Fruitful or unfruitful: strawberry and tomato specific immunoglobulin E testing at a tertiary pediatric center.

Background: Suspected strawberry and tomato (S/T) food allergy (FA) can be evaluated using specific immunoglobulin E (sIgE) testing despite its low specificity and positive predictive value. Objective: This study aims to understand ordering patterns for S/T sIgE testing and identify relevant factors to clinical decision-making. Methods: We retrospectively reviewed 814 patients with sIgE testing available for strawberries (651), tomatoes (276), or both (113) from January 2012 to May 2022 at a tertiary pediatric hospital. Patient demographics, provider specialty, and reasons for testing were collected. Student's t-test and multiple regression analyses were performed to test the association between the S/T sIgE level and clinically relevant outcome (CRO) status. Fisher's exact test and general linear models were used to evaluate and compare potential predictive factors for CRO status. Results: Allergy and immunology, gastroenterology, and general pediatrics ordered most S/T sIgE testing. Testing was ordered most frequently for non-IgE-mediated gastrointestinal symptoms, mild possible IgE-mediated reactions, and eczema. Testing was most often ordered for infants and school-age children. Mean sIgE levels were higher for S/T tests resulting in a CRO when controlling for other predictor variables (p = 0.015; p = 0.002 for S/T, respectively). Only 2.2% and 5.4% of tests resulted in a CRO for S/T, and severe allergy was rare. Testing for non-IgE-mediated GI symptoms or eczema, or in non-atopic patients, yielded no CROs. Exposure and reaction history of present illness (ERH) was associated with CROs (p < 0.001; p = 0.04) with a high negative predictive value (99.5%; 100%) and low positive predictive value (11.5%; 15.0%). ERH (p < 0.001, η2 = 0.073; p = 0.009, η2 = 0.123) was a more significant predictor than the sIgE level (p = 0.002, η2 = 0.037; p = 0.212, η2 = 0.030) for CRO status. Conclusion: The diagnosis of S/T food allergy is made primarily based on clinical history. S/T sIgE testing for children and adolescents should be avoided for patients without an ERH and in the workup of non-IgE-mediated GI symptoms. Testing for eczema and non-atopic patients is likely low-yield.

Cellular assays to evaluate B-cell function.

Inborn errors of immunity (IEI) that present with recurrent infections are largely due to antibody (Ab) deficiencies. Therefore, assessment of the B-cell and Ab compartment is a major part of immunologic evaluation. Here we provide an overview about cellular assays used to study B-cell function and focus on lymphocyte proliferation assay (LPA), opsonophagocytic assay (OPA), and the Enzyme-linked Immunosorbent Spot Assay (ELISPOT) including clinical applications and limitations of these techniques. LPAs assess ex-vivo cell proliferation in response to various stimuli. Clinically available LPAs utilize peripheral blood mononuclear cells and mostly assess T-cell proliferation with pokeweed mitogen considered the most B-cell specific stimulus. In the research setting, isolating B cells or using more B-cell specific stimuli such as CD40L with IL-4/IL-21 or the TLR9 ligand CpG can more specifically capture the proliferative ability of B cells. OPAs are functional in-vitro killing assays used to evaluate the ability of IgG Ab to induce phagocytosis applied when assessing the potency of vaccine candidates or along with avidity assays to evaluate the quality of secreted IgG. The B-cell ELISPOT assesses Ab production at a cellular level and can characterize the Ab response of particular B-cell subtypes. It can be used in patients on IgG therapy by capturing specific Abs produced by individual B cells, which is not affected by exogenous IgG from plasma donors, and when assessing the vaccine response in patients on immunomodulatory drugs that can affect memory B-cell function. Emerging approaches that are only available in research settings are also briefly introduced.

An enzyme-linked immunospot assay to evaluate Pneumovax response when on intravenous immunoglobulin.

BACKGROUND: Testing for common variable immunodeficiency (CVID) requires evaluation of specific antibody responses to vaccines. Current practice of evaluating pneumococcal serotype-specific immunoglobulin (Ig)G levels after Pneumovax (P23) has several limitations and is not accurate for patients already on immunoglobulin replacement. In contrast, the enzyme-linked immunospot (ELISPOT) assay can be interpreted in patients on immunoglobulin replacement as ex vivo measurement of specific antibody-secreting cells (ASCs). OBJECTIVE: To optimize and test an ELISPOT assay to evaluate vaccination response to P23 and compare with P23 serotype-specific IgG for patients on intravenous immunoglobulin (IVIG). METHODS: We prospectively enrolled a total of 15 adults: normal controls (n = 8), patients with CVID on IVIG replacement (n = 2), patients on IVIG replacement for recurrent infections who did not meet diagnostic criteria for CVID, considered IgG deficiency (n = 2), and patients without immunodeficiency on high-dose IVIG for other diagnosis (n = 3). We measured P23 serotype-specific IgG before and 4 weeks after P23 and ELISPOT ASCs before and 1 week after P23 (with B-cell subpopulation analysis by flow cytometry in patients on IVIG). RESULTS: Normal controls had a vaccination response by P23 serotype-specific IgG, whereas patients on IVIG did not. Except for true patients with CVID on IVIG, a P23 ELISPOT ASC response was found in normal controls (highest) and most patients on IVIG for recurrent infections or other diagnosis. CONCLUSION: Our pilot study suggests that an optimized ELISPOT protocol has utility to evaluate the P23-specific antibody response after vaccination. Our ELISPOT assay seemed reliable for patients on IVIG and may help differentiate true patients with CVID from those with a less stringent diagnosis while on IVIG.

Allergy and immunology interest and exposure among US medical students and residents.

Background: Despite the immense burden of allergic disease, the allergy and immunology (AI) workforce in the United States continues to shrink. Fellowship applications for AI have declined sharply in contrast to those in more popular specialties. Objectives: Here we have sought to evaluate the current level of AI interest and exposure among early trainees in the United States, as well as their perspective on how to improve interest in the field. Methods: An 18-item questionnaire was sent via e-mail list-serve to 2 groups: (1) mostly residents in the American Academy of Allergy, Asthma & Immunology (AAAAI) with interest in AI and (2) medical students in the American Medical Student Association (AMSA) whose specialty interests were not known. Results: In the AAAAI group, 412 members were surveyed and 70 responses were received. In the AMSA group, 4778 members were surveyed and 47 responses were received. More individuals in the AAAAI group interacted with their AI division than in the AMSA group (73% vs 19% [P < .001]). On average, the AAAAI group would "probably" pursue AI whereas the AMSA group who would "definitely not" do so (P < .001). Almost all of the AMSA group (94%) had heard of AI before, but only 19% of them interacted with AI at their program. Regarding ways to increase interest in AI, the top responses for both groups were clinical exposure via electives and shadowing (a score of 4.69 on a 5-point scale) and didactic exposure via lectures and presentations (a score of 4.29). Conclusions: Our study suggests that increasing AI opportunities for didactics and clinical exposure may lead medical students to develop more interest in pursuing the field. Some strategies are also discussed.

Factors Associated with Persistence of Severe Asthma from Late Adolescence to Early Adulthood.

RATIONALE: Asthma severity in children generally starts mild but may progress and stay severe for unknown reasons. OBJECTIVES: Identify factors in childhood that predict persistence of severe asthma in late adolescence and early adulthood. METHODS: The Childhood Asthma Management Program is the largest and longest asthma trial in 1041 children aged 5-12 years with mild to moderate asthma. We evaluated 682 participants from the program with analyzable data in late adolescence (age 17-19) and early adulthood (age 21-23). MEASUREMENTS: Severe asthma was defined using criteria from the American Thoracic Society and the National Asthma Education and Prevention Program to best capture severe asthma. Logistic regression with stepwise elimination was used to analyze clinical features, biomarkers, and lung function predictive of persistence of severe asthma. MAIN RESULTS: In late adolescence and early adulthood 12% and 19% of the patents had severe asthma, respectively; only 6% were severe at both time periods. For every 5% decrease in post bronchodilator FEV1/FVC in childhood, the odds of persistence of severe asthma increased 2.36-fold (95% CI: 1.70-3.28; p <0.0001), for participants with maternal smoking during pregnancy odds of persistence of severe asthma increased 3.17-fold (95% CI: 1.18-8.53, p=0.02). Reduced growth lung function trajectory was significantly associated with persistence of severe asthma compared to normal growth. CONCLUSIONS: Lung function and maternal smoking during pregnancy were significant predictors of severe asthma from late adolescence to early adulthood. Interventions to preserve lung function early may prevent disease progression.

Effects of sex, age, and apolipoprotein E genotype on hippocampal parenchymal fraction in cognitively normal older adults.

Early detection of Alzheimer's disease (AD) is important for timely interventions and developing new treatments. Hippocampus atrophy is an early biomarker of AD. The hippocampal parenchymal fraction (HPF) is a promising measure of hippocampal structural integrity computed from structural MRI. It is important to characterize the dependence of HPF on covariates such as age and sex in the normal population to enhance its utility as a disease biomarker. We measured the HPF in 4239 structural MRI scans from 340 cognitively normal (CN) subjects aged 59-89 years from the AD Neuroimaging Initiative database, and studied its dependence on age, sex, apolipoprotein E (APOE) genotype, brain hemisphere, intracranial volume (ICV), and education using a linear mixed-effects model. In this CN cohort, HPF was inversely associated with ICV; was greater on the right hemisphere compared to left in both sexes with the degree of right > left asymmetry being slightly more pronounced in men; declined quadratically with age and faster in APOE ϵ4 carriers compared to non-carriers; and was significantly associated with cognitive ability. Consideration of HPF as an AD biomarker should be in conjunction with other subject attributes that are shown in this research to influence HPF levels in CN older individuals.

Benefits of subspecialty adherence after asthma hospitalization and patient perceived barriers to care.

BACKGROUND: Comparative studies have demonstrated that asthma education to pediatric patients decreases average hospital usage and that allergy specialists provide stronger asthma education and more improved outcomes. OBJECTIVE: To evaluate the real-world benefits of allergy subspecialty involvement outside inpatient consultation and the impediments for patients in establishing allergy subspecialty care. METHODS: The study population was composed mostly of minority children 0 to 18 years old seen at a large university-affiliated stand-alone children's hospital who had a hospital discharge diagnosis of asthma from 2009 to 2013. The retrospective portion of the study compared all variables pertaining to asthma, teaching, and discharge reconciliation for the following subgroups: patients recommended to allergy and immunology (AI) follow-up who adhered to the appointment (adherent), patients recommended to AI follow-up who did not adhere (nonadherent), and patients not recommended to AI follow-up (non-referred). In the phone interview portion of the study, the nonadherent patients were contacted to identify barriers to AI follow-up. RESULTS: Of the referred sample, the adherent group had significantly fewer visits to the pediatric intensive care unit, days in the pediatric intensive care unit, and days in the hospital. Providing more specific hospital discharge instructions increased AI follow-up and hospital teaching given on the baseline admission decreased hospital visits. Phone interviews showed that nonadherent patients most commonly missed follow-up because the parents believed it unnecessary because their child showed acute improvement or from advice from their primary care physician. CONCLUSION: These results showed improvement in outcomes for patients who attended AI follow-up and specifically identified key barriers that could be addressed in a standardized form to prevent nonadherence in the future.

The Role of Skin Barrier in the Pathogenesis of Food Allergy.

Food allergy is a serious public health problem with an increasing prevalence. Current management is limited to food avoidance and emergency treatment. Research into the pathogenesis of food allergy has helped to shape our understanding of how patients become sensitized to an allergen. Classically, food sensitization was thought to occur through the gastrointestinal tract, but alternative routes of sensitization are being explored, specifically through the skin. Damaged skin barrier may play a crucial role in the development of food sensitization. Better understanding of how patients initially become sensitized may help lead to the development of a safe and effective treatment for food allergies or better prevention strategies.