Under-diagnosis of atopic dermatitis in Puerto Rican children

Background: Little is known about atopic dermatitis (AD) among children in Puerto Rico. Objective: To examine risk factors and identify approaches to better diagnose AD in Puerto Rican children. Methods: Case-control study of AD among 540 children aged 6–14 years in San Juan, Puerto Rico. AD was defined as: 1) physician-diagnosed AD, 2) RAST-AD: AD symptoms plus ≥1 positive IgE to allergens, and 3) STR-AD: AD-symptoms and skin test reactivity to ≥1 allergen. Logistic regression was used for the multivariable analysis. We also evaluated the diagnostic performance of various approaches by comparing their sensitivity, specificity, positive predicted value [PPV], negative predictive value [NPV], and area under curve [AUC]). Results: Of the 70 children with STR-AD, only 5 (7.1%) had PD-AD. In children without asthma, a positive IgE to Dermatophagoides (D.) pteronyssinus and signs of mold/mildew at home were significantly associated with 3.3 and 5 times increased odds of STR-AD, respectively. Among children with asthma, private/employer-based health insurance and a positive IgE to D. pteronyssinus were each significantly associated with approximately twofold increased odds of STR-AD. A combination of current eczema symptoms and a positive IgE to D. pteronyssinus yielded a sensitivity ≥70%, specificity and NPV ≥95%, PPV ≥88%, and an AUC ≥0.85 for STR-AD. Replacing a positive IgE to D. pteronyssinus with a positive IgE to ≥1 allergen slightly increased sensitivity without affecting other parameters. Conclusions: AD is markedly under-diagnosed by physicians in Puerto Rico. This could be improved by assessing eczema symptoms and measuring IgEs to common allergens. Keywords: Atopic dermatitis, Under-diagnosis, Puerto Rico, Childre

A genome-wide study of DNA methylation in white blood cells and asthma in Latino children and youth

Latinos are heavily affected with childhood asthma. Little is known about epigenetic mechanisms of asthma in Latino youth. We conducted a meta-analysis of two epigenome-wide association studies (EWAS) of asthma, using DNA from white blood cells (WBCs) from 1,136 Latino children and youth aged 6 to 20 years. Genes near the top CpG sites in this EWAS were examined in a pathway enrichment analysis, and we then assessed whether our results replicated those from publicly available data from three independent EWAS conducted in non-Latino populations. We found that DNA methylation profiles differed between subjects with and without asthma. After adjustment for covariates and multiple testing, two CpGs were differentially methylated at a false discovery rate (FDR)-adjusted P < 0.1, and 193 CpG sites were differentially methylated at FDR-adjusted P < 0.2. The two top CpGs are near genes relevant to inflammatory signalling, including CAMK1D (Calcium/Calmodulin Dependent Protein Kinase ID) and TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains). Moreover, 25 genomic regions were differentially methylated between subjects with and without asthma, at Šidák-corrected P < 0.10. An enrichment analysis then identified the TGF-beta pathway as most relevant to asthma in our analysis, and we replicated some of the top signals from publicly available EWAS datasets in non-Hispanic populations. In conclusion, we have identified novel epigenetic markers of asthma in WBCs from Latino children and youth, while also replicating previous results from studies conducted in non-Latinos

DNA methylation in nasal epithelium, atopy, and atopic asthma in children:a genome-wide study

Background Epigenetic mechanisms could alter the airway epithelial barrier and ultimately lead to atopic diseases such as asthma. We aimed to identify DNA methylation profiles that are associated with- and could accurately classify-atopy and atopic asthma in school-aged children. Methods We did a genome-wide study of DNA methylation in nasal epithelium and atopy or atopic asthma in 483 Puerto Rican children aged 9-20 years, recruited using multistage probability sampling. Atopy was defined as at least one positive IgE (>= 0.35 IU/mL) to common aeroallergens, and asthma was defined as a physician's diagnosis plus wheeze in the previous year. Significant (false discovery rate p Findings DNA methylation profiles were markedly different between children with (n=312) and without (n=171) atopy in the Puerto Rico discovery cohort, recruited from Feb 12, 2014, until May 8, 2017. After adjustment for covariates and multiple testing, we found 8664 differentially methylated CpGs by atopy, with false discovery rate-adjusted p values ranging from 9.58 x 10(-17) to 2.18 x 10(-22) for the top 30 CpGs. These CpGs were in or near genes relevant to epithelial barrier function, including CDHR3 and CDH26, and in other genes related to airway epithelial integrity and immune regulation, such as FBXL7, NTRK1, and SLC9A3. Moreover, 28 of the top 30 CpGs replicated in the same direction in both independent cohorts. Classification models of atopy based on nasal methylation performed well in the Puerto Rico cohort (area under the curve [AUC] 0.93-0.94 and accuracy 85-88%) and in both replication cohorts (AUC 0.74-0.92, accuracy 68-82%). The models also performed well for atopic asthma in the Puerto Rico cohort (AUC 0.95-1.00, accuracy 88%) and the replication cohorts (AUC 0.82-0.88, accuracy 86%). Interpretation We identified specific methylation profiles in airway epithelium that are associated with atopy and atopic asthma in children, and a nasal methylation panel that could classify children by atopy or atopic asthma. Our findings support the feasibility of using the nasal methylome for future clinical applications, such as predicting the development of asthma among wheezing infants. Copyright (C) 2018 Elsevier Ltd. All rights reserved

Mouse allergen level, selected covariates, and measures of lung function and atopy in children with asthma.

<p>Quintiles (and ranges) calculated using the combined cohort (San Juan and Hartford). Values shown are mean (SD) for continuous variables, except</p>a<p>presented as median (IQR), analyzed as log10.</p><p>STR = skin test reactivity.</p>*<p>FEV1 presented as absolute value due to lack of predicted values for Puerto Rican children.</p

Multivariate analysis of mouse allergen, FEV₁, and allergy markers in children with asthma.

<p>Values shown are ¹means or ²odds ratios and 95% confidence intervals, with P-values in parentheses. All allergens analyzed as log10. IgE analyzed as log10 and presented as percent increase/decrease. All models adjusted for age, sex, household income, and dust house levels of allergens. FEV1 adjusted additionally for height and height squared.</p

Distribution of allergen levels (log-transformed), by study site.

<p>Distribution of allergen levels (log-transformed), by study site.</p

Multivariate analysis of mouse allergen level and selected outcomes in cases, by skin test reactivity to mouse.

<p>Values shown are ¹means or ²odds ratios and 95% confidence intervals, with P-values in parentheses. All allergens analyzed as log10. IgE analyzed as log10 and presented as percent increase/decrease. ³All children allergic to mouse were also sensitized to ≥1 additional allergen. All models adjusted for age, sex, household income, other allergens, and study site. FEV1 adjusted additionally for height and height squared.</p

Main characteristics of study participants.

<p>Mean (SD) for continuous variables, except</p>a<p>presented as median (IQR), analyzed as log10.</p>*<p>P-value<0.05 and ^†P<0.10 for cases vs controls within each group.</p><p>STR = skin test reactivity.FEV₁ shown as absolute value because of lack of predicted values in Puerto Ricans.</p