臺灣博碩士論文加值系統

慢性肺病(Chronic pulmonary disease)是全球近10年來盛行率逐漸升高的肺部疾病，其成因複雜，與宿主本質及外在環境因子有關，有需要就國人的現況進行探討。本研究之重點即利用現有全民健保資料庫、空氣污染和氣象監測資料以及疾病管制局所提供之病毒合約實驗室檢測資料，進行外在環境因子對本國成人慢性呼吸道疾病之近年影響研究，以期能獲知外在環境因子、肺炎、流行性感冒以及流行性感冒疫苗接種對疾病盛行影響之程度。
研究進行分為四個方向。首先，利用全民健保資料分析國內慢性呼吸道疾病最近7年之就醫盛行率，並探討疾病嚴重度與個案本質之相關性；第二，建立氣象因子（尤其是極端氣象）和空氣污染物等外在環境因子，以波以松回歸模式(Poisson regression model)估計對疾病就醫之相對危險性；第三，分析國內肺炎及流感地區別就醫之盛行率，並針對氣象因子、空氣污染物及流感病毒活性之間進行一相關性分析；第四，針對慢性肺部疾病患者，探討其肺炎及流感就醫發生對其後續慢性肺病發生之存活分析，計算其危險比。
慢性肺部疾病盛行率有逐年下降之趨勢，盛行率以台北最低，高雄、花東地區最高，年長者為主要危險人口，並以肺炎與流感為慢性肺病住院個案最顯著的疾病合併症，勝算比為2.16 (95% CI: 2.00-2.34, p < 0.0001)。肺炎及流感盛行率升高至1998-1999年之後便逐年下降，地區盛行率台中、高雄地區相近，台北最低，年齡15歲以下族群具有較高的風險，並以慢性肺部疾病為最相關的疾病合併症。
氣候因子相關分析結果顯示，平均溫度(average temperature)在5百分位以下時對台灣三大都會區的慢性肺病就醫風險最高，RR=1.18 (95% CI: 1.13-1.23, p < 0.0001)，其次是最高溫度(maximum temperature)在5百分位以下時，RR=1.11 (95% CI: 1.07-1.15, p < 0.0001)，最低溫度(minimum temperature)與就醫危險並未達顯著相關性。分地區比較，台北及台中地區均在極低溫時(<5%)對慢性肺部疾病有較高的激發風險，但是在高雄卻是偏高溫時影響較大。分疾病比較，支氣管/肺氣腫/氣喘(bronchitis/emphysema/asthma)對大氣環境反應較顯著，慢性阻塞性肺病(chronic obstructive pulmonary disease)則無。研究期間(1996-2002)就醫次數介於7-28次的族群（疾病嚴重度2）對大氣環境也較為敏感。空氣污染物對慢性肺病的影響，在台北、高雄地區以NOx最具相關，台中地區則和PM10及SO2的相關最大。此外，春秋季的低濕度、夏秋季的低風速及夏秋季高日照率，均是除了平均溫度之外顯著增加慢性肺部疾病就醫風險的氣象相關因子。除了慢性阻塞性肺病，當週肺炎及流感就醫對當週慢性肺部疾病就醫風險均達顯著相關。
低溫和台北地區的肺炎及流感就醫相關最大，當週相對危險1.31 (95% CI: 1.20-1.42, p<0.0001)，在高雄地區，相對危險為1.19 (95% CI: 1.09-1.31, p<0.0001)，相較之下，台中約延遲四週才會看到低溫的影響。低相對濕度對肺炎及流感就醫亦有顯著的風險存在。空氣污染物以NOx增加就醫的相對危險最具一致性，每上升1 ppb NOx，整合三都會區的相對危險為1.005 (95% CI: 1.003-1.007, p<0.0001)，台北地區1.004 (95% CI: 1.001-1.007, p= 0.0175)，台中地區1.005 (95% CI: 1.002-1.008, p= 0.0027)以及高雄地區1.011 (95% CI: 1.007-1.015, p< 0.0001)。此外，台北地區PM10濃度亦是會增加就醫危險之空氣污染，相對危險1.003 (95% CI: 1.002-1.004, p<0.0001)。
觀察肺炎及流感暴露對慢性肺病就醫的存活分析，冷季(11 - 4月)30天累積存活率低於熱季(5 - 10月)的。流行性感冒疫苗接種實施後高於疫苗接種計畫實施前，男性低於女性。在接種前，高雄地區的30天累積存活率最低為0.42，接種後以花東地區累積存活率最低，為0.31。同樣的，疫苗接種前以0-14歲及50-69歲累積存活率最低，但在接種後，60-69歲族群累積存活率上升最多，由0.42至0.54。細分不同的慢性肺病，肺炎及流感對慢性阻塞性肺病就醫的危險比最高，達11.7 (95% CI: 8.64-15.7, p <0.0001)，支氣管/肺氣腫/氣喘次之，危險比4.82 (95% CI: 4.60-5.05, p <0.0001)；對兩種疾病均有被診斷的族群，影響最小，危險比2.59 (95% CI: 2.42-2.78, p <0.0001)。校正年齡、性別、地區、疫苗接種、個案疾病分類、時間（年）及季節的影響後，肺炎及流感暴露對慢性肺病就醫之危險比為3.91 (95% CI: 3.76-4.07, p <0.0001)。
本研究總結高雄地區為三都會區慢性肺部疾病及肺炎及流感就醫盛行率較高地區，大氣環境的低溫對台北及台中地區的慢性肺部疾病就醫風險貢獻較大，但空氣污染對高雄地區貢獻較大。相較之下，肺炎及流感的暴露危險性一致，並遠高於大氣環境的貢獻，然而，肺炎及流感亦受地區性氣象及空氣污染情形所影響。

Chronic pulmonary diseases (CPDs) are slowly progressive heterogeneous disorders of the airways with associated etiological factors remain nebulous and debatable. This study aimed to analyze the prevalence and risks of the diseases for the three metros, and Hualien/Taitung area in Taiwan. We used universal health insurance claims, measurements of air pollutants and weather, and virological surveillance data to clarify the relative importance of potential risk factors.
We first used the reimbursement claims file of an established cohort from the National Health Insurance programe to estimate the chronological prevalence of CPDs and pneumonia and influenza (P&I) and comorbidity associated with severity of these diseases by multiple polytomous regression analyses between 1996 and 2003. The Poisson regression model was used to estimate the risk for these two diseases associated with weather conditions and air pollution, etc. We also conducted survival analyses for patients to compare the difference between patients with and without pneumonia and influenza.
The chronological analysis for the population-based cohort demonstrated a dramatic pattern of declining prevalence of CPDs and P&I for the population in Taiwan two to three years after the launch of the nationwide health insurance. CPDs were the most common in the elderly but P&I were most prevalent in population aged 14 years and less that both with the highest rate in Kaohsiung, Taitung and Hualien and the lowest in Taipei. Pneumonia and influenza (P&I) were founded as the most important co-morbidities associated with the hospitalization for CPDs with an odds ratio of 2.16 (95% confidence interval (CI): 2.00-2.34, p < 0.0001).
The risk for CPDs was the highest when ambient average temperature was at extreme cold (less than 5 percentile in 3 metros) with an overall relative risk (RR) of 1.18 (95% CI: 1.13-1.23, p < 0.0001). This association was significant in Taipei and Taichung, but not in Kaohsiung. This atmospheric environment association was significant for both bronchitis/emphysema/asthma (BEA) and severity of the disease (7-28 clinic vists), but not the chronic obstructive pulmonary disease (COPD). NOx had a greater health impacts in Taipei and Kaohsiung, but PM10 and SO2 in Taichung. Low wind speed and high sunshine rate in summer and autumn, and low relative humidity in spring and autumn were also significant weather conditions associated with the occurrence of CPDs. In all association models, P&I was consistently a significant risk factor for CPDs.
The risk for P&I associated with extreme cold was greater in Taipei with a RR of 1.31 (95% CI: 1.20-1.42, p<0.0001) than in Kaohsiung with a RR of 1.19 (95% CI: 1.09-1.31, p<0.0001). Low relative humidity was also an important risk factor for P&I. Nitrogen oxides (NOx) was a significant air pollutant associated with P&I morbidity, with a RR of 1.004 (95% CI: 1.001-1.007, p= 0.0175) for per 1 ppb NOx increase in Taipei, 1.005 (95% CI: 1.002-1.008) in Taichung, and 1.011 (95% CI: 1.007-1.015) in Kaohsiung. The risk for P&I morbidity associated with PM10 of 1 microgram per cubic meter increase was also significant (RR=1.003, 95% CI: 1.002-1.004) in Taipei.
In the survival analysis for the association between clinic visits of P&I and CPDs, the results showed that a lower cumulative survival rate occurred in cold season, male, and period before the influenza vaccination program. Lower cumulative survival rates for CPDs also appeared in the Kaohsiung population and those aged 0-14 and 50-69 years old before vaccination. But, there was a significant increase in survival in cases aged 60-69 years old, rose from 0.42 to 0.54. There was a greater impact from P&I for COPD with a hazard ratio (HR) of 11.7 (95% CI: 8.64-15.7, p <0.0001) than for BEA (HR= 4.82, 95% CI: 4.60-5.05, p <0.0001). The effect was reduced for those diagnosed with both BEA and COPD (HR= 2.59, 95% CI: 2.42-2.78, p <0.0001). Overall, the HR associated with pneumonia and influenza for CPDs was 3.91 (95% CI: 3.76-4.07, p <0.0001) after controlling for age, sex, area, vaccination, disease category and season.
In conclusion, the prevalence of reimbursement claims for the care of CPDs during 1996-2002 in Taiwan varied by area in association with P&I prevalence, regional weather conditions and air pollution. P&I had strongest association with the risk for CPDs in the 3 study metros. Among the 3 areas, the ambient temperature was also a significant risk factor for CPDs in Taipei and Taichung and air pollution in Kaohsiung.

目錄
口試委員會審定書 i
誌謝 ii
中文摘要 iii
英文摘要 v
目錄 viii
表目錄 x
圖目錄 xiii
中英文名稱對照表 xvi
前言 1
研究目的 1
第一章 文獻回顧 2
第一節 研究背景及重要性 2
第二節 誘發因子與呼吸道疾病發生之關係 2
第三節 風險因子交互作用與呼吸道疾病發生之關係 6
第四節 其他影響因子 9
第五節 統計分析方法 11
第二章 材料與方法 12
第一節 研究材料 12
第二節 研究方法 12
第三節 分析步驟 17
第三章 結果 22
第一節 慢性肺部疾病盛行率及宿主合併症之影響 22
第二節 肺炎及流感盛行率及合併症之影響 23
第三節 大氣環境對慢性肺部疾病就醫之危險分析 23
第四節 病毒檢測與肺炎及流感就醫之關係 26
第五節 大氣環境對肺炎及流感就醫之危險分析 27
第六節 肺炎及流感對慢性肺部疾病就醫之存活分析 27
第四章 討論 30
第一節 慢性肺部疾病盛行率及宿主合併症之影響 30
第二節 大氣環境對慢性肺部疾病就醫之危險分析 32
第三節 肺炎及流感盛行率及宿主合併症之影響 34
第四節 大氣環境對肺炎及流感就醫之危險分析 36
第五節 肺炎及流感對慢性肺部疾病之存活分析 38
第六節 研究限制 40
第五章 結論 41
參考文獻 43
附錄一 112
橫斷式及世代盛行率分析中研究母群地區、年齡、性別之逐年變化 112
附錄二 119
PREVALENCE AND RISKS OF CHRONIC AIRWAY OBSTRUCTION - A POPULATION COHORT STUDY IN TAIWAN 119
附錄三 142
IMPACT OF PNEUMONIA AND INFLUENZA EPIDEMIC ON MORTALITY FROM CHRONIC CARDIOPULMONARY DISEASES IN TAIPEI 142
附錄四 167
CRITICAL RISKS FOR ENTEROVIRUSES INFECTION – RELATIVE SIGNIFICANCE OF CIRCULATED VIRUSES AND AMBIENT TEMPERATURE 167
口試委員審查意見書 191

表目錄
表 一：空氣污染物對成人呼吸道的健康影響 3
表 二：1996-2002年台灣地區全民健保20萬人世代之慢性肺部疾病個案人口學和疾病嚴重度分布 56
表 三：多分類邏輯式回歸分析人口學因子暨共發病症對支氣管/肺氣腫/氣喘(bronchitis/emphysema/asthma)個案門診就醫嚴重度之勝算比（95％信賴區間） 57
表 四：多分類邏輯式回歸分析人口學因子暨共發病症對慢性氣道阻塞(COPD)個案門診就醫嚴重度之勝算比（95％信賴區間） 58
表 五：邏輯式回歸分析人口學因子暨共發病症對慢性肺部疾病個案住院之勝算比（95％信賴區間） 59
表 六：人口學因子及宿主合併症對不同程度之肺炎及流感UHICs (unique health insurance claims)之勝算比(odds ratio) 60
表 七：1996-2002年台灣三大都會區氣象因子週次平均值之 百分位值 61
表 八：以波以松迴歸(Poisson regression model)分析週平均溫度百分位對慢性肺部疾病就醫相對危險，模式中5項指標空氣污染物與當週肺炎及流感UHIC之相對危險 - 單位為和每上升一單位相關的相對危險 62
表 九：以波以松迴歸(Poisson regression model)分析週平均溫度百分位對支氣管/肺氣腫/氣喘(bronchitis, emphysema and asthma)就醫相對危險，模式中5項指標污染物與當週肺炎及流感UHIC之相對危險 - 和當週污染物濃度每上升一單位相關的相對危險 63
表 十：以波以松迴歸(Poisson regression model)分析週平均溫度百分位對慢性阻塞性肺病（COPD）就醫相對危險，模式中5項指標污染物與當週肺炎及流感UHIC之相對危險 - 單位為和每上升一單位相關的相對危險 64
表 十一：以波以松迴歸(Poisson regression model)分析週次平均溫度對不同疾病嚴重度慢性肺部疾病就醫相對危險，模式中5項指標污染物與當週肺炎及流感UHIC之相對危險 - 單位為和每上升一單位相關的相對危險 65
表 十二：流行性感冒病毒陽性率之相關係數 67
表 十三：流感病毒陽性率與氣象因子的Pearson相關性 68
表 十四：校正時間參數後台灣地區週次別病毒陽性率對於65歲以下肺炎及流感就醫週次別總個案數發生之相對風險 69
表 十五：校正時間參數後台灣地區年齡別週次病毒陽性率對於當週年齡別肺炎及流感就醫個案數發生之相對風險 70
表 十六：校正地區、時間、年齡、性別、大氣壓力、相對濕度及5項指標空氣污染物濃度參數後台灣三大都會區地區週平均溫度百分位對於週次肺炎及流感就醫發生之相對風險 71
表 十七：校正時間、年齡、性別、大氣壓力、相對濕度及5項指標空氣污染物濃度參數後台北地區週平均溫度百分位對於週次肺炎及流感就醫發生之相對風險 71
表 十八：校正時間、年齡、性別、大氣壓力、相對濕度及5項指標空氣污染物濃度參數後台中地區週平均溫度百分位對於週次肺炎及流感就醫發生之相對風險 72
表 十九：校正時間、年齡、性別、大氣壓力、相對濕度及5項指標空氣污染物濃度參數後高雄地區週平均溫度百分位對於週次肺炎及流感就醫發生之相對風險 72
表 二十：校正地區、時間、年齡、性別、大氣壓力、平均溫度及5項指標空氣污染物濃度參數後台灣三大都會區地區別週平均相對濕度百分位對於當週肺炎及流感就醫發生之相對風險 73
表 二十一：以波以松迴歸(Poisson regression model)分析週平均溫度百分位肺炎及流感就醫相對危險，模式中5項指標污染物相對危險 - 和當週污染物濃度每上升一單位相關的相對危險 74
表 二十二：肺炎及流感暴露對慢性肺部疾病存活分析之族群特性 75
表 二十三：存活分析族群(n=4,241)月份別疾病就醫人次 75
表 二十四：疫苗接種前後（以1999年分隔）肺炎及流感對慢性肺部疾病就醫之性別及地區別危險比(hazard ratio, HR)及95％信賴區間 76
表 二十五：疫苗接種前後（以1999年分隔）肺炎及流感對慢性肺部疾病就醫之年齡別危險比(hazard ratio, HR)及95％信賴區間 77
表 二十六：疫苗接種前後（以1999年分隔）肺炎及流感對慢性肺部疾病就醫之危險比(hazard ratio, HR)及95％信賴區間 78
表 二十七：2000年台北、台中及高雄以及花蓮台東地區社會經濟結構212 79
表 二十八：1993-2003年台灣三大都會區指標空氣污染物百分位值 80



圖目錄
圖 一：研究架構圖 81
圖 二：Cox regression model資料分組 82
圖 三：世代分析人口數（左）與橫斷式分析人口數（右）逐年變化 83
圖 四：固定世代地區別、性別人數逐年變化 83
圖 五：三大都會區每日肺炎及流感就醫人次與與每次就醫事件的第一筆資料(unique health insurance claims, UHIC)趨勢圖 84
圖 六：1996-2002年台灣三大都會區與花蓮台東地區慢性肺部疾病年齡別就醫率（橫斷分析） 85
圖 七：台北都會區1996-2002慢性肺部疾病年齡別就醫率（世代分析） 86
圖 八：台中都會區1996-2002慢性肺部疾病年齡別就醫率（世代分析） 86
圖 九：高雄都會區1996-2002慢性肺部疾病年齡別就醫率（世代分析） 87
圖 十：花蓮台東1996-2002慢性肺部疾病年齡別就醫率（世代分析） 87
圖 十一：1996-2002年歸人檔慢性呼吸道疾病、肺炎及流感於每日就醫人次 88
圖 十二：1996-2003年歸人檔地區別慢性呼吸道疾病、肺炎及流感每月就醫人次 88
圖 十三：1996-2002年台灣三大都會區與花蓮台東地區肺炎及流行性感冒年齡別就醫率（橫斷分析） 89
圖 十四：台北都會區1996-2002肺炎及流行性感冒年齡別就醫率（世代分析） 90
圖 十五：台中都會區1996-2002肺炎及流行性感冒年齡別就醫率（世代分析） 90
圖 十六：高雄都會區1996-2002肺炎及流行性感冒年齡別就醫率（世代分析） 91
圖 十七：花蓮台東地區1996-2002肺炎及流行性感冒年齡別就醫率（世代分析） 91
圖 十八：1995-2003年台灣三大都會區與花蓮台東地區逐週氣象測值平均值 92
圖 十九：1994-2003年台灣三大都會區與花蓮台東地區指標空氣污染物逐週趨勢 93
圖 二十：台灣三大都會區季節性氣象因子對慢性肺部疾病就醫之相對危險 94
圖 二十一：台灣三大都會區季節性氣象因子對支氣管炎/肺氣腫/氣喘疾病就醫之相對危險 94
圖 二十二：台灣三大都會區季節性氣象因子對慢性阻塞性肺病疾病就醫之相對危險 95
圖 二十三：台灣三大都會區週次平均溫度對不同疾病嚴重度之慢性肺病疾病就醫之相對危險 95
圖 二十四：週次平均溫度對台北地區慢性肺部疾病不同疾病嚴重度之相對危險（左）及極端溫度之延遲效應（右） 96
圖 二十五：台灣三都會區氣象因子季節性變化對慢性肺部疾病之相對危險 97
圖 二十六：台北地區氣象因子季節性變化對慢性肺部疾病之相對危險 97
圖 二十七：腺病毒受檢陽性個案數及陽性率（陽性率＝週次別陽性個案數/週次別受檢總個案數） 98
圖 二十八：類流感病毒受檢陽性個案數及陽性率（陽性率＝週次別陽性個案數/週次別受檢總個案數） 98
圖 二十九：呼吸道融合病毒受檢陽性個案數及陽性率（陽性率＝週次別陽性個案數/週次別受檢總個案數） 99
圖 三十：B型流行性感冒病毒受檢陽性個案數及陽性率（陽性率＝週次別陽性個案數/週次別受檢總個案數） 99
圖 三十一：A型流行性感冒病毒受檢陽性個案數及陽性率（陽性率＝週次別陽性個案數/週次別受檢總個案數） 100
圖 三十二：台灣地區20萬人世代每月呼吸道疾病及心血管疾病就醫人次 100
圖 三十三：1997年11月-1998年3月間 北部地區每週肺炎及流感就醫人次與台北地區大氣環境測值 101
圖 三十四：1997年11月-1998年3月間 中部地區每週肺炎及流感就醫人次與台中地區大氣環境測值 102
圖 三十五：1997年11月-1998年3月間 南部地區每週肺炎及流感就醫人次與高雄地區大氣環境測值 103
圖 三十六：慢性肺病及肺炎及流感在存活分析世代中依就醫次數個案人數分布 104
圖 三十七：存活世代研究族群地區別逐年變化 104
圖 三十八：存活分析世代在1996-2003年間流感、肺炎、COPD及BEA之疾病別就醫人次 105
圖 三十九：疫苗接種計畫執行前後肺炎及流感暴露對慢性肺部疾病的存活曲線 106
圖 四十：1997/11-1998/04以及2000/11-2001/04期間性別肺炎及流感暴露對慢性肺部疾病的存活曲線 106
圖 四十一：1997/11-1998/04期間各地區肺炎及流感暴露對慢性肺部疾病的存活曲線 107
圖 四十二：2000/11-2001/04期間各地區肺炎及流感暴露對慢性肺部疾病的存活曲線 107
圖 四十三：1997/11-1998/04期間年齡別肺炎及流感暴露對慢性肺部疾病的存活曲線 108
圖 四十四：2000/11-2001/04期間年齡別肺炎及流感暴露對慢性肺部疾病的存活曲線 109
圖 四十五：疫苗接種前後肺炎及流感對慢性肺病疾病別就醫之存活曲線 110
圖 四十六：台灣地區20萬人世代依照年齡及疾病嚴重度區分慢性肺部疾病每月就診人次及個案 111

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