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대한내과학회지 : 제 83 권제 5 호 2012 http://dx.doi.org/10.3904/kjm.2012.83.5.562 특집 (Special Review) - 일차의료기관에서흔하게접하는하부기능성위장관질환증상의진단및치료 기능성팽만감 (Functional Bloating) 의진단과치료 고신대학교의과대학내과학교실 박무인 Diagnosis and Treatment of Functional Bloating Moo In Park Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea Functional abdominal bloating is a common and significant problem in men and women of all ages. Bloating is very common in patients with irritable bowel syndrome and constipation, and also occurs in patients with organic disorders and psychiatric conditions. If an organic or psychiatric cause are not found, then bloating can be considered to be functional. The possible causes of functional bloating are combination of several factors such as gut microflora, gas production, intestinal transit, intestinal propulsion of gas, and sensory function within the gastrointestinal tract. Evaluation of a patient with bloating should begin with a careful history and physical examination to rule out an organic disorders. Reassurance and education are the first essential step as a treatment for functional bloating. The therapeutic approach involving diet, probiotics, and medications usually improve bloating. (Korean J Med 2012;83:562-567) Keywords: Bloating; Pathophysiology; Treatment 서론복부팽만감 (abdominal bloating) 은흔하게호소하는증상이다. 복부팽만감을호소하는환자의절반정도에서객관적인복부팽만 (abdominal distention) 을볼수있다. 기질적인원인이나정신적인원인이없으면서팽만감을호소하는환자들을흔히진료하게되는데이런경우를기능성팽만감 (functional bloating) 이라고할수있다. 기능성팽만감을호소하는환자에대한평가와진단, 그리고효과적인치료법에대한근거는충분하지않아서아직도체계적인연구가필요한실정이 다. 이에본고에서는기능성팽만감의진단과치료에대하여기존의근거와보고들을종합하여서술하고자한다. 본론정의팽만감 (bloating) 은공기삼킴증 (aerophagy), 대식 (gluttony), 위배출구혹은장폐색, 흡수장애 (malabsorption), 위혹은장운동저하, 비만과복부내종괴혹은액체저류등으로인하여발생할수있다. 또한신경성식욕부진 (anorexia nervosa), 대 Correspondence to Moo In Park, M.D. Department of Internal Medicine, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 602-702, Korea Tel: +82-51-990-6719, Fax: +82-51-990-5055, E-mail: mipark@ns.kosinmed.or.kr Copyright c 2012 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 562 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

- Moo In Park. Diagnosis and treatment of functional bloating - 식증 (bulimia) 혹은신체화장애 (somatization disorder) 등으로인하여발생하기도한다. 이러한기질적, 정신적원인이없이팽만감이발생할때기능성팽만감 (functional bloating) 으로생각할수있다. 로마기준 III에서는반복적인복부팽창감이나측정가능한복부팽만이있으면서과민성장증후군이나기능성소화불량증혹은다른기능성위장관질환의진단기준에부합하지않을때기능성팽만감으로진단하자고제안하였다 (Table 1) [1]. 역학 1949년 Mayo Clinic의 Alvarez [2] 가정신질환을앓고있는여성에서발생한복부팽만에대해서처음으로기술하였다. 미국의일반인구를대상으로한연구들 [3-6] 에서응답자의 15-30% 정도에서팽만감을호소하였다. 아시아지역에서이루어진연구 [7] 에서도 15-23% 정도의유병률을보여인종간에큰차이가없어보였다. 최근에우리나라에서이루어진연구 [8] 에서도의원혹은 3차병원을방문한환자에서로마기준 III에의한팽만감의유병률은 14.8% 와 12.4% 였다. 다른연구에서는과민성장증후군 (irritable bowel syndrome, IBS) 환자의 90% 이상이팽만감을호소하였다 [7]. 일반인구연구에서는남녀차이가없었으나과민성장증후군환자들을대상으로한연구에서는여성이남성보다더많이팽만감을호소하였다 [3-6,9]. 또한주로변비우세형과민성장증후군환자들이팽만감을호소하였다 [5,6]. 팽만감을호소하는환자들은대부분증상이중등도이상으로심하다고하였으며 50% 이상에서일상생활에지장을받았다고하였다 [4]. 다른연구에서는과민성장증후군환자에서팽만감이과민성장증후군의심한정도를예측할수있는인자라고제시하였다 [10]. 임상양상팽만감 (bloating) 은증상이고팽만 (distention) 은징후이다. 한연구에서팽만감을호소하는변비주도형환자의 48% 에서만실제로복부둘레가증가하였다 [11]. 기능성복부팽만감 (functional abdominal bloating) 은지속적이지않아서완화와악화를반복한다. 대개식후에바로발생하는경우와저녁무렵에서서히심해지는경우로나눌수있는데전자는주로기능성소화불량증 (functional dyspepsia) 의한증상으로나타난다. 주로여성에서흔하며아침에는괜찮다가오후로갈수록점점심해진다. 금식하거나소량의음식을섭취할때는덜하다가과식하면심해지는경향이있다. 또한월경전에심해지는경향이있으며벨트를느슨하게하거나헐렁한옷으로갈아입는것이좋다. 트림 (burping), 방귀방출 (farting) 혹은배변 (defecation) 으로약간일시적으로완화된다. 팽만감을호소하는환자들은상당수에서과민성장증후군, 기능성소화불량증, 변비혹은월경전증후군 (premenstrual syndrome) 등의질환을가지고있다. 정신적혹은사회적문제를가지고있는경우도많다. 팽만을동반한기능성복부팽만감환자 46명에대한전향적인연구에서최근체중증가, 복부근육의약화와운동부족등을흔히동반하고있었다 [12]. 병태생리팽만감의병태생리는아직완전하게이해되고있지않으며여러가지요인들이복합적으로작용한다 (Table 2) [13]. 장내세균, 장내가스의생성, 장통과 (intestinal transit), 가스의장내이동 (propulsion), 소화관의감각기능, 음식과장내에저류되어있는액체, 대변, 복강내지방, 복부근육의운동이상등의인자들의이상이팽만감을초래할수있다. Table 1. C2. Diagnostic Criteria a for Functional Bloating Must include both of the following: 1. Recurrent feeling of bloating or visible distention at least 3 days/month in 3 months 2. Insufficient criteria for a diagnosis of functional dyspepsia, IBS, or other functional GI disorder a Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis. From Longstreth GF et al. [1]. Table 2. Suggested causes of functional abdominal bloating Intra-abdominal gas Fluid within the lumen of the gut Feces Low or inappropriately contracted diaphragm Exaggerated lumbar lordosis Intra-abdominal fat Weak or inappropriately relaxed abdominal muscles Psychiatric problems Modified from Sullivan SN [13]. - 563 -

- 대한내과학회지 : 제 83 권제 5 호통권제 627 호 2012 - 장내세균 (Gut microflora) 사람의대장에는약 500종의세균이살고있으며대부분혐기성세균이다. 대개 10 14 이상의균이살고있는데이는사람의총세포수보다많은수이다 [14]. 장내세균의종류는사람마다다양한데이는식이, 항생제, 감염력등이상이하기때문이다. 장내세균의경미한변화도장내가스생성등장기능의중요한변화를초래할수있다. 장내가스 (Intestinal gas) 사람의장에는 100-200 ml 정도의가스가항상존재한다 [15-17]. 장관내의가스는공기를삼키거나, 혈관으로부터확산되어왔거나장관내에서다양한화학반응의결과로발생한다. 주로 N 2, O 2, H 2, CO 2 와 CH 4 등으로이루어져있다. 건강자원자를대상으로한연구에의하면대개하루에 700 ml 정도의가스를생성하며 14-18번정도방귀를뀐다 [18]. 장내가스의이상은팽만감이나팽만을초래할수있다고여겨져왔다. 장내가스의생성양은정상인과과민성장증후군환자군사이에유의한차이를보이지않았다 [18-21]. 또한팽만감을주로호소하는환자 47명에서팽만감을심하게호소할때복부 CT를촬영하여장내가스의양을측정하였을때가스는약간만증가하였다 [22]. 이는장내가스의생성이증가하여팽만을유발하지않음을시사한다. 장내가스의통과시간은과민성장증후군환자에서정상인에비하여지연되어있었다 [20]. 또한, 장내에가스를주입한후가스제거 (clearance) 를비교하였을때, 소장과대장모두과민성장증후군환자에서정상인에비하여지연되어있었다 [23-25]. 내장과민성 (Visceral hypersensitivity) 58명의과민성장증후군환자를대상으로한연구에서팽만감을호소하였던군에서비호소군에비하여직장감각역치가유의하게더낮았다 [26]. 이는팽만감이내장과민성과연관이있음을보여준다. 비정상적인복부-횡격막반사 (Abnormal abdominaldiaphragmatic reflexes) 건강한성인에서장내에가스를주입하면복부근육이수축하고횡격막은이완된다 [27]. 팽만감을호소하는환자의장내에가스를주입하면복부근육의수축력이오히려저하되고내복사근 (internal oblique abdominal muscle) 은이완된다. 또한횡격막은수축되어하강하여팽만을초래한다 [22,28]. 진단 팽만감을호소하는환자는우선철저한병력조사와신체검사를시행하여기질적질환을배제하여야한다. 빈혈, 의도하지않은체중감소등경고증상이나징후가있는지우선점검하여야한다. 만약이러한증상이있다면혈액검사와내시경검사등을시행하도록한다. 또한팽만감과함께다른증상을호소한다면각각의증상에대한검사를시행한다. 만약팽만감과함께오심, 구토를호소한다면소장촬영과위배출능검사를시행하고설사가동반되어있다면분변검사와대장내시경검사를시행한다. 무엇보다중요한점은검사를통하여위장관폐색의유무를확인하는데있다. 서구에서는복강병 (celiac disease) 이원인질환일수있으므로배제해야한다고제시하고있다. 치료 팽만감이기질적인원인으로유발되지않았다고확인되면환자를일단안심시키고기능성팽만감에대하여자세하게설명한다. 아직까지근거에기초를둔치료알고리즘이없는실정이므로개개인에맞는치료를시행하여야한다 [29]. Lacy 등 [30] 은최근에팽만감과팽만에대한단계적접근방법을제시하였는데이를소개하고자한다 (Table 3). 우선환자가주로호소하는증상이팽만감과팽만중어느것인지혹은둘다인지파악한다. 이를통하여병태생리를어느정도짐작할수있다. 그다음에는이러한증상을일으켰을만한원인들에대하여환자에게설명한다. 비록증상이대단히심하 Table 3. Management of functional abdominal bloating Exclude an organic cause Explanation and reassurance Diet manipulation Probiotics Smooth muscle antispamodics Osmotic laxatives Prokinetic agents Chloride channel activators Tricyclic antidepressants Weight loss? Sit-ups? Excercise? A girdle? Psycho-or hypnotherapy Modified from Lacy BE et al. [30]. - 564 -

- 박무인. 기능성팽만감 (Functional bloating) 의진단과치료 - 고불쾌하지만대개경과는양호하다고환자를안심시킨다. 최종적으로특이적이고실현가능한목표를설정한다. 기능성복부팽만감환자의치료에대한무작위- 위약대조군연구가아직없는실정이며대부분은과민성장증후군에대한연구결과에근거를두고있다. 식이 (Diet) 자세한식이섭취력은아주중요한데특히대장에서발효하는식품인 dairy, fructose, frucans, fiber와 sorbitol 등에대해서반드시확인하여야한다 [31]. 이러한발효식품을삼가하였더니과민성장증후군환자에서팽만감이호전되었다는보고가있다 [32,33]. 팽만감을호소하는환자에서우선적으로시도해볼만하다. 운동과자세 (Exercise and Posture) 8명의팽만감을호소하는환자에서운동을한후장내가스의제거가원활하게이루어지고증상도완화되었다 [34]. 또한앙와위에서가스저류가더심해지고기립자세에서완화되므로낮에는되도록누워있지않도록교육시킨다. 한연구에의하면운동과자세에대하여교육한후환자의가스와팽만감이많이호전되었다 [35]. 프로바이오틱스 (Probiotics) 프로바이오틱스를투여하였을때팽만감이호전되었다는여러보고가있다 [36-41]. 60명의기능성장질환자를대상으로 Lactobacillus acidophilus와 Bifidobacterium lactis 혹은위약을 8주간투여하였을때프로바이오틱스투여군에서팽만감이현저히감소되었다 [36]. 과민성장증후군환자를대상으로한무작위- 위약대조군연구들에서도프로바이오틱스투여군에서위약군보다팽만감이유의하게감소되었다 [37-41]. 기능성팽만감환자에서도효과적일것으로기대되나이에대한무작위- 위약대조군연구는아직없는실정이다. 항생제 (Antibiotics) 비흡수성항생제인 rifaximin 이팽만감에대한치료제로서시도되어왔다 [42-44]. 124명의팽만감을호소하는환자에서 rifaximin 과위약을투여하였을때 rifaximin 군에서위약군보다유의하게팽만감이더호전되었다 (41.3% vs. 22.9%) [42]. 과민성장증후군환자에서도 rifaximin 의투여후위약에비해유의하게팽만감이호전되었다. 그렇지만, 팽만감에대한항생제의치료효과는정립되지않은상태이며향후더많은 후속연구가필요하다. 삼투성하제 (Osmotic laxatives) 만성변비환자에대한 polyethylene glycol 투여에대한한연구에서팽만감이호전되었다 [45]. 그렇지만, 기능성팽만감환자에대한연구는아직없는실정이다. 위장운동촉진제 (Prokinetic agents) 위장관운동촉진제는위식도역류질환, 위마비, 기능성소화불량증과과민성장증후군등의환자에서위장관증상을일부개선시키는효과가있다. Neostigmine은콜린에스테라제억제제 (cholinesterase inhibitor) 로서급성가성장폐색증시사용된다. 공장내가스를주입하여팽만감을유발한 28명의환자에서 neostigmine을정주한군에서위약군에비하여장내가스가유의하게더많이배출되었다 [46]. 최근에이루어진소규모연구에서 20명의팽만감을호소하는과민성장증후군환자에게 pyridostigmine을투여하였으나단지약간의증상개선효과만있었다 [46]. 또한 Metoclopramide를소화불량증환자에게투여하였을때도복부팽만은개선되지않았다 [47]. 위장운동촉진제가팽만감을개선시킨다는증거는아직부족한상태이지만향후효과적인새로운약제의개발이이루어지길기대한다. 염소통로활성화제 (Chloride channel activators) 최근에새롭게개발된 lubiprostone [48] 과 linacloitide [49,50] 는변비와변비우세형과민성장증후군환자에서효과적인약제이다. 이두약제모두팽만감에도개선효과를보였다 [48-50]. 아직우리나라에는도입되지않은상태이며향후더많은연구결과가축적되어임상에도입되길기대한다. 항우울제항우울제는기능성복통을경감시키기도한다 [51]. 무작위-위약대조군연구에서삼환계항우울제인 desipramine은심한기능성장질환자에서복통뿐만아니라팽만감도호전시켰다 [52]. 후속연구들의결과를기다려봐야되겠지만, 일반적인치료에반응하지않는경우항우울제는팽만감에대한치료방법으로시도해볼만하다고여겨진다. 결론기능성팽만감은대단히흔하며환자가심한불편감을호 - 565 -

- The Korean Journal of Medicine: Vol. 83, No. 5, 2012 - 소한다. 기능성팽만감의발생기전은아직도완전히이해되지못하고있는데장내가스, 내장과민성과비정상적인복부근육과횡격막의반사등의여러가지요인들이복합적으로작용할것으로여겨진다. 팽만감을호소하는환자가내원하게되면우선철저한병력청취, 신체검진과몇가지검사를통하여장폐색등의기질적질환을배제하여야한다. 기능성팽만감으로진단하게되면우선환자에게자세하게설명하여안심시킨다. 그다음식이, 프로바이오틱스, 기타약제등을시도하게되며대개증상은호전하게된다. 아직까지표준치료법이확립되지않은실정이므로개개인별에따른진단및치료접근을하게된다. 향후기능성팽만감에대한새로운치료법이개발되길기대한다. 중심단어 : 팽만감 ; 병태생리 ; 치료 REFERENCES 1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006;130:1480-1491. 2. Alvarez WC. Hysterical type of nongaseous abdominal bloating. Arch Intern Med (Chic) 1949;84:217-245. 3. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders: prevalence, sociodemography, and health impact. Dig Dis Sci 1993;38: 1569-1580. 4. Sandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci 2000;45: 1166-1171. 5. Ringel Y, Williams RE, Kalilani L, Cook SF. Prevalence, characteristics, and impact of bloating symptoms in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2009;7:68-72. 6. Jiang X, Locke GR 3rd, Choung RS, Zinsmeister AR, Schleck CD, Talley NJ. Prevalence and risk factors for abdominal bloating and visible distention: a populationbased study. Gut 2008;57:756-763. 7. Ho KY, Kang JY, Seow A. Prevalence of gastrointestinal symptoms in a multiracial Asian population, with particular reference to reflux-type symptoms. Am J Gastroenterol 1998;93:1816-1822. 8. Park JM, Choi MG, Cho YK, et al. Functional gastrointestinal disorders diagnosed by Rome III questionnaire in Korea. J Neurogastroenterol Motil 2011;17:279-286. 9. Lembo T, Naliboff B, Munakata J, et al. Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome. Am J Gastroententerol 1999;94: 1320-1326. 10. Spiegel B, Strickland A, Naliboff BD, Mayer EA, Chang L. Predictors of patient-assessed illness severity in irritable bowel syndrome. Am J Gastroenterol 2008;103:2536-2543. 11. Houghton LA, Lea R, Agrawal A, Reilly B, Whorwell PJ. Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit. Gastroenterology 2006;131:1003-1010. Erratum in: Gastroenterology 2006; 131:2029. 12. Sullivan SN. A prospective study of unexplained visible abdominal bloating. N Z Med J 1994;107:428-430. 13. Sullivan SN. Functional abdominal bloating with distention. ISRN Gastroenterol 2012;2012:721820. 14. Hart AI, Stagg AJ, Groffner H, et al. Gut Ecology. London: Martin Duntiz Ltd, 2002. 15. Levitt MD. Volume and composition of human intestinal gas determined by means of an intestinal washout technic. N Engl J Med 1971;284:1394-1398. 16. Lasser RB, Bond JH, Levitt MD. The role of intestinal gas in functional abdominal pain. N Engl J Med 1975;293: 524-526. 17. Perez F, Accarino A, Azpiroz F, Quiroga S, Malagelada JR. Gas distribution within the human gut: effect of meals. Am J Gastroenterol 2007;102:842-849. 18. Tomlin J, Lowis C, Read NW. Investigation of normal flatus production in healthy volunteers. Gut 1991;32:665-669. 19. King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet 1998;352:1187-1189. 20. Serra J, Azpiroz F, Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut 2001;48:14-19. 21. Caldarella MP, Serra J, Azpiroz F, Malagelada JR. Prokinetic effects in patients with intestinal gas retention. Gastroenterology 2002;122:1748-1755. 22. Accarino A, Perez F, Azpiroz F, Quiroga S, Malagelada JR. Abdominal distention results from caudo-ventral redistribution of contents. Gastroenterology 2009;136:1544-1551. 23. Hernando-Harder AC, Serra J, Azpiroz F, et al. Colonic responses to gas loads in subgroups of patients with abdominal bloating. Am J Gastroenterol 2010;105:876-882. 24. Salvioli B, Serra J, Azpiroz F, et al. Origin of gas retention and symptoms in patients with bloating. Gastroenterology 2005;128:574-579. 25. Salvioli B, Serra J, Azpiroz F, Malagelada JR. Impaired small bowel gas propulsion in patients with bloating during intestinal lipid infusion. Am J Gastroenterol 2006;101: 1853-1857. 26. Agrawal A, Houghton LA, Lea R, Morris J, Reilly B, - 566 -

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