根據羅馬III準則診斷功能性消化不良危險因子研究

Abstract

研究背景: 功能性消化不良(functional dyspepsia)是一個異質性很高的症狀型疾病 (heterogeneous symptom disease)。診斷依據為源自於上腸胃道(胃，十二指腸)的慢性或反覆性症狀，且常規檢查不能有可解釋症狀的器質病灶(organic lesions)及代謝性疾病(metabolic disease)。其盛行率很高，是臨床上常見的問題，雖無致命危險，但常造成患者生活品質不良。此類患者的高就醫率，也增加了整個社會在健康照護上的支出。許多致病機轉，包括腸胃道運動功能不良、內臟神經高敏感度、胃幽門桿菌、精神病理壓力、生活方式等都曾被報告與功能性消化不良的致病機轉有關，這可能是由於功能性消化不良是一高度異質性的疾病。於是新的診療準則(羅馬III準則，Rome III criteria) 提議以更專一的疾病診斷來取代功能性消化不良；同時作上腹痛症候群(epigastric pain syndrome)和餐後不適症候群(postprandial distress syndrome)的次分類。以往的研究發現教育程度、生活方式、精神病理壓力等危險因子和功能性消化不良有關，但未有一致的結果，且這些危險因子在不同次分類有無不同並不清楚。此外，臺灣本土的相關研究也不多。 研究目的: 探討功能性消化不良病人的危險因子並比較這些危險因子在不同次分類之間有無不同。 研究方法: 自2011年1月至2012年05月，我們以羅馬III準則來評估所有因上腹部症狀而到臺大醫院及雲林分院腸胃科門診的病人，收案病患必須填寫病史、腸胃科症狀問卷、生活習慣、簡式健康表、羅馬III準則的標準診斷問卷，以確認症狀符合功能性消化不良的定義，而且必須接受上消化道內視鏡檢查，併胃鏡切片，以確認無引起症狀的器質病灶。另於同時間，搜集所有來兩院區健檢中心接受健康檢查，無任何消化不良相關症狀的健康對照組，對照組也須填寫包括病史、症狀問卷等，排除重大疾病，並皆接受上消化道內視鏡檢查，排除器質病灶；且皆有接受C-13碳吹氣試驗，確認胃幽門桿菌的感染情形。我們先以多元線性回歸分析方法比較對照組、消化不良與功能性消化不良在各因子包括生活方式、胃幽門桿菌的感染情形等是否有獨立相關性。再以相同方法比較對照組、功能性消化不良不同次分類在各因子之間是否有獨立相關性。最後比較功能性消化不良的次分類之間各因子之間是否有獨立相關性。 研究結果: 對照組有1311位符合收案標準，但檢查後有46位癌症、86位糖尿病、2位慢性腎臟病變、3位肝硬化、58位逆流性食道炎、85位潰瘍遭到排除，總共1031位無症狀的對照組。兩院區計有共2378位主訴消化不良相關症狀病人，排除80位癌症、79位腹部開刀、256位糖尿病病史、38位肝硬化、13位慢性腎臟病變、14位問卷填寫不全、80位不願參與研究、116位曾接受胃幽門桿菌根除治療，而剩下的1702位中有818位符合羅馬III準則對功能性消化不良的診斷標準。經內視鏡檢查，306位有病灶(243位潰瘍、60位胃食道逆流)予以排除。最後共有512位功能性消化不良 (69.9%為女性，平均50歲)；其中310位(60.5%)可診斷為上腹痛症候群，而368位(71.9%)可診斷為餐後不適症候群，17位(3.3%)無法歸類，因此有176位病人(34.4%)在次分類診斷上是重疊的(同時符合上腹痛症候群和餐後不適症候群)。經多元線性回歸分析，發現功能性消化不良在下列因子都呈現獨立正相關：女性(勝算比1,82；95%信賴區間1.19~2.78)、嚼檳榔(勝算比5.04；95%信賴區間為1.92~13.20)、服用止痛藥習慣(勝算比7.52；95%信賴區間4.34~13.03)、重度睡眠障礙（勝算比2.64；95%信賴區間1.46~4.76）、緊張不安感【輕度(勝算比2.57；95%信賴區間1.69~3.94)；中度(勝算比4.09；95%信賴區間2.23~7.51)；重度(勝算比5.27；95%信賴區間1.95~14.30)】、憂鬱感【輕度(勝算比1.93；95%信賴區間1.24~3.00)；中度(勝算比2.42；95%信賴區間1.12~5.22)；重度(勝算比5.29；95%信賴區間1.59~17.66)】、幽門螺旋桿菌感染(勝算比1.60；95%信賴區間1.14~2.24)、合併非靡爛性食道炎(勝算比12.10；95%信賴區間7.92~18.49)、腸躁症(勝算比8.26；95%信賴區間4.78~14.30)。另外，年齡(勝算比0.95；95%信賴區間0.93~0.97)、大專以上學歷(勝算比0.42；95%信賴區間0.24~0.72)呈現負相關。其他各因子包括職業、婚姻、BMI、抽煙習慣等較無顯著相關。比較不同次分類診斷的病人與健康對照組發現餐後不適症候群診斷的患者下列因子呈現獨立正相關，但上腹痛症候群沒有相關性：喝酒(勝算比1.74；95%信賴區間為1.04~2.89)、睡眠障礙【輕度(勝算比2.24；95%信賴區間1.37~3.66)；中度(勝算比2.17；95%信賴區間1.23~3.82)；重度（勝算比5.89；95%信賴區間3.07~11.31）】、憂鬱感【輕度(勝算比1.86；95%信賴區間1.11~3.13)；中度(勝算比3.15；95%信賴區間1.29~7.68)；重度(勝算比8.25；95%信賴區間2.13~31.91）】、幽門螺旋桿菌感染(勝算比1.59；95%信賴區間1.08~2.35)。比較不同次分類診斷之間病人，發現符合餐後不適症後群與睡眠障礙呈現獨立正相關【輕度(勝算比2.05；95%信賴區間1.10~3.79)；中度(勝算比6.43；95%信賴區間2.83~14.58)；重度（勝算比8.20；95%信賴區間3.37~19.89）】。其他因子在次分類之間等較無顯著相關。 結論: 依據羅馬III準則對功能性消化不良的定義與分類，功能性消化不良有較高的吃止痛藥習慣、睡眠障礙、緊張不安感、憂鬱感覺、幽門螺旋桿菌感染、較多合併非靡爛性食道炎、腸躁症。而符合餐後不適症後群和喝酒、睡眠障礙、憂鬱感、胃幽門螺旋桿菌感染有獨立相關性。

Background: Functional dyspepsia (FD) is a heterogeneous symptom disease. The diagnosis of FD is based on chronic or recurrent symptoms thought to originate in gastroduodenal region without organic lesions or metabolic disease, on routine diagnostic examinations. FD is a common disorder with significant impact on quality of life and health care burden. Numerous pathophysiological mechanisms, such as gastroduodenal motor dysfunction, visceral hypersensitivity, Helicobacter pylori (H. pylori) infection, psychosocial factors, diet, and life style have been suggested to play a role in the development of FD. Because of its heterogeneity, new Rome III criteria are implemented for diagnosis and further subgroup classification of FD, consisting of epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Although previous studies have revealed several risk factors such as life style, H. pylori, and psychopathological factors were associated with FD, the results were still controversial. Moreover, studies based on new Rome III criteria and addressing risk factors in different subgroups are few. We also noted that studies from Taiwan are scanty. Aims: We aimed to investigate risk factors of FD in Taiwan based on the Rome III criteria and compare different risk factors in two subgroups of FD. Methods: From January 2011 to May 2012, consecutive dyspeptic outpatients were assessed with standard Rome III diagnostic questionnaire in National Taiwan University Hospital and its Yuan-Lin Branch. All patients received detailed history taking, including demographic data, lifestyle and 5-item Brief Symptom Rating Scale (BSRS-5). Then they underwent upper gastrointestinal endoscopy and laboratory checkup to exclude organic disease or other metabolic disorder. Radom biopsy was obtained from antrum and body for pathology, Helicobacter pylori (H. pylori) culture, and rapid urea test. To select control, we enrolled all consecutive asymptomatic subjects participating in self-paid health checkup from Health Examination Center. Similar work up was performed for control group except that they received additional 13-UBT. Multiple linear regression models were used for statically analyses. Results: There were 1311 health subjects enrolled for screening as control. After exclusion of 46 subjects with cancer history, 86 diabetes mellitus, 2 chronic kidney disease, 3 liver cirrhosis, 58 reflux esophagitis and 85 peptic ulcers, a total of 1031 subjects were selected as control. There were 2378 symptomatic patients from outpatient department. Among them, 80 patients with cancer, 79 with history of abdominal operation, 74 diabetes mellitus, 38 liver cirrhosis, 13 chronic kidney diseases, 14 incomplete questionnaires, 80 refusal, and 116 with history of H. pylori eradication were excluded. Before investigation, 818 patients fulfilled Rome III criteria for FD. After eaxinations, 306 patients with organic lesions (243 peptic ulcers, 60 reflux esophagitis) were excluded. Finally, 512 patients (69.9% female mean age 50 years old) were subjected for analyses. There was an overlap (n=176, 34.4%) between the patients diagnosed with EPS (n=310, 60.5%) and those with PDS (n=368, 71.9%). Seventeen patients did not fit diagnostic criteria of PDS and EPS (3.3%). By multivariable linear regression analysis, the following factors were associated with increasing risk of FD：female gender (odd ratio(OR):1,82, 95% confidence interval（CI）1.19~2.78)、bet nut chewing(OR:5.04, 95% CI1.92~13.20)、NASID (OR:7.52, 95% CI 4.34~13.03)、severe sleep disturbance（OR:2.64, 95% CI1.46~4.76）、anxiety【mild(OR:2.57, 95% CI 1.69~3.94)；moderate(OR:4.09, 95% CI 2.23~7.51)；serve(OR:5.27, 95%CI 1.95~14.30)】、depression【mild(OR:1.93；95% CI 1.24~3.00)；moderate(OR:2.42, 95% CI 1.12~5.22)；serve(OR:5.29, 95%CI1.59~17.66)】、H.pylori (OR:1.60, 95% CI 1.14~2.24)、combined non-erosive esophagitis(OR:12.10,95%CI 7.92~18.49)、irritable bowel syndrome(OR:8.26, 95% CI 4.78~14.30). In contrast, age (OR: 0.95, 95%CI0.93~0.97) and education with college level (OR: 0.42, 95% CI0.24~0.72) were associated with decreased risk. The subdivision of FD revealed the following factors were associated with increased risk of PDS but not for EPS：drinking(OR:1.74, 95%CI1.04~2.89)、sleep disturbance mild(OR:2.24, 95%CI1.37~3.66)；moderate(OR:2.17, 95%CI1.23~3.82)；serve（OR:5.89, 95%CI3.07~11.31）】、depression【mild(OR:1.86, 95%CI1.11~3.13)；moderate(OR:3.15, 95%CI1.29~7.68)；serve(OR:8.25, 95%CI2.13~31.91）】、H.pylori (OR:1.59, 95%CI1.08~2.35)。Comparison of PDS and EPS demonstrated that the diagnosis of PDS was independently associated with higher proportion of sleep disturbance (p<0.001). Conclusions: Patients fulfilling Rome III FD criteria had more NASID usage, sleep disturbance, anxiety, depression, overlap syndrome with NERD or IBS, and H.pylori infection. Diagnosis of PDS, but not EPS, is independently associated with sleep disturbance.