隨著工商業的發達，氣喘及過敏性鼻炎等過敏症盛行率有逐年上升的趨勢。國中小的學童可說是國家未來發展的主幹，同時也是呼吸道過敏性疾病最高的族群，對環境污染感受性也最高。在1995至1996年環保署曾利用空氣污染防治費，委託多所大學同時進行全國國中學童呼吸道健康問卷的調查與肺功能抽測。結果發現氣喘盛行率在如台北市等高度都市化及工業化的城市要比其他縣市高出許多。但到底是什麼原因造成此種城鄉差距呢？因此，篩檢國小與國中學童的氣喘與過敏性鼻炎等呼吸道相關疾患，詳細評估其環境與遺傳危險因子，並進一步瞭解國小與國中學童在基因易感性上的不同，探討空氣污染對氣喘與呼吸道疾患之影響，在不同基因易感族群是否有不同的效應，相信對訂定預防政策，降低社會與醫療成本並增進學童健康，應有很大的幫助。
　　氣喘是一由多因子共同作用參與的疾病。主要的影響因素可分成遺傳因子與環境污染因子兩大類。環境因子方面，最常被討論的是室內過敏原暴露。常見的過敏原有塵蹣、蟑螂、貓毛與狗毛；在遺傳因子方面，β2-adrenergic receptor（β2AR；用來治療氣喘的β-agonist之受器），腫瘤壞死因子tumor necrosis factor（TNF）等基因特定的基因型，可能與氣喘的發生有關。過去的研究顯示β2AR基因多型性與肺部的發育有關，Lymphotoxin-α（LTα）被認為與IgE的產生有關，TNFα、以及Glutathione S-transferase （GST）P1也與呼吸道的高反應性（bronchial hyper-responsiveness）有關。我們想知道這些特殊標的基因的基因型，是否在我們的研究族群分佈與國外研究相同。本研究也同時討論環境與遺傳因子交互作用。
　　在取得1995至1996年環保署的全國國中學童呼吸道健康問卷資料之後，我們透過管道取得1994至今環保署全國空氣污染監測站的資料，首先連結此兩個龐大的資料庫，以了解台灣本島之溫度、濕度和空氣污染物的濃度，與國中學童氣喘及過敏性鼻炎等過敏症盛行率的相關性。因為1995至1996年的調查並未仔細探討室內室外環境因子與遺傳因素，因此在2001年，我們再次進行一次全國學童的呼吸道健康問卷抽樣調查，在問卷中加入許多有關問題進行詳細評估，以釐清它們與氣喘等過敏症之間的相關性。最後，我們利用支氣管激發試驗（bronchial challenge test）來辨識支氣管的高反應性，並且以口腔黏膜細胞採檢，進行B2AR-16、B2AR-27、B2AR-167、TNFα-308、LTα、IL4 -590、FcεRIβ及GST P1等基因型分析。期望瞭解我國學童在這些相關的基因型態分佈與氣喘等呼吸道過敏症的關聯。另外，進一步探討基因---環境（gene—environment interaction）交互作用的關係，並計算不同基因易感型態（genetic susceptibility）的孩童，各承受多少倍的相對罹病風險。
　　本研究期望能回答以下四點疑問：1)室外空氣污染程度與國中學童氣喘及過敏性鼻炎的盛行率是否相關？2)除了室外空氣污染，是否還有其他室內環境因子或遺傳因素能夠造成氣喘的發生？其在男性與女性的貢獻性各為多少？3)基因多型性與各種氣喘相關症狀以及支氣管高反應性是否相關？4)不同的空氣污染程度，對於台灣學童各種基因易感性，在氣喘發生率以及支氣管高反應性上，是否有修飾效應（effect modification）的關係？
　　結果發現，室外的空氣污染指標，尤其是與汽機車排放相關的NOx與CO，與學童氣喘盛行率成正線性相關，每降低NOx 17.3 ppb或CO 326 ppb，在男生可以降低0.88％的氣喘發生率，女生可降低0.50％的氣喘發生率。而且，除了非夏季的氣溫之外，國中學童之氣喘與過敏性鼻炎盛行率，的確與交通相關之空氣污染物的劑量成正比。因此我們認為室外的空氣污染，確實是學童呼吸道疾病的重要危險因子。
　　2001年的調查結果顯示，經醫師診斷的氣喘（physician-diagnosed asthma）盛行率，男性為8.1％而女性為5.6％。較低學童年齡、較高的父母親教育程度、較少的兄弟姊妹、以及母親在懷孕時吸菸都是學童氣喘的危險因子。雖然男生的氣喘盛行率比女生高出許多，女生比男生在室內環境因子的易感性較高（OR 1.24 vs 1.04）。但是，遺傳因子與室外環境因子則對兩性間的影響沒有太大的差別。若比起各項危害因子，在學齡孩童的氣喘發生原因上，不論在男生或是女生，遺傳因子遠比各種環境因子的貢獻度高出許多。對於2001年全台灣約195,300位氣喘學童而言，若消除室外環境因子，大約可減少26,500個氣喘個案，而消除室內環境因子，則可減少16,500個個案，因此，積極控制環境因子，尤其是室外的空氣品質，對於學童的氣喘防制應該會有顯著的效果。
　　經過了問卷以及支氣管激發試驗結果的篩選，在61位氣喘確定病例與95位控制組間，各種氣喘相關基因型上，均無統計顯著差異。但是在校正年齡、性別等可能的干擾因素後，在高室外空氣污染環境之下，GSTP1-105基因帶有Ile/Ile基因型的勝算比對於氣喘發生，則到達了統計上顯著的影響程度（OR = 3.79; 95% CI: 1.01 to 17.08; population attributable risk = 62.4%）。這種情況在較低空氣污染的環境中則不顯著。所以室外空氣污染程度對於台灣學童GSTP1-105基因易感型態，在氣喘發生率以及支氣管高反應性上，有交互作用（interaction）以及修飾效應的關係。基於以上研究我們認為，在政府極力進行空氣污染減量的同時，若能針對特殊的基因易感族群進行防制動作，相信對學童呼吸道疾患的罹病率，會有明顯的改善效果。

　　Many epidemiological studies showed that the increase of asthma prevalence was associated with the growing industrialization worldwide. Studies in other countries supported that the prevalence of asthma increased year by year. A nation-wide screening for childhood asthma among middle school students in Taiwan revealed that the prevalence rates were higher in more urbanized cities, such as Taipei, than less urbanized areas. However, the risk factors for childhood asthma in Taiwan have not been well studied. It is a good time to examine the prevalence of asthma in 2001. We used the standard “International Study of Asthma and Allergies in Childhood”-Chinese version（ISAAC-C） questionnaire to investigate the relationships between asthma prevalence and environmental factors, and the interaction with selected genes.
　　Asthma is a multi-factorial disease. Risk factors could be categorized as environmental and hereditary groups. Indoor environmental allergens were most discussed, which included dust, mites, cockroaches, cat, and dog danders. The polymorphisms of β2-adrenergic receptor（β2AR）, and tumor necrosis factor （TNF）gene cluster were recognized as important hereditary factors for asthma. Lymphotoxin-α（LTα）was associated with IgE productions. The TNFα-308 and Glutathione S-transferase （GST） P1 polymorphisms were also related to bronchial hyper-responsiveness. We also want to know whether such specific genetic distributions in our research population were comparable with the results from international studies.
　　This study was dedicated to solve following questions: 1) Is asthma prevalence in childhood associated with outdoor air pollution? 2) Do other environmental and/or hereditary factors attribute to asthma occurrence? 3) Are genetic polymorphisms associated with respiratory symptoms or bronchial hyper-responsiveness? 4) Is there any interaction between genetic polymorphisms and outdoor air pollution in the risk of childhood respiratory allergic diseases?
　　After we gathered data of 1995 questionnaire survey, it was combined with air monitoring data from air pollution monitoring stations for further analysis. The association of childhood asthma, allergic rhinitis, and outdoor data of temperature, relative humidity, and air pollutants were investigated. In 2001, we performed questionnaire survey again for respiratory diseases in Taiwanese schoolchildren. Because many indoor/outdoor environmental and hereditary factors were not studied in detail in 1995 study, we also included many related questions in the new version questionnaire. Data was used to evaluate the association of respiratory health and these factors, and to calculate their attributable risks respectively. Finally, we suggested bronchial challenge test for determination of bronchial hyper-responsiveness and oral mucosa sampling for polymorphism analyses, including B2AR-16, B2AR-27, B2AR-167, TNFα-308, LTα, IL4 –590, FcεRIβ, and GST P1. We also wanted to know the attributable risks in high outdoor air pollution level and relative risks between different genetic groups. All the study reports could be used as reference for governmental air pollution control act.
　　Outdoor air pollution level, especially NOx and CO, was associated with asthma prevalence in schoolchildren. If NOx and CO were reduced in interquartile level, we could find a decrease in asthma prevalence of 0.88% in boys and 0.50% in girls. Except for nonsummer warmth, traffic-related air pollution was positively correlated with the prevalence of asthma and allergic rhinitis. The relationship also showed clear dose-responsiveness.
　　From 2001 study, physician-diagnosed asthma was reported for 8.1% of the boys and 5.6% of the girls. Older children, higher parental education level, fewer siblings, and history of maternal smoking during pregnancy were proved the predictors of childhood asthma. The risk of physician-diagnosed asthma was also significantly associated with parental atopy and perceived ambient air pollution in both sexes. Although the prevalence of asthma was higher in boys, girls might be more susceptible to indoor factors. Parental atopy contributed more to childhood asthma than indoor or outdoor environmental factors. Of the estimated 195,300 cases of asthma in Taiwanese schoolchildren in 2001, we estimated that approximately 26,500 excess cases and 16,500 excess cases were attributed by outdoor and indoor factors, respectively. Therefore, in order to decrease the prevalence of childhood asthma, it is beneficial and important to well control the environmental factors, especially outdoor air quality.
　　Between 61 definite asthma cases and 95 control subjects selected from questionnaire and bronchial challenge results, there did not exist significant difference in GSTP1-105 and other genetic polymorphisms. After adjustment for age, sex, and potential confounders, odds ratio of Ile/Ile was higher in high air pollution area and showed statistical significance （OR = 3.79; 95% CI: 1.01 to 17.08; population attributable risk = 62.4%）, but those who carried two Ile-105 alleles in low or median air pollution districts did not possess similar tendencies. We could conclude that interaction effects or effect modifications actually showed between outdoor air pollution, genetic factors, childhood asthma, and bronchial hyper-responsiveness. Our data also suggested further air pollution control act in government on those children who carry special susceptible genes.

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