世界各國以及台灣地區的研究皆指出兒童氣喘及過敏性疾病之盛行率及嚴重性有不斷攀升的趨勢，然而至今對於不同的遺傳條件及環境因子所貢獻之影響性仍未完全明確，特別是各項危險因子在單獨及共同存在下對不同遺傳條件及年齡層之作用情形尚待評估。此外，全球的工業發展帶動整體生活環境條件的變遷，越來越多新興化學汙染物介入亦嚴重影響相關疾病的發展與表現，有待更多的綜合研究去釐清探討。台灣地處相對高溫高濕的亞熱帶氣候，再加以生活型態以及遺傳特性等多項不同於西方國家之環境因素共同影響，有必要針對本土特殊之條件對於兒童氣喘及過敏性疾病之發展進行系統性評估。本研究的主要目的即針對學齡前孩童評估遺傳特性與環境因子，包含生物性氣膠及新興化學物質的暴露，對於氣喘及過敏性疾病發展及表現的可能影響。本研究包含兩種研究設計，第一部份為利用前期建立之出生世代追蹤研究，了解遺傳特性及室內環境因子對於孩童疾病發展及表現之交互影響情形；第二部份為橫斷式研究，透過大規模問卷調查了解學齡前孩童居家環境之危險因子，並從中選取代表性之研究對象進行居家環境調查，深入評估生物及化學性環境汙染物濃度之變化對於孩童疾病表現及嚴重度之影響。

有鑒於氣喘及過敏性疾病常起源於父母親基因的遺傳，本研究首先利用出生世代研究族群評估父母親的遺傳特性及發生在懷孕及嬰兒時期的其它因素對於日後疾病發生之影響。相似於在其他國家及台灣其他研究團隊前期發表之結果，母親的過敏疾病史及血清中總免疫球蛋白E (IgE)濃度皆與嬰兒臍帶血中的IgE (cord blood IgE, CBIgE)有關；然而，出生時CBIgE的高低及母親疾病史對於日後孩童在3至5歲時過敏及氣喘的疾病表現並無可觀察到的影響。然而，父親的氣喘與過敏疾病史反而是導致孩童在3至5歲時出現過敏及氣喘疾病表現的重要因素；在同時考量父母親的遺傳特性後，居家特性，如燃燒拜香的習慣或是家戶曾遭受淹水等，皆為影響孩童疾病發展的主要環境因子。另外，母親哺乳時食用海鮮類食物的習慣乃孩童日後表現氣喘及過敏性疾病的一大風險因子，對於母親已有過敏疾病史之孩童，此因素尤其重要。對於父母親沒有疾病史的孩童，本研究亦發現在五個月大前即開始餵食副食品可以顯著降低其罹患過敏疾病之風險。

相較於自然環境中其他大部分的汙染物，生物性因子，如過敏原及微生物的暴露，在時代的變遷下是相對恆定的存在，特別是暴露的濃度。延續第一部份發現”家中曾遭受淹水”為影響孩童日後表現氣喘及過敏性疾病的重要因素，本研究進一步評估各類生物氣膠暴露因子對於疾病表現的影響權重。首先透過橫斷式研究中大規模的居家環境問卷調查，發現台灣南部地區的居家環境有偏高的潮濕及霉斑比例，且再次驗證了前期研究結果，的確穩定地影響學齡前孩童呼吸道及過敏性疾病的健康表現。繼而篩選一部份具目標代表性的研究對象，從實境採樣證實，淹水過後的居家環境確實會有顯著較高之活性總真菌濃度室內外比值，佐證世界各國過去僅透過調查問卷所得之發現，即”家中曾遭受淹水與室內較高的生物氣膠暴露濃度有關”。有鑒於此，我們進一步透過全面且完整的居家生物性汙染物調查來比較不同生物氣膠汙染物濃度的變化，並證明不同環境汙染指標，如「室內外活性真菌濃度比值」及「室內真菌孢子濃度」對於評量疾病表現及其嚴重度的重要角色與相對權重，特別是真菌孢子中的Penicillium/Aspergillus對於孩童過敏性症狀的影響最為顯著。最後，本研究亦透過分析孩童體內IgE濃度變化與居家霉斑嚴重程度的相關性，初步驗證真菌暴露對於人體免疫過敏機制可能不僅扮演過敏原的功能，亦有輔助性角色 (adjuvant effect)的潛勢。

在現代社會高度工業化之下，伴隨日常生活中日益增加的便利性，衍伸新的健康危機。根據大規模的問卷調查及數據分析，我們發現孩童使用奶瓶的時間越長，表現過敏性鼻炎及具有呼吸道症狀表現的風險亦隨之增加。在高度懷疑該相關性與長期慢性的化學物質暴露有關之下，我們選定目前在日常用品中被大量使用的塑化劑- 鄰苯二甲酸酯類 (phthalate esters)進行探討。透過全面性的暴露評估調查，並考量其他居家生物性暴露因子後，發現家戶地板之上灰塵中benzylbutyl phthalate (BBzP)及dibutyl phthalate (DBP)之濃度高低與被醫師診斷出過敏性鼻炎及濕疹的機率有關，且孩童尿液中代謝物mono-n-butyl phthalate (MBP)及mono-2-ethylhexyl phthalate (MEHP)亦影響氣喘疾病及過敏性鼻炎嚴重度的表現。

本研究首次在東亞族群的流行病學研究中發現父親遺傳特性對於兒童氣喘及過敏性疾病表現的關鍵性角色，並透過大規模問卷及居家環境中各項汙染物的實境採樣評估調查，證明室內真菌暴露乃影響本土孩童過敏及氣喘疾病發展及嚴重度表現的重要危險因子之一。尤其重要者，本研究係亞洲地區經由流行病學調查首次證實新興化學物質，如鄰苯二甲酸酯類的暴露，對於影響孩童過敏及氣喘疾病與症狀表現的貢獻程度。希望藉本研究系列性之探溯，將有助於了解我國一般居家環境整體環境暴露之現況及潛在的健康危害風險，以作為未來在環境控制及衛生管理上的依據及參考。

The rising prevalence and morbidity of childhood asthma and allergic diseases has been evident throughout the world and in Taiwan. However, both the qualitative and quantitative contributions of individual risk factors, including variables related to indoor environments, on the development and exacerbation of childhood allergic disease has not been fully understood. Due to its nature as a subtropical island, Taiwan presents a unique environmental exposure profile highly attributable to the development of disease that is little reported in the literatures. In addition, the effect of genetic heredity on childhood asthma and allergic disease in Taiwan population is also expected to be different from what has been demonstrated elsewhere, mostly in the Western Hemisphere. The overall objective of this study was to explore the effects of hereditary and environmental risk factors on reporting allergy and asthma of children at pre-school age in Taiwan. In addition to looking into the relative contribution of each individual factor, either single or concurrent presence, the effects of various combinations of different factors were further examined. This study was designed to consist of two major components; the first of which was the Birth Cohort Study to assess how the hereditary and environmental factors would influence the development of allergy and asthma. The second was a Cross-Sectional Study with a large-scale questionnaire survey and field investigation of selected subjects in order to verify the potential risk factors contributing to the reporting of disease and symptoms.

Since the diseases of interest in this study were fundamentally facilitated by genetic heredity, the first part of this study focused on how hereditary and certain parental factors would influence the development of childhood asthma and allergy. The results indicated that maternal history and total IgE levels during pregnancy were both associated with the detectable Cord Blood Immunoglobine (CBIgE) level of infants; yet, in 3 to 5 years old children, the allergic morbidities was not related to their CBIgE levels at birth. The consumption of seafood by the mother during the breastfeeding stage would increase the risk of her child in developing allergy-related diseases at the age of 3 to 4 years old. On the contrary, the introduction of complementary foods before the age of 5 months was inversely associated with the development of allergic disease in the group of children without parental allergic history. Paternal history of allergy and asthma was the significant determinant of allergic and respiratory morbidities in 3 to 5 year old children, while various housing factors had an increasingly significant effect on children’s health if their fathers had a history of asthma or allergy. Incense burning and water damage in the home were the most attributable housing factors in the development of allergic disease.

Regardless of the changing of times, the exposure of allergens and microbes in nature was thought to be steadier in quantitative exposure levels compared to other pollutants. Consequently, assessing the role of bioaerosol exposure was therefore be the main focus in the second part of this study to verify the significance of exposure to water damage through a cross-sectional Study. It was found that Taiwan had a higher prevalence of the dampness problem than many other areas and the significant effect of dampness and visible mold exposure on reporting allergic status in pre-school children was confirmed again through a large-scale questionnaire survey. However, it is still unclear whether the factor of water damage at homes is directly associated with higher levels of fungal exposure indoors. Therefore, the increasing Indoor-Outdoor (I/O) ratio of fungal levels in homes after a major flooding event was confirmed in current study. We further conducted a household investigation to compare the relative effects of each bioaerosol indicator, including culturable fungi, fungal spores and other agents, on the childhood health. A higher fungal I/O ratio and indoor spore levels affect allergic and respiratory morbidities of children. Moreover, among all fungal species investigated, only exposure to airborne Penicillium/Aspergillus spores was associated with the reporting allergic symptoms of children. The role of fungal exposure as an adjuvant on the immune mechanism of children was preliminarily suggested through this study.

For the last part, the potential health effect of children exposed to emerging pollutants, which have dramatically increased in amounts of usage in recent years, was discussed. The dose-effect relationship between the length of time that feeding bottles are used and the increase in the risk of reporting rhinitis and respiratory symptom in children was first established in this study. Moreover, benzylbutyl phthalate (BBzP) and dibutyl phthalate (DBP) levels in settled dust as well as levels of mono-n-butyl phthalate (MBP) and mono-2-ethylhexyl phthalate (MEHP) in urine were associated with the presence of diseases and symptoms in our study taking into account the concurrent assessment of other indoor pollutants was performed.

While genetic heredity, especially in relation to paternal history, was the most significant determinant of allergic and asthmatic diseases of children, fungal exposure was found as one of the most important risk factor associated with the development and exacerbation of the disease in our population. Moreover, the correlation between recent increases in the amount of exposure to phthalates and the increased presence of allergy and asthma was first shown among the Asian population in our study. Potential health effects from increasing exposure to chemicals should become a high point of concern in the coming days. The current study provides better understandings about the profile of indoor exposures in general household, and indicates the potential health concerns in children of Taiwan. It was used as a reference for future environmental control and health management programs designed to improve the public health.

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