<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><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>Universal screening is recommended to reduce the age of diagnosis for autism spectrum disorder (ASD). However, there are insufficient data on children who screen negative and no study of outcomes from truly universal screening. With this study, we filled these gaps by examining the accuracy of universal screening with systematic follow-up through 4 to 8 years.</p>

<p><strong>METHODS: </strong>Universal, primary care-based screening was conducted using the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F) and supported by electronic administration and integration into electronic health records. All children with a well-child visit (1) between 16 and 26 months, (2) at a Children's Hospital of Philadelphia site after universal electronic screening was initiated, and (3) between January 2011 and July 2015 were included ( = 25 999).</p>

<p><strong>RESULTS: </strong>Nearly universal screening was achieved (91%), and ASD prevalence was 2.2%. Overall, the M-CHAT/F's sensitivity was 38.8%, and its positive predictive value (PPV) was 14.6%. Sensitivity was higher in older toddlers and with repeated screenings, whereas PPV was lower in girls. Finally, the M-CHAT/F's specificity and PPV were lower in children of color and those from lower-income households.</p>

<p><strong>CONCLUSIONS: </strong>Universal screening in primary care is possible when supported by electronic administration. In this "real-world" cohort that was systematically followed, the M-CHAT/F was less accurate in detecting ASD than in previous studies. Disparities in screening rates and accuracy were evident in traditionally underrepresented groups. Future research should focus on the development of new methods that detect a greater proportion of children with ASD and reduce disparities in the screening process.</p>

<p>Despite the importance of adverse event (AE) reporting, AEs are under-reported on clinical trials. We hypothesized that electronic medical record (EMR) data can ascertain laboratory-based AEs more accurately than those ascertained manually. EMR data on 12 AEs for patients enrolled on two Children's Oncology Group (COG) trials at one institution were extracted, processed and graded. When compared to gold standard chart data, COG AE report sensitivity and positive predictive values (PPV) were 0-21·1% and 20-100%, respectively. EMR sensitivity and PPV were &gt;98·2% for all AEs. These results demonstrate that EMR-based AE ascertainment and grading substantially improves laboratory AE reporting accuracy.</p>