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1 대한내과학회지 : 제 78 권제 2 호 2010 특집 (Special Review) - 상부소화관운동질환의최신지견 위식도역류질환의진단 : 식도및식도외증상들 부산대학교의학전문대학원내과학교실 이봉은 김광하 Diagnosis of gastroesophageal reflux disease: Esophageal and extraesophageal manifestations Bong Eun Lee, M.D., and Gwang Ha Kim, M.D. Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea The manifestations of gastroesophageal reflux disease (GERD) have been classified into either esophageal or extraesophageal symptoms. Esophageal manifestations include classic symptoms of reflux, such as heartburn and regurgitation, and atypical noncardiac chest pain. Laryngitis, chronic cough, hoarseness, asthma or dental erosion are classified as extraesophageal symptoms, and they have a common pathophysiology, including microaspiration of gastric content into the larynx and pharynx, and vagally mediated bronchospasm and laryngospasm. In extraesophageal GERD, patients usually do not display the classic symptoms, so it is difficult to confirm the diagnosis of GERD. Endoscopy and ph monitoring have proved to have poor sensitivity and therefore are often not diagnostically helpful. Recently, anti-secretory therapy by proton pump inhibitor (PPI) is thought to be well-established, cost-effective tool and it is broadly used as both a diagnostic trial and as a therapeutic management. Diagnostic testing, such as ph monitoring, may be useful in those with partial or poor response to the initial treatment with PPI. (Korean J Med 78: , 2010) Key Words: Gastroesophageal reflux disease; Esophageal manifestation; Extraesophageal manifestation 서론위식도역류질환은최근몬트리올합의에따르면위내용물이식도내로역류하여일상생활에지장을주는증상을발생시키거나합병증을유발한경우로정의되고있다 1). 대부분의환자가의사를찾기까지는수년의세월이걸리고, 증상의호전과악화가반복되면서자연적으로는좋아지지않는만성경과를보여다른어떤질환보다도삶의질을저하시키는질환으로알려져있다 2,3). 아직서구에비해서는빈도가적은편이지만최근국내에서도위식도역류질환에대한관심이증가하고있으며, 여러연구에서이질환의유병률이증가됨이보고되고있다 4,5). 위식도역류질환의진단검사법으로우리나라에서는내시경이우선적으로많이사용 되고있지만환자들중절반이상이내시경검사에서식도염이없기때문에역류증상에대한자세한병력청취가진단에중요한단서가될수있다. 본글에서는위식도역류질환에서나타날수있는다양한증상을식도및식도외증상으로구분하여임상적인면을중심으로알아보고 ( 그림 1), 특히최근에관심이증가되고있는식도외증상에대해서는기전과진단적접근을포함해서좀더자세히기술하고자한다. 식도증상과징후위식도역류질환의전형적인식도증상으로는흉부작열감 (heartburn) 과역류증상 (regurgitation) 을들수있다. 흉부작열

2 - The Korean Journal of Medicine: Vol. 78, No. 2, Figure 1. The Montreal definition of gastroesophageal reflux disease and its constituent syndromes. 감은흉골뒤쪽가슴이타는듯한증상으로검상돌기에서목으로전파되며, 과식을하거나맵고지방을많이포함한음식, 초콜릿, 술과같은특정한음식을섭취한후에주로유발된다 6). 이러한증상은눕거나앞으로구부리면심해지고, 야간에발생하는흉부작열감 (nighttime heartburn) 은수면장애를일으켜다음날활동에지장을주기도한다 7). 일반적으로식후 30분에서 2시간에나타나 10분이상지속되고, 한번에수시간씩지속되지는않으며, 흉부작열감이경한경우는제산제나우유를마신후수분이내에증상이소실되기도한다. 미란성식도염이있는환자에서의흉부작열감은역류된위내용물이손상된식도점막에접촉하면서점막의통각수용체 (nociceptor) 를자극하여유발되는것으로알려져있지만, 비미란성식도염환자에서흉부작열감이일어나는기전은내장과민성 (esophageal visceral hypersensitivity), 식도수축의지속 (sustained esophageal contraction), 비정상적조직저항성 (abnormal tissue resistance) 으로추정된다 8). 우리나라에서는흉부작열감에해당하는적절한표현이없어가슴앓이, 가슴쓰림정도로표현되고있으며, 환자들마다호소하는증상의표현에차이가있어세심한병력청취가중요하고, 또한환자와의의사소통에주의가필요하다. 역류증상은위액이나위내용물이식도로역류하는현상을말하며내용물에따라짠맛, 신맛또는쓴맛을호소하는데, 대개다량의음식을먹은뒤또는누운자세에서많이일어난다. 역류증상은식후수분에서한시간사이에복근의수축이나위원위부의운동이상에기인되는되새김 (rumination) 과는구분되어야한다. 매일역류증상을호소하는환자들은대개하부식도괄약근압력이낮고, 위마비 (gastroparesis) 를동반하며내시경적식도염이흔해서전형적인흉부작열감을호소하는환자와비교하였을때그치료가어려운것으로알려져있 다 9). 이러한전형적인증상의빈도및강도는식도점막손상의정도와는일치하지않는데, 이는환자마다식도점막의감수성이다르기때문으로생각된다 10). 식도점막의감수성이증가하는조건으로는젊은연령, 여자, 스트레스등이있으며, 바렛식도환자는증상이없거나적은것으로보고되고있다 11). 흉부작열감또는역류증상이주 1회이상인경우를위식도역류질환의기준으로하였을때그유병률은서양에서는 10~20%, 아시아에서는 5% 미만정도로보고되고있다 12). 우리나라에서도최근에유병률에관한보고가많으며, 신뢰도가검증된설문지를이용하여건강검진자를대상으로한조사에서는주 1회이상의흉부작열감이나역류증상을경험하는유병률을 8.5%, 지역사회를대상으로한조사에서는 2.7% 로보고하였다 13,14). 위식도역류질환을진단하는데있어흉부작열감이나역류증상의평가가중요한것은분명하나, 그임상적정확도 (clinical accuracy) 를규정하기는어렵다. 최근한문헌고찰에서는내시경적식도염이있었던환자들의 30~76% 만이전형적인역류증상을호소하여, 진단적예민도가비교적낮다고하였다 15). 이는비전형적인역류증상을보이거나무증상의위식도역류질환환자에대한적절한진단적접근이필요함을의미한다. 내시경검사는위식도역류질환의진단에있어특이도는 90~95% 로높지만예민도가 50% 로낮기때문에서양에서는경고증상이있는환자에게우선적으로시행하도록권고되고있으며, 24시간보행성식도산도검사가병적인역류를진단하는데가장유용한검사법이긴하나내시경적식도염이없는환자에서는그특이도가 85~90%, 예민도가 60% 로식도염이있는환자에비해그진단적유용성이떨어진다 16-18). 양자펌프억제제 (proton pump inhibitor, PPI) 검사법은예민도가 78%, 특이도가 54%

3 - Bong Eun Lee, et al. Diagnosis of gastroesophageal reflux disease: Esophageal and extraesophageal manifestations - 이지만, 비교적간단하고부작용없이쉽게시행할수있다는점에서유용하게사용되는검사법이다 19). 흉부작열감과역류증상외식도증상으로는비심인성흉통 (noncardiac chest pain) 이있으며, 이는위식도역류질환의비전형적인증상으로분류된다 20,21). 협심증과유사한흉골하통증이반복되지만, 심장에기인한경우가아닐때를비심인성흉통으로정의하며, 비심인성흉통을유발할수있는여러가지원인질환중위식도역류질환이가장흔한것으로알려져있다 20-22). 과거한때식도의운동성질환이식도에서기인하는비심인성흉통의주된원인으로이해되었으나, 최근에는비심인성흉통환자에서시행한 24시간보행성식도산도검사결과 50~60% 에서비정상적인위식도역류가있으며, 이러한환자에서위산억제제투여에의해흉통이호전됨이알려지면서위식도역류질환이비심인성흉통의가장흔한원인으로확립되었다 21-24). 위식도역류질환이흉통을유발하는기전에대해서는잘알려져있지는않지만, Balaban 등은산역류로인한식도종주근의수축에의해흉통이유발될수있다고제시하였다 25). 심장과식도가같은발생학적기원을가지므로식도에의한통증과심장에의한통증이명확히구별되지못하는것은당연한면이있지만다음과같은몇가지차이로구별해볼수있다. 위식도역류에의한흉통은협심증에서처럼쥐어짜는듯한또는흉골아래의타는듯한통증으로등이나팔로전파되기도한다. 그러나식사후특히누운자세에서통증이악화되고통증때문에잠에서깨기도하며, 스트레스로인해서증상이심해질수있다. 또한통증의지속시간은수시간또는수일까지지속되기도하고, 음식이나제산제에의해서완화된다는차이가있다. 하지만증상만으로두질환을감별하는것은다소어려운점이있다. 실제로관상동맥질환을가지고있는환자의약 50% 에서적어도한가지이상의식도질환의증세를보일수있으며, 운동량이증가함에따라흉통이심해지면협심증의가능성이높지만몸을앞으로웅크린채격한운동을하면위식도역류가조장되어흉통이발생하기도하고이러한경우에설하 nitrate 투여로흉통이완화될수있어협심증과의감별이더욱어려워진다 24,26). 누운자세에서증세가발생하면위식도역류에의한통증일가능성이크지만드물게는협심증도누운자세에서유발될수있으며, 또한위산의역류가미주신경을자극하여관상동맥의경련을일으킨다는보고도있다. 이러한여러가지이유로두질환을감별하는데많은어려움이따르며실제로흉통이발생한환자에서는우선적으로심장에대한 검사를시행하는것이추천된다. 여러가지검사로심인성흉통의가능성이배제된후에는통증의양상에대한병력청취와신체검진을통해서흉통을유발할수있는상부위장관질환, 담도질환, 흉벽질환및폐질환을감별해야한다. 미란성식도염및바렛식도는위식도역류에의한비심인성흉통환자에서 10% 미만에서동반되는것으로보고되어, 내시경검사의비용- 효과적유용성은떨어지지만삼킴곤란이나삼킴통증과같은경고증상이있는경우는위내시경검사가선행되어야겠다 21). 24시간보행성식도산도검사는비정상적인위식도역류를진단하는가장유용한검사법이지만, 검사중에흉통이기록되는경우가적고검사에대한환자의인지부족으로증상지수 (symptom index) 를통한위식도역류와의연관성을증명하는것이쉽지가않다 27). 또한고가이면서침습적인검사법으로널리사용하는데에는한계가있겠다. 최근에는비심인성흉통환자에서고용량의 PPI를단기간투여하는 PPI 검사법이 69~95% 의민감도와 67~86% 의특이도를보이면서, 무엇보다도간단하고부작용이거의없다는점에서또한비용- 효과적인면에서가장유용한진단방법으로제시되고있다 28,29). 식도외증상과징후 Minnesota에거주하는인구를대상으로시행한한조사에서는주 1회이상의가슴쓰림을호소하는위식도역류질환환자들의 80% 에서비전형적인식도외증상이동반됨을보고하였고, 유럽의한전향적연구에서는미란성식도염환자의 32.8%, 비미란성식도염환자의 30.5% 에서비전형적증상을호소함을보고하였다 30,31). 거꾸로비전형적인증상을호소하는환자의 50~60% 가위식도역류와연관된것으로알려져있는데, 이환자들의대부분은가슴쓰림이나역류와같은전형적증상을가지고있지않으면서, 전형적인증상을가지는환자들에비해내시경적식도염의빈도가 10~30% 로낮아진단에주의를기울여야할것으로생각된다 32-34). 임상에서위식도역류질환을의심해야하는식도외증상으로는쉰목소리 (hoarseness), 인두구 (globus pharyngeus), 잦은목청소 (throat clearing) 와같은이비인후과증상이있으며, 호흡기증상으로는기관지천식 (bronchial asthma) 과만성기침등이있다 33,35-38). 이비인후과검사에서위식도역류질환과관련하여후인두역류 (laryngopharyngeal reflux) 를시사하는후부후두염 (posterior laryngitis) 이나성대결절 (vocal nodule), 성대및피골내벽부종 (vocal fold or arytenoid edema),

4 - 대한내과학회지 : 제 78 권제 2 호통권제 594 호 Table 1. Extraesophageal manifestations of gastroesophageal reflux disease ENT Pulmonary Other Hoarseness Globus Laryngitis Sinusitis Otitis Vocal granuloma Vocal polyp Subglottic stenosis Laryngeal carcinoma Chronic cough Asthma Aspiration pneumonia Bronchiectasis Idiopathic pulmonary fibrosis Dental erosion Halitosis Sleep apnea 육아종 (granuloma), 부비동염 (sinusitis), 치아후식 (dental caries) 등이관찰될수있으며, 또한후두암 (laryngeal carcinoma), 성대문연축 (laryngospasm), 후두협착 (laryngeal stenosis) 과의연관성도보고되었다 22,39-46). 호흡기질환으로는특발성폐섬유증 (idiopathic pulmonary fibrosis), 흡인성폐렴 (aspiration pneumonia), 만성기관지염 (chronic bronchitis), 기관지확장증 (bronchiectasis) 이위식도역류질환과연관성이있는것으로알려져있다 47-49). 우리나라 3차의료기관에서진단된위식도역류질환환자들을대상으로하였던한연구는쉰목소리 (55%), 인두구 (45%), 만성기침 (25%), 비심인성흉통 (20%) 등의순으로비전형적인증상이있었음을보고하였고, 많은환자들에서한가지이상의증상을같이호소하였다 50). 지금부터위식도역류질환의각각의식도외증상과징후및기전을알아보고, 진단적접근에대해좀더자세히살펴보고자한다 ( 표 1, 2). 1. 호흡기증상 1) 만성기침만성기침은보고마다약간의차이는있지만대개 3주이상지속되는기침을말하며, 그빈도는성인비흡연자들중 14~23% 로보고되고있다 51,52). 안지오텐신전환효소억제제 (angiotensin converting enzyme inhibitor) 를복용하지않으면서정상흉부방사선소견을보이는비흡연자에서만성기침의원인으로기침이형천식, 후비루 (postnasal drip), 위식도역류, 만성기관지염이 90% 이상을차지하는것으로알려져있으며, 일반적으로위식도역류는기침이형천식과후비루에이어만성기침의세번째로가장흔한원인이다 53,54). 이러한세질환에의한만성기침에서증상의특징, 증상발생시간및합병증의정도는차이가없다고알려져있다 55). 외국의한연구에서는위식도역류에의한만성기침의빈도 Table 2. Proposed mechanisms for extraesophageal manifestations of gastroesophageal reflux disease Direct contact with gastric contents (Reflux theory) - microaspiration of acid into the larynx and pharynx Neurally mediated reflex (Reflex theory) - vagovagal reflex triggered by distal esophageal acid reflux 를 13% 로보고하였고, 만성기침환자의 56% 에서위식도역류가기침이지속되는데있어중요한기여인자임을보고하였다 56). 위식도역류가기침을유발하는기전에대해서는여러가지가설이있다. 첫째로, 역류물이후두나기도에도달하게되면후두나기도의기침수용체를직접자극하기도하며, 미주신경을통하여하부호흡기의점액분비를촉진시킴으로써기관이나기관지의기침수용체를자극할수있다 57). 두번째로는역류된위산에의하여원위부식도의점막하수용체가자극되어기침이유발된다는식도- 기관지기침반사 (esophago-tracheobronchial cough reflex) 가있으며일반적으로이기전이가장중요하게생각되고있다 54). 위식도역류에의한기침은주로낮에서있는자세에서발생하는것으로알려져있지만, 일부환자들은밤에증상이발생하기도하며, 마른기침혹은다량의점액질가래를동반한기침이모두가능하다 57). 이외에도발성중또는식사중발생하는기침이나침대에서일어날때하는기침이위식도역류와관련이있을것으로생각되어지고있다. 환자의 40~ 75% 는가슴쓰림이나산역류와같은전형적인증상이없으며, 많은환자에서쉰목소리, 후두통, 발성장애 (dysphonia) 가동반된다 27). 다른원인의만성기침자체에의해서도위식도역류가유발될수있으며 (cough-reflux cycle), 위식도역류는다른진단이붙은환자에서기침을악화시키는인자로작용할수있다. 많은환자에서전형적인위식도역류증상이없기때문에위식도역류질환과연관된만성기침을진단하는것은어렵다. 우선자세한병력을청취하여안지오텐신전환효소억제제나흡연에의한원인을제외하여야하며, 흉부 X-선을포함하여기침을유발할만한호흡기계질환을찾기위한적절한검사를시행해야한다. 내시경검사는만성기침환자에서대부분정상소견을보이므로거의도움이되지않으며, 고용량의 PPI 검사가비교적저렴하고간단하므로우선적으로시행해볼수있겠다. 산억제치료에반응이없는환자에서는 24시간보행성식도산도검사가추천되지만기침과위식도역류의정확한인과관계를밝히기어렵고, 비산성역류를감지할수없다는단점이있으며, 일부환자에서는매

5 - 이봉은외 1 인. 위식도역류질환의진단 : 식도및식도외증상들 - 우적은양의위식도역류에의해서도식도수용체의자극을통한기침을유발할수있어 24시간보행성식도산도검사에서정상소견을보일수가있다. 상부식도괄약근상부 2 cm에서인두부 ph를측정하는방법이상부기도에도달하는위산역류를진단하는데좋은정확도를보인다는보고가있지만, 아직까지는널리사용되고있지않은검사법이다 55). 최근에는식도내임피던스를측정하는방법이시도되고있는데, 이방법은 24시간식도산도를측정하면서산역류와비산역류를구별할수있어, 검사에서역류와호흡기증상의시간적연관성만증명된다면위식도역류질환의정확한진단이가능할것으로생각되며, 또한위산분비억제제치료의효과를예측하는데도움이될것으로생각된다 58). 2) 기관지천식기관지천식은여러유발인자에의해발생할수있는만성염증성폐질환으로기관지천식을가진환자의 80% 에서병적인위식도역류가관찰된다고한다 59). 많은역학연구에서위식도역류질환과기관지천식의연관성을보고하였고, 성인에서기관지천식의중요한원인의하나로서위식도역류질환을제시하였다 60). 일부연구에서는두질환이동시에존재하여서로인과관계를가지며, 위식도역류로인해기존천식증상이악화되거나이로인한입원의위험성이커지며고용량의약물치료가필요한경우가증가할수있음을보고하였다 61,62). 이는기관지천식에의한흉곽내압력상승과반가로막교정 (hemidiaphragm rectification) 등의생리적변화로인하여항역류장벽이약화된결과로생각된다 60). 위식도역류는다음과같은두가지기전을통해서천식을야기하게된다. 첫째는위내용물의미세흡인에인해호흡상피가지속적인자극을받고여러염증매개체들이분비됨으로써기관지수축과최대날숨유량 (peak expiratory flow) 의감소가발생한다는것이다 63). 두번째기전으로는미주미주신경반사 (vagovagal reflex) 에의한기전으로, 기관기관지나무 (tracheobronchial tree) 와식도가태생학적으로동일하게앞창자 (foregut) 에서유래한다는사실과두장기모두미주신경을통하여동일한자율신경계신경분포를받는다는데그근거를두고있다 64,65). 즉, 하부식도가산에노출되면산에민감한수용체가자극되어반사작용을통해기관지수축이발생한다는것이다. 위식도역류에의한기관지천식환자는만성기침환자에서와마찬가지로가슴쓰림이나산역류와같은전형적인위식도역류질환의증상을보이지않는경우가많고내시경검 사에서도하부식도에이상소견이없는경우가대부분이므로, 실제임상에서관련성을파악하고정확한진단을이끌어내는데는어려움이있다. 임상적으로위식도역류와관련된기관지천식을의심할수있는경우는 (1) 성인에서시작된천식 (2) 천식의가족력이없는경우 (3) 천식이있기전에역류증상이선행된경우 (4) 식후에쌕쌕거림 (wheezing) 이심해질때 (5) 야간에기침이나쌕쌕거림이있을때 (6) theophylline이나 β2-길항제에의해악화되는천식의경우이다. 위식도역류로유발된천식을진단하는데경험적 PPI 검사가간단하며합병증이적고, 비침습적인검사로우선적으로사용되며, 많은연구에서도높은민감도와특이도를보고하였다 66-68). 실제로 O Connor 등은천식의유발이나악화의원인이위식도역류라고진단하는데있어 3개월간매일 omeprazole 20 mg을사용하는 PPI 검사가가장비용- 효과면에서우수하다고보고하였다 69). 위산억제치료에도불구하고증상이지속될때에는다른질병을감별하기위해서 24시간 ph 검사를시행하고, 내시경검사는삼킴곤란, 빈혈, 체중감소또는출혈등의경고증상이있을때필요하겠다 70). 진단시주의할점은위식도역류와연관된천식환자에서의쌕쌕거림증상은하부식도로의위산역류와는연관이없고상부식도로의위산역류와연관이있다는보고가있어서, 반드시두개이상의 ph 전극을가진 24시간 ph 검사를하는것이바람직할것으로생각된다 71). 3) 특발성폐섬유증특발성폐섬유증과위식도역류질환과의연관이일부연구에서제시되었다 47,72). 원인을알수없는폐섬유증환자 48 명을대상으로식도, 위, 십이지장의방사선학적검사를시행한한연구에서환자의많은수가틈새탈장 (hiatal hernia) 이나병적인위식도역류를보였으며, 조직검사에서특발성폐섬유증으로확진된 17명의환자를대상으로두채널 ph 검사를시행했을때전형적인위식도역류질환의증상을보인환자는 25% 에불과하였으나 94% 의환자에서병적인위식도역류가관찰되었다고보고하였다 47,72). 이러한결과들은위식도역류질환이특발성폐섬유증의원인이될수있으며, 위식도역류에대한치료가폐질환의자연경과를변화시킬가능성을시사하는것으로앞으로이에대한연구가필요하다. 4) 기타호흡기증상위식도역류질환과폐렴, 기관지확장증, 만성폐쇄성폐

6 - The Korean Journal of Medicine: Vol. 78, No. 2, 질환 (chronic obstructive pulmonary disease) 과의연관성이보고되고있지만이에대해서는좀더많은연구가필요할것으로생각된다 73). 2. 이비인후과증상일반적으로위식도역류질환을가진환자의 25% 에서이비인후과적증상이나이상소견을가지는것으로알려져있으며, 이비인후과에방문하는환자의약 4~10% 정도에서위식도역류질환과관련된이비인후과적증상과징후를보이는것으로추정되고있다 74). 많은이비인후과질환들이위식도역류질환과관련이있지만, 가장현저한소견은후두염으로, 후부후두염, 산후두염 (acid laryngitis), 소화성후두염 (peptic laryngitis), 그리고최근에는역류성후두염 (reflux laryngitis) 등으로다양하게불리고있다 49). 기타위식도역류에의한이비인후과질환으로는성대결절, 성대및피골내벽부종, 접촉성궤양및육아종, 후두연화증 (laryngomalacia), 성대문연축, 후두협착, 부비동염등이있다. 위식도역류질환과관련된이비인후과증상으로는쉰목소리가가장흔한데, 쉰목소리환자의 50% 이상에서 24시간 ph 검사에서이상소견을보이며, 실제로역류성후두염이있는환자의 92% 이상에서목쉼이발생하는것으로알려져있다. 그외다른증상들로인두구, 잦은목청소, 삼킴통증, 목소리변화, 성대피로, 구취등이있다 33,75). 위식도역류가이비인후과증상을유발하는기전은다른위식도역류질환의식도외증상에서와유사하다. 위산과펩신을포함한위내용물의후두부역류로인한직접적인자극으로후두조직의염증반응을일으켜증상을유발한다는기전과하부식도에서의위산역류가미주신경을매개로한반사작용을일으켜증상을유발한다는기전이있다 36). 식도-인두역류는상부식도괄약근이자율적으로이완될때, 식후트림과동반하여또는연하작용과동반하여상부식도괄약근이이완될때발생하는데, 후두의점막은정상적으로위산과접촉되지않으며타액에의하여중화될수없으므로역류된위내용물에대한방어기전이매우약하다 76,77). 그런데밤에는상부식도괄약근의압력이낮에비하여낮으며기침과타액분비와같은다른방어기전도약해지므로위내용물의인후로의역류와이에의한부종이나염증과같은손상이쉽게일어날수있어, 밤에간헐적으로발생하는식도 -인두역류 (intermittent nocturnal esophageal-pharyngeal reflux) 가역류성후두염의가장중요한인자로생각되고있다 32,43). 위식도역류질환이의심되는이비인후과증상을가진환 자에서초기검사로후두경검사를어렵지않게시행할수있다. 이때후인두역류를의심할수있는후두경소견으로후두부발적, 후두부후벽의부종, 성대결절및육아종, 성문하협착등이있으나대부분이비특이적인징후로흡연, 술, 후비루등의다른원인에의해서도관찰될수있고관찰자간의일치율도낮은것으로알려져있다 78). 한연구에서는역류점수척도 (reflux scoring scale) 를이용하여점수가 7점이상인경우후두의염증이후인두역류에의한것으로정의하였다 79). 후두경검사에서역류성후두염으로추정되는환자에서위식도역류의존재를확인하기위해현재까지가장유용한진단검사법은 24시간보행성식도산도검사이다. 그러나 30% 정도의환자에서는이상소견이없을수있으며, 정상 24시간보행성식도 ph 검사결과를보인역류성후두염환자의 23% 에서후두부에추가적인전극을부착하여검사하였을때식도- 인두역류가관찰된다는보고가있어, 인두부산도검사 (pharyngeal ph monitoring) 가후두질환이있는환자에서위식도역류와의인과관계를밝히는데가장좋은방법으로생각된다 76,80). 하지만인두의공간이식도보다넓어전극이인두의점막에접촉되지않을경우산이역류되어도측정이되지않는다거나반대로전극이건조되어인후부 ph가감소하는가음성및가양성의결과를보일수있기때문에결과의해석에주의를기울일필요가있다. 고용량의 PPI 검사의유용성에대해서는아직이견이있는상태로, 한전향적연구에서는 PPI 검사후 63% 의환자에서후두증상의호전을보였다고하나통계적유의성은없었다고보고하였는데, 이는비특이적인후두징후가역류성후두염으로과다진단되었을가능성을고려해보아야겠고, 또후두증상을보이는경우여러원인들이복합되어있는경우가많기때문에 PPI 검사시행후반응에대한효과적인예측인자를찾기어려웠기때문으로생각된다 81). 3. 치아미란이전부터치아미란과위식도역류질환과의연관성에대해서는보고가있어왔으나, 2006년위식도역류질환의 Montreal 정의와분류에 치아미란증후군 (dental erosion syndrome) 이라는용어가사용됨으로써최근에관심이증가되고있다 1). 치아미란은세균에의하지않고화학적인반응의결과로치아의구조에비가역적인손상이오는것으로정의한다 82,83). 치아미란의내재적인원인으로는폭식증 (bulimia), 되새김증후군 (rumination syndrome), 알코올중독으로인한무증상역류, 구강건조증 (xerostomia), 위식도역류

7 - Bong Eun Lee, et al. Diagnosis of gastroesophageal reflux disease: Esophageal and extraesophageal manifestations - Figure 2. Suggested approach to the patient with extraesophageal symptoms of gastroesophageal reflux disease. 질환등이있다 84). 일반인에서치아미란의빈도는 2~18% 인데비해위식도역류질환을가진환자에서치아미란의빈도는 17~68% 이며, 치아미란이있는환자에서위식도역류질환의빈도는 25~83% 로위식도역류질환이치아미란의중요한원인의하나로제시되고있다 85). 이러한치아미란은하악어금니 (mandibular molar) 부위에서가장흔히관찰되며, 내시경검사중에도자세히관찰해보면발견할수있다. 결론최근우리나라에서위식도역류질환에대한관심이증가하고있으며, 실제로이질환의국내유병률이증가하고있음이보고되어질환에대한올바른이해를통한적절한진단적접근이필요할것으로생각된다. 위식도역류질환의증상은다양한형태로나타날수있으며, 환자들중절반이상이내시경검사에서식도염이없기때문에역류증상에대한자세한병력청취가진단에중요한단서가된다. 가슴쓰림이나역류와같은전형적인증상을호소하는경우는위식도역류질환에대한진단이비교적용이하지만, 비전형적인증상을호소하거나증상이없는경우도많기때문에이에대한주의와관심이없다면임상에서진단하기가쉽지는않다. 비전형적증상을호소하는환자에서는다른질환을배제한후위식도역류질환의진단을위해내시경검사, 24시간보행성식도산도검사, PPI 검사법등이주로이용되며, 예전에는 24시간보행성식도산도검사가우선적으로추천되었지만최근에는간단하고부작용이적은 PPI 검사법이진 단및치료의목적으로많이선호되고있다 ( 그림 2). 중심단어 : 위식도역류질환 ; 식도증상 ; 식도외증상 REFERENCES 1) Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 101: , ) Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340: , ) Isolauri J, Luostarinen M, Isolauri E, Reinikainen P, Viljakka M, Keyrilainen O. Natural course of gastroesophageal reflux disease: year follow-up of 60 patients. Am J Gastroenterol 92:37-41, ) 윤영호, 강영우, 안성훈, 박승국. 최근역류성식도염의유병률변화 : 건강검진자군과소화기증상군을대상으로. 대한소화기내시경학회지 23: , ) 정성애, 정훈용, 김기락, 민영일 년대한국성인에서역류성식도염의유병률변화. 대한소화관운동학회지 7: , ) Carlsson R, Dent J, Bolling-Sternevold F, Johnsson F, Junghard O, Lauritsen K, Riley S, Lundell L. The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease. Scand J Gastroenterol 33: , ) Shaker R, Catell DO, Schoenfeld PS, Spechler SJ. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Asso

8 - 대한내과학회지 : 제 78 권제 2 호통권제 594 호 ciation. Am J Gastroenterol 98: , ) Barlow WJ, Orlando RC. The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis. Gastroenterology 128: , ) Richter JE. The many manifestations of gastroesophageal reflux disease: presentation, evaluation, and treatment. Gastroenterol Clin North Am 36: , ) Johnson DA, Fennerty MB. Heartburn secerity underestimates erosive esophagitis severity in elderly patients with gastroesophageal reflux disease. Gastroenterology 126: , ) Johnson DA, Winters C, Spurling TJ, Chobanian SJ, Cattau EL Jr. Esophageal acid sensitivity in Barrett s esophagus. J Clin Gastroenterol 9:23-27, ) Dent J, El Serag HB, Wallander MA, Johansson S. Epidemiology of gastroesophageal reflux disease: a systematic review. Gut 54: , ) 전성국, 손정일, 김지은, 박기호, 황일순, 김은주, 박창영, 김병익, 전우규, 정을순, 이풍렬, 이종철, 최규완, 이화영. 성인건강검진자에서위식도역류증상의빈도. 대한내과학회지 58: , ) 추교영, 최명규, 박수헌. 우리나라위식도역류증상의유병율 : 표본인구설문조사 [Abstract]. 대한소화관운동학회지 7:88, ) Moayyedi P, Talley NJ, Fennerty MB, Vakil N. Can the clinical history distinguish between organic and functional dyspepsia? JAMA 295: , ) Richter JE. Severe reflux esophagitis. Gastrointest Endosc Clin N Am 4: , ) Wo JM, Mendez C, Harrell S, Joubran R, Bressoud PF, McKinney WP. Clinical impact of upper endoscopy in the management of patients with gastroesophageal reflux disease. Am J Gastroenterol 99: , ) Kahrilas OJ, Quigley EM. Clinical esophageal ph recording: a technical review for practice guideline development. Gastroenterology 110: , ) Numans ME, Lau J, dewit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med 140: , ) Bortolotti M, Pandolfo N, Miglioli M. Abnormal esophagocardiac reflex in patients with non-cardiac chest pain. Dis Esophagus 14:57-59, ) Fass R, Navarro-Rodriguez T. Noncardiac chest pain. J Clin Gastroenterol 42: , ) Fang J, Bjorkman D. A critical approach to noncardiac chest pain: pathophysiology, diagnosis, and treatment. Am J Gastroenterol 96: , ) Hewson EG, Sinclair JW, Dalton CB, Richter JE. Twenty-fourhour esophageal ph monitoring: the most useful test for evaluating noncardiac chest pain. Am J Med 90: , ) Singh S, Richter JE, Hewson EG, Sinclair JW, Hackshaw BT. The contribution of gastroesophageal reflux to chest pain in patients with coronary artery disease. Ann Intern Med 117: , ) Balaban DH, Yamamoto Y, Liu J, Pehlivanov N, Wisniewski R, DeSilvey D, Mittal RK. Sustained esophageal contraction: a marker of esophageal chest pain identified by intraluminal ultrasonography. Gastroenterology 116:29-37, ) Schofield PM, Bennett DH, Whorwell PJ, Brooks NH, Bray CL, Ward C, Jones PE. Exertional gastro-oesophageal reflux: a mechanism for symptoms in patients with angina pectoris and normal coronary angiograms. Br Med J 294: , ) Dekel R, Martinez-Hawthorne SD, Guillen RJ, Fass R. Evaluation of symptom index in identifying gastroesophageal reflux disease-related noncardiac chest pain. J Clin Gastroenterol 38:24-29, ) Pandak WM, Arezo S, Everett S, Jesse R, DeCosta G, Crofts T, Gennings C, Siuta M, Zfass A. Short course of omeprazole: a better first diagnostic approach to noncardiac chest pain than endoscopy, manometry, or 24-hour esophageal ph monitoring. J Clin Gastroenterol 35: , ) Bautista J, Fullerton H, Briseno M, Cui H, Fass R. The effect of an empirical trial of high-dose lansoprazole on symptom response of patients with non-cardiac chest pain: a randomized, double-blind, placebo-controlled, crossover trial. Aliment Pharmacol Ther 19: , ) Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 112: , ) Jaspersen D, Kulig M, Labenz J, Leodolter A, Lind T, Meyer-Sabellek W, Vieth M, Willich SN, Lindner D, Stolte M, Malfertheiner P. Prevalence of extra-oesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD Study. Aliment Pharmacol Ther 17: , ) Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour ph monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 101(4 pt 2 Suppl 53):1-78, ) McNally PR, Maydonovitch CL, Prosek RA, Collette RP, Wong RK. Evaluation of gastroesophageal reflux as a cause of idiopathic hoarseness. Dig Dis Sci 34: , ) Richter JE. Extraesophageal presentations of gastroesophageal reflux disease. Semin Gastrointest Dis 8:75-89, ) Chevalier JM, Brossard E, Monnier P. Globus sensation and gastroesophageal reflux. Eur Arch Otorhinolaryngol 260: , ) Tauber S, Gross M, Issing WJ. Association of laryngopharyngeal symptoms with gastroesophageal reflux disease. Laryngoscope

9 - 이봉은외 1 인. 위식도역류질환의진단 : 식도및식도외증상들 - 112: , ) Mays EE. Intrinsic asthma in adults: association with gastroesophageal reflux. JAMA 236: , ) Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 141: , ) Jacob P, Kahrilas PJ, Herzon G. Proximal esophageal ph-metry in patients with reflux laryngitis. Gastroenterology 100: , ) Kuhn J, Toohill RJ, Ulualp SO, Kulpa J, Hofmann C, Arndorfer R, Shaker R. Pharyngeal acid reflux events in patients with vocal cord nodules. Laryngoscope 108: , ) Ylitalo R, Ramel S. Gastroesophagopharyngeal reflux in patients with contact granuloma: a prospective controlled study. Ann Otol Rhinol Laryngol 111: , ) DiBaise JK, Olusola BF, Huerter JV, Quigley EM. Role of GERD in chronic resistant sinusitis: a prospective, open label, pilot trial. Am J Gastroenterol 97: , ) Schroeder PL, Filler SJ, Ramirez B, Lazarchik DA, Vaezi MF, Richter JE. Dental erosion and acid reflux disease. Ann Intern Med 122: , ) Ward PH, Hanson DG. Reflux as an etiological factor of carcinoma of the laryngopharynx. Laryngoscope 98: , ) Loughlin CJ, Koufman JA. Paroxysmal laryngospasm secondary to gastroesophageal reflux. Laryngoscope 106: , ) Toohill RJ, Ulualp SO, Shaker R. Evaluation of gastroesophageal reflux in patients with laryngotracheal stenosis. Ann Otol Rhinol Laryngol 107: , ) Tobin RW, Pope CE 2nd, Pellegrini CA, Emond MJ, Sillery J, Raghu G. Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 158: , ) Gislason T, Janson C, Vermeire P, Plaschke P, Bjornsson E, Gislason D, Boman G. Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries. Chest 121: , ) Napierkowski J, Wong RK. Extraesophageal manifestations of GERD. Am J Med Sci 326: , ) 이성희, 최명규, 추교영, 왕준호, 문성배, 최황, 박수헌, 방춘상, 김재광, 최규용, 정규원, 선희식. 우리나라위식도역류질환의임상상. 대한소화관운동학회지 6:1-10, ) Ours TM, Kavura MS, Schilz RJ, Richter JE. A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gatroenterol 94: , ) Schappert SM. National ambulatory medical care survey, 1991: summary. Vitals and Health Statistics No p. 1-20, US Department of Health and Human Services, ) Baldi F, Cappirllo R, Cavoli C, Ghersi S, Torresan F, Roda E. Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough: a comparison between two different daily doses of lansoprazole. World J Gastroenterol 12:82-88, ) Fennerty MB. Extraesophageal gastroesophageal reflux disease: presentations and approach to treatment. Gastroenterol Clin North Am 28: , ) Eubanks TR, Omelanczuk P, Hillel A, Maronian N, Pope CE, Pellegrini CA. Pharyngeal ph measurements in patients with respiratory symptoms before and during proton pump inhibitor therapy. Am J Surg 181: , ) Poe RH, Kallay MC. Chronic cough and gastroesophageal reflux disease: experience with specific therapy for diagnosis and treatment. Chest 123: , ) Irwin RS, Richter JE. Gastroesophageal reflux and chronic cough. Am J Gastroenterol 95(8 Suppl):S9-S14, ) Sifrim D, Dupont L, Blondeau K, Zhang X, Tack J, Janssens J. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, ph, and impedance monitoring. Gut 54: , ) Sontag SJ, O Connell S, Khandelwal S, Miller T, Nemchausky B, Schnell TG, Serlovsky R. Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy. Gastroenterology 99: , ) Gurski RR, da Rosa AR, do Valle E, de Borba MA, Valiati AA. Extraesophageal manifestations of gastroesophageal reflux disease. J Bras Pneumol 32: , ) Harding SM, Richter JE. The role of gastroesophageal reflux in chronic cough and asthma. Chest 111: , ) Harding SM, Guzzo MR, Richter JE. 24-h esophageal ph testing in asthmatics: respiratory symptom correlation with esophageal acid events. Chest 115: , ) Koufman JA, Belafsky PC, Bach KK, Daniel E, Postma GN. Prevalence of esophagitis in patients with ph-documented laryngopharyngeal reflux. Laryngoscope 112: , ) Mansfield LE. Gastroesophageal reflux and asthma. Postgrad Med 86: , ) Fass R, Achem SR, Harding S, Mittal RK, Quigley E. Review article: supra-oesophageal manifestations of gastro-oesophageal reflux disease and the role of night-time gastro-oesophageal reflux. Aliment Pharmacol Ther 20(Suppl 9):26-38, ) Fass R, Ofman JJ, Gralnek IM, Johnson C, Camargo E, Sampliner RE, Fennerty MB. Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease. Arch Intern Med 159: , ) Juul-Hansen P, Rydning A, Jacobsen CD, Hansen T. High-dose proton-pump inhibitors as a diagnostic test of gastro-oesophageal reflux disease in endoscopic-negative patients. Scand J Gastroenterol 36: , ) Bate CM, Riley SA, Chapman RW, Durnin AT, Taylor MD

10 - The Korean Journal of Medicine: Vol. 78, No. 2, Evaluation of omeprazole as a cost-effective diagnostic test for gastro-oesophageal reflux disease. Aliment Pharmacol Ther 13:59-66, ) O Connor JF, Singer ME, Richter JE. The cost-effectiveness of strategies to assess gastroesophageal reflux as an exacerbating factor in asthma. Am J Gastroenterol 94: , ) Moraes-Filho J, Cecconello I, Gama-Rodrigues J, Castro L, Henry MA, Meneghelli UG, Quigley E. Brazilian consensus on gastroesophageal reflux disease: proposals for assessment, classification, and management. Am J Gastroenterol 97: , ) Patti MG, Debas HT, Pellegrini CA. Esophageal manometry and 24-hour ph monitoring in the diagnosis of pulmonary aspiration secondary to gastroesophageal reflux. Am J Surg 163: , ) Mays EE, Dubois JJ, Hamilton GB. Pulmonary fibrosis associated with tracheobronchial aspiration: a study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology. Chest 69: , ) el-serag HB, Sonnenberg A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology 113: , ) Tutuian R, Castell DO. Diagnosis of laryngopharyngeal reflux. Curr Opin Otolaryngol Head Neck Surg 12: , ) Toohill RJ, Kuhn JC. Role of refluxed acid in pathogenesis of laryngeal disorders. Am J Med 103:100S-106S, ) Wong RK, Hanson DG, Waring PJ, Shaw G. ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 95(8 Suppl):S15- S22, ) Little FB, Koufman JA, Kohut RI, Marshall RB. Effect of gastric acid on the pathogenesis of subglottic stenosis. Ann Otol Rhinol Laryngol 94: , ) Noordzij JP, Khidr A, Desper E, Meek RB, Reibel JF, Levine PA. Correlation of ph probe-measured laryngopharyngeal reflux with symptoms and signs of reflux laryngitis. Laryngoscope 112: , ) Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope 111: , ) Koufman JA, Aviv JE, Casiano RR, Shaw GY. Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngol Head Neck Surg 127:32-35, ) Williams RB, Szczesniak MM, Maclean JC, Brake HM, Cole IE, Cook IJ. Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis. Am J Gastroenterol 99: , ) Eccles JD, Jenkins WG. Dental erosion and diet. J Dent 2: , ) Gandara BK, Truelove EL. Diagnosis and management of dental erosion. J Contemp Dent Pract 1:16-23, ) Barron RP, Carmichael RP, Marcon MA, Sandor GK. Dental erosion in gastroesophageal reflux disease. J Can Dent Assoc 69:84-89, ) Lazarchik DA, Filler SJ. Dental erosion: predominant oral lesion in gastroesophageal reflux disease. Am J Gastroenterol 95(8 Suppl):S33-S38,