https://scholars.lib.ntu.edu.tw/handle/123456789/111008
標題: | 小兒異位性皮膚炎之環境因子及生物標記 Environmental Factors and Biomarkers for Pediatric Atopic Dermatitis |
作者: | 王怡人 Wang, I-Jen |
關鍵字: | 異位性皮膚炎;神經增長因子;基因多形性;懷孕期香煙暴露;atopic dermatitis;nerve growth factor;genetic polymorphisms;gestational smoke exposure | 公開日期: | 2008 | 摘要: | Part I 經介質作為異位性皮膚炎之預測因子景: 關於異位性皮膚炎的預測因子之研究大多致力於基因和免疫學方面。神經介質的角色仍然未明,需被進一步探討。旨: 評估神經增長因子(NGF), 血管腸生肽(VIP) 和介質P (SP) 是否能預估小兒異位性皮膚炎及探討他們和內因性和外因性異位性皮膚炎的相關性。法: 我們進行一建立在臺灣出生世代上之病例對照研究。臍帶血和母血及相關問卷在出生時即被收集。在後續追蹤期間,我們找到了40個異位性皮膚炎案例,並從出生世代這群人中取80個當對照組。用免疫酵素分析法(ELISA)來驗臍帶血和母血中IgE、NGF、VIP 和SP的濃度。由ROC曲線來看各生物標記是否能精確預估異位性皮膚炎。果: NGF濃度在異位性皮膚炎患者明顯高於對照組(平均值及標準差在臍帶血為 65.47±44.45比49.21±12.18 pg/ml;在母血為89.68±41.04比66.96±23.05 pg/ml) (P<0.05)。VIP和SP濃度也會升高但統計上並不顯著。血漿NGF比IgE是一個更好的預估異位性皮膚的生物標記(ROC曲線下之區域在臍帶血為0.65比0.61;在母血為0.69比0.61)。母親NGF濃度在內因性患者(96.18±48.15 pg/ml)和外因性患者(86.18±37.23 pg/ml)皆顯著高於對照組(66.96±23.05 pg/ml) (P<0.05)。懷孕期間之壓力和母親NGF濃度間有顯著之相關(r=0.22, P=0.02)。論: 我們的結果建議,NGF可提供預估小兒異位性皮膚炎生物標記之另類選擇。art II 孕期香煙暴露對小孩異位性皮膚炎之影響-以cotinine當客觀性生物標記景:煙對兒童呼吸系統和出生結果有害是眾所周知。但是,香煙暴露包括二手煙(ETS)及母親懷孕期抽煙對異位性皮膚炎的影響不是很清楚。旨:這項研究的目的將依據臍帶血cotinine值來評估懷孕期香煙暴露對小孩異位性皮膚炎之影響。法: 在2004年我們收集了261對母親和新生兒。臍帶血和孩子的資料在出生時即被取得。在2歲時收集後天環境暴露資料及判定小孩是否得過異位性皮膚炎。我們用高性能色層分析質譜儀(HPLC-MS/MS)測量並比較得病與沒得病小孩之臍帶血及母血cotinine濃度。多重邏輯氏迴歸被用來評估cotinine濃度和異位性皮膚炎之關係。果: 150對母親和小孩完成了追蹤研究及抽血。38個(25.3%)孩子得異位性皮膚炎。2個(1.3%)母親在懷孕期間抽煙, 38個(25.3%)母親在懷孕期間有二手煙之暴露。臍帶血Cotinine濃度和母親血濃度高度相關(r=0.71,p<0.001)。我們發現當臍帶血cotinine值上升時,異位性皮膚炎之風險便會增加,且以劑量趨勢反應方式增加(p for trend=0.01)。尤其對於暴露濃度高於第75百分位者,異位性皮膚炎的風險更是顯著增加。論: 懷孕期香煙暴露會增加小孩異位性皮膚炎的風險。產前避免香煙暴露對於早期預防異位性皮膚炎是很重要的。 art III STM1及GSTP1基因多形性和懷孕期香煙暴露對小孩異位性皮膚炎之影響景: 近年來異位性皮膚炎盛行率的增加可能和基因易感族群之特殊暴露有關。旨: 這項研究的目的將依據臍帶血cotinine值來評估Glutathione S-transferase (GST)基因多形性和懷孕期香煙暴露對小孩異位性皮膚炎之影響。法: 在2004年我們收集了261對母親和新生兒。臍帶血和孩子的資料在出生時即被取得。在2歲時收集後天環境暴露資料及判定小孩是否得過異位性皮膚炎。我們將cotinine濃度分層,比較得病與沒得病小孩之GTM1和GSTP1多形性。多重邏輯氏迴歸被用來評估基因多形性和cotinine濃度對異位性皮膚炎之影響。果: 我們發現當臍帶血cotinine值上升時,異位性皮膚炎之風險便會增加,且以劑量趨勢反應方式增加。GSTM1 null及GSTP1 Ile/Ile基因型被發現會增加異位性皮膚炎之風險。對於臍帶血cotinine值小於0.1 ng/ml的小孩, GSTP1 Ile/Ile基因型會增加異位性皮膚炎之風險。對於大於等於0.1 ng/ml的,GSTM1 null基因型與異位性皮膚炎風險有顯著相關。論: GSTM1和GSTP1基因多形性可解釋懷孕期香煙暴露對小孩異位性皮膚炎易感性的不同。 art IV 打流行性感冒嗜血桿菌疫苗會增加過敏疾病之風險嗎?景: 對疫苗接種和過敏疾病之關係流行病學研究結果並不一致。旨: 這項研究的目的將評估全面施打白喉破傷風百日咳小兒痲痺疫苗之後,接種流行性感冒嗜血桿菌疫苗對過敏疾病的影響。法: 我們在西元2005年用多層次系統取樣方法從臺灣全國出生登記中抽取24,200對之母親及小孩。在健兒手冊疫苗卡上查明疫苗接種狀態,在6個月大時藉由問卷收集過敏疾病之危險因子,並詢問是否有被醫師診斷過異位性皮膚炎及反覆喘鳴(大於3次,排除免疫缺失和氣管結構異常問題)。多重邏輯氏迴歸被用來估計流行性感冒嗜血桿菌疫苗和過敏疾病的關係。果: 在6個月時,有21,010個(86.8%)參加者完成追蹤研究。1460個(6.9%)嬰兒有異位性皮膚炎, 154個(0.8%)嬰兒有反覆喘鳴之現象。11156個(53.1%)嬰兒接受了至少一劑量之流行性感冒嗜血桿菌疫苗之接種。在單變量的分析上,流行性感冒嗜血桿菌疫苗接種會增加異位性皮膚炎的風險(勝算比1.65; 95%信賴區間1.48-1.85)。在調整各種潛在的干擾因子後仍具統計意義(勝算比1.29; 95%信賴區間1.15-1.45) 。流行性感冒嗜血桿菌疫苗也可能會增加反覆喘鳴之危險性(勝算比1.31; 95%信賴區間0.94-1.83),雖統計上不鮮著。論: 結果顯示流行性感冒嗜血桿菌疫苗接種會潛在性的增加過敏病的風險。但是,是否這些副作用大過它在公共衛生上防治傳染病的重要性有待進一步驗證。 Part I euro-mediators as predictors of pediatric atopic dermatitisackground: Attempts to identify predictors of atopic dermatitis (AD) have focused on genetic and immunologic factors. However, the role of neuro-mediators remains to be elucidated. bjective: To evaluate nerve growth factor (NGF) and vaso-active intestinal peptide (VIP) in predicting pediatric AD and assess their correlation with intrinsic and extrinsic types of AD. ethods: We performed a nested case-control study in the prospective Taiwan birth panel cohort study. Cord and maternal plasma and questionnaires were gathered at birth. During follow-up, we identified 40 available AD cases, which were matched to 80 unaffected controls chosen from this cohort. The concentration of IgE, NGF, and VIP in cord and maternal plasma of these subjects were performed by enzyme-linked immuno-sorbent assay (ELISA). Receiver-operating-characteristic (ROC) curves were generated to see how well each biomarker could predict AD. esults: The NGF levels were significantly higher in AD patients than controls (mean ± SD: 65.47 ± 44.45 vs. 49.21 ± 12.18 pg/ml for cord plasma and 89.68 ± 41.04 vs. 66.96 ± 23.05 pg/ml for maternal plasma) (P<0.05). VIP levels were also higher but not statistically significant. Plasma NGF may be a better biomarker than IgE in detecting pediatric AD (area under the ROC curve = 0.65 vs. 0.61 for cord plasma and 0.69 vs. 0.61 for maternal plasma). Maternal NGF levels were significantly higher in patients with both intrinsic (96.18 ± 48.15 pg/ml) and extrinsic (86.18 ± 37.23 pg/ml) types of AD compared to controls (66.96 ± 23.05 pg/ml) (P<0.05). We assessed a significant correlation between self-reported stress during pregnancy and maternal NGF levels (r=0.22, P=0.02). onclusions: Our results suggest that NGF is a good alternative biomarker in predicting children with risk of AD.art II he effect of gestational smoke exposure on atopic dermatitis in the offspring – using cotinine as an objective biomarker ackground: The adverse impact of smoking on respiratory diseases and birth outcomes in children is well-known. However, the influence of smoke exposure including environmental tobacco smoke (ETS) and maternal smoking during pregnancy on atopic dermatitis (AD) is not clear. bjective: The purpose of this study was to evaluate the effect of gestational smoke exposure on the development of AD in the offspring on the basis of the maternal and cord blood cotinine. ethods: We recruited 261 mother and newborn pairs in 2004. Cord blood and information on perinatal factors of children were gathered at birth. At 2 years of age, information about development of AD and environmental exposures were collected. We compared AD with non-AD children for the concentration of cotinine in cord and maternal blood measured by high performance chromatography-mass spectrometry (HPLC-MS/MS). Multiple logistic regressions were performed to estimate the relationship of cotinine levels and AD. esults: 150 mother and child pairs completed the follow-up study and specimen collection with 38 (25.3%) children developing AD. Two (1.3%) out of 150 mothers smoked during pregnancy while 38 (25.3%) mothers reported having ETS exposure. Cotinine levels in cord blood and maternal blood were highly correlated (r=0.71, p<0.001). The risk of AD was found to increase with maternal and cord blood cotinine levels in a dose-response-manner (p for trend=0.01). Children exposed to high levels (> 75th percentile) had a significantly increased risk of AD. onclusions: Smoke exposure during pregnancy might increase the risk of AD in children. Avoidance of prenatal smoke exposure may be warranted for early prevention. art III ffects of GSTM1 and GSTP1 polymorphisms and gestational smoke exposure on atopic dermatitis in the offspringackground: The evidence that both genes and environment play etiologic roles suggests that the increase in atopic dermatitis (AD) prevalence is likely to involve changes in specific exposures among the population of genetically susceptible individuals. The purpose of this study was to evaluate the effect of Glutathione S -transferase (GST) genotypes polymorphisms and gestational smoke exposure on pediatric AD on the basis of the cord blood cotinine. ethods: We recruited 261 mother and newborn pairs in 2004. Cord blood and information on perinatal factors of children were gathered at birth. At 2 years of age, information about development of AD and environmental exposures were collected. We compared AD with non-AD children for GTM1 and GSTP1 polymorphisms stratified by the cotinine level. Multiple logistic regressions were performed to estimate the association of genotypes polymorphisms and cotinine levels with AD. esults: The risk of AD was found to increase with cord blood cotinine levels in a dose-response manner (p for trend=0.02). GSTM1 null and GSTP1 Ile/Ile genotypes showed a significant increase in the risk of AD with OR(95% CI) of 3.61 (1.40–9.31) and 3.11 (1.30–7.46) respectively. In children with cotinine level<0.1 ng/ml, the risk of AD increased for those carrying two GSTP1 Ile-105 alleles (OR = 6.63, 95% CI 1.46-30.18). In children with cotinine level≧0.1 ng/ml, GSTM1 null genotype was significantly related to AD (OR = 5.21, 95% CI 1.32–20.58).onclusion: Genetic polymorphism in GSTM1 and GSTP1 may be responsible for children differences in susceptibility to AD with regard to gestational smoke exposure. art IV oes Haemophilus influenzae type b vaccination increase the risk of atopic disease?ackground: Epidemiologic evidence for an association between vaccinations and atopy development is inconsistent. bjective: The aim of this study was to determine the influence of neonatal Haemophilus influenzae type b (Hib) vaccination on the prevalence of atopic disorders in addition to diphtheria-pertussis-poliomyelitis- tetanus (DPPT) vaccination and other neonatal vaccinations.ethods: We used multistage, stratified systematic sampling to recruit 24,200 mother–newborn pairs from the Taiwan national birth registration in 2005. Vaccination status was ascertained through officially vaccine cards while risk factors for atopic disorders were gathered by questionnaires at 6 months of age. Information about development of physician-diagnosed atopic dermatitis (AD) and recurrent wheezing (> 3 episodes, excluding immune deficiencies and structural airway abnormalities) was also collected. Multiple logistic regression was performed to estimate the association of Hib vaccination and atopic disorders. esults: There were 21,010 (86.8%) participants completed the follow-up study at the age of 6 months. AD was noted in 1460 (6.9%) infants while recurrent wheezing was found in 154 (0.8%). 11156 (53.1%) of the infants received at least one dose of Hib vaccination. In the univariate analysis, Hib vaccination was associated with a higher risk of AD (OR, 1.65; 95% CI, 1.48-1.85). Statistical significance retained even after adjusting for various potential confounders (adjOR, 1.29; 95% CI, 1.15-1.45). Hib vaccination was positively associated with recurrent wheezing (adjOR, 1.31; 95% CI, 0.94-1.83), though failed to reach statistical significance.onclusion: These results demonstrate a potential of Hib vaccination to increase the risk of atopic disorders in the early life in addition to DPPT vaccination. However, whether these adverse effects outweigh its importance in public health for infectious diseases spreading warrants further investigation. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/182315 |
顯示於: | 環境與職業健康科學研究所 |
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