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Medical Journal Review

June 2017

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.

1. Phenotypes of atopic dermatitis depending on the timing of onset and progression in childhood
Roduit C, Frei R, Depner M, Karvonen AM, Renz H et al.
JAMA Pediatrics 2017; 171(7): 655-662. doi: 10.1001/jamapediatrics.2017.0556

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In this study, Roduit and colleagues attempted to identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and furthermore to determine whether some subtypes are at greater risk for developing other allergic diseases. To do so, they utilized the PASTURE European cohort stratifying by latent class analysis to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Following which, multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases.

When analyzing 1038 children; of these, 506 were girls, latent class analysis model separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95%CI, 1.31-6.31), while the late phenotype was only positively associated with allergic rhinitis.

2. Oral immunotherapy for food allergy
Wood RA
Journal of Investigational Allergology and Clinical Immunology 2017; 27(3): 151-159. doi: 10.18176/jiaci.0143

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This is a wonderful review of oral immunotherapy (OIT) for food allergy. This article by Dr. Wood focuses on selected studies of OIT for the treatment of common food allergies such as cow’s milk, hen’s egg, and peanut. OIT is an experimental treatment in which patients consume gradually increasing quantities of the food to which they are allergic in an attempt to induce some level of desensitization. As is noted by the author, desensitization is possible in most patients but carries significant risks for allergic reactions, and sadly the ability to induce long-term tolerance has not yet been established. Certainly much more research is needed in this arena; however, as there is presently no proactive intervention for food allergy, it is a high priority.

3. Effectiveness of pneumococcal vaccines in preventing pneumonia in adults, a systematic review and meta-analyses of observational studies
Tin Tin Htar M, Stuurman AL, Ferreira G, Alicino C, Bollaerts K et al.
PLoS ONE 2017; 12(5): e0177985. doi: 10.1371/journal.pone.0177985

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In this systematic review by Tin Tin Htar and colleagues, the authors examined pneumococcal vaccine effectiveness (VE) against community-acquired pneumonia (CAP) in adults among the general population, those immunocompromised as well as subjects with underlying risk factors, in real-world setting. They retrieved 1159 unique articles of which 33 were included in the analysis. No studies evaluating PCV13 effectiveness were found, while wide ranges in PPV23 effectiveness estimates for any-CAP were observed among adults >65 years (-143% to 60%). Specifically, the meta-analyzed VE estimate for any-CAP requiring hospitalization in the general population was 10.2% (95%CI: -12.6; 33.0) and the meta-regression indicates that VE against any-CAP requiring hospitalization is significantly lower in studies with a maximum time since vaccination >60 months vs. <60 months and in countries with the pediatric PCV vaccine available on the private market. The authors note however that these results should be interpreted cautiously due to the high influence of two studies. Lastly they found that the VE estimates for pneumococcal CAP hospitalization ranged from 32% (95%CI: -18; 61) to 51% (95%CI: 16; 71) in the general population.

4. Inflammatory phenotypes in severe asthma are associated with distinct airway microbiology
Taylor SL, Leong LEX, Choo JM, Wesselingh S, Yang IA et al.
Journal of Allergy and Clinical Immunology 2017; Article in press. doi: 10.1016/j.jaci.2017.03.044

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Recent research in asthma has focused on phenotypes as well as microbiota. Thus far, the relationship between airway microbiology and asthma phenotype has not been well studied. Thus, this study by Taylor and colleagues aimed to characterize airway microbiota in patients with symptomatic stable asthma, and explore the composition to airway inflammatory phenotype and other phenotypic characteristics. To do so, they examined the composition of induced sputum specimens collected from adult patients screened for a multicenter randomized controlled trial.

Inflammatory phenotypes were defined by sputum neutrophil and eosinophil cell proportions and microbiota were defined using alpha and beta diversity measures, and inter phenotype differences identified using SIMPER, network analysis, and taxon fold change. Through this analysis they found that airway microbiology was significantly less diverse (p=0.022) and more dissimilar (p=0.005) in neutrophilic compared to eosinophilic subjects. Sputum neutrophil proportion, but not eosinophil proportion, correlated significantly with diversity measures (alpha-diversity: Spearman’s r=-0.374, p<0.001; beta-diversity: r=0.238,p=0.002). Inter-phenotype differences were characterized by a greater frequency of pathogenic taxa at high relative abundance, and reduced Streptococcus, Gemella and Porphyromonas relative abundance in neutrophilic asthma. Multivariate regression confirmed sputum neutrophil proportion was the strongest predictor of microbiota composition. The authors postulate that these differences in microbiota composition may influence response to antimicrobial and steroid therapies, as well as risk of lung infection.

5. Allergen-encoding bone marrow transfer inactivates allergic T cell responses, alleviating airways inflammation
AL-Kouba J, Wilkinson AN, Starkey MR, Rudraraju R, Werder RB et al.
JCI Insight 2017; 2(11): e85742. doi:10.1172/jci.insight.85742

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It is known that memory Th2 cell responses underlie the development and perpetuation of allergic illness. New approaches that overcome these detrimental effects of immune dysregulation are hoped to aid in the treatment of allergic disease. In this study, AL-Kouba and colleagues examined whether memory Th2 cell responses could be “silenced” using a therapeutic approach where allergen expression in DCs was transferred to sensitized recipients using BM cells as a vector for therapeutic gene transfer. They did indeed find that transfer of BM encoding allergen expression targeted to DCs terminated, in an allergen-specific manner, Th2 responses in sensitized recipients. Importantly, when preexisting airway inflammation was present, there was effective silencing of Th2 cell responses, airway inflammation was alleviated, and airway hyperreactivity was reversed. The authors conclude that this data would indicate that utilizing cell-intrinsic T cell tolerance pathways could lead to development of highly effective immunotherapies.