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Medical Journal Review

April 2018

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 from Juan Carlos Ivancevich, MD, WAO Web Managing Editor, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor.

Uses of biologics in allergic diseases: What to choose and when

Saco TV, Pepper A, Casale TB
Annals of Allergy Asthma and Immunology 2018; 120(4): 357-366. Doi:10.1016/j.anai.2018.02.029

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This is a wonderful review regarding the use of biologic therapies for the treatment of asthma, urticaria, nasal polyposis and atopic dermatitis. As noted by the authors, this rapid rise in therapeutic options for these illnesses can make it quite daunting for the allergist when considering the optimal therapy; however, choosing an agent based on biomarkers, convenience for the patient, comorbid conditions for which the agent may have overlapping benefit, and pharmacoeconomic considerations can greatly aid in making the correct choice.

Associations between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood

Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM
JAMA Pediatrics 2018; Published online ahead of print (2 April). doi:10.1001/jamapediatrics.2018.0315


In this study, Mitre and colleagues attempted to determine if there is an association between the use of acid-suppressive medications or antibiotics in the first 6 months of infancy and development of allergic diseases in early childhood. They performed a retrospective cohort study of almost 800,000 Department of Defense TRICARE beneficiaries with a birth medical record in the Military Health System database between October 1, 2001, and September 30, 2013. Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H2RA), proton pump inhibitor (PPI), or antibiotic, and the main outcome was allergic disease (presence of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy).

They found adjusted hazard ratios (aHRs) in children prescribed H2RAs. PPIs, respectively, were: 2.18 (95% CI, 2.04-2.33) and 2.59 (95% CI, 2.25-3.00) for food allergy, 1.70 (95% CI, 1.60-1.80) and 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.51 (95% CI, 1.38-1.66) and 1.45 (95% CI, 1.22-1.73) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) and 1.44 (95% CI, 1.36-1.52) for allergic rhinitis, and 1.25 (95% CI, 1.21-1.29) and 1.41 (95% CI, 1.31-1.52) for asthma. The aHRs after antibiotic prescription in the first 6 months of life were: 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis.

The results are consistent with those of prior studies, providing further impetus that antibiotics and acid-suppressive medications should be used during infancy only in situations of clear need with clinical benefit. The authors reinforce that further studies are needed to confirm causality and determine the mechanism of this association.

Primary prevention of food allergy: Translating evidence from clinical trials to population-based recommendations

Turner PJ, Campbell DE, Boyle RJ, Levin ME
Journal of Allergy and Clinical Immunology: In Practice 2018; 6(2): 367-375. doi:10.1016/j.jaip.2017.12.015

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This is a very interesting article that explores issues regarding translating the evidence of efficacy studies (performed under optimal conditions), such as the LEAP study, into the development of policy recommendations (at a population level). The authors focus on potential benefits, harms, and unintended consequences of making population-based recommendations based upon randomized controlled trials, and focus on the complexity and barriers to effective primary and secondary prevention intervention implementation in resource-poor settings. In essence, what works in the lab may not necessarily be easily translated in the real world.

Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33

Cayrol C, Duval A, Schmitt P, Roga S, Camus M et al
Nature Immunology 2018; 19(4): 375-385. doi:10.1038/s41590-018-0067-5


In this article, Cayrol and colleagues found that full-length interleukin 33 (IL-33FL), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor, detecting proteolytic activities associated with disparate environmental allergens: including fungi, house dust mites, bacteria and pollens. They specifically found that when exposed to allergen proteases, IL-33FL was rapidly cleaved in its central “sensor” domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells and preventing cleavage of IL-33FL reduced allergic airway inflammation. Overall, these findings reveal a molecular mechanism for the rapid induction of allergic type 2 inflammation following allergen exposure, with important implications for allergic illness. The authors conclude by suggesting that targeting the sensor domain to prevent the cleavage and activation of IL-33FL might represent a new approach for reducing allergic responses in asthma and other allergic diseases.

Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis

Garcia-Larsen V, Ierodiakonou D, Jarrold K, Cunha S, Chivinge J et al
PLoS Medicine 2018; 5(2): e1002507. Doi:10.1371/journal.pmed.1002507

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There have been conflicting reports regarding the impact of variations in maternal or infant diet and the associated risk of the development of allergic or autoimmune disease. To better understand this potential association, the authors performed a systematic review of this topic as part of a series of systematic reviews commissioned by the UK Food Standards Agency in order to inform dietary recommendations of the United Kingdom for infants and their pregnant or lactating mothers. They found that diet during pregnancy and lactation may influence the risk that a child will develop allergic disease with two specific implications for pregnant women. First, a daily probiotic supplement such as L. rhamnosus, taken from around 36 to 38 weeks gestation through the first 3 to 6 months of lactation, may reduce risk of eczema in the child. Second, a fish oil supplement, taken from around 20 weeks gestation through the first 3 to 4 months of lactation, may reduce risk of allergic sensitization to egg or peanut in the child. The authors do warn that although probiotics are generally considered safe, their pro-inflammatory effects may have potential adverse consequences when used earlier in pregnancy and conclude by suggesting that current infant feeding guidance needs revision. Specifically, they recommend that guideline committees need to carefully consider these key findings together with an evaluation of the safety, acceptability, and cost implications of advising probiotic or fish oil supplementation for pregnant and lactating women.

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