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研究生:楊孝友
研究生(外文):Hsiao-Yu Yang
論文名稱:台灣中醫藥從業人員腎臟危害流行病學研究
論文名稱(外文):Epidemiological study of renal diseases in Chinese herbalists
指導教授:王榮德王榮德引用關係
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2010
畢業學年度:98
語文別:英文
論文頁數:71
中文關鍵詞:中藥從業人員馬兜鈴酸防己泌尿系統癌症慢行腎衰竭
外文關鍵詞:Chinese Herbal DrugsChinese HerbalistAristolochic AcidUrothelial CarcinomaUrological CancerChronic Renal FailureUrological Cancer
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背景簡介:於1993年 Vanherweghem發表因服用含馬兜鈴酸中藥廣防己,導致腎毒性、泌尿上皮癌症研究後,中草藥安全性越來越受到重視。馬兜鈴酸已被證實會導致腎衰竭與泌尿上皮癌症,而許多傳統中藥含有馬兜鈴酸成分。由於中藥從業人員比一般民眾更習慣使用中藥,有較高機會因曾經服用含馬兜鈴酸中藥,或因長期接觸含馬兜鈴酸中藥,傳統中藥房工作的中藥從業人員可能是潛在暴露含馬兜鈴酸中藥的最高族群。但該族群但否有較高的腎臟或泌尿系統危害,目前缺乏足夠流行病學研究。
研究目的︰分析中醫藥從業人員是否有較高的泌尿系統與腎臟疾病危險性。並釐清疾病危險,與暴露含馬兜鈴酸中藥之相關性。研究假設,傳統中藥行的中藥製造從業人員,可能因較常服用中草藥或因工作處理中藥材,增加馬兜鈴酸暴露風險,增高罹患慢性腎衰竭風險。
研究方法:(1)台灣中藥從業人員泌尿系統癌症、慢性腎病變與腎衰竭標準化死亡率比(standardized mortality ratio, SMR)研究。以回溯性世代追蹤研究,選取於民國74至89年間投保於中藥製造職業工會所有會員共6555名中藥從業人員為研究世代,以勞工投保資料串連行政院衛生署死因資料連結,回溯追蹤該世代至民國93年為止之死亡個案數與死亡原因,並以台灣地區民眾為參考族群,進行年齡、性別間接標準化,計算泌尿系統疾病之標準化死亡率比。(2)中藥從業人員泌尿系統癌症標準化發生率比(standardized incidence ratio, SIR)研究,以回溯性世代追蹤研究,連結衛生署之癌症登記檔資料庫,追蹤該世代至民國90年為止癌症新發生個案,並以台灣地區民眾為參考族群,進行年齡、性別間接標準化,分析該世代是否有較高的泌尿系統癌症標準化發生率比。(3)分析中藥從業人員罹慢性腎衰竭,是否與處理販售中草藥職業暴露、或服用含防己類中藥有關。以中藥製造從業人員職業世代進行nested case-control study,串連全民健康保險資料庫重大傷病檔,追蹤該世代於民國84年至民國89年新發生慢性腎衰竭病患為病例組,經由性別、年齡個別配對,以隨機抽樣方法,由該世代無慢性腎衰竭族群中選取對照組。經由訪員問卷訪視,實際蒐集從事中藥製作販售工作狀況、服用含防己中藥習慣、飲食習慣、抽煙、喝酒、服用西藥止痛藥情形、飲用水來源、過去泌尿系統疾病史、家族疾病史資料,以conditional logistic regression,控制非中草藥暴露之其他潛在干擾因素,分析處理販售或服用防己對慢行腎衰竭之罹病勝算比(morbidity odds ratio)。
研究結果:中藥從業人員泌尿系統癌症標準化死亡率比顯著升高(SMR = 3.10; 95% CI: 1.41 to 5.87)。腎臟癌(SIR = 4.24, 95% CI 2.47-6.80)與膀胱癌(SIR = 2.86, 95% CI 1.52-4.89)標準化發生率顯著升高。經校正年齡與長期使用止痛劑習慣干擾因素後,中藥從業人員發生慢性腎衰竭,與實際從事中藥製造或販售工作(OR = 3.18, 95% CI 1.11-9.12)、處理、販售、或調劑含防己之中藥材(OR = 3.91, 95% CI 1.32-11.64)、服用含防己中藥方劑(OR = 5.76, 95% CI 1.30-25.51)有顯著相關。
結論:中藥從業人員可能因工作接觸或服用含馬兜鈴酸中藥暴露,增加罹患泌尿系統疾病之風險。

Chapter 1. Introduction........................................................................................ 1
Chapter 2. Standardized Mortality Ratios Study .......................................... 4
Section 2.1: Introduction.................................................................... 4
Section 2.2: Methods ........................................................................ 4
Section 2.3: Results............................................................................ 5
Section 2.4: Discussion.,.................................................................... 15
Chapter 3. Standardized Incidence Ratios Study................................................. 17
Section 3.1: Introduction.................................................................... 17
Section 3.2: Methods......................................................................... 17
Section 3.3: Results ........................................................................... 19
Section 3.4: Discussion...................................................................... 26
Chapter 4. Nested Case-control Study................................................................. 30
Section 4.1: Introduction.................................................................... 30
Section 4.2: Methods......................................................................... 30
Section 4.3: Results ........................................................................... 32
Section 4.4: Discussion...................................................................... 41
Chapter 5. Pathogenesis of Aristolochic Acids-related Urological Diseases...... 44
Chapter 6. Exposure Routes................................................................................ 49
Chapter 7. Influence of Gender........................................................................... 51
Chapter 8. Implication in Public Policy.............................................................. 54
Reference ............................................................................................................ 56
Appendix 1. Chinese herbalists with urinary organs cancers in the SIRs study..... 61
Appendix 2. Standardized incidence ratio (SIR) of cancer in Chinese herbalists in the SIRs study................................................................................ 63
Appendix 3. Epidemiological studies of urothelial carcinoma in Balkan endemic nephropathy (BEN) regions............................................................... 65
Appendix 4. 台灣地區腎臟疾病家族研究問卷.................................................... 66


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