Concordance of provider chart notation and guideline-based classification of asthma severity.

OBJECTIVE: To evaluate concordance of asthma severity classification via physician chart notation compared with guideline-based criteria in adolescents with diagnosed asthma. METHODS: Of 284 urban primary care and subspecialty clinic patients aged 13-18 years approached through convenience sampling, 203 surveys were completed (RR = 71.5%). We assessed concordance with sensitivity, specificity, and positive predictive values; overall agreement was evaluated with weighted kappa coefficients and McNemar's test. RESULTS: When considering prescribed treatment according to NAEPP guidelines as a gold standard, the sensitivity for chart notation was very good for intermittent (95%) and less for non-intermittent severity ratings (51%, 58%, and 67% for moderate, severe, and mild persistent asthma, respectively). Overall agreement between chart notation and guideline-based asthma criteria ranged from fair-to-good for mild- (k = 0.36), moderate- (k = 0.44), and severe-persistent severity (k = 0.66). Although the agreement for intermittent severity was highest (k = 0.88), it did not significantly differ by between the two classifications (p ≥ 0.05). CONCLUSIONS: Concordance for all non-intermittent asthma severity classifications varied between physician and medication-driven 2007 NAEPP guideline classifications in an ethnically diverse urban adolescent patient sample. Physicians should remain aware of the potential for this discordance and refer to the guidelines to classify and treat adolescents with asthma.

Health disparities in pediatric food allergy.

OBJECTIVE: To review the current literature regarding the health disparities in the prevalence, diagnosis, and management of pediatric food allergy and discuss possible interventions. DATA SOURCES: Literature search of PubMed and Google Scholar databases regarding pediatric food allergy and health disparities. STUDY SELECTIONS: Original research articles, reviews, and guidelines on health disparities in pediatric food allergy were included in this review. RESULTS: The overall prevalence of food allergy appears to be increasing and disproportionately affecting minority groups. Racial and socioeconomic disparities are evident across all aspects of food allergy care: diagnosis, prevention, acute management (eg, access to epinephrine autoinjectors, visits to emergency department), and long-term management (eg, oral immunotherapy). Children of minority populations and those of low socioeconomic status are at a greater risk of food insecurity, which is further exacerbated by the high cost of allergen-free foods and limited support from food assistance programs. CONCLUSION: Racial, ethnic, and socioeconomic disparities in food allergy among children in the United States are evident and negatively affect the outcomes of children with food allergies. Active efforts to decrease racial and socioeconomic disparities, through education, research, and advocacy, will be important to help improve health outcomes in food allergy for all children, regardless of their race, ethnicity, or socioeconomic status.

Infectious Complications Predict Premature CD8+ T-cell Senescence in CD40 Ligand-Deficient Patients.

PURPOSE: CD40 ligand (CD40L)-deficient patients display increased susceptibilities to infections that can be mitigated with effective prophylactic strategies including immunoglobulin G (IgG) replacement and prophylactic antibiotics. CD8+ T-cell senescence has been described in CD40L deficiency, but it is unclear if this is an intrinsic feature of the disease or secondary to infectious exposures. To address this question, we assessed CD8+ T-cell senescence and its relationship to clinical histories, including prophylaxis adherence and infections, in CD40L-deficient patients. METHODS: Peripheral CD8+ T-cells from seven CD40L-deficient patients and healthy controls (HCs) were assessed for senescent features using T-cell receptor excision circle (TREC) analysis, flow cytometry, cytometry by time of flight (CyTOF) and in vitro functional determinations including CMV-specific proliferation and cytokine release assays. RESULTS: Three patients (5, 28, and 34 years old) who were poorly adherent to immunoglobulin G replacement and Pneumocystis jirovecii pneumonia (PJP) prophylaxis and/or experienced multiple childhood pneumonias (patient group 1) had an expansion of effector memory CD8+ T-cells with the senescent phenotype when compared to HCs. Such changes were not observed in the patient group 2 (four patients, 16, 22, 24, and 33 years old) who were life-long adherents to prophylaxis and experienced few infectious complications. CyTOF analysis of CD8+ T-cells from the 5-year-old patient and older adult HCs showed similar expression patterns of senescence-associated molecules. CONCLUSIONS: Our findings support that recurrent infections and non-adherence to prophylaxis promote early CD8+ T-cell senescence in CD40L deficiency. Premature senescence may increase malignant susceptibilities and further exacerbate infectious risk in CD40L-deficient patients.

Successful Management of Eosinophilic Esophagitis Using Traditional Chinese Medicine: A Case Report.

Eosinophilic Esophagitis (EoE) is a relatively recently described condition, with rapidly increasing prevalence over the past several years. There is unfortunately no cure for EoE, and treatment involves food elimination and off-label use of topical steroids. These treatments can have significant impacts on quality of life for patients. Traditional Chinese Medicine (TCM) has been shown to decrease Th2 cytokines which are implicated in the pathophysiology of EoE. We present an 11-year-old male with severe EoE who was treated with TCM and able to achieve complete remission. Further modalities of treatment for EoE should continue to be pursued.

Allogeneic hematopoietic stem cell transplantation is associated with cure and durable remission of late-onset primary isolated central nervous system hemophagocytic lymphohistiocytosis.

Primary isolated CNS presentation of HLH is exceedingly rare and typically associated with significant morbidity and mortality. We describe an adolescent patient with late-onset, primary isolated CNS HLH and a compound heterozygous PRF1 mutation (c50delT (p.L17 fs); c.1229G>C (p.R410P)), not previously reported with this phenotype. He was successfully treated with allogeneic HSCT following a reduced-intensity conditioning regimen, despite a high pre-HSCT comorbidity index. Two years after transplant, he is alive and in disease remission. While patients with systemic HLH and active CNS disease have relatively poorer outcomes, a high index of suspicion may aid with early diagnosis of primary isolated CNS HLH; prompt treatment with HSCT may be associated with improved cure and durable remission of this rare disease.

Racial, Ethnic, and Socioeconomic Differences in Food Allergies in the US.

Importance: Food allergies affect approximately 8% of children and 11% of adults in the US. Racial differences in food allergy outcomes have previously been explored among Black and White children, but little is known about the distribution of food allergies across other racial, ethnic, and socioeconomic subpopulations. Objective: To estimate the national distribution of food allergies across racial, ethnic, and socioeconomic groups in the US. Design, Setting, and Participants: In this cross-sectional survey study, conducted from October 9, 2015, to September 18, 2016, a population-based survey was administered online and via telephone. A US nationally representative sample was surveyed. Participants were recruited using both probability- and nonprobability-based survey panels. Statistical analysis was performed from September 1, 2022, through April 10, 2023. Exposures: Demographic and food allergy-related participant characteristics. Main Outcomes and Measures: Stringent symptom criteria were developed to distinguish respondents with a "convincing" food allergy from those with similar symptom presentations (ie, food intolerance or oral allergy syndrome), with or without physician diagnosis. The prevalence of food allergies and their clinical outcomes, such as emergency department visits, epinephrine autoinjector use, and severe reactions, were measured across race (Asian, Black, White, and >1 race or other race), ethnicity (Hispanic and non-Hispanic), and household income. Complex survey-weighted proportions were used to estimate prevalence rates. Results: The survey was administered to 51 819 households comprising 78 851 individuals (40 443 adults and parents of 38 408 children; 51.1% women [95% CI, 50.5%-51.6%]; mean [SD] age of adults, 46.8 [24.0] years; mean [SD] age of children, 8.7 [5.2] years): 3.7% Asian individuals, 12.0% Black individuals, 17.4% Hispanic individuals, 62.2% White individuals, and 4.7% individuals of more than 1 race or other race. Non-Hispanic White individuals across all ages had the lowest rate of self-reported or parent-reported food allergies (9.5% [95% CI, 9.2%-9.9%]) compared with Asian (10.5% [95% CI, 9.1%-12.0%]), Hispanic (10.6% [95% CI, 9.7%-11.5%]), and non-Hispanic Black (10.6% [95% CI, 9.8%-11.5%]) individuals. The prevalence of common food allergens varied by race and ethnicity. Non-Hispanic Black individuals were most likely to report allergies to multiple foods (50.6% [95% CI, 46.1%-55.1%]). Asian and non-Hispanic White individuals had the lowest rates of severe food allergy reactions (Asian individuals, 46.9% [95% CI, 39.8%-54.1%] and non-Hispanic White individuals, 47.8% [95% CI, 45.9%-49.7%]) compared with individuals of other races and ethnicities. The prevalence of self-reported or parent-reported food allergies was lowest within households earning more than $150 000 per year (8.3% [95% CI, 7.4%-9.2%]). Conclusions and Relevance: This survey study of a US nationally representative sample suggests that the prevalence of food allergies was highest among Asian, Hispanic, and non-Hispanic Black individuals compared with non-Hispanic White individuals in the US. Further assessment of socioeconomic factors and corresponding environmental exposures may better explain the causes of food allergy and inform targeted management and interventions to reduce the burden of food allergies and disparities in outcomes.

A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist.

Lyme disease is an infection caused by Borrelia burgdorferi sensu lato, which is transmitted to humans through the bite of an infected Ixodes tick. The majority of patients recover without complications with antibiotic therapy. However, for a minority of patients, accompanying non-specific symptoms can persist for months following completion of therapy. The constellation of symptoms such as fatigue, cognitive dysfunction, and musculoskeletal pain that persist beyond 6 months and are associated with disability have been termed post-treatment Lyme disease syndrome (PTLDS), a subset of a broader term "chronic Lyme disease." Chronic Lyme disease is a broad, vaguely defined term that is used to describe patients with non-specific symptoms that are attributed to a presumed persistent Borrelia burgdorferi infection in patients who may or may not have evidence of either previous or current Lyme disease. The diagnoses of chronic Lyme disease and of PTLDS have become increasingly relevant to the practice of immunologists due to referrals for consultation or for intravenous immunoglobulin (IVIG) treatment. This review aims to explore the relationship between chronic Lyme disease, post-treatment Lyme disease syndrome, and the immune system. Here, we review the current literature on (1) issues in conventional and alternative diagnostic testing for Lyme disease, (2) the hypothesis that B. burgdorferi infection can persist despite appropriate use of recommended antibiotics, (3) current theories regarding B. burgdorferi's role in causing both immune dysregulation and protracted symptoms, and (4) the use of IVIG for the treatment of Lyme disease.

Safety Considerations for Natural Products Commonly Used By Patients with Allergic Disease.

Natural products are a category of Complementary and Alternative Medicine that includes medicinal plants, vitamins, and dietary supplements. These products are often utilized by patients with allergies in conjunction with, or as an alternative to, their conventional medical therapies. Despite the wide use of these modalities, many clinicians often have limited knowledge and training in their use. It is important for health care providers to know the safety and risks of these products that their patients may use. This Clinical Commentary reviews the side effects and adverse reactions of several natural products commonly used by patients with allergies and gives an overview of the U.S. Food and Drug Administration requirements for manufacturing, advertising and distribution.

Induction of Severe Eosinophilic Esophagitis and Multi-Organ Inflammation by Airborne Allergens is Associated with IL-4/IL-13 and CCL11 but Not IgE in Genetic Susceptible Mice.

Background: Eosinophilic Esophagitis (EoE) is an increasingly common chronic inflammatory disease. The pathological mechanisms underlying EoE are largely unknown. Objective: We sought to understand the mechanisms underlying aeroallergen-induced EoE in Sharpin gene deficient (Sharpin-/-) mice that is prone to inflammatory response. Methods: Sharpin-/-mice were exposed with Aspergillus fumigatus and ovalbumin intranasally every alternate day for 4 weeks. Wild type (WT) naïve mice, WT exposed, and un-exposed Sharpin-/- mice were controls. Histopathological analysis was performed by H&E, trichrome and major basic protein staining. Total and specific IgE, IgG, and IgA levels were measured by ELISA and Th2 cytokine and CCL11 chemokine gene expression were determined. Results: Airborne allergen exposed Sharpin-/- mice showed severe eosinophilic inflammation in the esophagus (p < 0.001), and markedly increased epithelial thickening (p < 0.0001) compared to WT normal controls, whereas airborne allergen exposed WT mice and unexposed Sharpin-/- mice only showed mild eosinophilic inflammation in the esophagus. These exposed Sharpin-/- mice also showed over 7-fold increase in blood eosinophils (p < 0.0001), 60-fold increase in eosinophils in bronchoalveolar lavage fluid (p < 0.0001) and 4-fold increase in eosinophils in the skin (p < 0.0001) compared to normal controls. Surprisingly, exposed Sharpin-/- mice did not show elevation of serum total or antigen-specific IgE levels but reduced total IgA and IgG levels than normal controls There was a marked increase in IL-4, IL-13 and CCL11 gene expression in esophageal tissue (p < 0.001) in exposed Sharpin-/- mice compared to WT normal mice. Conclusion: Th2 cytokines and chemokines, but not IgE may play an important pathologic role in aeroallergen-induced EoE. This study may provide insight into new therapeutics for EoE.

Computational analysis to define efficacy & molecular mechanisms of 7, 4'- Dihydroxyflavone on eosinophilic esophagitis: Ex-vivo validation in human esophagus biopsies.

Introduction: Eosinophilic Esophagitis (EoE) is a chronic condition characterized by eosinophilic inflammation of the esophagus which leads to esophageal dysfunction with common symptoms including vomiting, feeding difficulty, dysphagia, abdominal pain. Current main treatment options of EoE include dietary elimination and swallowed steroids. Diet elimination approach could lead to identifying the trigger food(s), but it often requires repeated upper endoscopy with general anesthesia and potentially could negatively affect nutrition intake and growth of the child and individuals' quality of life. Although the swallowed steroid treatment of effective, the EoE will universally recur after discontinuation of the treatment. Digestive Tea formula (DTF) has been used by the Traditional Chinese Medicine (TCM) practice to improve GI symptoms in EoE patients, including abdominal pain, GE reflux, and abnormal bowel movement. Previously, a flavonoid small molecule compound 7, 4 dihydroxy flavone (DHF) from Glycyrrhiza uralensis in DTF inhibited eotaxin, Th2 cytokine and IgE production in vitro and in vivo. Method: This study comprehensively evaluates the potential therapeutic and immunological mechanisms underlying DHF improvement of symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, in silico molecular docking and dynamic simulation followed by ex-vivo target validation by qRT-PCR using cultured human esophagus biopsy specimen with or without DHF from patients with EoE. Results: Computational analyses defined 29 common targets of DHF on EoE, among which TNF-α, IL-6, IL1ß, MAPK1, MAPK3 and AKT1 were most important. Docking analysis and dynamic simulation revealed that DHF directly binds TNF-α with a free binding energy of -7.7 kcal/mol with greater stability and flexibility. Subsequently, in the human esophagus biopsy culture system, significant reduction in levels of TNF-α, IL-6, IL-8 and IL1-ß was found in the supernatant of biopsy sample cultured with DHF. Furthermore, the gene expression profile showed significant reduction in levels of TNF-α, IL1-ß, IL-6, CCND and MAPK1 in the esophagus biopsy sample cultured with DHF. Discussion: Taken together, the current study provides us an insight into the molecular mechanisms underlying multi-targeted benefits of DHF in the treatment of EoE and paves the way for facilitating more effective EoE therapies.

An integrative medicine review of primary prevention of allergy in pediatrics.

The prevalence of allergic disease has been rapidly increasing in the developed world for over fifty years. The prevention of allergic disease remains one of the most elusive topics in medicine. Integrative medicine emphasizes prevention of disease and utilizes many interventions to help modify long-term outcomes of health. Primary prevention refers to the arrest of manifestations of a disease before they present clinically. Preventing allergy is not simply about preventing sensitization, but also about developing tolerance. This narrative review article will discuss integrative medicine approaches that may help to prevent atopic disease in the pediatric population. It is organized chronologically to aid in counseling patients: 1) prevention during pregnancy and 2) prevention after birth. While research into allergy prevention is in its infancy, Integrative Medicine is well-suited to provide many insights into the prevention and mitigation of atopic disease.

Community Private Practice Clinical Experience with Peanut Oral Immunotherapy.

BACKGROUND: Peanut oral immunotherapy is an effective treatment for desensitizing peanut-allergic patients, but the frequency of adverse reactions has limited its widespread use. OBJECTIVE: To review the frequency of adverse reactions that patients on peanut oral immunotherapy experience during build-up and maintenance phases and explore factors that may contribute to adverse events. METHODS: A retrospective chart review of children and adults with peanut allergy undergoing peanut oral immunotherapy at the New England Food Allergy Treatment Center in West Hartford, Conn was performed. Data on patient demographics, allergic profile, peanut allergy testing, and details of reactions in build-up and maintenance phases were collected. A systemic reaction was defined as one of the following: (1) severe reaction involving 1 system, such as generalized hives and/or angioedema; (2) 2 or more of the following symptoms: cutaneous or oral, respiratory, or gastrointestinal symptoms; (3) drop in blood pressure; or (4) need for epinephrine. RESULTS: Data were available on 783 patients aged 3.5 to 48.3 years. During buildup, 78 patients (10%) experienced at least 1 systemic reaction, 660 (84%) at least 1 gastrointestinal adverse event, 369 (47%) at least 1 cutaneous adverse event, and 157 (20%) at least 1 respiratory adverse event. Thirty-four patients (4%) required epinephrine during buildup. Six hundred ninety-seven patients (89%) completed buildup and progressed to maintenance. During maintenance, 131 patients (19%) experienced at least 1 systemic reaction, 190 (27%) at least 1 gastrointestinal adverse event, 104 (15%) at least 1 cutaneous adverse event, and 50 (7%) at least 1 respiratory adverse event. Seventy-four patients (11%) required epinephrine during maintenance. None of the adverse events required hospitalizations, and there were no mortalities. Nine patients (1%) were diagnosed with eosinophilic esophagitis during buildup or maintenance. Increasing pretreatment peanut specific IgE levels were associated with increased odds of a systemic reaction during buildup. Increasing age, pretreatment peanut specific IgE level, and a systemic reaction in buildup were associated with increased odds of a systemic reaction during maintenance. CONCLUSIONS: Peanut oral immunotherapy may be an effective and safe treatment for carefully selected peanut-allergic patients under the guidance of experienced providers. Specific patient characteristics and immunologic factors may help predict adverse events.

Successful Graded Dose Challenge to Iodixanol Radiocontrast Media in a Patient With Delayed Anaphylaxis to Iohexol.

We present a case of an 82-year-old male with known radiocontrast media (RCM) hypersensitivity who was admitted to our hospital with gangrene of his right toe. The plan for revascularization of his lower extremity required an angiogram. This presented a management challenge as the patient had experienced 2 episodes of delayed anaphylaxis to Omnipaque (iohexol) RCM, and based on a literature review, there was no known or established precedent on a safe procedure in these situations. The patient was premedicated and given a graded dose challenge of an alternative RCM (iodixanol) prior to the radiographic study. He was given 1% of the total expected dose 1 hour before to the procedure and an additional 10% for the 30 minutes prior. He was then given the final dose in the operating room. Following angiogram, the patient was monitored for 18 hours in the postanesthesia care unit, with no adverse reactions. He was placed on a prednisone taper for 1 week, with daily diphenhydramine. The patient remained asymptomatic throughout the hospital course. This novel approach to RCM hypersensitivity management lends itself to a hope that graded dose challenges may play a greater role in the management of these patients.