The journal of allergy and clinical immunology. Global最新文献

Background: Adverse effects following immunizations (AEFIs) can contribute to vaccine hesitancy.

Objective: We evaluated clinical outcomes of AEFIs subsequent to administration of the coronavirus disease 2019 (COVID-19) vaccine at 2 pediatric allergy centers.

Methods: Data on pediatric patients referred for COVID-19 AEFI concerns between March 2021 and October 2022 were reviewed. The collected data included patient demographics, clinical characteristics, outcomes of prior COVID-19 vaccination, recommendations after consultation, and outcomes of revaccination.

Results: The 163 patients were separated into 2 groups based on the absence (n = 89 [54.6%]) or presence (n = 74 [45.4%]) of prior COVID-19-related AEFIs. The most common reason for referral without a prior AEFI was another suspected drug allergy (n = 58 [35.6%]). All patients in this group were recommended for COVID-19 vaccination. Of the 163 patients, 82 (92.1%) proceeded with vaccination, with 77 of them (93.9%) tolerating vaccination. Most of those with a prior COVID-19-related AEFI had a delayed cutaneous reaction (n = 60 [37.0%]); 1 patient (0.6%) had suspected anaphylaxis. In this group, 6 (8.1%) were advised to postpone COVID-19 vaccination until their debilitating skin conditions had improved in response to further treatment, whereas 45 (77.6%) tolerated subsequent vaccination to the same or an alternate COVID-19 vaccine type. The most common AEFI on revaccination was urticaria (in 8 of 11 patients [72.7%]). AEFI on revaccination was significantly associated with a history of spontaneous urticaria or angioedema (relative risk = 3.6 [95% CI = 1.30-9.99]; P = .020) and urticaria following COVID-19 vaccination previously (relative risk = 4.12 [95% CI = 1.22-13.87]; P = .017).

Conclusions: Children with a history of urticaria or angioedema related or unrelated to prior COVID-19 vaccination were at higher risk of a COVID-19-related AEFI on revaccination, although most were able to complete the vaccination series under the management of our immunology/allergy service.

Background: Omalizumab (OMA), a recombinant humanized IgG monoclonal anti-IgE antibody, is approved for treatment for chronic spontaneous urticaria (CSU) refractory to second-generation H₁-antihistamine (SGAH) therapy. However, currently, there are no validated serum biomarkers to reliably predict response to OMA treatment.

Objective: We explored the real-world clinical utility of using serum biomarkers for predicting response to OMA for CSU patients with disease refractory to high-dose SGAH therapy.

Methods: A single-center, retrospective chart review of CSU patients treated with OMA enrolled patients who had at their initial evaluation collection of a basophil histamine release assay for detecting IgG antibodies targeting FcεR1α subunit before starting OMA treatment. In addition, total IgE, IgG-anti-thyroid peroxidase (TPO), C-reactive protein, and absolute eosinophil count, if available, were analyzed as predictors for OMA response. The validated Outcome and Assessment Information Set Database (OASIS-D) rating system was used to assess responsiveness to OMA.

Results: High levels of IgG-anti-TPO were significantly associated with a poor response to OMA. However, basophil histamine release assay, total IgE, C-reactive protein, and absolute eosinophil count, as well as IgG-anti-TPO/total IgE ratios, were not predictive of a response to OMA therapy.

Conclusions: This real-world study confirms previous reports that a high IgG-anti-TPO level is a reliable predictor of poor response to OMA. However, better validation of basophil histamine release assay and other immunoassays that measure IgG antibodies to FcεR1α subunit are required before they can be recommended as predictors for OMA response. Whether any of these biomarkers are relevant for predicting response to novel advanced therapeutics under current development requires further investigation.

Background: Many patients with X-linked agammaglobulinemia (XLA) nowadays have reached adulthood, as well as their sisters, possibly carriers of a deleterious Bruton tyrosine kinase variant. Studies on motherhood outcomes in families with XLA are lacking.

Objective: We sought to investigate adherence to carrier status screening, interest in preconception and prenatal genetic counseling, and reproductive decisions in relatives with XLA.

Methods: In this multicenter, retrospective cohort study, we collected a 3-generation pedigree and data on mothers and sisters of patients with XLA, including carrier status and pregnancy outcome.

Results: Data on 53 adults with XLA, 52 mothers, and 33 sisters were collected. All XLA sisters received genetic counseling. Forty percent of the sisters chose to undergo carrier status determination, and 60% of them chose invasive prenatal testing. The main reasons for the sisters to decide not to undergo genetic testing were their young age and the willingness to carry on with the pregnancy regardless of the outcome of the genetic test, followed by the willingness to postpone the decision at the time of pregnancy and the decision to not have children. Prenatal testing resulted in 5 XLA diagnoses, with 2 pregnancy terminations, 1 miscarriage, and 2 XLA live births. Three carriers refused prenatal testing and had 6 live births, including 3 XLA-affected sons. One sister was diagnosed as a carrier after the birth of an XLA-affected son. In total, 9 XLA diagnoses were made, including 6 live births.

Conclusions: A number of XLA sister carriers decided to carry on with their pregnancy after receiving the diagnosis of an affected fetus or after refusing prenatal testing. We propose to initiate a more extensive collaborative study to verify the effect of genetic counseling on families with XLA in other cohorts from different countries.

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder marked by eosinophilic infiltration of the esophageal mucosa. Despite advances in understanding and management, optimal therapeutic strategies remain unclear, with conflicting guidelines.

Objective: We sought to evaluate effectiveness and safety of topical corticosteroids (TCSs) and proton pump inhibitors (PPIs) in managing EoE and their economic implications in Italy.

Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2023 and 78 publications were included, covering treatment outcomes and adverse events. Meta-analyses were performed to evaluate treatment efficacy and safety across various patient populations and study designs.

Results: TCSs showed superior efficacy over PPIs in achieving histologic, endoscopic, and partial clinical responses. Older patients responded better to both treatments. Treatment outcomes varied by sex and presence of atopic conditions. TCSs discontinuation increased the risk of clinical relapse (0.70 cases per person-year), whereas continuous use was linked to a rise in nonserious adverse events (dilation, infections, upper respiratory tract infections, and skin disorders). Economic analysis indicated cost variations based on treatment regimens and follow-up protocols, with dilation and relapse being significant cost drivers in Italy.

Conclusions: This review provides insights into efficacy, safety, and economic impact of TCSs and PPIs in managing EoE. TCSs were more effective in achieving histologic and endoscopic responses, whereas PPIs were effective in reducing symptoms. Standardized treatment guidelines are needed because of varied treatment efficacy across studies. Future research and new therapies may enhance outcomes and reduce health care costs, improving patient quality of life.

Background: The incidence of food allergy (FA) has been increasing worldwide, causing growing concern on a global scale.

Objective: This birth cohort study analyzes the incidence of reported FA and other atopic comorbidities in children from birth to age 2 years who were living in 4 urban and semiurban areas in Iran.

Methods: Children were followed from birth until age 24 months, with follow-up questionnaires administered through parent or guardian interviews conducted when the children were aged 2, 4, 6, 12, and 24 months.

Results: The rate of physician-diagnosed FA reported by parents or guardians was higher than expected, with a cumulative incidence of 7.7% in children younger than 24 months. The highest prevalence of FA was found in Yazd, the most urban of the 4 cities studied. Breast-feeding was associated with a decreased cumulative risk of FA at age 12 months, with only 5% of breast-fed children developing parent-reported pediatrician-diagnosed FA compared with 13% of infants who never received breast milk after birth.

Conclusion: This study provides valuable insight into the incidence of FA in the Middle East, which has previously not been reported on, and it is crucial in our understanding of global FA prevalence. The study demonstrates a high incidence of FA in an area with historically lower rates and confirms that breast-feeding does prevent FA during infancy in this population.

Background: Oral immunotherapy is an established approach to desensitize the immune system in the context of allergic disease; however, the only currently approved product is for peanut allergy. ADP101 is a novel, pharmaceutical-grade, multifood oral immunotherapy in development to simultaneously treat single or multiple food allergies, containing allergenic proteins from 15 foods in equal parts by protein weight.

Objective: The phase 1/2 Harmony trial (NCT04856865) evaluated efficacy and safety of ADP101 in participants with qualifying allergy to 1 to 5 foods in ADP101, defined as dose-limiting symptoms with a ≤100 mg challenge dose during double-blind, placebo-controlled food challenge (DBPCFC).

Methods: Participants were randomized to low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or matched placebo, with dose escalation followed by daily maintenance dosing over 40 weeks. The primary endpoint was the proportion of participants tolerating a ≥600 mg challenge dose of a single qualifying food without dose-limiting symptoms at the Week 40 Exit DBPCFC (ie, responders).

Results: In the primary analysis population (61 pediatric participants aged 4-17 years), a greater response rate was observed in both the high-dose ADP101 (55.0%) and low-dose ADP101 (38.1%) groups compared with pooled placebo (20.0%) (nominal P = .048, P = .306, respectively; adjusted for multiple comparisons, P = .097, P = .306, respectively). Desensitization to ≥2 foods was observed in individuals with multiple food allergies, as was desensitization at levels over 600 mg. ADP101-treated participants showed an overall reduction in skin-prick test reactivity, with an increase in maximum tolerated dose across the majority of foods tested. Adverse events were mostly mild or moderate, with no life-threatening events or deaths.

Conclusions: The study did not meet its primary endpoint, but ADP101 demonstrated a favorable safety profile and increased the reactive threshold in DBPCFC in pediatric participants with single or multiple food allergies across multiple endpoints, warranting further clinical investigation.

Background: Management of patients with food allergies is complex, especially in cases of patients with multiple and potentially severe food allergies. Although international guidelines exist for food allergy management, the role of the allergist in the decision-making process is key.

Objective: Our aim was to investigate the management patterns and educational needs of practicing allergists treating patients with food allergies.

Methods: An online survey was e-mailed to United States-based practicing allergists (N = 2833) in November-December 2021. The allergists were screened for managing 1 or more patients (including ≥25% pediatric patients) with food allergies per month. The allergists responded to questions regarding food allergy management in response to 2 hypothetical pediatric case studies, their familiarity with available guidelines and emerging treatments, and their future educational preferences. A descriptive analysis of outcomes was conducted.

Results: A total of 125 responding allergists (4.4%) met the eligibility criteria and completed the survey. The allergists prioritized written exposure action plans, patient-caregiver communication, prevention of serious reactions, and consideration of both food allergy severity and allergic comorbidities in the management of patients with food allergies. With regard to recommending biologics in the future, the allergists identified patient history of anaphylaxis and hospitalizations, food allergy severity, and allergic comorbidities as all being important factors to consider when deciding on appropriate treatment options. The allergists noted their ongoing educational needs, especially for current and emerging treatments for food allergies.

Conclusion: With the treatment landscape for food allergies evolving rapidly, the decision-making priorities and continuing educational needs of allergists will be important in optimizing the management of patients with food allergies.

Background: Food allergy has been shown to negatively impact children's mental health and quality of life. However, its impact on school performance is unknown.

Objective: We aimed to investigate whether food allergy, severe and nonsevere, is associated with school performance when accounting for measured and unmeasured familial factors.

Methods: This was a register-based cohort study, with sibling controls, including all children born in Sweden 2001-5 (n = 456,164) with food allergy information based on hospital visits and prescriptions, grades, and national test results from all Swedish schools and confounders. Primary exposure was food allergy severity (none, nonsevere, or severe) in school years 7-9, and the primary outcome was total grades from year 9, with secondary exposures/outcomes also at younger ages. The primary outcome was analyzed by linear regression and, for sibling/twin control analyses, fixed effect linear regression. Results were replicated in a twin cohort (n = 31,609).

Results: In unadjusted and analyses adjusted for measured confounders, children with severe food allergy appeared to have better total grades than children without food allergy (β_unadjusted = 10.6 [95% confidence interval (CI), 8.6, 12.6] and β_adjusted = 5.5 [95% CI, 3.7, 7.4]). When also adjusting for unmeasured confounders shared by siblings, the difference was close to null and statistically nonsignificant (β_sibling = 1.6 [95% CI, -1.5, 4.7]; for nonsevere food allergy, β_sibling = -0.0 [95% CI, -2.2, 2.1]). The twin cohort results were similar.

Conclusions: We found no consistent evidence of a negative effect of food allergy, either severe or nonsevere, on school performance when adjusting for measured and unmeasured confounders shared by siblings.