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Medical Journal Review

January 2020

WAO Reviews – Editors' Choice

The Editors’ Choice comes to you from Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD, FACAAI, FAAAAI. They select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible, for their accessibility to everyone.

State-of-the-art in marketed adjuvants and formulations in allergen immunotherapy: A position paper of the European Academy of Allergy and Clinical Immunology (EAACI)
Jensen-Jarolim E, Bachmann M, Bonini S, Jacobsen L Jutel M et al.
Allergy 2019; Published online ahead of print (27 Nov). doi: 10.1111/all.14134.
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Ever since the introduction of allergen immunotherapy (AIT) over 100 years ago, the focus has been on standardization of the allergen extracts, with molecular composition receiving the highest attention. As adjuvants play a major role in European AIT and have been less well studied, this EACCI Position Paper summarizes the current understanding as well as unmet needs of adjuvants in AIT. The intended mode of action of adjuvants is to simultaneously enhance the immunogenicity of the allergen, while also precipitating the allergen at the injection site to reduce the risk of anaphylaxis. Different adjuvants appear to have disparate immune effects. As an example, aluminum hydroxide initially boosts Th2 responses, while the other adjuvants utilized in AIT (microcrystalline tyrosine, monophosphorylate lipid A, and calcium phosphate) redirect the Th2 immune response toward Th1 immunity. In the end, after varying lengths of time, each of the adjuvants supports tolerance. The expert panel suggested that further studies of the mechanisms of action of adjuvants may allow shorter treatment periods than the current three-to-five-year regimens, which could improve overall adherence with AIT.

Efficacy of the Enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy
Perkin MR, Logan K, Bahnson HT, Marrs T, Radulovic S et al
Journal of Allergy and Clinical Immunology 2019; 144(6):1606-1614.e2. doi: 10.1016/j.jaci.2019.06.045.
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The Enquiring About Tolerance (EAT) study was a randomized trial which explored the early introduction of allergenic solids into the infant diet from 3 months of age. While the intervention effect did not reach statistical significance in the intention-to-treat analysis of the primary outcome in this paper, the authors examined whether the subgroup of infants with high risk of developing a food allergy benefited from early introduction. The authors found that in infants with sensitization to 1 or more foods at enrollment (>0.1 kU/L), infants in the early introduction group (EIG) developed significantly less food allergy to 1 or more foods than the standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P =.03). Furthermore, among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02). Overall, this study demonstrates that early introduction was effective in preventing the development of food allergy in infants at high risk of developing food allergy and this occurred despite low adherence to the early introduction regimen. The authors stress that this study has significant implications for the new infant feeding recommendations.

The cellular functions of eosinophils: Collegium Internationale Allergologicum (CIA) update 2020
Simon HU, Yousefi S, Germic N, Arnold IC, Haczku A et al.
International Archives of Allergy and Immunology 2020; 181(1):11-23. doi: 10.1159/000504847.
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It is well known that eosinophils and their secretory mediators play an important role in the pathogenesis of infectious and inflammatory disorders. Surprisingly the physiologic functions of eosinophils are not well understood, but with the availability of new eosinophil-targeted depletion therapies, there has been a renewed interest in researching eosinophil biology. Recent data suggest that eosinophils are not only involved in immunological effector functions, but they also carry out tissue protective and immunoregulatory functions that actively contribute to the maintenance of homeostasis. Furthermore, prolonged depletion of eosinophils may therefore result in the development of secondary disorders. In this excellent review, the authors reinforce the important roles eosinophils have in promoting immune defense, antibody production, activation of adipose tissue, and tissue remodeling and fibrosis.

Efficacy of allergen immunotherapy for allergic asthma in real world practice
Rhyou HI, Nam YH
Allergy, Asthma et Immunology Research 2020; 12(1):99-109. doi: 10.4168/aair.2020.12.1.99.
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Despite multiple studies demonstrating the clinical efficacy of AIT in the treatment of allergic asthma, optimal use of this treatment for asthma control in clinical trials is still unclear. To better understand the utility of AIT, the authors investigated the efficacy of AIT with respect to changes in the inhaled corticosteroid (ICS) dose in patients with allergic asthma. In this single center Korean study of 117 adults with allergic asthma who had used ICS for more than 1 year, the authors retrospectively compared the clinical outcomes between the AIT group (ICS with AIT, n = 48) and the non-AIT group (ICS without AIT, n = 69) by applying an inverse probability of treatment weighting method. The patients in the AIT group had received subcutaneous AIT monthly as a maintenance treatment for more than 1 year and the changes in the ICS dose from baseline were evaluated in the 2 groups for 3 years. They found that the proportion of responders who discontinued or decreased their ICS dose while maintaining control of their asthma was significantly higher in the AIT group than in the non-AIT group throughout the study period (at 6 months, 52.1% vs. 24.6%; at 1 year, 70.8% vs. 34.7%; at 2 years, 89.5% vs. 35.6%; at 3 years, 96.3% vs. 51.2%). Treatment responses did not differ significantly by type of allergen (single- or multi-allergens or 3 different products) used throughout the study period. Overall, this indicates that irrespective of the type of allergen, long-term maintenance, AIT helps to reduce the ICS dose while maintaining better control in patients with allergic asthma in real-world clinical practice.

Characterization of severe asthma worldwide: Data from the International Severe Asthma Registry
Wang E, Wechsler ME, Tran TN, Heaney LG, Jones RC et al.
Chest 2019; Published online before print (27 Nov). doi: 10.1016/j.chest.2019.10.053.
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To date, clinical characteristics of the international severe asthma population are unknown. Inter-country comparisons are hindered by variable data collection within regional/national severe asthma registries. For this reason, the authors examined demographic and clinical characteristics of patients managed in severe asthma services in the USA as well as European and Asia/Pacific regions. To do so, they developed the International Severe Asthma Registry (ISAR) which retrospectively and prospectively collected data on severe asthma patients (≥18 years old), who received GINA Step 5 treatment or remained uncontrolled on GINA Step 4. Baseline demographic and clinical data were collected from the USA, UK, South Korea, Italy, and the SAWD registry (including Australia, Singapore and New Zealand) from December 2014-December 2017. Of the 4,990 patients included in this analysis, the average age was 55.0 (SD: 15.9) years, and age at asthma onset was 30.7 (SD: 17.7) years. Patients were predominantly female (59.3%), white (72.6%), had never smoked (60.5%), and were over-weight/obese (70.4%). Of this group, 34.9% were on GINA Step 5 and 57.2% had poorly controlled disease. 51.1% of patients were on regular intermittent OCS and 25.4% were receiving biologics (72.6% for those on GINA Step 5). The mean exacerbation rate was 1.7 (SD: 2.7) per year. Not surprisingly, inter-country variation was observed in clinical characteristics, prescribed treatments as well as biomarker profiles.

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