OBJECTIVES: Describe clinical and epidemiologic patterns of pediatric allergy using longitudinal electronic health records (EHRs) from a multistate consortium of US practices.

METHODS: Using the multistate Comparative Effectiveness Research through Collaborative Electronic Reporting EHR database, we defined a cohort of 218 485 children (0-18 years) who were observed for ≥5 years between 1999 and 2020. Children with atopic dermatitis (AD), immunoglobulin E-mediated food allergy (IgE-FA), asthma, allergic rhinitis (AR), and eosinophilic esophagitis (EoE) were identified using a combination of diagnosis codes and medication prescriptions. We determined age at diagnosis, cumulative incidence, and allergic comorbidity.

RESULTS: Allergic disease cumulative (and peak age of) incidence was 10.3% (4 months) for AD, 4.0% (13 months) for IgE-FA, 20.1% (13 months) for asthma, 19.7% (26 months) for AR, and 0.11% (35 months) for EoE. The most diagnosed IgE-FAs were peanut (1.9%), egg (0.8%), and shellfish (0.6%). A total of 13.4% of children had ≥2 allergic conditions, and respiratory allergies (ie, asthma, AR) were commonly comorbid with each other, and with other allergic conditions.

CONCLUSIONS: We detail pediatric allergy patterns using longitudinal, health care provider-based data from EHR systems across multiple US states and varied pediatric practice types. Our results support the population-level allergic march progression and indicate high rates of comorbidity among children with food and respiratory allergies.

<p><strong>BACKGROUND: </strong>Respiratory viruses, air pollutants, and aeroallergens are all implicated in worsening pediatric asthma symptoms, but their relative contributions to asthma exacerbations are poorly understood. A significant decrease in asthma exacerbations has been observed during the COVID-19 pandemic, providing a unique opportunity to study how major asthma triggers correlate with asthma activity.</p>

<p><strong>OBJECTIVE: </strong>To determine whether changes in respiratory viruses, air pollutants, and/or aeroallergens during the COVID-19 pandemic were concomitant with decreased asthma exacerbations.</p>

<p><strong>METHODS: </strong>Health care utilization and respiratory viral testing data between January 1st, 2015 and December 31st, 2020 were extracted from the Children's Hospital of Philadelphia (CHOP) Care Network's electronic health record. Air pollution and allergen data were extracted from U.S. Environmental Protection Agency public databases and a National Allergy Bureau-certified station, respectively. Pandemic data (2020) were compared to historical data.</p>

<p><strong>RESULTS: </strong>Recovery of in-person asthma encounters during phased re-opening (June 6 - November 15, 2020) was uneven: primary care well and specialty encounters reached 94% and 74% of pre-pandemic levels, respectively, while primary care sick and hospital encounters reached 21% and 40% of pre-pandemic levels, respectively. During the pandemic, influenza A and influenza B decreased to negligible frequency when compared to pre-pandemic cases, while RSV and rhinovirus infections decreased to low (though non-negligible) pre-pandemic levels, as well. No changes in air pollution or aeroallergen levels relative to historical observations were noted.</p>

<p><strong>CONCLUSIONS: </strong>Our results suggest that viral respiratory infections are a primary driver of pediatric asthma exacerbations. These findings have broad relevance to both clinical practice and the development of health policies aimed at reducing asthma morbidity.</p>

<p>Several early-life environmental factors have been associated with altered risk for the development and/or severity of individual allergic conditions. These include exposures implicated in the modulation of the microbiome, such as infant delivery mode, diet, and exposure to antibiotics and antacids. The impact of these early-life factors on allergic multimorbidity remains unknown. To address this knowledge gap, we used electronic medical records for a birth cohort of 158,510 children to track development of atopic dermatitis (AD), IgE-mediated food allergy (IgE-FA), asthma, and allergic rhinitis (AR) in individual children over time. We measured hazard ratios (HRs), adjusted for birth year, race, ethnicity, sex, and insurance payer type, to assess how development of both individual and multiple allergic conditions is influenced by birth mode, feeding practice during the first year of life, or exposure to antibiotics and/or antacids during the first six months of life. We found that vaginal delivery (VD; HR 0.89, 0.83, 0.84, 0.79 for at least 1, 2, 3, 4 conditions, respectively; p≤0.001) and exclusive breastmilk (BM) feeding (HR 0.74, 0.75, 0.89, for at least 1, 2, 3 conditions, respectively; p≤0.001) are associated with reduced cumulative allergic burden, while antibiotic exposure (HR 1.40, 1.44, 1.48, 1.63 for at least 1, 2, 3, 4 conditions, respectively; p≤0.001) and antacid exposure (HR 1.26, 1.35, 1.32 for at least 1, 2, 3 conditions, respectively; p≤0.001) are associated with increased cumulative allergic burden during childhood. This work expands our understanding of how a child's early-life environment may influence their risk of allergy development and progression.</p>

<p><strong>BACKGROUND: </strong>The COVID-19 pandemic caused dramatic changes in daily routines and healthcare utilization and delivery patterns in the United States. Understanding the influence of these changes and associated public health interventions on asthma care is important to determine effects on patient outcomes and identify measures that will ensure optimal future healthcare delivery.</p>

<p><strong>OBJECTIVE: </strong>We sought to identify changes in pediatric asthma-related healthcare utilization, respiratory viral testing, and air pollution during the COVID-19 pandemic.</p>

<p><strong>METHODS: </strong>For the time period Jan 17-May 17, 2015-2020, asthma-related encounters and weekly summaries of respiratory viral testing data were extracted from Children's Hospital of Philadelphia (CHOP) electronic health records, and pollution data for four criteria air pollutants were extracted from AirNow. Changes in encounter characteristics, viral testing patterns, and air pollution before and after Mar 17, 2020, the date public health interventions to limit viral transmission were enacted in Philadelphia, were assessed and compared to data from 2015-2019 as a historical reference.</p>

<p><strong>RESULTS: </strong>After Mar 17, 2020, in-person asthma encounters decreased by 87% (outpatient) and 84% (emergency + inpatient). Video telemedicine, which was not previously available, became the most highly utilized asthma encounter modality (61% of all visits), and telephone encounters increased by 19%. Concurrently, asthma-related systemic steroid prescriptions and frequency of rhinovirus test positivity decreased, while air pollution levels did not substantially change, compared to historical trends.</p>

<p><strong>CONCLUSION: </strong>The COVID-19 pandemic in Philadelphia was accompanied by changes in pediatric asthma healthcare delivery patterns, including reduced admissions and systemic steroid prescriptions. Reduced rhinovirus infections may have contributed to these patterns.</p>

<p><strong>BACKGROUND: </strong>The allergic march refers to the natural history of allergic conditions during infancy and childhood. However, population-level disease incidence patterns do not necessarily reflect the development of allergic disease in individuals. A better understanding of the factors that predispose to different allergic trajectories is needed.</p>

<p><strong>OBJECTIVE: </strong>Determine the demographic and genetic features that associate with the major allergic march trajectories.</p>

<p><strong>METHODS: </strong>Presence or absence of common allergic conditions (atopic dermatitis, AD; IgE-mediated food allergy, IgE-FA; asthma; and allergic rhinitis, AR) was ascertained in a pediatric primary care birth cohort of 158,510 subjects. Hierarchical clustering and decision tree modeling was used to associate demographic features with allergic outcomes. Genome-wide association study (GWAS) tested for risk loci associated with specific allergic trajectories.</p>

<p><strong>RESULTS: </strong>We found an association between self-identified "Black" race and progression from AD to asthma. Conversely, "Asian or Pacific Islander" race associated with AD to IgE-FA, and "White" race associated with AD to AR. GWAS of trajectory groups identified risk loci associated with progression from AD to Asthma (rs60242841), and AD to AR (rs9565267, rs151041509, rs78171803). Consistent with our epidemiologic associations, rs60242841 is more common in individuals of African ancestry (AA) than European ancestry (EA), while rs9565267 and rs151041509 are more common in EA than AA individuals.</p>

<p><strong>CONCLUSION: </strong>We identify novel associations between race and progression along distinct allergic trajectories. Ancestral genetic differences may contribute to these associations. These results uncover important health disparities, refine the concept of the allergic march, and represent a step towards developing individualized medical approaches for these conditions.</p>

<p>Compared with historical trends, we describe a dramatic decrease in pediatric asthma-related emergency department utilization for all levels of acuity coincident with coronavirus disease 2019&nbsp;emergence. These findings have implications for clinicians and researchers seeking to understand the drivers of asthma exacerbations.</p>

<p><strong>BACKGROUND: </strong>Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. Its relationship to the major atopic manifestations (atopic dermatitis, AD; IgE-mediated food allergy, IgE-FA; allergic rhinitis, AR; asthma) is not understood.</p>

<p><strong>OBJECTIVE: </strong>Determine the clinical characteristics, epidemiologic features, and natural history of FPIES in relation to the major atopic manifestations.</p>

<p><strong>METHODS: </strong>We examined our primary care birth cohort of 158,510 pediatric patients, of which 214 patients met 2017 FPIES diagnostic criteria. We measured the influence of FPIES on developing subsequent atopic disease.</p>

<p><strong>RESULTS: </strong>Pediatric FPIES incidence was between 0.17% and 0.42% depending on birth year. As in prior reports, most patients had an acute presentation (78%) and milk, soy, oat, rice, potato, and egg were common triggers. The mean age of diagnosis was 6.8 months. Atopic comorbidity was higher in FPIES patients compared to healthy children (AD, 20.6% vs. 11.7%; IgE-FA, 23.8% vs. 4.0%; asthma, 26.6% vs. 18.4%; AR, 28.0% vs. 16.7%; p&lt;0.001 Chi-squared). However, longitudinal analyses indicated that prior FPIES did not influence the rate of atopy development.</p>

<p><strong>CONCLUSIONS: </strong>The incidence of FPIES in our cohort was initially low, but is increasing. Food allergen distribution, presentation, and age of onset are similar to prior reports. FPIES patients have high rates of atopic comorbidity, however, longitudinal analysis does not support direct causation as the etiology of these associations. Rather it suggests a shared predisposition to both types of allergy, or associative bias effects. This work refines our understanding of the natural history of FPIES by elucidating associations between FPIES and atopy.</p>

<p><strong>BACKGROUND: </strong>The allergic march describes the natural history of allergic conditions as they develop during childhood. Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that can be triggered by specific foods. Despite its allergic pathophysiology, the epidemiologic relationship between EoE and established members of the allergic march is unknown.</p>

<p><strong>OBJECTIVE: </strong>We sought to determine whether EoE meets epidemiologic criteria for being considered a member of the allergic march.</p>

<p><strong>METHODS: </strong>Using a primary care birth cohort of 130,435 children, we determined the natural histories of atopic dermatitis (AD), IgE-mediated food allergy (IgE-FA), asthma, EoE, and allergic rhinitis (AR) in individual patients. We then performed case-control analyses to establish the extent that existing allergic conditions influence the rate of subsequent EoE diagnosis.</p>

<p><strong>RESULTS: </strong>A total of 139 children developed EoE during the observation period (prevalence of 0.11%). The peak age of EoE diagnosis was 2.6 years, as compared with 0.3 years, 1 year, 1.1 years, and 2.1 years for AD, IgE-FA, asthma, and AR, respectively. The presence of AD (hazard ratio [HR] 3.2, 95% confidence interval [CI] 2.2-4.6), IgE-FA (HR 9.1, 95% CI 6.5-12.6), and asthma (HR 1.9, 95% CI 1.3-2.7) was independently and cumulatively associated with subsequent EoE diagnosis. The presence of AR was associated with subsequent EoE diagnosis (HR 2.8, 95% CI 2.0-3.9), and the presence of EoE was associated with subsequent AR diagnosis (HR 2.5, 95% CI 1.7-3.5).</p>

<p><strong>CONCLUSIONS: </strong>Allergic comorbidities are positively associated with EoE diagnosis. Together, our findings suggest that EoE is a late manifestation of the allergic march.</p>

<p><strong>BACKGROUND: </strong>The rates of childhood allergic conditions are changing, prompting the need for continued surveillance. Examination of healthcare provider-based diagnosis data is an important and lacking methodology needed to complement existing studies that rely on participant reporting.</p>

<p><strong>METHODS: </strong>Utilizing our care network of 1,050,061 urban and sub-urban children, we defined two retrospective cohorts: (1) a closed birth cohort of 29,662 children and (2) a cross-sectional cohort of 333,200 children. These cohorts were utilized to determine the epidemiologic characteristics of the conditions studied. Logistic regression was utilized to determine the extent to which food allergy was associated with respiratory allergy.</p>

<p><strong>RESULTS: </strong>In our birth cohort, the peak age at diagnosis of eczema, asthma, rhinitis, and food allergy was between 0 and 5&nbsp;months (7.3&nbsp;%), 12 and 17&nbsp;months (8.7&nbsp;%), 24 and 29&nbsp;months (2.5&nbsp;%), and 12 and 17&nbsp;months (1.9&nbsp;%), respectively. In our cross-sectional cohort, eczema and rhinitis prevalence rates were 6.7&nbsp;% and 19.9&nbsp;%, respectively. Asthma prevalence was 21.8&nbsp;%, a rate higher than previously reported. Food allergy prevalence was 6.7&nbsp;%, with the most common allergenic foods being peanut (2.6&nbsp;%), milk (2.2&nbsp;%), egg (1.8&nbsp;%), shellfish (1.5&nbsp;%), and soy (0.7&nbsp;%). Food allergy was associated with development of asthma (OR 2.16, 95&nbsp;% CI 1.94-2.40), and rhinitis (OR 2.72, 95&nbsp;% CI 2.45-3.03).</p>

<p><strong>CONCLUSIONS: </strong>Compared with previous reports, we measure lower rates of eczema and higher rates of asthma. The distribution of the major allergenic foods diverged from prior figures, and food allergy was associated with the development of respiratory allergy. The utilization of provider-based diagnosis data contributes an important and lacking methodology that complements existing studies.</p>