臺灣學齡前兒童血中金屬濃度與過敏反應相關性研究

Abstract

近年來氣喘、過敏性鼻炎、異位性皮膚炎等過敏疾病的盛行率在許多國家都有上升的趨勢，台灣地區的過敏疾病也有一樣的發展趨勢，其中又以青少年及兒童的盛行率明顯偏高。造成過敏的原因有很多，像是接觸到過敏原、性別、年齡、環境暴露等；另外，體內金屬濃度改變時也可能導致過敏反應產生。本研究即以學齡前兒童血中多種金屬濃度和過敏反應之相關性進行探討。 本研究之研究個案為2011年國民健康局學齡前兒童血中鉛濃度調查研究計畫中的研究個案，以各級行政區域為基礎，分層隨機抽樣自全國80家幼稚園。研究個案個人與家庭背景資料，以及可能的環境金屬暴露來源等資料係以問卷資料來蒐集。本研究自上述2011年國民健康局研究計畫中，選取已完成全血鉛、銅、錳、鋅、砷、硒、汞濃度分析，以及已完成血清中總IgE濃度分析，且剩餘血清樣本量足夠的樣本，進行血清中特定過敏原IgE之濃度分析。全血中金屬濃度之檢測分析使用感應耦合電漿質譜分析儀。血清中總IgE和特定過敏原IgE則分別使用電化學冷光分析法和特定過敏原免疫檢驗分析法。 本研究之研究個案血中鉛平均濃度為21.9±14.8 μg/L；銅平均濃度為965±163 μg/L；錳平均濃度為14.6±3.73 μg/L；鋅平均濃度為4758±772 μg/L；砷平均濃度為4.06±2.8 μg/L；硒平均濃度為111±19.3 μg/L；汞平均濃度為5.44±3.01 μg/L。另外，研究個案血清中總IgE平均濃度為291±415 IU/mL。特定過敏原IgE部分以CLA冷光光度計分級標準分為四級，研究個案對粉塵蟎及屋塵蟎達第四級過敏的比例最高，分別為56位(31.5%)和55位(30.9%)，對家塵達第四級過敏的研究個案有28位(15.7%)，對蟑螂達第四級過敏的則有12位(6.7%)。其它過敏原像是乳膠、蚌殼類、黃豆、雞羽毛、尤加利、日本杉、貓毛及狗毛等有過敏的人數較少，分別只有2~5位研究個案有第二級以上的過敏狀況。 本研究發現血中銅濃度每增加1 μg/L會使打噴嚏、流鼻水或鼻塞(OR=1.004, 95% CI=1.001~1.006)，以及患有異位性皮膚炎(OR=1.005, 95% CI=1.001~1.01)和對屋塵蟎(OR=1.004, 95% CI=1.000~1.007)、粉塵蟎(OR=1.003, 95% CI=1.000~1.007)過敏的勝算比增加。研究個案血中錳濃度每增加1 μg/L，會使其對家塵(OR=0.837, 95% CI=0.723~0.968)、粉塵蟎(OR=0.787, 95% CI=0.675~0.918)及屋塵蟎(OR=0.82, 95% CI=0.707~0.944)過敏的勝算比降低。血中硒濃度每增加1 μg/L會使研究個案對蟑螂過敏的勝算比增加(OR=1.08, 95% CI=1.003~1.15)。 本研究結果顯示，兒童血中金屬濃度改變會使兒童對特定過敏原過敏的勝算比改變，其中又以血中錳濃度的改變對特定過敏原IgE的影響較大。另一方面，本研究發現表示曾患有氣喘疾病的研究個案，其血中錳、鋅、硒濃度有較低的情形，雖然未達統計上顯著差異，但氣喘與金屬濃度之間的相關性和先前研究觀察結果相符。鑑於目前針對人體內金屬濃度和特定過敏原IgE相關性之探討仍少，因此本研究的結果可提供金屬暴露與特定過敏原之間關係的初步瞭解，未來仍須後續研究進一步探討，期對金屬暴露和特定過敏原IgE的互動機制有更深入的瞭解。

In many countries, the prevalence of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis is arising in recent years. Similar trend was also observed in Taiwan, especially for the high prevalence among young people and children. The causes leading to allergy vary, such as allergen contact, gender, age, and environmental exposures. Even the blood metal concentrations might affect allergic reactions. Thus, in this study, we tried to investigate the relationship between allergic reactions and multiple blood metal levels of the preschool children in Taiwan. Study subjects in this study were recruited from a previous study entitled “Survey on blood lead levels of the preschool children”, sponsored by the Bureau of Health Promotion (BHP) in 2011. Through a stratified sampling strategy based on different administrative division levels, study subjects were recruited from 80 kindergartens nationwide. Questionnaires were administered to get study subjects’ demographic information, allergic status, and environmental metal exposure factors. The blood samples being successfully analyzed for lead, copper, manganese, zinc, arsenic, selenium, mercury and total IgE in the previous BHP study in 2011 were used to determine allergen-specific IgE in the present study for the study subjects who have sufficient amount of serum left from the previous study. ICP-MS(inductively coupled plasma mass spectrometry) was applied for the determination of metal levels in blood samples, while the analyses for serum total IgE and allergen-specific IgE were carried out using ECLIA(electrochemiluminescence immunoassay) and MAST(multiple antigen simultaneous test), respectively. The means of blood Pb, Cu, Mn, Zn, As, Se, Hg levels were 21.9±14.8 μg/L, 965±163 μg/L, 14.6±3.73 μg/L, 4758±772 μg/L, 4.06±2.8 μg/L, 111±19.3 μg/L, 5.44±3.01 μg/L, respectively. The mean total IgE level was 291±415 IU/mL. On the other hand, allergen-specific IgE were classified into four levels based on CLA-1 Luminometer grading criteria. The highest proportions of study subjects classified as CLA IV were found to be allergic to D. Farinae (31.5%, 56 study subjects) and D. Pterony (30.9%, 55 study subjects), respectively. Twenty eight study subjects (15.7%) were classified as CLA IV for being allergic to house dust. Another 12 study subjects (6.7%) were classified as CLA IV for being allergic to cockroach. Few study subjects were reported to be allergic to latex, clam, soybeans, chicken feathers, eucalyptus, Japanese cedar, cat fur and dog fur, only 2~5 study subjects being classified as CLA II for these allergens, respectively. The results showed that the increment in blood copper level by 1 μg/L would enhance the odds ratio for sneeze, running nose (OR=1.004, 95% CI=1.001~1.006), atopic dermatitis (OR=1.005, 95% CI=1.001~1.01), and being allergic to D. Farinae (OR=1.003, 95% CI=1.000~1.007) and D. Pterony (OR=1.004, 95% CI=1.000~1.007). Study subjects characterized with relatively high blood manganese level by 1 μg/L tended to have low odds ratios for being allergic to D. Farinae (OR=0.787, 95% CI=0.675~0.918), D. Pterony (OR=0.82, 95% CI=0.707~0.944) and house dust (OR=0.837, 95% CI=0.723~0.968). Meanwhile, the increment in blood selenium level by 1 μg/L would decrease the odds ratio for being allergic to cockroach (OR=1.08, 95% CI=1.003~1.15). Findings in the present study suggested that children’s blood metal levels would modify the odds ratios for being allergic to specific allergens, especially for the impact of blood manganese level on the response of allergen-specific IgE. On the other hand, study subjects who had asthma tended to present relatively low blood manganese, zinc, selenium levels, similar to the relationship found in previous studies, though not statistically significant. Results of the present study provided preliminary information regarding the relationship between blood metal levels and the responses of allergen-specific IgE, for which the relevant studies are limited at the current time. However, more evidences are warranted to confirm such a relationship for better understanding the interaction mechanisms between metal exposure and the response of allergen-specific IgE.