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Medical Journal Review

March 2016

WAO Reviews - Editors' Choice

The Editors select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible they seek articles that everyone can access freely. The Editors’ Choice comes to you each month from Juan Carlos Ivancevich, MD, WAO Web Editor-in-Chief, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor.

1. Pharmacological therapy of bronchial asthma: The role of biologicals

Heck S, Nguyen J, Le DD, Bals R, Dinh QT. Pharmacological therapy of bronchial asthma: The role of biologicals. International Archives of Allergy and Immunology 2015; 168(4): 241-252. (doi:10.1159/000443930)

Abstract

This comprehensive review examines potential therapeutic approaches with likely future promise for the treatment of severe asthma. Beyond anti-IgE, they also explore the utility of anti-IL-4,5, 9,13,17, TNFα, CCR3 and 4, CRTH2, as well as drugs that inhibit tyrosine kinase. It is clearly written and very well referenced. The future is near, and it is worth reading about.

2. Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients

Liao HY, Tao L, Zhao J, Qin J, Zeng GC et al. Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients. Scientific Reports 2016;6:20418. (doi:10.1038/srep20481)

Full Texts

Liao and colleagues hypothesize that probiotics could facilitate dust mite specific immunotherapy (SIT) to regain immune tolerance in the airway mucosa of patients with allergic asthma. In this study, they treated allergic asthma patients with both dust mite SIT and the probiotic Clostridium butyricum (CB) compared to individual components. They found that after 3-months of treatment, the total asthma clinical score and serum specific IgE were improved in subjects treated with SIT, and this was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB also increased p300 and STAT3 activation, up regulated IL-10 gene transcription. Thus indicating CB’s potential to upregulate regulatory cells when added to SIT.

3. Diagnosis and management of recurrent respiratory tract infections in children: A practical guide

Schaad UB, Esposito S, Razi CH. Diagnosis and Management of Recurrent Respiratory Tract Infections in Children: A Practical Guide. Archives of Pediatric Infectious Diseases 2016; 4(1):e31039. (doi:10.5812/pedinfect.31039)

Full Text

Children are particularly susceptible to respiratory tract infections (RTIs) due to the relative immaturity of their immune systems, genetic factors (such as family history of atopy) and/or environmental factors (such as exposure to pollution and pathogens) also render certain populations more vulnerable to infection. Furthermore, RTIs tend to be recurrent and can result in multiple infections per year. Most RTIs are viral; however bacterial infections are also common. Although antibiotics are rarely indicated they are often still used to treat RTIs. The authors acknowledge that recurrent RTIs pose a tremendous challenge for physicians, as we have only a limited armamentarium to alleviate patients’ symptoms, treat their disease, and prevent recurrences.Antibiotic overuse however results in an increase in bacterial resistance and drug-related side effects and underscores the need for alternative strategies to manage RTIs. This article uses a pediatric case study to review central issues in the diagnosis and management of recurrent RTIs in children, with an emphasis on the role of immunostimulatory agents such as immunomodulatory bacterial lysates (i.e., OM-85), herbal extracts (i.e., echinacea and garlic), thymic extracts (i.e., thymomodulin), and synthetic compounds (i.e., pidotimod) as a preventive strategy.

4. Vibratory urticaria associated with a Missense Variant in ADGRE2

Boyden SE, Desai A, Cruse G, Young ML, Bolan HC et al. Vibratory urticaria associated with a Missense Variant in ADGRE2. New England Journal of Medicine 2016;374:656-663. (doi:10.1056/NEJMoa1500611)

Summary

Patients with autosomal dominant vibratory urticaria develop localized hives in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in the serum. In this New England Journal article, Boyden and collegues identified a novel missense variant in ADGRE2 as the basis of autosomal dominant vibratory urticaria. ADGRE2 encodes a cell-surface receptor, in contrast to the mutant cytoplasmic proteins underlying cold urticarias. The data from this paper suggests that the p.C492Y substitution effects a pathogenic gain of function in ADGRE2 by destabilizing the inhibitory interaction between the α and β subunits, thereby sensitizing mast cells to vibration-induced degranulation. This is a very interesting example of basic science translating to clinical medicine.

5. Potential mechanisms for IgG4 inhibition of immediate hypersensitivity reactions

James LK, Till SJ. Potential mechanisms for IgG4 inhibition of immediate hypersensitivity reactions. Current Allergy and Asthma Reports 2016; 16(23). (doi:10.1007/s11882-016-0600-2)

Full Text

Recent advances in our understanding of the structural features of human IgG4 have highlighted the unique functional and immunologic properties of this immunoglobulin subclass. In this article, the authors review our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE-mediated allergic responses. It is known that increase in IgG4 occurs following chronic exposure to antigen and is generally associated with states of immune tolerance. Thus, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms: 1) by acting as a blocking antibody, preventing cross-linking of receptor bound IgE and 2) IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcγRIIb, which can negatively regulate FcεRI signaling and in turn inhibit effector cell activation. As the authors note, understanding the precise molecular determinants that control the fate of IgG4 could result in potential therapeutic targets for the prevention of allergy and promotion of clinical tolerance.