Clinical and Translational Allergy最新文献

Background: Anaphylaxis is an acute, severe, and potentially fatal reaction marked by the fast onset of symptoms and organ involvement that may lead to death from vascular collapse or airway obstruction. Despite adrenaline (epinephrine) being the first-line medication for reversing anaphylactic symptoms, misconceptions about its safe and correct use persist and lead to improper administration.

Methods: This review provides a comprehensive overview of clinical use of adrenaline autoinjectors (AAIs) in the management of anaphylaxis, key safety considerations, and pharmacokinetic/pharmacodynamic profile of three of the currently marketed AAIs.

Results: When administered intramuscularly (IM) at the recommended dose for anaphylaxis, adrenaline is considered safe; however, adequate training in emergency care is essential to minimize dosage errors and mitigate safety risks. In specific situations, such as refractory anaphylaxis, intravenous (IV) administration is advised under specialized settings due to the potential risk of severe cardiovascular complications that can result from dosing errors.

Conclusion: Although adrenaline can cause mild and transient side effects even when administered correctly at the recommended dosage, the potential side effects should not deter its use in critical situations such as anaphylaxis. This review aims to highlight the role of AAIs in improving patient outcomes during anaphylactic emergencies.

Background: Robust data are essential for clinical and epidemiological research, yet in chronic spontaneous urticaria (CSU), certain patient groups, such as the elderly or comorbid patients, are often underrepresented. In clinical trials, strict inclusion and exclusion criteria frequently limit recruitment, making it difficult to achieve sufficient statistical power. Similarly, real-world observational studies may lack sufficient sample sizes for robust analysis. To address these limitations, we generated synthetic patient data that reflect these groups' clinical characteristics and variability. This approach enables more comprehensive analyses, facilitates hypothesis testing in otherwise inaccessible populations, and supports the generation of evidence where traditional data sources are insufficient.

Methods: A tree-based decision model was applied to generate synthetic data based on an existing set of real-world data (RWD) from the Chronic Urticaria Registry (CURE). Descriptive characteristics and association strength between relevant RWD variables and their synthetic counterparts were analyzed as indicators of replication accuracy, providing insight into how closely the synthetic data aligns with the RWD. Finally, we determined the minimum sample size required to generate high-quality synthetic data.

Results: The algorithm produced extensive synthetic data records, closely mirroring patient demographics and disease clinical characteristics. Smaller subgroups of the data were equally replicated and followed the same distribution as RWD. Known associations and correlations between disease-specific factors (disease control) and risk factors (age) yielded similar results, with no significant difference (p > 0.05). The lowest threshold at which synthetic data could be generated while maintaining high accuracy in RWD was identified to be 25%, enabling a fourfold increase in the synthetic population.

Conclusion: Synthetic data could replicate RWD with reasonable accuracy for patients with CSU down to 25% of the original population size. This method has the potential to extend small patient subgroups in clinical and epidemiological research.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by tissue eosinophilia and itch. We evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in the skin of patients with AD.

Methods: After a 4-week washout from oral anti-inflammatory medications 20 patients with moderate to severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses q4wk 30 mg subcutaneous benralizumab to placebo. Lesional and unaffected skin biopsies were collected before and after 28 and 65 days of treatment, respectively, for quantification of eosinophils and IL-5Rα-bearing cells in papillary dermis. Histological measurements of epidermal thickness, spongiosis, neutrophilic and lymphocytic infiltration, as well as clinical scores EASI, SCORAD, IGA, DLQI, and POEM were conducted throughout the study. Outcomes were compared between placebo and benralizumab treatment groups using a Mann-Whitney U-test.

Results: Benralizumab, compared to placebo, reduced IL-5Rα+ cells and MBP+ EG2+ eosinophils in lesions and unaffected skin (p < 0.05). In skin lesions, benralizumab reduced MBP+ eosinophils and basophils but had no effect on eosinophil progenitor (EoP; CD34+ IL-5Rα+) or mast cell numbers. There was no change in other skin histological measurements or IGA scoring of the observational lesion, nor improvement in clinical scores.

Conclusion: Benralizumab treatment significantly inhibited accumulation of MBP+ eosinophils and basophils in lesional skin of patients with moderate to severe AD. However, a lack of improvement in histological and clinical outcomes suggests that other inflammatory pathways are central to the pathobiology of severe atopic dermatitis.

Trial registration: (ClincialTrials.gov number, NCT03563066).