- 學位論文
(1) 痰細胞化生之流行病學調查 (2) 嚴重急性呼吸道症候群死亡之血液生化預測因子
(1) Epidemiology of sputum metaplasia (2) Hematological and Biochemical Factors in Predicting SARS Fatality in Taiwan
摘要
(1) 痰細胞化生之流行病學調查 民國80~82年國人的肺癌死亡率相當於發生率，但自83年起，死亡率增加的趨勢大於發生率，顯示肺癌不易被診斷。肺部疾病（包括肺癌）與暴露於二手菸及炒菜油煙之環境等因子相關，本研究即為探討大台北地區民眾痰細胞化生盛行率及其危險因子，進而瞭解餐飲業者健康狀況及痰細胞化生盛行情形。 本研究於2000年至2001年在大台北地區包括基隆市、台北市及台北縣三縣市，以自願方式收集研究對象。利用橫斷研究法進行問卷調查、健康檢查（包括胸部X光檢查）及痰檢體收集，並進行細胞學檢驗。 共收集513位的有效檢體，包括基隆市158位、台北市130位及台北縣225位，其中185位有痰細胞化生現象，328位無痰細胞化生現象。發現有痰細胞化生現象者較年輕，健康狀況亦較好，但是目前仍有吸菸的盛行率較高，為無痰細胞化生者的1.4倍（p=0.046）。在控制年齡、性別、籍貫、教育程度及吸菸習慣情形後，發現不論是全部研究對象、或是吸菸者、或是烹調者，在家中烹調因子均與痰細胞化生間具有統計顯著性，尤其是吸菸者有烹調行為，且每週下廚至少4天及以上者發生痰細胞化生現象之危險性竟高達7.6倍（95%信賴區間為1.5~39.2），故具有油煙暴露及吸菸者會有較高的痰細胞化生情形。另目前仍吸菸者發生痰細胞化生的危險性是已戒菸者與不吸菸者的1.7~1.9倍，而已戒菸者與不吸菸者發生痰細胞化生的危險性差不多，顯示吸菸行為與痰細胞化生有關。吸菸者除了在家中烹調因子外，吸菸時未使用濾嘴及有肺氣腫疾病者，發生痰細胞化生之危險性各達3.5倍及5.8倍。 因每週在家中下廚至少會有4天及以上者與痰細胞化生現象之相關均達統計顯著意義，故自研究對象中選取工作地點在台北縣、市之餐飲業者59人及社區民眾126人，進一步探討餐飲業者與社區居民生活型態、健康狀況及痰細胞學檢驗結果之相關。餐飲業者較社區民眾年輕，大多為女性，其教育程度與目前吸菸習慣均較低，但健康狀況較好。餐飲業者除了在工作上會暴露在油煙的環境下外，在家中亦較社區民眾有較多的機會暴露在油煙的環境下。 餐飲業者及社區民眾痰細胞化生盛行率差不多。若將餐飲業者以工作性質細分為廚師、餐務處理者及外場行政者，其中廚師約13.3%有肺部鈣化現象是值得注意的。雖然痰細胞化生盛行率在三組間之差異不具統計意義，但仍以廚師痰細胞化生盛行率最高約為45.0%，是外場行政者36.4%的1.2倍，比餐務處理者23.5%的1.9倍顯著。 本研究結果顯示家中烹調情形及吸菸習慣與發生痰細胞化生現象之相關性強。建議改變烹調行為及吸菸習慣，可能降低發生痰細胞化生的危險性。 (2) 嚴重急性呼吸道症候群死亡之血液生化預測因子 嚴重急性呼吸道症候群全球致死率為10.9%。本研究探討台灣嚴重急性呼吸道症候群病例在流行病學、臨床徵候及臨床檢驗值之死亡預後因子。由於血漿C-反應蛋白質（C-reactive protein，CRP）與發炎有關，亦探討CRP值與有無呼吸困難及存活間之關係。 研究對象以台灣地區自2003年3月14日至6月15日通報至傳染病監視通報系統之資料，並經SARS之冠狀病毒相關檢驗分析方法檢出陽性結果者為主，共有346例SARS確定病例。蒐集病患之基本資料、入院時臨床徵候及臨床檢驗初始資料，整理後進行分析。 結果顯示SARS病患有高的初始CRP值及低的初始淋巴球（lymphocyte）數，SARS死亡者（n=73或21.1%）之CRP平均值為47.7 mg/L比存活者的24.6 mg/L高（p=0.0001）。而死亡者之淋巴球數平均值為814 /mL比存活者的1019 / /mL低(p=0.004)。在探討SARS死亡預測因子之多變項分析時，於控制年齡及性別因子後，病患初始中性球數在7000 /mL以上者死亡的勝算比是7000 /mL 以下者的6.4倍（95%信賴區間為1.1~36.0）。其他具有統計顯著意義之死亡預測因子有初始CRP值大於47.5 mg/L者（5.8倍）及初始乳酸脫氫酶（lactic acid dehydrogenase，LDH）大於593.5 IU/L者（4.2倍）。另SARS病患具有慢性阻塞性肺疾病、腦中風或心臟病之一者，有高的初始CRP值，約61.5 mg/L。在控制年齡及性別因子下，發現有呼吸困難死亡者、有呼吸困難存活者及沒有呼吸困難死亡者，發生CRP值大於47.5mg/L之勝算比各為沒有呼吸困難存活者的6.0倍（95%信賴區間為1.8~20.3）、3.5倍（95%信賴區間為1.3~9.0）及2.8倍（95%信賴區間為1.0~7.4），其差異均具有統計顯著意義。 高初始中性球數、高初始CRP值及高初始LDH濃度是SARS死亡的重要預測因子。其中初始CRP值不僅僅為死亡預測因子，亦是嚴重感染SARS冠狀病毒的一個很好的預測因子。
並列摘要
(1) Epidemiology of sputum metaplasia In Taiwan, the annual mortality rate from lung cancer was approximately similar to the incidence rate of the disease in 1991~1993. Pulmonary diseases, including lung cancer, have been associated with the exposure to environmental tobacco smoking (ETS) and cooking oil fumes in addition to smoking. This study evaluated the detection of metaplsia in sputum and investigated corresponding prevalence and risk factors for metaplsia in sputum among general residents in Taipei areas. These associations were also evaluated for restaurant employees as separate sample. Study subjects being recruited in 2000~2001 received a pulmonary X-ray examination, completed a self-reported questionnaire for information on socio-demographic characteristics and life-style, and provided a specimen of the first sputum in the morning. This study included a total of 513 volunteer persons, recruited from Keelung City (158), Taipei City (130), and Taipei County (225). The results indicated that the subjects with metaplasia in sputum were younger than those without metaplasia in sputum, and had the best health status. The proportion of smokers among those with metaplasia in the sputum specimen was 35.7% or 1.4 times higher than that with no metaplasia in the sputum. After adjusting for age, gender, residential town and education, it was found that cooking and smoking history were significantly associated with developing metaplsia in sputum (p<0.05). Particularly, the odd ratio（OR） of metaplasia in sputum was 7.6 （95% confidence interval (CI)=1.5-39.2）for smokers with cooking, compared with smokers with no cooking or rarely cooked. In addition, the risk of metaplsia for smokers was 1.7~1.9 times higher than ex-smokers and non-smokers. No difference was found in the risk of metaplsia between ex-smokers and non-smokers. These results implied that smoking was likely related to the development of metaplsia in sputum. Using cigarette filter and emphysema were also risk factors of metaplasia positive for smokers. This study recruited 59 restaurant employees and 126 community residents in Taipei city/county. Restaurant employees were younger, with larger portion of females and lower education level, and more prevalent in cooking oil fume exposure at home than community residents. The restaurant chefs had the highest prevalence rate (13.3%) of calcification at pulmonary X-ray and metaplasia (45.5%) in sputum examinations. The prevalence of metaplasia in sputum for restaurant chefs was 1.2 times higher than restaurant staff (36.4%) and 1.9 times higher than cook assistants (23.5%). The study results suggest that the development of metaplasia in sputum is likely associated with cooking and smoking. Improved ventilation while cooking and smoking cessation may reduce the likelihood of developing the metaplasia in sputum. (2) Hematological and Biochemical Factors in Predicting SARS Fatality in Taiwan Severe acute respiratory syndrome (SARS) has a high fatality rate (10.9%) worldwide. We examined the epidemiological and clinical patterns associated with deaths for all SARS patients. Plasma C-reactive protein (CRP) is an important indicator of inflammation. We also investigated factors associated with the CRP concentration among SARS patients in Taiwan. Using initial data in medical records reported by hospitals to the Center for Disease Control in Taiwan, we analyzed whether hematological, biochemical and arterial blood gas measures for patients predict the fatality for 346 SARS patients. Both fatalities (n=73 or 21.1%) and survivors had elevated plasma concentration of initial CRP with higher average in fatalities (47.7±43.3 mg/L) than in survivors (24.6±28.2 mg/L), and low lymphocytes counts in both fatalities(814 /mL±378 /mL)and survivals(1019 /mL±480 /mL). After controlling for age and sex, the multivariate model showed that patients with neutrophils higher than 7000 /mL were at the highest risk of fatality (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 1.1-36.0). Other significant conditions independently associated with deaths included CRP (OR=5.8) and lactic acid dehydrogenase (LDH, OR=4.2). This study also found SARS patients with chronic obstructive pulmonary disease, cerebrovascular accident and/or cardiac diseases had a higher average level of CRP approximately 61.5 mg/L. Compared with survivors with no dyspnea, the age-sex-adjusted odds ratios in patients with CRP levels greater than 47.5 mg/L were 6.0 (95% CI = 1.8-20.3) for fatalities with dyspnea, 3.5 (95% CI = 1.3-9.0) for survivors with dyspnea, and 2.8 (95% CI = 1.0-7.4) for fatalities with no dyspnea. Neutrophil counts, and CRP and LDH levels are important predictors of deaths from SARS. The initial CRP not only is a marker associated with the progress of SARS, but also can be used to predict the severity of the coronavirus infection.