Given the potent immunological properties of the skin, epicutaneous immunotherapy (EPIT) emerges as a promising treatment approach for inducing immune tolerance, particularly for food allergies. Targeting the highly immunocompetent, non-vascularized epidermis allows for the application of microgram amounts of allergen while significantly reducing the risk of allergen passage into the bloodstream, thus limiting systemic allergen exposure and distribution. This makes EPIT highly suitable for the treatment of potentially life-threatening allergies such as food allergies. Multiple approaches to EPIT are currently under investigation for the treatment of food allergy, and these include the use of allergen-coated microneedles, application of allergen on the skin pretreated by tape stripping, abrasion or laser-mediated microperforation, or the application of allergen on the intact skin using an occlusive epicutaneous system. To date, the most clinically advanced approach to EPIT is the Viaskin technology platform. Viaskin is an occlusive epicutaneous system (patch) containing dried native allergen extracts, without adjuvants, which relies on frequent application for the progressive passage of small amounts of allergen to the epidermis through occlusion of the intact skin. Numerous preclinical studies of Viaskin have demonstrated that this particular approach to EPIT can induce potent and long-lasting T-regulatory cells with broad homing capabilities, which can exert their suppressive effects in multiple organs and ameliorate immune responses from different routes of allergen exposure. Clinical trials of the Viaskin patch have studied the efficacy and safety for the treatment of life-threatening allergies in younger patients, at an age when allergic diseases start to occur. Moreover, this treatment approach is designed to provide a non-invasive therapy with no restrictions on daily activities. Taken together, the preclinical and clinical data on the use of EPIT support the continued investigation of this therapeutic approach to provide improved treatment options for patients with allergic disorders in the near future.
Low- and middle-income countries (LMICs) contribute to a major proportion of asthma morbidity and mortality globally, even though the prevalence is higher in high income countries. Mortality due to asthma is avoidable and patients should be able to live a near normal life. There are factors that influence overall disease prevalence and poor health outcomes due to asthma in LMICs. This article summarizes the gaps in asthma diagnosis and management in LMICs. The gaps are diverse. Each challenge needs to be addressed through policy decisions, upgrade of infrastructure, knowledge and skills for early diagnosis and correct management among health care providers, both clinicians and paramedics. Healthcare accessibility and affordability are genuine challenges, and the public healthcare system needs to be geared up to address these at primary and tertiary levels. Mass education of the population through national level government initiatives is needed to help bridge the sociocultural gaps.
Angioedema is characterized by swelling localized to the subcutaneous and submucosal tissues. This review provides an overview of angioedema, including the different types, triggers, and underlying pathophysiologic mechanisms. Hereditary and acquired angioedema are caused by dysregulation of the complement and kinin pathways. In contrast, drug-induced and allergic angioedema involve the activation of the immune system and release of vasoactive mediators. Recent advances in the understanding of the pathophysiology of angioedema have led to the development of targeted therapies, such as monoclonal antibodies, bradykinin receptor antagonists, and complement inhibitors, which promise to improve clinical outcomes in patients with this challenging condition. To accurately diagnose and manage angioedema, an understanding of this condition's complex and varied pathophysiology is both necessary and critical.
Background: Azelastine hydrochloride (AZE) is a selective, non-sedating H1 antagonist with anti-inflammatory and mast cell stabilizing properties, which can be used as an alternative to intranasal corticosteroids. The objective of this study was to evaluate the efficacy of the new formulation of 0.15% AZE compared to that of the placebo at a dosage of two sprays per nostril twice daily for 4 weeks in patients with perennial allergic rhinitis (PAR).
Materials and methods: A total of 581 subjects were randomized in this double-blind (DB) placebo-controlled trial (NCT00712920) that compared 0.10% (1,096 μg daily) and 0.15% AZE (1,644 μg daily) to the placebo in PAR patients. The study consisted of a 7-day single-blind placebo lead-in period and a 28-day DB treatment period. The primary endpoint was the change from baseline in the 12-h reflective total nasal symptom score (rTNSS) for the entire 28-day study period of 0.15% AZE, two sprays per nostril BID compared to the placebo. The efficacy and safety of 0.15% AZE were compared to the placebo.
Results: Least square (LS) mean improvement from baseline in the morning (AM) and evening (PM) combined rTNSS was statistically significant for the 0.15% AZE group (p = 0.04) compared to the placebo group. LS mean improvement from baseline in the AM and PM combined rTNSS was 4.10 (4.26) units for 0.15% AZE and 3.81 (3.99) for 0.10% AZE. For individual symptoms, there was a statistically significant change in the LS mean (p = 0.04) improvement from baseline on the 12-h reflective assessment for the 0.15% AZE group for runny nose. Further numerical improvements were shown for itchy nose, nasal congestion, runny nose, and sneezing compared to the placebo. No deaths or serious adverse events related to the study medication were reported.
Conclusion: The present formulation of 0.15% AZE is safe and effective in relieving PAR symptoms. It effectively relieves nasal and non-nasal symptoms.
Clinical trial registration: ClinicalTrials.gov, identifier: NCT00712920.
Background: Omalizumab has been approved for treating moderate-to-severe asthma in children aged over 6 years. Its application to asthmatic children with other allergic diseases has been rarely explored. The present study aims to explore the therapeutic efficacy of omalizumab in children with moderate-to-severe allergic asthma combined with chronic sinusitis.
Methods: The clinical data of children diagnosed with moderate-to-severe allergic asthma combined with chronic sinusitis and treated with omalizumab between September 2020 and April 2022 were retrospectively analyzed. Lung function indexes such as Childhood Asthma Control Test (C-ACT) scores, fractional exhaled nitric oxide (FeNO), and forced expiratory volume in the first second (FEV1) percent predicted (FEV1%pred), small airway function indexes, and the clinical symptoms of chronic sinusitis were analyzed.
Results: A total of 26 children were observed for 16 weeks. After 16 weeks of omalizumab treatment, the significantly increased C-ACT scores (15.57 ± 3.25 points vs. 24.98 ± 5.21 points, F = 15.7112, P < 0.001) and decreased FeNO (31.55 ± 15.57 ppb vs. 19.86 ± 9.80 ppb, F = 4.4265, P = 0.0022), compared with those at baseline, were suggestive of well-controlled symptoms of asthma and improved lung function. FEV1%pred and FEV1/forced vital capacity (FVC) ratio (the ratio of the forced expiratory volume in the first 1 s to the forced vital capacity) increased after omalizumab treatment, although no significant differences were detected (P = 0.9954 and 0.9382, respectively). Peak expiratory flow (PEF) percent predicted (PEF%pred) and forced expiratory flow at 75% of FVC (FEF75%), 50% of FVC (FEF50%), and 25%-75% of FVC (FEF25%-75%) significantly increased after omalizumab treatment (P = 0.0477, <0.001, <0.001, and <0.001, respectively). Visual analog scale scores significantly decreased after omalizumab treatment (6.40 ± 2.98 points vs. 0.85 ± 0.40 points, t = 27.2419, P < 0.001), suggesting alleviation in the clinical symptoms of chronic sinusitis.
Conclusion: In this study, it was found that omalizumab can effectively alleviate clinical symptoms and improve lung function and quality of life in children with moderate-to-severe allergic asthma combined with chronic sinusitis.
Background: Suspected strawberry and tomato (S/T) food allergy (FA) can be evaluated using specific immunoglobulin E (sIgE) testing despite its low specificity and positive predictive value.
Objective: This study aims to understand ordering patterns for S/T sIgE testing and identify relevant factors to clinical decision-making.
Methods: We retrospectively reviewed 814 patients with sIgE testing available for strawberries (651), tomatoes (276), or both (113) from January 2012 to May 2022 at a tertiary pediatric hospital. Patient demographics, provider specialty, and reasons for testing were collected. Student's t-test and multiple regression analyses were performed to test the association between the S/T sIgE level and clinically relevant outcome (CRO) status. Fisher's exact test and general linear models were used to evaluate and compare potential predictive factors for CRO status.
Results: Allergy and immunology, gastroenterology, and general pediatrics ordered most S/T sIgE testing. Testing was ordered most frequently for non-IgE-mediated gastrointestinal symptoms, mild possible IgE-mediated reactions, and eczema. Testing was most often ordered for infants and school-age children. Mean sIgE levels were higher for S/T tests resulting in a CRO when controlling for other predictor variables (p = 0.015; p = 0.002 for S/T, respectively). Only 2.2% and 5.4% of tests resulted in a CRO for S/T, and severe allergy was rare. Testing for non-IgE-mediated GI symptoms or eczema, or in non-atopic patients, yielded no CROs. Exposure and reaction history of present illness (ERH) was associated with CROs (p < 0.001; p = 0.04) with a high negative predictive value (99.5%; 100%) and low positive predictive value (11.5%; 15.0%). ERH (p < 0.001, η2 = 0.073; p = 0.009, η2 = 0.123) was a more significant predictor than the sIgE level (p = 0.002, η2 = 0.037; p = 0.212, η2 = 0.030) for CRO status.
Conclusion: The diagnosis of S/T food allergy is made primarily based on clinical history. S/T sIgE testing for children and adolescents should be avoided for patients without an ERH and in the workup of non-IgE-mediated GI symptoms. Testing for eczema and non-atopic patients is likely low-yield.
Sputum induction is a technique that covers the induction and the subsequent processing of the expectorate primarily for the analysis of cells and different inflammatory biomarkers present in the airways to further understand the pathophysiology of different inflammatory respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) as well as the diagnosis of lung diseases such as lung cancer, tuberculosis, and Pneumocystis jirovecii pneumonia. It is a non-invasive, safe, cost-effective, and reliable technique reported to exhibit a high success rate. However, due to being technically demanding and time-consuming and having the need of employing trained staff, this technique is only used in restricted research centres and in limited centres of clinical use. When the sputum is collected after induction, the primary goal is to obtain a differential cell count and evaluate the molecular biomarkers of airway inflammation such as eosinophil cationic protein, eosinophil-derived neurotoxin, major basic protein, tryptase, cytokine production [e.g., interleukin (IL)-5], albumin, and fibrinogen. In addition, cytospins from the processed sputum are used for immunocytochemical staining of cellular products such as EG-2 reactive protein, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor alpha, and IL-8 that play significant roles in understanding the pathophysiology of inflammatory airway diseases. Nowadays, this technique can be further used by performing an additional analysis such as flow cytometry and in situ hybridisation on the sputum supernatant to investigate more the immune response and pathophysiological process of such various respiratory diseases. In addition, the application of sputum fluid phase to assess the biomarkers could be used more routinely in pathological laboratories for diagnosing lung cancer, COPD, and asthma as well as for monitoring lung cancer progression and asthma and COPD treatment, allowing for early detection and a better treatment provided by the clinicians.
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