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Medical Journal Review

March 2021

WAO Reviews – Editors’ Choice

Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor.

Allergen immunotherapy: Biomarkers and clinical outcome measures
Pitsios C
Journal of Asthma and Allergy 2021;14:141-148

In this review of allergy immunotherapy, the authors aptly point out that while there are numerous studies that have explored the efficacy and safety of this intervention, there is a paucity of data regarding in vitro biomarkers, which might provide a more practical and objective tool to explore mechanism(s) and predict clinical effects of allergen immunotherapy. The aim of this review is to describe how to adapt and use biomarkers and clinical outcomes in the everyday practice of allergists who perform allergen immunotherapy.

Expert consensus on practical aspects in the treatment of chronic urticaria
Bauer A, Dickel H, Jakob T et al
Allergo Journal International 2021;1-12 (24 February)

While the current urticaria guideline describes the evidence-based diagnosis and treatment of chronic urticaria, the purpose of this paper is to answer questions that often arise in everyday practice that are not addressed by the guideline. This publication provides practical advice on issues in everyday practice, including delivering care in the current coronavirus disease 2019 pandemic, the cardiac risk of high dose H1 antihistamines, the self-administration of omalizumab, and vaccination under omalizumab therapy.

PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite
Saito T, Ichikawa T, Numakura T et al
Respiratory Research 2021;22:63 (19 February)

It is well known that the airway epithelial barrier function is disrupted in the airways of asthmatic patients. Furthermore, abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens. To do so, the authors exposed BEAS-2B cells to house dust mite (HDM). The expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells.

The authors also examined the effect of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fuoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction. They found that the amount of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells, and SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. Likewise, GB83, LPS-RS, E64, and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin. Overall, this demonstrated that HDM disrupted the airway barrier function through the PAR2/ TLR4/PGC-1α-dependent pathway. The authors suggest that modulation of this pathway could be a new approach for the treatment of asthma.

Anti-IgE: A treatment option in allergic rhinitis?
Pfaar O, Gehrt F, Li H et al
Allergologie select 2021;5(1):119-127 (24 February)

While Omalizumab has been established in the routine management of allergic asthma and chronic idiopathic urticaria, it presently is not approved for the treatment of allergic rhinitis (AR). A systematic literature review has been completed including randomized controlled trials, meta-analyses, and reviews on the treatment of AR with omalizumab, demonstrating strong evidence supporting the use of omalizumab in the treatment of AR including improved symptom control, safety profile, and management of comorbidities. The authors point out the need for further study, and certainly this should include consideration of the optimal use to ensure maximal cost effectiveness. 

Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease
Patrick GJ, Liu H, Alphonse MP et al
The Journal of Clinical Investigation 2021;131(5):e143334 (1 March)

IgE induced by type-2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. In this study, the authors rely upon a mouse model of atopic dermatitis – skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL‑36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels. They demonstrated that all of these findings were abrogated in IL-36R–deficient mice or anti-IL‑36R–blocking antibody–treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings to humans, elevated IL‑36 cytokines in human atopic dermatitis skin and in IL‑36 receptor antagonist–deficiency patients coincided with increased serum IgE levels. Overall, this demonstrated that keratinocyte-initiated IL‑36 responses represent a key mechanism and potential therapeutic target against allergic diseases.

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