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Medical Journal Review

August 2022

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.

Current and future strategies for the diagnosis and treatment of the Alpha-Gal Syndrome (AGS)
Vaz-Rodrigues R, Mazuecos L, de la Fuente J
Journal of Asthma and Allergy 2022;15:957-970 (18 July)

The α-Gal syndrome (AGS) is an immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal), including mammalian meat and dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines, or mammalian serum-based antivenom. The initial IgE sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise, or gut-related symptoms. As a consequence of the delayed reactions and a wide variety in patients’ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods in making the diagnosis, but also explores potentially relevant next-generation diagnostic tools, such as the mast cell activation test (MAT), the histamine- release (HR) assay, omics technologies, and model-based reasoning (MBR).

Long-term efficacy of the sublingual and subcutaneous routes in allergen immunotherapy
Penagos M, Durham SR
Allergy and Asthma Proceedings 2022;43(4):292-298 (1 July)

Allergen immunotherapy is highly effective in selected patients with allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. Unlike anti-allergic drugs, both subcutaneous and sublingual immunotherapies have been shown to modify the underlying cause of the disease, with proved long-term clinical benefits after treatment cessation. In this review, the authors examined 10 randomized, double-blind, placebo controlled clinical trials of allergen immunotherapy that included blinded follow-up for at least 1 year after treatment withdrawal. Three studies of pollen subcutaneous immunotherapy provided evidence that a sustained, tolerogenic effect of subcutaneous immunotherapy can be achieved after 3 years of treatment. Six trials of sublingual immunotherapy provided robust evidence for long-term clinical benefit and persistent immunologic changes after grass pollen, house-dust mite, or Japanese cedar immunotherapy; whereas, a clinical trial of both sublingual and subcutaneous grass pollen immunotherapies showed that 2 years of immunotherapy were efficacious, but insufficient to induce long-term tolerance. Overall, these studies strongly supported international guidelines that recommend at least 3 years of allergen immunotherapy to achieve disease modification and sustained clinical and immunologic tolerance.

Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study
Reinke SN, Naz S, Chaleckis R, Gallart-Ayala H, Kolmert J et al
European Respiratory Journal 2022;59(6):2101733 (30 June)

Asthma is a heterogeneous disease with multiple, poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment such as OCS, may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. In this study, the authors aimed to identify dysregulated metabolic processes in relation to asthma severity and medication via measuring baseline urine prospectively from healthy participants (n=100), patients with mild to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analyzed using univariate and multivariate methods.

Metabolomics data were acquired using high-resolution mass spectrometry and analyzed using univariate and multivariate methods. The investigators identified 90 metabolites of which 40 significantly altered (p <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. It should be noted that this is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. The authors suggest that altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma.

A meta-analysis on randomized controlled trials of treating eosinophilic esophagitis with budesonide
Liu X, Xiao X, Liu D, Tan C
Annals of Medicine 2022;54(1):2078-2088 (21 July)

Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated inflammatory esophageal disease. Although Budesonide is recommended as one of the first-line drugs for EoE treatment, studies have shown inconsistent outcomes. In the study, the authors performed and updated a meta-analysis in which they retrieved 958 articles, of which 10 articles met inclusion criteria, yielding a sample size of 712 cases. The main outcome indicators of the meta-analysis were as follows: (1) Histological remission: the budesonide group performed better than the placebo control group when it came to histological remission of injuries [RR = 23.82, 95%CI = (13.46, 42.21), p < .001]; (2) Eosinophil count: the budesonide group was superior to the control group in terms of reduced eosinophil count [SMD = -1.34, 95%CI = (-1.52, -1.15), p < .001]. The authors conclude that overall, high-quality randomised controlled trials show that oral budesonide in the treatment of eosinophils esophagitis was better than placebo. While mounting high-quality RCTs have confirmed the efficacy of oral budesonide in the treatment of eosinophilic esophagitis, it should be noted that the effects of this drug may not be so dose-dependent. Furthermore, they found that it is safe to take budesonide for a prolonged period of time

Prevalence of sensitization to molecular food allergens in Europe: A systematic review
Lisik D, Ioannidou A, Spolidoro G, Ali M, Sungkutu N et al
Clinical and Translational Allergy 2022;12(7):e12175 (6 July)

This review explores the sensitization to molecular food allergens, finding that overall, it is low, especially for primary sensitizers from the food, such as peanut storage proteins. The highest sensitization rates were seen in cross-reactive PR-10 proteins, for which birch pollen is known to be the primary sensitizer.  The authors conclude by noting that more population-representative studies are needed to better understand sensitization patters to molecular food allergens in Europe.


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