.00 ± 4.23 0.086 ANS-PNS-P ( o ) 125.83 ± 5.63 128.57 ± 6.38 125.67 ± 6.28 126.16 ± 4.79 0.336 SPW (mm) 12.04 ± 2.00 a,b 11.91 ± 1.67 a 13.08 ± 1.66 a,b 13.38 ± 1.99 b 0.017 Nph1 (mm) 21.85 ± 4.21 23.38 ± 3.76 23.33 ± 2.91 21.67 ± 3.46 0.277 Nph2 (mm) 13.61 ± 3.39 13.43 ± 2.47 12.67 ± 2.75 12.86 ± 2.97 0.725 Oph1 (mm) 11.72 ± 3.19 12.90 ± 3.74 11.08 ± 4.49 14.09 ± 5.07 0.103 Oph2 (mm) 10.76 ± 2.99 12.38 ± 3.74 10.63 ± 4.25 12.94 ± 4.88 0.164 PAS (mm) 10.48 ± 2.89 12.30 ± 3.84 10.29 ± 4.33 12.98 ± 4.92 0.085 Tongue length (mm) 85.50 ± 5.18 a 89.75 ± 7.10 a,b 87.17 ± 7.23 a 93.23 ± 6.17 b 0.000 Tongue thickness (mm) 39.48 ± 4.38 40.70 ± 3.62 40.83 ± 4.57 40.53 ± 4032 0.722 Hyoid bone positions MP-Hyoid (mm) 18.50 ± 5.68 a 20.75 ± 5.90 a,b 19.50 ± 3.72 a 24.59 ± 5.65 b 0.001 C3-Hyoid (mm) 42.78 ± 2.58 a 44.58 ± 4.84 a,b 43.63 ± 4.26 a 47.59 ± 4.32 b 0.000 All data are presented as mean±sd; the same letters indicate non-significant difference between groups based on Scheffe's multiple comparison test. 206
Vol. 38, No. 3, 2008. Korean J Orthod 한국인성인남성폐쇄성수면무호흡환자의측모두부방사선계측학적비교 21.72) 의평균이 2 배이상높은것으로나타났다 (Table 2). 각군간측모두부방사선계측치들의비교 4 개군간의평균값이통계적으로유의하게차이가나는항목은하악각 (Mn plane angle), 연구개두께 (SPW), 혀길이 (tongue length), 설골 (hyoid bone) 관련계측치들 (MP-Hyoid, C3-Hyoid) 이었다 (Table 3). 통계적으로유의한차이는없었지만, 비비만수면무호흡군의 ANB 계측치가가장크고전하안면고경 (ANS-Gn) 도가장길었으며, 후안면고경 (S-Go) 도 가장짧았고, Gonial angle 도가장컸으며, 하악각 (Mn palne angle) 은 29.54 ± 4.65 o 로비만수면무호흡군의 23.67 ± 4.68 o 보다통계적으로도유의하게큰값을보여다른군들과비교시좀더골격성 II 급부정교합의양상을나타내었다. 연조직계측치들중에서비만수면무호흡군의연구개두께 (SPW) 가 13.38 ± 1.99 mm 로비만단순코골이군의 11.91 ± 1.67 mm 보다유의하게더두꺼운것으로나타났으며, 통계적으로유의하지는않았지만, 하기도폭경인 Oph1, Oph2, PAS 항목에서비비만수면무호흡군의평균값이 4 군중가장작았고, Table 4. Correlations between cephalometric measurements and AHI (apnea-hypopnea index) in OSA patients Parameters Total Non-obese Obese (n = 44) (n = 12) (n = 32) BMI (kg/m 2 ) 0.540 0.123 0.353 * Bony structures SNA ( o ) 0.092 0.271 0.249 SNB ( o ) 0.069 0.337 0.150 ANB ( o ) 0.240 0.077 0.125 N-S-Ba ( o ) 0.154 0.153 0.290 N-ANS (mm) 0.227 0.134 0.237 ANS-Gn (mm) 0.086 0.134 0.102 S-Go (mm) 0.120 0.064 0.057 Cd-Gn (mm) 0.011 0.192 0.033 Mn plane angle ( o ) 0.264 0.101 0.038 Gonial angle ( o ) 0.224 0.330 0.049 Soft tissues PNS-P (mm) 0.025 0.107 0.016 ANS-PNS-P ( o ) 0.041 0.055 0.022 SPW (mm) 0.271 0.238 0.283 Nph1 (mm) 0.423 0.533 0.368 * Nph2 (mm) 0.008 0.343 0.009 Oph1 (mm) 0.286 0.140 0.234 Oph2 (mm) 0.316 * 0.011 0.287 PAS (mm) 0.320 * 0.007 0.275 Tongue length (mm) 0.516 0.268 0.470 Tongue thickness (mm) 0.011 0.328 0.078 Hyoid bone positions MP-Hyoid (mm) 0.409 0.375 0.329 C3-Hyoid (mm) 0.430 0.604 * 0.437 * All data are correlation coefficient values; * p < 0.05; p < 0.01. 207
황상희, 박인숙, 남기영, 김종배, 조용원, 서영성, 안병훈, 박신구, 박효상 대치교정지 38 권 3 호, 2008 년 비만수면무호흡군의평균값이가장큰것을확인할수있었다. 비만수면무호흡군의혀길이 (tongue length) 는 93.23 ± 6.17 mm 로비비만단순코골이군의 85.50 ± 5.18 mm 나비비만수면무호흡군의 87.17 ± 7.23 mm 보다통계적으로유의하게길었다. 설골 (hyoid bone) 의위치와관련된항목들은모두유의한차이를보였는데, MP-Hyoid 나 C3-Hyoid 에서비만수면무호흡군의설골 (24.59 ± 5.65 mm, 47.59 ± 4.32 mm) 이비비만단순코골이군 (18.50 ± 5.68 mm, 42.78 ± 2.58 mm) 이나비비만수면무호흡군 (19.50 ± 3.72 mm, 43.63 ± 4.26 mm) 보다전하방으로위치함을확인할수있었다. 측모두부방사선계측치들과수면무호흡지수 (AHI) 와의상관관계수면무호흡환자들의수면무호흡지수 (AHI) 와상관관계가큰측모두부방사선계측치들을알아내기위하여 Pearson correlation analysis 를시행한결과연조직계측치들중에서상기도폭경인 Nph1, 하기도폭경인 Oph2 와 PAS, 혀길이 (tongue length) 와유의한상관관계가있었고, 설골 (hyoid bone) 의위치를나타내는항목들 (MP-Hyoid, C3-Hyoid) 도모두수면무호흡지수 (AHI) 와유의한상관관계를보였다 (Table 4). 수면무호흡군중에서비비만군과비만군을나누어비교하였을때, 비비만수면무호흡군에서는 C3- Hyoid ( 0.604) 만이수면무호흡지수 (AHI) 와유의한상관관계가있었고, 비만수면무호흡군에서는 Nph1 ( 0.368), tongue length (0.470), C3-Hyoid (0.437) 가유의한상관관계가있었다. 수면무호흡지수 (AHI) 와관련인자확인을위한다중회귀분석각계측항목중수면무호흡지수 (AHI) 에가장큰영향을미치는인자를확인하기위하여수면무호흡군에다중회귀분석 (stepwise multiple regression test) 을시행한결과상기도폭경 (Nph1), 혀길이 (tongue length), 하악각 (Mn plane angle) 등의항목이통계적으로유의한결과를보여주었다 (Table 5). 수면무호흡군을다시비비만군과비만군으로나누어각각다중회귀분석을시행한결과, 비만군에서는혀길이 (tongue length) 가비비만군에서는 C3-Hyoid 가유의한것으로나타났다. 고찰 전반적인생활수준이높아지면서양질의수면에대한사회적관심이높아지고있는가운데, 최근에중장년층이상에서확진이증가되고있는폐쇄성수면무호흡증은야간수면다원검사가필수적인표준진단법 9 이지만, 검사비용이비싸고, 시공간적제약이크며, 전문인력에의해서만수행이가능하다는점에서제약이있다. 따라서단순히폐쇄성수면무호흡증이의심되는환자들을대상으로야간수면다원검사를무차별적으로시행하는것보다는폐쇄성수면무호흡증이확실시되는환자들에게우선적으로실시하는것이바람직한데, 이를위해서는폐쇄성수면무호흡증의예측인자에대한평가가선행되어야하겠다. 여러가지임상증상들과함께치과에서보다손쉽게촬영가능한측모두부방사선계측 Table 5. Stepwise multiple regression model for AHI (apnea-hypopnea index) in OSA patients according to obesity Group R 2 Selected variables Total 0.430 Beta SE p value Tongue length (mm) 1.283 0.383 0.002 Nph1 (mm) 2.047 0.792 0.013 Mn plane angle ( ) 1.167 0.479 0.019 Obese 0.221 Tongue length (mm) 1.656 0.568 0.007 Non-obese 0.365 C3-Hyoid (mm) 1.071 0.447 0.038 1, Regression equation (Total), AHI = 5.562 + 1.283 (Tongue length) 2.047 (Nph1) 1.167 (Mn plane angle); 2, Regression equation (Obese), AHI = 111.336 + 1.656 (Tongue length); 3, Regression equation (Non-obese), AHI = 67.886 1.071 (C3-Hyoid). 208
Vol. 38, No. 3, 2008. Korean J Orthod 한국인성인남성폐쇄성수면무호흡환자의측모두부방사선계측학적비교 사진분석을통해예측인자들을찾아내고예측항목들의관련성이높은환자들을대상으로야간수면다원검사를시행한다면환자들의불필요한부담도줄일수있고폐쇄성수면무호흡증의보다정확한진단과원인규명및치료결과수립에도움이될것이다. 본연구에서는인종 20-22 이나성별 19 의차이를배제하기위해한국인성인남성만을대상으로체질량지수 25 를기준 28 으로비비만군과비만군으로분류하여비교한결과각군간의평균연령차이도없었고, 87 명의환자들이적당한비율로각군으로나뉘어져서로비교대상으로삼기에충분한조건이었다 (Table 2). Li 등 21 에의하면백인에비해아시아인폐쇄성수면무호흡환자들은상하악골의돌출, 좁은두개저의각도, 더큰후기도폭경, 보다상방에위치한설골등의특징이있다고하였으나, 본연구결과에서는상하악골의돌출도나두개저의각도, 후기도폭경등의항목에서수면무호흡군과단순코골이군사이에유의한차이가없는것으로나타났고, 혀길이나설골의위치는서로유의하게차이가나는것으로조사되었다 (Table 3). 이러한차이는같은수면무호흡군내에서도비비만군과비만군을서로나누어비교할때더욱명확하게나타난다. 비비만수면무호흡군이비만수면무호흡군환자들에비해하악각이더크며비록통계적으로유의하지는않았지만전체적으로하악골이시계방향으로회전하는골격성 II 급부정교합의특징을보여주고있어서비만한수면무호흡환자들보다하안면부의골격성불균형이더크다는것을알수있었다. 이는비만도가낮은수면무호흡환자들은하악이후퇴되어있고, 하악각이큰반면, 비만도가높은수면무호흡환자들은설골의위치가낮고혀가크며연조직이더두껍다는 Tsuchiya 등 30 의연구와유사한결과로, 비만단순코골이군보다비만수면무호흡군의연구개두께가더두껍고비만수면무호흡군의혀길이가비비만단순코골이군이나비비만수면무호흡군보다긴것으로나타나비만과기도주위연조직의지방축적이수면무호흡에상당한영향을미친다는것을확인할수있었다. 이런추측은비만한폐쇄성수면무호흡환자의기도주변과혀에지방조직침착이증가됨을확인한 Horner 등 23 의 MRI 연구로뒷받침될수있다. 반면, 단순코골이군내에서는비비만단순코골이군이나비만단순코골이군사이에통계적으로유의한차이가나는계측치가없어서비만 도에의한영향이수면무호흡군에서만큼크지않은것으로추측된다. 기존의연구결과들과일치하게 14,18,29,31,32 본연구에서도비만수면무호흡환자의설골이비비만단순코골이군이나비비만수면무호흡군보다전하방으로위치하였는데, Oph2나 PAS 같은하기도폭경의큰차이가없음에도불구하고비비만수면무호흡군에비해비만수면무호흡군의혀길이가더길고설골의위치가보다전하방으로위치하는것은큰혀와기도주변연조직의지방침착등으로설골이전하방으로밀려나게된결과로추측해볼수있다. 14,32 한편, deberry-borowiecki 등 16 에의하면, 하방에위치하게된설골은혀의기저부를더욱하방으로재위치시키게되어하인두부위의기도폐쇄가더쉽게올수있다고한다. 수면무호흡지수와상관관계가큰계측치들을살펴본결과 (Tables 4 and 5) 에서는혀길이가길수록, 상기도폭경이좁을수록, 하악각이작을수록수면무호흡의정도가심해지는것을확인할수있었는데이것은지금까지의여러연구들과도일치하는양상 33 이었지만비비만수면무호흡군과비만수면무호흡군으로나누어비교시에는서로조금다른양상을보였다. 비만수면무호흡군에서는설골의위치가전방으로위치할수록수면무호흡지수가높아졌는데, 이는긴혀길이와기도주변의지방조직침착등이수면무호흡의원인이었음을추측가능하게한다. 반면, 비비만수면무호흡군에서는설골의위치가후방에위치할수록수면무호흡지수가커지는것으로나타났다. 비록통계적으로유의하지는않았지만하기도폭경인 Oph1, Oph2, PAS 항목에서비비만수면무호흡군의계측치가제일작았다는사실은 (Table 3), 비만하지않은수면무호흡환자에서는지방조직의침착보다하악의후퇴위나기도구조자체의폭경감소같은골격성불균형이수면무호흡에더큰영향을미친다고추측하는근거가될수있을것이다. 그러나본연구에서비비만수면무호흡환자의수가다소적었고, 개개의환자들에게서기도의폐쇄부위는다양한형태로관찰될수있으며, 한환자에게서도동시에여러부위의기도가좁아질수있기 34 때문에, Finkelstein 등 35 이지적한것처럼측면과다른방향에서의방사선학적계측을보완하여보다다수를상대로한기도부위의전후적폭경및좌우적폭경도고려하는연구가앞으로더필요하다고생각한다. 특히, 서양인연구결과들과다른양상을보이는한국인환자들에게서이런입체적검사는더욱중요하다고볼수있겠다. 209
황상희, 박인숙, 남기영, 김종배, 조용원, 서영성, 안병훈, 박신구, 박효상 대치교정지 38 권 3 호, 2008 년 또한, 본연구는서있는자세로깨어있는상태에서촬영하였기때문에누운자세로수면중에발생하는환자의상기도를그대로반영한다고보기는힘들다. 그러나, Pracharktam 등 36 은앉은자세와누운자세에서의두부방사선사진을비교한결과근육긴장도로인하여두군간의계측값에는차이가없었다고보고하였다. 따라서편안하게선자세로두부방사선사진을촬영하여도누운자세와비슷한값을보이고, 개인마다차이가심한수면중의자세를정확히재현하기힘들기때문에연구의용이성을고려하여이번연구에서는선자세로측모두부방사선사진을촬영하였지만, 앞으로이에대한보완연구가필요할것으로생각한다. 본연구결과에서나타난것처럼, 단순히폐쇄성수면무호흡군과단순코골이군으로나누지않고, 체질량지수 25 이상의비만한수면무호흡환자들과비만하지않은수면무호흡환자들을구분하여비교시각종측모두부방사선계측학적특성들이다르게나타날수있으므로앞으로서양인뿐만아니라동양인에서도수면무호흡환자들의진단시비만도에따른분류는반드시고려되어야할점이다. 또한, Kong 등 37 에의하면, 한국인폐쇄성수면무호흡환자들에게서도 40 cm 이상의굵은목둘레와큰허리- 엉덩이둘레비가독립적으로유의한예측인자이므로, 앞으로단순히키와몸무게에따른비만도뿐만아니라수면무호흡이일어나는부위와보다밀접한관련이있는목둘레등의계측치도함께측정하여고려한다면보다정확한예측인자파악이가능할것으로생각한다. 비만한수면무호흡환자와비만하지않은수면무호흡환자의측모두부방사선계측학적특징들과기여인자들이다르다는것은이들의치료방법도서로다르게접근해야한다는것을의미한다. 14,32 체중이증가한폐쇄성수면무호흡환자들은하악을전방으로위치시키는구강내장치물의치료가성공적이지못했다는후향적보고 38 도있는만큼, 치료방법선택시에도비만도는우선고려사항이되어야할것이다. 비만한폐쇄성수면무호흡환자들에게는일단행동조절을통한체중감량이먼저권고되어야하며, 이와병행하여상기도부위가협소한것이주된문제라면경비적양압공급치 (nasal continuous positive airway pressure, nasal CPAP) 39 등이적용될수있고, 연구개조직이두껍고구개후방부에서주된폐쇄가일어난다면인두부수술 ( 구개수구개인두부성형술 : uvulopalatopharyngoplasty, UPPP) 40 을시행 할수있는반면, 설근후방부의기도가폐쇄되어있는경우에는수술에대한효과가그다지크지않으므로하악을전방으로이동시켜기도확장의효과를볼수있는구강내장치물 41 등이대신선택될수있을것이다. 본연구에서도 12 명의비비만수면무호흡환자들중 7 명에게는구개수구개인두부성형술을, 3 명에게는경비적양압공급치료를, 1 명에게는구강내장치물치료를추천하여좋은치료결과를얻었다. 향후폐쇄성수면무호흡환자의진단시단순히측모두부방사선계측사진분석뿐만아니라환자의비만도나목둘레굵기등도함께고려한다면, 폐쇄성수면무호흡환자들의특성과병인을보다정확하게파악하게될뿐만아니라그에따른보다적절한치료방법의선택도가능하게되어환자들에게더큰도움을줄수있을것으로기대된다. 결론 비만도에따른한국인남성폐쇄성수면무호흡환자의측모두부방사선계측학적특성을파악하기위하여계명대학교의과대학동산의료원수면클리닉에수면장애를주소로내원하여수면다원검사후치과에서측모두부방사선계측사진촬영을한 87 명의성인환자들을체질량지수 (BMI) 와수면무호흡지수 (AHI) 에따라비비만단순코골이군, 비만단순코골이군, 비비만수면무호흡군, 비만수면무호흡군의 4 군으로나누어비교하여다음과같은결과를얻었다. 1. 비만수면무호흡군의수면무호흡지수가가장컸다. 2. 비비만수면무호흡군보다비만수면무호흡군의설골이유의하게더전하방에위치하였다 (p < 0.05). 3. 수면무호흡지수에영향을미치는기여인자는비만수면무호흡군에서는혀길이, 비비만수면무호흡군에서는설골의후방위치였다. 이처럼비만수면무호흡환자와비비만수면무호흡환자의측모두부방사선계측학적특성과기여인자가다르게나타나므로, 치료방법도따라서다르게선택해야할것이다. 비만수면무호흡환자들에게는먼저체중감량이권고되어야할것이고, 비비만수면무호흡환자들은폐쇄부위에따라구강 210
Vol. 38, No. 3, 2008. Korean J Orthod 한국인성인남성폐쇄성수면무호흡환자의측모두부방사선계측학적비교 내장치나 Nasal CPAP, UPPP 등이추천될수있을것이다. 참고문헌 1. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes. Annu Rev Med 1976;27:465-84. 2. American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999;22:667-89. 3. Hoffstein V, Mateika S. Differences in abdominal and neck circumferences in patients with and without obstructive sleep apnoea. Eur Respir J 1992;5:377-81. 4. Schmidt-Nowara W, Lowe A, Wiegand L, Cartwright R, Perez-Guerra F, Menn S. Oral appliances for the treatment of snoring and obstructive sleep apnea: a review. Sleep 1995;18: 501-10. 5. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middleaged adults. N Engl J Med 1993;328:1230-5. 6. Kripke DF, Ancoli-Israel S, Klauber MR, Wingard DL, Mason WJ, Mullaney DJ. Prevalence of sleep-disordered breathing in ages 40-64 years: a population-based survey. Sleep 1997;20: 65-76. 7. Bixler EO, Vgontzas AN, Lin HM, Ten Have T, Rein J, Vela-Bueno A, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001;163:608-13. 8. Kim J, In K, Kim J, You S, Kang K, Shim J, et al. Prevalence of sleep-disordered breathing in middle-aged Korean men and women. Am J Respir Crit Care Med 2004;170:1108-13. 9. Practice parameters for the indications for polysomnography and related procedures. Polysomnography task force, American sleep disorders association standards of practice committee. Sleep 1997;20:406-22. 10. Haraldsson PO, Carenfelt C, Diderichsen F, Nygren A, Tingvall C. Clinical Symptoms of sleep apnea syndrome and automobile accidents. ORL J Otorhinolaryngol Relat Spec 1990;52:57-62. 11. George CF, Smiley A. Sleep apnea & automobile crashes. Sleep 1999;22:790-5. 12. Parish JM, Somers VK. Obstructive sleep apnea and cardiovascular disease. Mayo Clin Proc 2004;79:1036-46. 13. Riley R, Guilleminault C, Herran J, Powell N. Cephalometric analysis and flow-volume loops in obstructive sleep apnea patients. Sleep 1983;6:303-11. 14. Tangugsorn V, Krogstad O, Espeland L, Lyberg T. Obstructive sleep apnea: a canonical correlation of cephalometric and selected demographic variables in obese and nonobese patients. Angle Orthod 2001;71:23-35. 15. Ono T, Lowe AA, Ferguson KA, Fleetham JA. Associations among upper airway structure, body position, and obesity in skeletal Class I male patients with obstructive sleep apnea. Am J Orthod Dentofacial Orthop 1996;109:625-34. 16. deberry-borowiecki B, Kukwa A, Blanks RH. Cephalometric analysis for diagnosis and treatment of obstructive sleep apnea. Laryngoscope 1988;98:226-34. 17. Partinen M, Guilleminault C, Quera-Salva MA, Jamieson A. Obstructive sleep apnea and cephalometric roentgenograms. The role of anatomic upper airway abnormalities in the definition of abnormal breathing during sleep. Chest 1988;93: 1199-205. 18. Baik UB, Suzuki M, Ikeda K, Sugawara J, Mitani H. Relationship between cephalometric characteristics and obstructive sites in obstructive sleep apnea syndrome. Angle Orthod 2002;72:124-34. 19. Guilleminault C, Quera-Salva MA, Partinen M, Jamieson A. Women and the obstructive sleep apnea syndrome. Chest 1988;93:104-9. 20. Ong KC, Clerk AA. Comparison of the severity of sleep disordered breathing in Asian and Caucasian patients seen at a sleep disorders center. Respir Med 1998;92:843-8. 21. Li KK, Powell NB, Kushida C, Riley RW, Adornato B, Guilleminault C. A comparison of Asian and white patients with obstructive sleep apnea syndrome. Laryngoscope 1999; 109:1937-40. 22. Liu Y, Lowe AA, Zeng X, Fu M, Fleetham JA. Cephalometric comparisons between Chinese and Caucasian patients with obstructive sleep apnea. Am J Orthod Dentofacial Orthop 2000; 117:479-85. 23. Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED, Longmore DB, et al. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls. Eur Respir J 1989;2:613-22. 24. Davies RJ, Stradling JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apnoea syndrome. Eur Respir J 1990;3:509-14. 25. Deegan PC, McNicholas WT. Predictive value of clinical features for the obstructive sleep apnea syndrome. Eur Respir J 1996;9:117-24. 26. Rubinstein I, Colapinto N, Rotstein LE, Brown IG, Hoffstein V. Improvement in upper airway function after weight loss in patients with obstructive sleep apnea. Am Rev Respir Dis 1988;138:1192-5. 27. Schwartz AR, Gold AR, Schubert N, Stryzak A, Wise RA, Permutt S, et al. Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. Am Rev Respir Dis 1991;144:494-8. 28. World Health Organization Western Pacific Region, International Association for the Study of Obesity, and International Obesity Task Force. The Asian-Pacific perspective: redefining obesity and its treatment. Geneva, Switzerland: WHO Western Pacific Region;2000. 29. Li KK, Kushida C, Powell NB, Riley RW, Guilleminault C. Obstructive sleep apnea syndrome: a comparison between Far-East Asian and white men. Laryngoscope 2000;110: 1689-93. 30. Tsuchiya M, Lowe AA, Pae EK, Fleetham JA. Obstructive sleep apnea subtypes by cluster analysis. Am J Orthod Dentofacial Orthop 1992;101:533-42. 31. Hui DS, Ko FW, Chu AS, Fok JP, Chan MC, Li TS, et al. Cephalometric assessment of craniofacial morphology in Chinese patients with obstructive sleep apnoea. Respir Med 211
황상희, 박인숙, 남기영, 김종배, 조용원, 서영성, 안병훈, 박신구, 박효상 대치교정지 38 권 3 호, 2008 년 2003;97:640-6. 32. Yu X, Fujimoto K, Urushibata K, Matsuzawa Y, Kubo K. Cephalometric analysis in obese and nonobese patients with obstructive sleep apnea syndrome. Chest 2003;124:212-8. 33. Miles PG, Vig PS, Weyant RJ, Forrest TD, Rockette HE Jr. Craniofacial structure and obstructive sleep apnea syndrome-a qualitative analysis and meta-analysis of the literature. Am J Orthod Dentofacial Orthop 1996;109:163-72. 34. Wilms D, Popovich J, Conway W, Fujita S, Zorick F. Anatomic abnormalities in obstructive sleep apnea. Ann Otol Rhinol Laryngol 1982;91:595-6. 35. Finkelstein Y, Wexler D, Horowitz E, Berger G, Nachmani A, Shapiro-Feinberg M, et al. Frontal and lateral cephalometry in patients with sleep-disordered breathing. Laryngoscope 2001; 111:634-41. 36. Pracharktam N, Hans MG, Strohl KP, Redline S. Upright and supine cephalometric evaluation of obstructive sleep apnea syndrome and snoring subjects. Angle Orthod 1994:64:63-73. 37. Kong HW, Lee HJ, Choi YS, Rha JH, Ha CK, Hwangc DU, et al. Clinical predictors of obstructive sleep apnea. J Korean Neurol Assoc 2005;23:324-9. 38. Otsuka R, Almeida FR, Lowe AA, Ryan F. A comparison of responders and nonresponders to oral appliance therapy for the treatment of obstructive sleep apnea. Am J Orthod Dentofacial Orthop 2006;129:222-9. 39. Littner M, Hirshkowitz M, Davila D, Anderson WM, Kushida CA, Woodson BT, et al. Practice parameters for the use of auto-titrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome. An American Academy of Sleep Medicine report. Sleep 2002;25:143-7. 40. Fujita S, Conway W, Zorick F, Roth T. Surgical correction of anatomic abnormalities in obstructive sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981; 89:923-34. 41. American Sleep Disorders Association. Practice parameters for the treatment of snoring and obstructive sleep apnea with oral appliances. American Sleep Disorders Association. Sleep 1995; 18:511-3. 212
ORIGINAL ARTICLE Cephalometric differences in obstructive sleep apnea between obese and non-obese Korean male patients Sang-Hee Hwang, DDS, MSD, PhD, a In-Suk Park, DDS, MSD, b Ki-Young Nam, DDS, MSD, PhD, a Jong-Bae Kim, DDS, MSD, PhD, c Yong-Won Cho, MD, MSc, PhD, d Young-Sung Suh, MD, MSc, PhD, e Byung-Hoon Ahn, MD, MSc, PhD, f Shin-Goo Park, MD, MSc, PhD, g Hyo-Sang Park, DDS, MSD, PhD h Objective: The purpose of this study was to compare the cephalometric measurements of obese and non-obese Korean male patients with obstructive sleep apnea syndrome (OSA). Methods: Eighty-seven adults who had visited the Sleep Disorder Clinic Center in Keimyung University, Daegu, Korea were examined and evaluated with polysomnography (PSG) and lateral cephalogram. They were divided into 4 groups (non-obese simple snorers, obese simple snorers, non-obese OSA patients, obese OSA patients) according to AHI (Apnea-Hypopnea Index) and BMI (Body Mass Index). Results: The obese OSA group had the highest AHI among the 4 groups. The non-obese OSA group had a significantly steeper mandibular angle and shorter tongue length than the obese OSA group. The hyoid bone of the obese OSA group was positioned anterior and inferior as compared with the non-obese OSA group. Multiple regression analysis showed that tongue length in the obese OSA group and retroposition of hyoid bone in the non-obese OSA group were significant determinants for the severity of AHI. Conclusions: From a cephalometric point of view, the obese and non-obese pateints with OSA may be characterized by different pathogeneses. Therefore, they have to be managed by individualized treatment. For the obese OSA patients, weight control must be advised as a first choice and for the non-obese OSA patients, oral appliance, nasal CPAP, UPPP and others could be chosen according to the obstructive sites. (Korean J Orthod 2008;38(3):202-213) Key words: BMI, OSA, Lateral cephalogram, Individualized treatment a Assistant Professor, b Clinical Full Time Lecturer, c Professor, Department of Dentistry, College of Medicine, Keimyung University. d Associate Professor, Department of Neurology, College of Medicine, Keimyung University. e Associate Professor, Department of Family Medicine, College of Medicine, Keimyung University. f Associate Professor, Department of Otolaryngology, College of Medicine, Keimyung University. g Assistant Professor, Department of Occupational & Environmental Medicine, College of Medicine, Inha University. h Associate Professor, Department of Orthodontics, College of Dentistry, Kyungpook National University. Corresponding author: Sang-Hee Hwang. Department of Dentistry, Dong-San Medical Center, College of Medicine, Keimyung University, 194, Dongsan-dong, Jung-gu, Daegu 700-712, Korea. +82 53 250 7803; e-mail, hsh99@dsmc.or.kr. Received March 13, 2007; Last Revision June 20, 2007; Accepted June 22, 2007. 213