Journal of Allergy and Clinical Immunology-In Practice最新文献

Background: In phase 3 VOYAGE (NCT02948959), dupilumab showed clinical efficacy with an acceptable safety profile in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb).

Objective: We analyzed dupilumab's efficacy in children with type 2 asthma by high- or medium-dose inhaled corticosteroids (ICS) at baseline.

Methods: Children were randomized to receive add-on dupilumab 100/200 mg (by body-weight ≤30 kg/>30 kg) every 2 weeks or placebo for 52 weeks and stratified by high- or medium-dose ICS at baseline. Endpoints were annualized severe exacerbation rate, changes from baseline in percent-predicted forced expiratory volume in 1 second (ppFEV₁) and 7-item Asthma Control Questionnaire - Interviewer Administered (ACQ-7-IA) score, proportions of ACQ-7-IA responders (improvement ≥0.5), and biomarker changes.

Results: In children receiving high- (n = 152) or medium- (n = 195) dose ICS at baseline, dupilumab versus placebo reduced severe exacerbation rates by 63% (P < .001) and 59% (P = .003), respectively. At week 52, dupilumab improved ppFEV₁ by least squares mean difference versus placebo of 5.7 percentage points (P = .02) and 9.35 points (P < .001), and reduced ACQ-7-IA scores by 0.53 points (P < .001) and 0.40 points (P < .001), respectively. No significant treatment interactions between ICS subgroups were detected at week 52. Significant improvements were observed in ACQ-7-IA responder rates and most type 2 biomarker levels.

Conclusion: Dupilumab reduced severe exacerbation rates and improved lung function and asthma control in children with uncontrolled, moderate-to-severe type 2 asthma, regardless of ICS dose at baseline.

Background: Hymenoptera venom is one of the most frequent causes of anaphylaxis. Studies from adults indicate the clinical profiles and risk factors of Hymenoptera venom induced anaphylaxis (VIA). Much less is known about pediatric VIA.

Objective: To better understand elicitor and age related factors determining pediatric VIA by analyzing data from the anaphylaxis registry.

Methods: We selected pediatric VIA, pediatric food induced anaphylaxis (FIA) and adult VIA cohorts from the anaphylaxis registry and performed a comparative data analysis regarding elicitors, symptoms and management.

Results: 725 pediatric VIA, 3,149 pediatric FIA and 5,534 adult VIA were identified. In pediatric VIA, boys were more frequently affected, atopy was not increased and the onset of the reaction after exposure was fast (≤ 30 min; 91%) when compared to pediatric FIA. Symptoms in pediatric VIA were age dependent, and although respiratory symptoms occurred besides skin symptoms most frequent in both, pediatric VIA and FIA, cardiovascular symptoms were more frequently reported in pediatric VIA than pediatric FIA. The analysis of pediatric versus adult VIA reveled clear differences of the frequency of involved organ systems (skin: 93/78%, respiratory: 77/64%, and cardiovascular: 61/85%). Among both, the pediatric and adult VIA, the rates of adrenaline application by a professional were low (29/31%) but the hospitalization rates were higher in children than in adults (61%/42%). Venom immunotherapy (VIT) was initiated frequently regardless of age (78% each).

Conclusion: Pediatric VIA is more frequent in boys, symptoms are age dependent and often hospitalization is required. Adrenaline should be applied according the current guidelines. VIT is an important treatment option in pediatric VIA and should be considered in severely affected children.

Background: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission.

Objective: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months.

Methods: The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period.

Results: Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent.

Conclusions: This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

Patients with Hymenoptera venom allergy (HVA), especially those with severe anaphylaxis, frequently have concomitant clonal mast cell disease (MCD) in the form of systemic mastocytosis or monoclonal mast cell activation syndrome. Detection of clonal MCD is important since it will have significant consequences for management of HVA. Therefore, we recommend patients with HVA be systematically screened for clonal MCD. The pre-test probability of clonal MCD can be assessed in a stepwise fashion starting with examination of the skin for typical monomorphic maculopapular cutaneous mastocytosis (MPCM) lesions; measurement of the baseline serum tryptase (BST) and tryptase genotyping for patients with BST>11 ng/mL; followed by the REMA score which is calculated by utilizing anaphylaxis clinical features, BST, and patient sex. A bone marrow biopsy should be performed in patients with monomorphic MPCM, a REMA score ≥2, or an elevated BST based upon tryptase genotype. Patients with HVA and a clonal MCD should be treated with immunotherapy directed against the Hymenoptera venom for which they are sensitized. For this high-risk subgroup of HVA patients, it is recommended to continue immunotherapy for more than 5 years or indefinitely and to carry at least three epinephrine autoinjectors. Future studies should determine whether KIT D816V-selective tyrosine kinase inhibitors are effective at preventing or reducing severity of Hymenoptera-venom triggered anaphylaxis in patients with clonal MCD.

Background: Nearly 80% of patients with eosinophilic esophagitis have co-existing atopic disease, yet a subset do not. It is unclear if this lack of atopy impacts presentation or response to therapy.

Objectives: To characterize the presentation and response to therapy in atopic versus non-atopic pediatric patients with EoE METHODS: A case-control study of EoE patients, ages 6 months to 18 years (between 2018-2021) was performed. Patients were eligible if they had allergy testing, assessment of atopic history, and at least one endoscopy following initiation of treatment. Patients were considered non-atopic if they had negative allergy testing and no history of significant atopy. Response to therapy was classified as complete (peak eos < 15/hpf), partial (≥ 15 eos/hpf but at least a 50% reduction in peak eos), or non-response.

Results: 168 participants were enrolled. The majority were white (n=141, 84%), male (n=124, 74%), and non-Hispanic (n=158, 95%). Mean age at diagnosis was 9.4 years (SD: ± 4.8). 123 participants (73.2%) were atopic and 45 (26.8%) were non-atopic. There was no significant difference between atopic and non-atopic for most demographics or presenting symptoms. Non-atopic participants presented younger than atopic participants (8.14 vs. 9.8 years, p=0.046). Swallowed topical corticosteroids (STC) and food elimination diets (FED) were utilized at a similar rate. There were no differences in treatment response between atopic/non-atopic participants in regards to STC, FED, or STC+FED.

Conclusion: Atopic status does not significantly impact presentation or response to treatment in pediatric EoE, but a lack of atopy may be a risk for earlier onset of disease.

Background: Documented penicillin allergies are associated with increased morbidity, increased hospital stay, and an increase in resistant infections. Penicillin allergy evaluations using direct oral challenge with or without skin testing has been recommended as a delabeling strategy for patients with penicillin reaction histories. Barriers for achieving equitable access, however, exist. Understanding patient perceptions regarding their penicillin allergy across diverse populations is crucial to mitigate potential obstacles to penicillin allergy testing (PAT) and the use of penicillin-like antibiotics after delabeling.

Objective: The objective of this study is to gather perceptions of patients delabeled of their penicillin allergy after testing through a PAT program.

Methods: Patients who underwent PAT and had a subsequent allergy removal due to a negative result were interviewed using closed and open-ended questions.

Results: A total of 100 patient interviews were completed. Awareness of the risks associated with unnecessary penicillin avoidance and PAT was low. Initial concerns regarding PAT were common, however, were frequently alleviated with targeted education. Most patients undergoing testing reported a positive experience and would recommend PAT to others. A minority of patients continued to have discordant perceptions regarding their penicillin allergy label with mistrust in the negative result being a critical theme identified.

Conclusion: Future interventions increasing the awareness of penicillin allergy labels and the risks and benefits of PAT in the general population are needed and must consider health literacy levels, languages, and cultural contexts. Measures to offer PAT within a clinical setting that has built high levels of patient trust will likely achieve the greatest long-term success.