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Medical Journal Review

January 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. Barrier function of the nasal mucosa in health and type-2 biased airway diseases

Zhang N, van Crombruggen K, Gevaert E and Bachert C. Barrier function of the nasal mucosa in health and type-2 biased airway diseases. Allergy 2015; Accepted article. (doi:10.1111/all.12809).

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This is a very thorough review of the airway barrier function in type 2 mediated illnesses, calling upon over 100 references.  In this paper, Zhang et al. examine the importance of airway barrier including such topics as: the physical barrier, antimicrobial proteins, and molecular pattern changes following barrier damage. They also explore the immune barrier and its dysfunction in disease, highlighting the role of innate lymphoid cells, the airway epithelium as a source of cytokines and chemokines, as well as focusing on the inflammatory cells, eosinophils and neutrophils. They complete this review by utilizing this science to discuss potential future therapeutic interventions. 

2. Role of maternal dietary peanut exposure in development of food allergy and oral tolerance

Järvinen KM, Westfall J, De Jesus M, Mantis NJ, Carroll JA et al. Role of maternal dietary peanut exposure in development of food allergy and oral tolerance. PLOS One 2015; 10(12): e0143855. (doi:10.1371/journal.pone.0143855)

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The impact of maternal ingestion of peanut during pregnancy as well as lactation on an offspring’s risk for peanut allergy is an area of great debate. Thus, to better understand this potential association, Järvinen and colleagues investigated the influence of maternal dietary peanut exposure and breast milk on an offspring’s risk of allergy, utilizing a mouse model in which preconceptionally peanut-exposed C3H/HeJ females were either fed or not fed peanut during pregnancy and lactation and the offspring’s status regarding sensitization to peanut was then assessed. The authors also assessed the impact of immune murine milk on tolerance induction pre- or post-weaning.

The authors found that preconceptional peanut exposure resulted in the production of varying levels of maternal antibodies in serum (and breast milk), which were transferred to the offspring. Surprisingly, despite this, maternal peanut exposure either preconceptionally or during pregnancy and lactation, when compared to no maternal exposure, had no impact on peanut allergy. Lastly, they found that early introduction of peanut directly to baby mice, induced dose-dependent tolerance, which was not further facilitated by co-administration of immune breast milk. From this data, the authors suggest that no dietary restrictions are needed for pregnant and breastfeeding mothers in attempt to prevent food allergy. Furthermore, they note that large doses of peanut were better at inducing tolerance to peanut than small doses and tolerance induction was not impacted by co-administration of immune milk either pre- or post-weaning, suggesting that the trace amounts of dietary protein detected in breast milk appeared not be sufficient to induce significant tolerance. The authors close by reinforcing that randomized controlled clinical studies are needed to address the impact of maternal exposure to peanut and the “window of opportunity” for early introduction of foods on allergy risk in humans.

3. The eosinophil in infection

Ravin KA and Loy M. The eosinophil in infection. Clinical Reviews in Allergy & Immunology 2015; published online before print, December 21. (doi:10.1007/s12016-015-8525-4)

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In this review, Ravin and Loy provide an excellent discussion of the eosinophil in infection. Although once thought to function solely as an end-effector cell in host defense against helminth infections and implicated as a cause of inflammation and tissue damage, the true role of the eosinophil in human health and disease is likely much more complex. Eosinophils possess many unique qualities, including numerous and unique cell surface receptors, as well as an ability to store preformed mediators which allow them to play a key role in immune regulation. In the end, the authors stress that the eosinophil both responds to and regulates a wide variety of innate and adaptive immune cells, responding to infections and inflammation as well as acting to maintain homeostasis.

4. Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood

Zolkipli Z, Roberts G, Cornelius V, Clayton B, Pearson S et al. Randomized controlled trial of primary prevention of atopy using house dust mite allergen oral immunotherapy in early childhood. Journal of Allergy and Clinical Immunology 2015; 136(6): 1541-1547. (doi:10.1016/j.jaci.2015.04.045)

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In this study, Zolkipli et al. performed a proof of concept trial examining oral immunotherapy to high-dose house dust mite (HDM) allergen during infancy in attempt to prevent allergen sensitization and development of allergic diseases. This was a prospective, randomized, double-blind, placebo-controlled, study involving 111 infants less than 1 year of age who were at high risk of developing atopy (>2 first-degree relatives with allergic disease) but with negative skin prick test responses to common allergens at time of randomization. HDM extract (active) or placebo solution was administered orally twice daily for 12 months, and children were assessed every 3 months for the coprimary outcomes of cumulative sensitization to HDM and sensitization to any common allergen during treatment. Secondary outcomes included development of eczema, wheeze, and food allergy. 

They found that active HDM therapy resulted in a significant (P=.03) reduction in sensitization to “any” common allergen. There was however no treatment effect on the coprimary outcome of HDM sensitization or the secondary outcomes of eczema, wheeze, and food allergy. The authors reinforce that because the sample size was relatively small, further proof of efficacy of early intervention requires larger multicenter studies. Certainly, further studies are also required to elucidate the mechanism(s) of action of oral immunotherapy in infants at risk of sensitization as well as to evaluate the long-term efficacy of the treatment to prevent clinical atopic diseases such as asthma.

5. The past, present, and future of monoclonal antibodies to IL-5 and eosinophilic asthma: a review

Patterson MF, Borish L and Kennedy JL. The past, present, and future of monoclonal antibodies to IL-5 and eosinophilic asthma: a review. Journal of Asthma and Allergy 2015; 8: 125-134. (doi:10.2147/JAA.S74178)

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Our understanding of asthma has greatly increased over the last several decades. There is no better place to acknowledge this than through this review by Patterson et al, entitled “The past, present, and future of monoclonal antibodies to IL-5 and eosinophilic asthma: a review.” As noted in this paper, we now accept that asthma is really a “heterogeneous syndrome.”  The authors explore the development and clinical data regarding several of the new biologic agents for asthma, and through this journey they note the need for better non-invasive biomarkers to stratify our asthmatic patients regarding who are likely to respond to these new agents. In essence, the addition of these biologics to our asthma armamentarium has not just been an advance in care, but it also may be a catalyst to moving clinicians towards personalized medicine.