Asia Pacific Allergy最新文献

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease that affects a large proportion of the global population. The treatment of CRSwNP, especially eosinophilic CRSwNP (ECRSwNP), has always been of great obstacle. Our previous phase 2 trial showed that CM310, a monoclonal antibody that targets interleukin-4 receptor alpha, was both safe and effective in reducing the size of nasal polyps, improving symptom scores, and increasing the quality of life for those with severe ECRSwNP.

Objective: This phase 3 trial aims to evaluate the efficacy, safety, pharmacokinetic, pharmacodynamic, and immunogenicity of CM310 in participants with CRSwNP.

Result: The CROWNS-2 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 trial. The study consisted of a screening/run-in period (up to 4 weeks), a treatment period (24-week double-blind treatment period plus 28-week maintenance period), and a safety follow-up period (8 weeks). The study planned to enroll 180 participants with CRSwNP (at least 60% of ECRSwNP) to receive CM310 300 mg/placebo every 2 weeks (Q2W) subcutaneously for a total of 12 doses in double-blind treatment period and 300 mg CM310 Q2W subcutaneously for a total of 14 doses in maintenance period. Enrolled participants continued to use mometasone furoate nasal spray throughout the study. The primary endpoints are a change from baseline in nasal polyp score and nasal congestion score at week 24 between CM310 and placebo in both ECRSwNP and CRSwNP.

Conclusion: The CROWNS-2 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical study to evaluate the efficacy and safety of CM310 in patients with CRSwNP.

Trial registration: NCT05436275.

Lipid transfer protein (LTP) has been documented as the dominant protein involved in food-induced anaphylaxis and food-dependent exercise-induced anaphylaxis (FDEIA) patients from Mediterranean European countries. To date, there is no report of FDEIA triggering by LTP in China. A 12-year-old Chinese boy experienced recurrent anaphylaxis during intense exercise for 3 months. Specific immunoglobulin E was performed using ImmunoCAP (Thermo Fisher Scientific, Sweden) and Euroline (EUROIMMUN, Germany). He was sensitized to several pollens, mainly mugwort (62 KUA/L), and was found to have detectable immunoglobulin E in multiple foods: cereal (wheat, barley, oat maize, rice, buckwheat, and common millet), fruits (peach, apple, grape, cherry, and orange), vegetables (lettuce, cabbage, broccoli, cauliflower, tomato, and celery), and legumes and nuts (soybean, peanut, and walnut). He also showed sensitization to LTP components from mugwort Art v3 (79.7 KUA/L) and wheat Tri a14 (12.4 KUA/L), but negative to gluten, gliadin, and omega-5 gliadin. We advised our patient to carry an epinephrine auto-injector, not to exercise alone, and to avoid wheat and fruit/vegetable ingestion for at least 4 hours before exercise or when taking non-steroidal anti-inflammatory drugs. After a 6-month follow-up, the patient has experienced no episode of anaphylaxis. We reported the first documented FDEIA case suspected triggered by LTP in a Chinese child. Clinicians should be aware of LTP sensitization when anaphylaxis occurs during exercise in individuals with multiple pollen and food sensitization.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment landscape for various malignancies by harnessing the body's immune system to target cancer cells. However, their widespread use has unveiled a spectrum of immune-related adverse events, highlighting a critical balance between antitumor immunity and autoimmunity. This review article delves into the molecular immunology of ICIs, mapping the journey from their therapeutic action to the unintended induction of immune-related adverse events. We provide a comprehensive overview of all available ICIs, including cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, programmed death-ligand 1 inhibitors, and emerging targets, discussing their mechanisms of action, clinical applications, and the molecular underpinnings of associated immune-related adverse events. Special attention is given to the activation of autoreactive T cells, B cells, cytokine release, and the inflammatory cascade, which together contribute to the development of immune-related adverse events. Through a molecular lens, we explore the clinical manifestations of immune-related adverse events across organ systems, offering insights into diagnosis, management, and strategies to mitigate these adverse effects. The review underscores the importance of understanding the delicate interplay between enhancing antitumor responses and minimizing immune-related adverse events, aiming to guide future research and the development of next-generation ICIs with improved drug safety profiles.

Background: Respiratory allergies are one of the most common allergic diseases that affect Filipinos. Grass pollen accounts for the majority of the outdoor allergens triggering these respiratory allergies. Cross-reactivity among the Philippine grass pollen grains has not been extensively studied.

Objective: This study aims to investigate the cross-reactivity of our local grasses and identify the cross-reactive allergens.

Methods: Grass pollen grains were collected and processed into crude allergenic extracts. The IgE-reactivity of these crude allergenic pollen extracts was studied using sera from patients who tested positive for the mentioned extracts. The proteins from the immunoblots of cross-reactive pollen allergen extracts were sequenced and identified.

Results: Allergenic pollen proteins were identified as cross-reactive among the grass pollen extracts. Four of these have not been listed yet as grass allergens in the World Health Organization/International Union of Immunological Societies allergen nomenclature database.

Conclusion: Local grass pollen allergens are cross-reactive with probable new allergens identified.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome belong to a family of severe cutaneous adverse reactions that can be life-threatening and carry a risk of significant morbidity and potential mortality in the event of re-exposure. Lifelong avoidance of the culprit agent is mandated, which can lead to the exclusion of multiple medications if the trigger is unclear. This can result in adverse health outcomes analogous to that of a penicillin allergy label. We present a case in which the patient would progress to fatal myeloma in the absence of treatment, however, multiple medications were administered prior to the occurrence of TEN following previous chemotherapy. Available risk stratification tools including human leucocyte antigen assessment and the algorithm of drug causality for epidermal necrolysis scoring system were utilized followed by patch testing which identified a lesser-suspected agent as possibly causative. Further evidence-based in vivo testing and subsequent challenges allowed for the reintroduction of life-saving chemotherapy.

Background: The diagnosis of allergic rhinitis (AR) primarily relies on symptoms and laboratory examinations. Due to limitations in outpatient settings, certain tests such as nasal provocation tests and nasal secretion smear examinations are not routinely conducted. Although there are clear diagnostic criteria, an accurate diagnosis still requires the expertise of an experienced doctor, considering the patient's medical history and conducting examinations. However, differences in physician knowledge and limitations of examination methods can result in variations in diagnosis.

Objective: Artificial intelligence is a significant outcome of the rapid advancement in computer technology today. This study aims to present an intelligent diagnosis and detection method based on ensemble learning for AR.

Method: We conducted a study on AR cases and 7 other diseases exhibiting similar symptoms, including rhinosinusitis, chronic rhinitis, upper respiratory tract infection, etc. Clinical data, encompassing medical history, clinical symptoms, allergen detection, and imaging, was collected. To develop an effective classifier, multiple models were employed to train on the same batch of data. By utilizing ensemble learning algorithms, we obtained the final ensemble classifier known as adaptive random forest-out of bag-easy ensemble (ARF-OOBEE). In order to perform comparative experiments, we selected 5 commonly used machine learning classification algorithms: Naive Bayes, support vector machine, logistic regression, multilayer perceptron, deep forest (GC Forest), and extreme gradient boosting (XGBoost).To evaluate the prediction performance of AR samples, various parameters such as precision, sensitivity, specificity, G-mean, F1-score, and area under the curve (AUC) of the receiver operating characteristic curve were jointly employed as evaluation indicators.

Results: We compared 7 classification models, including probability models, tree models, linear models, ensemble models, and neural network models. The ensemble classification algorithms, namely ARF-OOBEE and GC Forest, outperformed the other algorithms in terms of the comprehensive classification evaluation index. The accuracy of G-mean and AUC parameters improved by nearly 2% when compared to the other algorithms. Moreover, these ensemble classifiers exhibited excellent performance in handling large-scale data and unbalanced samples.

Conclusion: The ARF-OOBEE ensemble learning model demonstrates strong generalization performance and comprehensive classification abilities, making it suitable for effective application in auxiliary AR diagnosis.

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by atopic dermatitis, recurrent skin and lung infections, and significantly elevated serum immunoglobulin E levels. Autosomal dominant and loss-of-function pathogenic variants in the STAT3 gene are the most common causes of the disease and studies have shown that the presence of IL-4 receptor (IL-4R) is upregulated in patients with dominant-negative mutations in the STAT3 gene expression. Dupilumab is a monoclonal antibody that targets the IL-4α receptor and improves the symptoms of atopic dermatitis by inhibiting IL-4 and IL-13. We used dupilumab to treat severe dermatitis in a patient with STAT3-HIES and achieved satisfactory results.