Environmental Factors and Biomarkers for Pediatric Atopic Dermatitis

• Main Authors: I-Jen Wang, 王怡人
• Other Authors: Pau-Chung Chen
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/32934215339607669332

博士 === 國立臺灣大學 === 職業醫學與工業衛生研究所 === 96 === Part I Neuro-mediators as predictors of pediatric atopic dermatitis Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusions: Our results suggest that NGF is a good alternative biomarker in predicting children with risk of AD. Part II The effect of gestational smoke exposure on atopic dermatitis in the offspring – using cotinine as an objective biomarker Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: Smoke exposure during pregnancy might increase the risk of AD in children. Avoidance of prenatal smoke exposure may be warranted for early prevention. Part III Effects of GSTM1 and GSTP1 polymorphisms and gestational smoke exposure on atopic dermatitis in the offspring Background: 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. Methods: 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. Results: 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). Conclusion: Genetic polymorphism in GSTM1 and GSTP1 may be responsible for children differences in susceptibility to AD with regard to gestational smoke exposure. Part IV Does Haemophilus influenzae type b vaccination increase the risk of atopic disease? Background: Epidemiologic evidence for an association between vaccinations and atopy development is inconsistent. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.