Project description:A correlation between the harmful effects of air pollutants and atopic dermatitis has been reported. There are few studies on the correlation between the concentration of heavy metals in the indoor atmosphere and symptoms of atopic dermatitis. Twenty-two homes of children showing atopic dermatitis symptoms were enrolled, and eighteen homes with similarly aged children without symptoms or a history of atopic dermatitis participated as a control group. We measured the concentrations of various air pollutants (particulate matter 10, carbon dioxide, carbon monoxide, formaldehyde, nitrogen dioxide, volatile organic compounds (VOCs), ozone, radon, bacterial aerosols, and mold) as well as various heavy metals, such as lead, cadmium, and mercury, in the living room and children's bedroom of each home. Lead was more commonly detected in the indoor air in houses of children with atopic dermatitis (15/22) as compared to in the control group (3/18) (chi square test, p = 0.002). In adjusted logistic regression analysis, VOCs and lead were significantly associated with atopic dermatitis (p < 0.05). Our study shows that lead in indoor air might be associated with atopic dermatitis, even if the concentrations of airborne lead are below the safety levels suggested by health guidelines.
Project description:BackgroundPerfluoroalkyl substance (PFAS) exposure was found associated with atopic diseases. Atopic dermatitis (AD) is a childhood skin disorder. However, the effect of interaction between PFASs and glutathione S-transferase (GST) T1/M1 genotype on AD remains unclear.ObjectiveTo investigate the association between gene-environmental interaction and childhood AD using a birth cohort study.MethodsFrom 2001 to 2005, 1,264 mother-newborn pairs were recruited from eight Taiwanese maternity hospitals. PFAS levels and Genotypes were analysed from cord blood. Information on children's health status including AD occurrence was obtained via phone interviews at 6 months and 2 years. Cord plasma concentrations of nine PFASs were measured via ultra-high performance liquid chromatography/tandem mass spectrometry. GSTT1/M1 was genotyped (null/present) via polymerase chain reaction. Environment-gene interaction effects on AD were assessed using multiple logistic regression analysis.ResultsOverall, 839 mother-newborn pairs completed all measurements. The prevalence of ever having physician-diagnosed AD by 2 years of age was 5.4%. Among PFASs, perfluorooctanoic acid (PFOA) was positively associated with AD adjusted for potential confounders. After grouping PFOA levels into three groups: undetected, below and above the median in those with detected, children in above the median group who had the GSTT1-null, or GSTM1-null genotype exhibited a higher odds ratio for AD (OR [95%CI] = 3.45 [1.26-9.99] and 2.92 [1.12-7.91], respectively) as compared to the undetected group.ConclusionsOur data demonstrated that in-utero PFOA exposure with GSTT1/M1 null genotype were associated with AD. Minimizing early-life PFAS exposure may help against AD development, especially in genetically susceptible individuals.
Project description:ObjectivesThis post hoc analysis of pooled data from two phase III studies (AD-301: NCT02118766; AD-302: NCT02118792) explored the efficacy and safety of crisaborole ointment, 2%, a nonsteroidal phosphodiesterase 4 inhibitor, for the treatment of mild-to-moderate atopic dermatitis (AD) in pediatric patients (aged 2 to < 18 years) only, stratified by baseline characteristics.MethodsPediatric patients with mild or moderate AD per Investigator's Static Global Assessment (ISGA) and percentage of treatable body surface area (%BSA) ≥ 5 at baseline were assessed. Crisaborole or vehicle (2:1 randomization ratio) was applied twice daily for 28 days. Of the 1313 pediatric patients included in this study, 874 received crisaborole and 439 received vehicle. ISGA success was defined as clear (0) or almost clear (1) with ≥ 2-grade improvement from baseline. Efficacy and safety were stratified by age group, sex, baseline ISGA, baseline %BSA per published severity strata, and prior AD therapy.ResultsOverall, the proportions of crisaborole-treated and vehicle-treated pediatric patients with ISGA success at week 4 were 32.5 and 21.5%, respectively. ISGA success rates at day 29 (week 4) were generally higher in crisaborole-treated (21.9-38.1%) than vehicle-treated (15.7-26.9%) patients across subgroups. Rates of treatment-related application site pain were 2.4-10.1% for crisaborole-treated patients and 0.6-2.2% for vehicle-treated patients across subgroups. No new safety concerns were noted in any patient subgroup.ConclusionCrisaborole improved global disease severity and was reasonably well tolerated across all pediatric baseline characteristic subgroups. Application site discomfort was greater with crisaborole than with vehicle, but few patients discontinued treatment.ClinicaltrialsGov registration numbersNCT02118766; NCT02118792 (registration date: April 21, 2014).
Project description:BackgroundAtopic dermatitis (AD) and food allergy (FA) may share genetic risk factors. It is unknown whether genetic factors directly cause FA or are mediated through AD, as the dual-allergen hypothesis suggests.ObjectiveTo test the hypothesis that AD mediates the relationship between an IL-4 receptor alpha chain gene (IL4RA) variant, the human IL-4 receptor alpha chain protein-R576 polymorphism, and FA.MethodsA total of 433 children with asthma enrolled in the School Inner-City Asthma Study underwent genotyping for the IL4RA576 allele. Surveys were administered to determine FA, AD, and associated allergic responses. Mediation analysis was performed adjusting for race and ethnicity, age, sex, and household income. Multivariate models were used to determine the association between genotype and FA severity.ResultsAD was reported in 193 (45%) and FA in 80 children (19%). Each risk allele increased odds of AD 1.39-fold ([1.03-1.87], P = .03), and AD increased odds of FA 3.67-fold ([2.05- 6.57], P < .01). There was an indirect effect of genotype, mediated by AD, predicting FA; each risk allele increased the odds of FA by 1.13 (odds ratio [95% CI], Q/R = 1.13 [1.02-1.24], R/R = 1.28 [1.04-1.51]; P < .01). Each risk allele increased the odds of severe FA symptoms 2.68-fold ([1.26-5.71], P = .01).ConclusionsIn a cohort of children with asthma, AD is part of the causal pathway between an IL4RA variant and FA. This variant is associated with increased risk of severe FA reactions. Addressing AD in children with an IL4RA polymorphism may modulate the risk of FA.
Project description:BackgroundIt is critical to investigate the underlying pathophysiological mechanisms in the development of atopic dermatitis. The microbiota hypothesis suggested that the development of allergic diseases may be attributed to the gut microbiota of mother-offspring pairs. The purpose of this study was to investigate the relationship among maternal-offspring gut microbiota and the subsequent development of atopic dermatitis in infants and toddlers at 2 years old.MethodsA total of 36 maternal-offspring pairs were enrolled and followed up to 2 years postpartum in central China. Demographic information and stool samples were collected perinatally from pregnant mothers and again postpartum from their respective offspring at the following time intervals: time of birth, 6 months, 1 year and 2 years. Stool samples were sequenced with the 16S Illumina MiSeq platform. Logistic regression analysis was used to explore the differences in gut microbiota between the atopic dermatitis group and control group.ResultsOur results showed that mothers of infants and toddlers with atopic dermatitis had higher abundance of Candidatus_Stoquefichus and Pseudomonas in pregnancy and that infants and toddlers with atopic dermatitis had higher abundance of Eubacterium_xylanophilum_group at birth, Ruminococcus_gauvreauii_group at 1 year and UCG-002 at 2 years, and lower abundance of Gemella and Veillonella at 2 years. Additionally, the results demonstrated a lower abundance of Prevotella in mothers of infants and toddlers with atopic dermatitis compared to mothers of the control group, although no statistical difference was found in the subsequent analysis.ConclusionThe results of this study support that gut microbiota status among mother-offspring pairs appears to be associated with the pathophysiological development of pediatric atopic dermatitis.
Project description:BackgroundPrenatal folic acid supplementation is recommended to prevent birth defects. Some foods are fortified in the USA to ensure sufficient intake among reproductive-aged women. However, high prenatal folate exposure may be a risk factor for childhood atopic diseases. We investigated associations between prenatal folate and early childhood wheeze and atopic dermatitis in a US cohort.MethodsWe studied 858 mother-child dyads, enrolled prenatally. Folate was measured in 2nd and 3rd trimester maternal plasma. Parents reported current wheeze (previous 12 months) and healthcare provider diagnosis of atopic dermatitis at 3 years. We examined associations using logistic regression, modeling folate continuously and dichotomously (< or ≥20 ng/mL), a level often considered supraphysiologic.ResultsOver half of women were African American and on Medicaid. Median (interquartile range) folate levels were 22.6 (15.9-30.0) and 23.1 (16.1-30.0) ng/mL for 2nd and 3rd trimesters, respectively. Current wheeze and atopic dermatitis were reported for 20.4% and 26.8% of children, respectively. Second trimester folate as a continuous exposure was not significantly associated with outcomes. Decreased odds of current wheeze were observed in children born to mothers who had 2nd trimester folate ≥20 ng/mL (adjusted odds ratios = 0.67, 95% confidence interval = 0.46, 0.97) compared to children with maternal levels <20 ng/mL. Third trimester folate was not associated with outcomes.ConclusionsHigh plasma folate in mid-pregnancy was associated with decreased odds of current wheeze at age 3. Our findings do not support harmful effects of high prenatal folate levels on childhood atopic diseases in this setting.
Project description:ImportancePruritus, a hallmark of atopic dermatitis (AD), is thought to disrupt sleep, yet little is known about how variations in disease activity and severity of this common childhood condition may be associated with sleep patterns over time.ObjectiveTo determine whether children with active AD have impaired sleep duration and quality at multiple time points throughout childhood and whether disease severity affects sleep outcomes.Design, setting, and participantsThis longitudinal cohort study used data of children enrolled in the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in Avon, United Kingdom. Participants were children (N = 13 988) alive at 1 year and followed up with repeated measures of self-reported AD and sleep through 16 years of age. This study was based on data collected from 1990 to 2008. Data analysis was performed from September 2017 to September 2018.Main outcomes and measuresStandardized measure of sleep duration and composite measure of sleep quality, including nighttime awakenings, early morning awakenings, difficulty falling asleep, and nightmares, were repeated at multiple time points between 2 and 16 years of age.ResultsThe study sample comprised 13 988 children (7220 male [51.6%]) followed up for a median (interquartile range [IQR]) duration of 11 (5-14) years. Of this total, 4938 children (35.3%) met the definition of having atopic dermatitis between 2 and 16 years of age. Total sleep duration was similar between children with active AD and without AD at all ages, and the average estimated difference across childhood was a clinically negligible difference of 2 minutes less per day for children with AD (95% CI, -4 to 0 minutes). In contrast, children with active AD were more likely to report worse sleep quality at all time points, with a nearly 50% higher odds of experiencing more sleep-quality disturbances (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33 to 1.66). Children with more severe active disease (quite bad or very bad AD: aOR, 1.68; 95% CI, 1.42 to 1.98) and with comorbid asthma or allergic rhinitis (aOR, 1.79; 95% CI, 1.54 to 2.09) had worse sleep quality. However, even children with mild AD (OR, 1.40; 95% CI, 1.27 to 1.54) or inactive AD (OR, 1.41; 95% CI, 1.28 to 1.55) had statistically significantly increased odds of impaired sleep quality.Conclusions and relevanceAtopic dermatitis appeared to be associated with impaired sleep quality throughout childhood; thus, it is suggested that clinicians should consider sleep quality among all children with AD, especially those with comorbid asthma or allergic rhinitis and severe disease, and that interventions to improve sleep quality are needed.
Project description:Valproate sodium is used for the treatment of epilepsy and other neuropsychiatric disorders in women of childbearing potential. However, there are concerns about impaired cognitive development in children who have been exposed to valproate during pregnancy.To estimate the association between long-term school performance and prenatal exposure to valproate and a number of other antiepileptic drugs (AEDs).In a prospective, population-based cohort study conducted from August 1, 2015, to May 31, 2017, data used in the study were provided by Statistics Denmark on April 15, 2016. All children born alive in Denmark between 1997 and 2006 (n = 656 496) were identified. From this cohort, children who did not participate in the national tests, with presumed coding errors in gestational age and children missing information on their mother's educational level or household income were excluded (n = 177 469) leaving 479 027 children for the analyses. Children were identified and linked across national registers that had information on exposure, covariates, and outcome. The primary outcome was performance in national tests, an academic test taken by students in Danish primary and lower secondary state schools. We assessed performance in Danish and mathematics at different grades among valproate-exposed children and compared their performance with that of unexposed children and children exposed to another AED (lamotrigine). Test scores were standardized to z scores and adjusted for risk factors.Difference in standardized z scores in Danish and mathematics tests among valproate-exposed children compared with unexposed and lamotrigine-exposed children.Of the 656 496 children identified, 479 027 children who participated in the national tests were evaluated, including children exposed to the following AEDs in monotherapy: valproate, 253; phenobarbital, 86; oxcarbazepine, 236; lamotrigine, 396; clonazepam, 188; and carbamazepine, 294. The mean (SD) age of the 244 095 children completing the sixth-grade Danish test was 12.9 (0.39) years; 122 774 (50.3%; 95% CI, 50.1% to 50.5%) were boys and 121 321 (49.7%; 95% CI, 49.5% to 49.9%) were girls. Valproate-exposed children scored worse on the sixth-grade Danish tests (adjusted difference, -0.27 SD; 95% CI, -0.42 to -0.12) and sixth-grade mathematics tests (adjusted difference, -0.33 SD; (95% CI, -0.47 to -0.19) compared with unexposed children and children exposed to lamotrigine (adjusted difference, -0.33 SD; 95% CI, -0.60 to -0.06). Also, children exposed to clonazepam scored worse in the sixth-grade Danish tests (adjusted difference, -0.07 SD; 95% CI, -0.12 to -0.02). Carbamazepine, lamotrigine, phenobarbital, and oxcarbazepine were not linked to poor school performance compared with unexposed children.Maternal use of valproate was associated with a significant decrease in school performance in offspring compared with children unexposed to AEDs and children exposed to lamotrigine. Findings of this study further caution against the use of valproate among women of childbearing potential.
Project description:Early-life antibiotic use is associated with allergic diseases. The risk factors for the progression from atopic dermatitis (AD) to asthma or allergic rhinitis are still unknown. We aimed to investigate the association between exposure to different antibiotics and the risk of new-onset asthma in children with AD. By using the Longitudinal Health Insurance Database 2005, we selected AD patients less than 6 years old identified by ICD-9-CM code 691.8. The case group was defined as those having new-onset asthma, and the control group was defined as those without an asthma history. Information on antibiotic exposure in the 5 years prior to the index date was collected from drug prescription records. We estimated the adjusted odds ratio by using conditional logistic regression, adjusted for age, sex, index year, other potential risk factors and antibiotics. Antibiotic exposure was associated with the development of asthma in patients with AD (aOR = 3.68, 95% CI 2.13-6.36), particularly for patients less than 5 years old (aOR = 4.14, 95% CI 2.24-7.64) (p for trend < 0.001), even though lower cumulative antibiotic defined daily doses (DDDs) were associated with new-onset asthma occurrence. Antibiotic exposure, especially macrolide exposure, is associated with an increased risk of asthma in patients with AD.
Project description:BackgroundNormalisation of medicinal and recreational marijuana use has increased the importance of fully understanding effects of marijuana use on individual-and population-level health, including prenatal exposure effects on child development. We undertook a systematic review of the literature to examine the long-term effects of prenatal marijuana exposure on neuropsychological function in children aged 1-11 years.MethodsPrimary research publications were searched from Medline, Embase, PsychInfo, CINAHL EbscoHost, Cochrane Library, Global Health and ERIC (1980-2018). Eligible articles documented neuropsychological outcomes in children 1-11 years who had been prenatally exposed to marijuana. Studies of exposure to multiple prenatal drugs were included if results for marijuana exposure were reported separately from other substances. Data abstraction was independently performed by two reviewers using a standardised protocol.ResultsThe eligible articles (n = 21) on data from seven independent longitudinal studies had high quality based on the Newcastle-Ottawa Scale. Some analyses found associations (P < 0.05) between prenatal marijuana exposure and decreased performance on memory, impulse control, problem-solving, quantitative reasoning, verbal development and visual analysis tests; as well as increased performance on attention and global motion perception tests. Limitations included concurrent use of other substances among study participants, potential under-reporting and publication biases, non-generalisable samples and limited published results preventing direct comparison of analyses.ConclusionsThe specific effects of prenatal marijuana exposure remain unclear and warrant further research. The larger number of neuropsychological domains that exhibit decreased versus increased psychological and behavioural functions suggests that exposure to marijuana may be harmful for brain development and function.