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Medical Journal Review

January 2023

WAO Reviews – Editors' Choice

The WAO Reviews editors, Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, select articles on a monthly basis for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases.

Immediate hypersensitivity reactions to iodinated contrast media: The diagnosis of allergy by skin testing
Caron J, Graf S, Delebarre-Sauvage C
Clinical and Translational Allergy 2022;12(12):e12214 (4 December)
https://doi.org/10.1002/clt2.12214

In the retrospective analysis by Caron et al, they found that among 74 patients with an immediate hypersensitivity reaction (IHR) to iodinated contrast media (ICM), the rate of allergic patients confirmed by positive prick test or diluted intradermal test was 8.1%. They also found that 12.5% of re‚Äźexposed patients had a recurrent IHR despite negative skin tests.  The authors conclude that evaluation with IDT to ICM and development of DPT may provide an additional “safety net” to uncover recurrent ICM reactors.

Role of chemokines and inflammatory cells in respiratory allergy
Bao Y, Zhu X
Journal of Asthma and Allergy 2022;15:1805-1822 (21 December)
https://doi.org/10.2147/JAA.S395490

In the review Bao and colleagues explore the role of the chemokine system in the respiratory immune response and discuss how respiratory disease modulates overall chemokines to shape the type and outcome of the immune response to the treatment of respiratory allergic disease so that we can further deepen our knowledge of chemokines and their role in respiratory allergy. The concept of “one airway, one disease” has been espoused for some time, whereby in the upper and lower airways, allergic mechanisms interact with each other. In the initial stage of respiratory allergic inflammation, allergens contact the respiratory epithelium, which produces chemokines and inflammatory factors, which cause allergic reactions by binding to the corresponding receptors and chemotactic various inflammatory cells to reach the epithelium and tissues. It also drives inflammatory cells to activate and produce more inflammatory factors, thus producing an amplification effect. Inflammatory cell aggregation and activation are very complex and interact with each other in a lattice structure. By blocking the action of various chemokines, inflammatory cell aggregation is reduced, and ultimately the symptoms of respiratory allergy are alleviated. Chemokines can serve as cues for coordinated recruitment of immune cells into and out of tissues, as well as directing the spatial organization of immune cells within tissues and cellular interactions. Chemokines are critical in directing immune cell migration and thus have an important role in the direction of respiratory allergy: however, chemokines are also involved in the production and recruitment of immune cells that contribute to respiratory allergy. The authors conclude by suggesting that future drug research and development should consider this network structure in their new research directions.

A sputum bioassay for airway eosinophilia using an eosinophil peroxidase aptamer
Ali MM, Wolfe MG, Mukherjee M et al
Science Reports 2022;12:22476 (28 December)
https://doi.org/10.1038/s41598-022-26949-7

Eosinophils are well known to play a significant role in the pathogenesis of asthma and other airway diseases. Directing patient treatment based on the level of eosinophilia has been shown to be extremely effective in reducing exacerbations and therefore has tremendous potential as a routine clinical test. In this manuscript Ali et al. describe the in vitro selection and optimization of DNA aptamers that bind to eosinophil peroxidase (EPX). Fifteen rounds of magnetic bead aptamer selection were performed prior to high throughput DNA sequencing. The top 10 aptamer candidates were assessed for EPX binding using a mobility shift assay. This process identified a lead aptamer candidate termed EAP1-05 with low nanomolar affinity and high specificity for EPX over other common sputum proteins. This aptamer sequence was further optimized through truncation and used to develop an easy-to-use colourimetric pull-down assay that can detect EPX over a concentration range from 1 – 100 nM in processed sputum. Following this, 46 clinical samples were processed using a new sputum dispersal method, appropriate for a rapid assessment assay, which avoids centrifugation and lengthy processing times. The assay demonstrated 89% sensitivity and 96% specificity in detecting eosinophilia (compared to gold standard sputum cytometry), with results being available in under an hour. The authors suggest that this assay could allow for an easy assessment of eosinophil activity in the airway to guide anti-inflammatory therapy for several airway diseases.

Resistant Chronic Spontaneous Urticaria - A Case Series Narrative Review of Treatment Options
Khan S, Chopra C, Mitchell A et al
Allergy & Rhinology 2022;13 (21 December)
https://doi.org/10.1177/21526575221144951

Chronic spontaneous urticaria (CSU) can be extremely debilitating to sufferers and challenging for the treating clinician. The National Institute of Health and Clinical Excellence (NICE) in the United Kingdom (UK) recommendation of omalizumab for patients who fail to respond to high-dose anti-histamines has improved treatment options and quality of life; however, there is still a lack of clear guidelines for treatment of patients resistant to standard and anti-IgE therapies. In this paper, Khan et al. explore the therapeutic strategies available by examining nine extremely resistant CSU cases, highlighting the heterogeneity between guidelines from different societies. Patients with anti-histamine-resistant urticaria either remained on omalizumab or were started on immunosuppressive drugs (dapsone or ciclosporin) when they stopped responding to omalizumab. Clinical assessment, skin biopsies (when available) and previously published reports were considered before using dapsone (for predominantly neutrophilic infiltration), or ciclosporin at doses between 2 and 4 mg/kg/day. One patient with ciclosporin-resistant urticaria responded to mycophenolate mofetil. Two patients remained on long-term omalizumab due to its relative safety and efficacy. Its safety was especially important in one patient with underlying antibody deficiency where omalizumab was preferred over risks of using immunosuppressive medications. The authors stress that these case studies highlight the real-world difficulties in managing patients with resistant CSU and the need for generating evidence-based recommendations regarding alternative therapeutic options, including consideration of the use of biologics in tandem with immunosuppressive drugs.

Peanut-Induced Anaphylaxis in Children: A Literature Review
Alshajarah HA, Alghamdi HA, Alberi ZA et al
Cureus 2022;14(12): e32946 (26 December)
https://doi.org/10.7759/cureus.32946

Peanut allergy has become more common among children and is considered one of the most common triggers for fatal anaphylaxis. Treatment of symptoms during a reaction is only one aspect of managing anaphylaxis; other elements include rigorous dietary avoidance and education about settings that could put the patient at a high risk of unintentional exposure. In this review, the authors examine the prevalence, mechanism, diagnosis, treatment, and emergency action of peanut-induced anaphylaxis among children. Peanuts are the most common food to cause fatal anaphylaxis and a common cause of food allergies. The research cited in this review, demonstrates that the peanut allergy prevalence differs across cultures, and that while early oral peanut exposure may reduce the occurrence of peanut allergy, early non-oral exposure may have the opposite effect. They close by stressing that research involving oral immunotherapy, anti-IgE antibody, and herbal formulations have all demonstrated promise, but more research is needed. To conclude, peanut allergies have increased frequently during the past 10 years, especially in Westernized nations. Given that peanut allergy poses a danger for fatal anaphylaxis, response management is crucial. The current standard of care for those with nut allergies comprises complete food avoidance and the administration of injectable epinephrine to treat systemic symptoms.

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