COVID-19 and Asthma Onset in Children.

BACKGROUND AND OBJECTIVES: Respiratory viral infections increase risk of asthma in infants and children. Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause severe lung inflammation and prolonged respiratory symptoms. We sought to determine whether SARS-CoV-2 infection modified pediatric incident asthma risk. METHODS: This retrospective cohort study examined children ages 1 to 16 within the Children's Hospital of Philadelphia Care Network who received polymerase chain reaction (PCR) testing for SARS-CoV-2 between March 1, 2020 and February 28, 2021. Multivariable Cox regression models assessed the hazard ratio of new asthma diagnosis between SARS-CoV-2 PCR positive and SARS-CoV-2 PCR negative groups within an 18-month observation window. Models were adjusted for demographic characteristics, socioeconomic variables, and atopic comorbidities. RESULTS: There were 27 423 subjects included in the study. In adjusted analyses, SARS-CoV-2 PCR positivity had no significant effect on the hazard of new asthma diagnosis (hazard ratio [HR]: 0.96; P = .79). Black race (HR: 1.49; P = .004), food allergies (HR: 1.26; P = .025), and allergic rhinitis (HR: 2.30; P < .001) significantly increased the hazard of new asthma diagnosis. Preterm birth (HR: 1.48; P = .005) and BMI (HR: 1.13; P < .001) significantly increased the hazard of new asthma diagnosis for children <5 years old. CONCLUSIONS: SARS-CoV-2 PCR positivity was not associated with new asthma diagnosis in children within the observation period, although known risk factors for pediatric asthma were confirmed. This study informs the prognosis and care of children with a history of SARS-CoV-2 infection.

Patterns in the Development of Pediatric Allergy.

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.

COVID-19 Pandemic-Related Reductions in Pediatric Asthma Exacerbations Corresponded with an Overall Decrease in Respiratory Viral Infections.

BACKGROUND: 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 coronavirus disease 2019 pandemic, providing a unique opportunity to study how major asthma triggers correlate with asthma activity. OBJECTIVE: To determine whether changes in respiratory viruses, air pollutants, and/or aeroallergens during the coronavirus disease 2019 pandemic were concomitant with decreased asthma exacerbations. METHODS: Health care utilization and respiratory viral testing data between January 1, 2015, and December 31, 2020, were extracted from the Children's Hospital of Philadelphia Care Network's electronic health record. Air pollution and allergen data were extracted from US Environmental Protection Agency public databases and a National Allergy Bureau-certified station, respectively. Pandemic data (2020) were compared with historical data. RESULTS: Recovery of in-person asthma encounters during phased reopening (June 6 to November 15, 2020) was uneven: primary care well and specialty encounters reached 94% and 74% of prepandemic levels, respectively, whereas primary care sick and hospital encounters reached 21% and 40% of prepandemic levels, respectively. During the pandemic, influenza A and influenza B decreased to negligible frequency when compared with prepandemic cases, whereas respiratory syncytial virus and rhinovirus infections decreased to low (though nonnegligible) prepandemic levels, as well. No changes in air pollution or aeroallergen levels relative to historical observations were noted. CONCLUSIONS: 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.

Unsupervised modeling and genome-wide association identify novel features of allergic march trajectories.

BACKGROUND: 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. OBJECTIVE: Our aim was to determine the demographic and genetic features that are associated with the major allergic march trajectories. METHODS: 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. Hierarchic clustering and decision tree modeling were used to associate demographic features with allergic outcomes. Genome-wide association study was used to test for risk loci associated with specific allergic trajectories. RESULTS: We found an association between self-identified black race and progression from AD to asthma. Conversely, Asian or Pacific Islander race was associated with progression from AD to IgE-mediated food allergy, and white race was associated with progression from AD to AR. Genome-wide association study of trajectory groups identified risk loci associated with progression from AD to asthma (rs60242841) and from AD to AR (rs9565267, rs151041509, and rs78171803). Consistent with our epidemiologic associations, rs60242841 was more common in individuals of African ancestry than in individuals of European ancestry, whereas rs9565267 and rs151041509 were more common in individuals of European ancestry than in individuals of African ancestry. CONCLUSION: We have identified 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 toward developing individualized medical approaches for these conditions.

Pediatric Asthma Health Care Utilization, Viral Testing, and Air Pollution Changes During the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused dramatic changes in daily routines and health care 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 health care delivery. OBJECTIVE: We sought to identify changes in pediatric asthma-related health care utilization, respiratory viral testing, and air pollution during the COVID-19 pandemic. METHODS: For the time period January 17 to May 17, 2015 to 2020, asthma-related encounters and weekly summaries of respiratory viral testing data were extracted from Children's Hospital of Philadelphia electronic health records, and pollution data for 4 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 with data from 2015 to 2019 as a historical reference. RESULTS: After March 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 used 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, although air pollution levels did not substantially change, compared with historical trends. CONCLUSIONS: The COVID-19 pandemic in Philadelphia was accompanied by changes in pediatric asthma health care delivery patterns, including reduced admissions and systemic steroid prescriptions. Reduced rhinovirus infections may have contributed to these patterns.

Elevated Atopic Comorbidity in Patients with Food Protein-Induced Enterocolitis.

BACKGROUND: 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. OBJECTIVE: To determine the clinical characteristics, epidemiologic features, and natural history of FPIES in relation to the major atopic manifestations. METHODS: We examined our primary care birth cohort of 158,510 pediatric patients, of whom 214 patients met 2017 FPIES diagnostic criteria. We measured the influence of FPIES on developing subsequent atopic disease. RESULTS: 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 patients with FPIES compared with 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 < .001 χ2). However, longitudinal analyses indicated that prior FPIES did not influence the rate of atopy development. CONCLUSIONS: 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. Patients with FPIES 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.

Accuracy of Autism Screening in a Large Pediatric Network.

BACKGROUND: 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. METHODS: 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 (N = 25 999). RESULTS: 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. CONCLUSIONS: 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.

Using electronic medical record data to report laboratory adverse events.

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 >98·2% for all AEs. These results demonstrate that EMR-based AE ascertainment and grading substantially improves laboratory AE reporting accuracy.

The Prevalence of Eosinophilic Esophagitis in Pediatric Patients with IgE-Mediated Food Allergy.

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Recently, EoE has been identified in patients who underwent oral immunotherapy (OIT) for IgE-mediated food allergy, suggesting an association. OBJECTIVE: We sought to ascertain whether significant associations exist between IgE-mediated food allergies and EoE. METHODS: Using the analysis of electronic medical record data and manual chart review, we examined our subspecialty care network of 35,528 children and adolescents to identify and characterize patients with IgE-mediated and EoE food allergy. The most common food allergens were defined, and the prevalence of EoE in patients with IgE-mediated food allergy was determined. Logistic regression was used to measure the extent to which IgE-mediated food allergy to specific foods is associated with EoE. RESULTS: The most common causes of EoE were milk, soy, egg, grains, and meats, an allergen pattern that is distinct from that of IgE-mediated food allergy. The prevalence of EoE in patients with IgE-mediated food allergy was higher than that reported in the general population (4.7% vs 0.04%). The distribution of IgE-mediated food allergens in patients with EoE was similar to that of the general population, and IgE-mediated allergy to egg (2.27; 1.91-2.64), milk (4.19; 3.52-4.97), or shellfish (1.55; 1.24-1.92) was significantly associated with an EoE diagnosis. CONCLUSIONS: Our findings support a clinical association between these conditions that has implications for the management of children with food allergy, and particular relevance to patients undergoing OIT.