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Medical Journal Review

February 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.

Diagnostic accuracy, risk assessment, and cost-effectiveness of component-resolved diagnostics for food allergy: A systematic review

Flores Kim J, McCleary N, Nwaru BI, Stoddart A, Sheikh A
Allergy 2018; accepted article, published online ahead of print (10 January). doi: 10.1111/all.13399

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In the allergy world, we have been longing for a tool to better assess risk related to food allergy. It was hoped that component resolved diagnostic (CRD) would answer this need. Unfortunately, the diagnostic accuracy of these tests varies across studies. In attempt to better understand the utility of these tests, Kim and colleagues performed a systematic review on the topic. The quality of included studies was assessed using QUADAS and due to heterogeneity of these studies, they narratively synthesized the evidence. Eleven studies met inclusion criteria, recruiting a total of 1,098 participants, studying multiple food allergies, including: cow’s milk, hen’s egg, peanut, hazelnut, and shrimp. The components with the highest diagnostic accuracy for each allergen, along with their sensitivity specificity pairs, were Bos d 4 for cow’s milk (62.0% and 87.5%), Gal d 1 for hen’s egg (84.2% and 89.8% for heated egg, and 60.6% and 97.1% for raw egg), Ara h 2 for peanut (80.3% and 95.1%), Cor a 14 for hazelnut (100% and 93.8%), and Lit v 1 for shrimp allergy (82.8% and 56.3%). The authors conclude that selected components of cow’s milk, hen’s egg, peanut, hazelnut, and shrimp allergen demonstrate high specificity but lower sensitivity. They reinforce that few studies exist for each component and studies vary widely regarding the cut off values used. This results in an inability to synthesize findings across studies. Further research is dearly needed to determine clinically appropriate cut off values, risk assessment abilities, not to mention cost effectiveness of the addition of CRD.

Effect of air quality alert on human health: A regression discontinuity analysis in Toronto, Canada

Chen H, Li Q, Kaufman JS, Wang J, Copes R et al
The Lancet Planetary Health 2018; 2(1): e19-e26. doi:10.1016/S2542-5196(17)30185-7

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In attempt to reduce adverse health effects on days when air pollution is high, government agencies worldwide have implemented air quality alert programs. Surprisingly, despite their widespread use, little is known about whether these programs produce any observable public-health benefits.

To better understand this issue, Chen et al., assembled a population-based cohort comprising all individuals who resided in the city of Toronto, Canada from 2003 to 2012, examining seven health outcomes known to be affected by short-term elevation of air pollution, using provincial health administrative databases. These health outcomes were: cardiovascular-related mortality; respiratory-related mortality; and hospital admissions or emergency department visits for acute myocardial infarction, heart failure, stroke, asthma, and chronic obstructive pulmonary disease, using a regression discontinuity design to assess the effectiveness of an intervention (i.e., the air quality alert program). To quantify the effect of the air quality alert program, they estimated for each outcome both the absolute rate difference and the rate ratio attributable to program eligibility (by intention-to-treat analysis) and the alerts themselves (by two-stage regression approach), respectively.

Overall, in this population-based cohort, the air quality alert program was related to some reductions in respiratory morbidity, but not any other health outcome examined. This indicates that issuing air quality alerts alone has a limited effect on public health and that implementing enforced public actions to reduce air pollution on high pollution days could be warranted. The authors conclude that in light of the accumulating evidence of substantial burden from long-term air pollution exposure, this study underscores the need for further strengthening of global efforts that can lead to long-term improvement of overall air quality.

Guiding principles for use of newer biologics and bronchial thermoplasty for patients with severe asthma

Blaiss MS, Castro M, Chipps BE, Zitt M, Panettieri RA Jr, Foggs MB
Annals of Allergy Asthma and Immunology 2017; 119(6): 533-540. doi:10.1016/j.anai.2017.09.058

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Addressing important unmet medical needs in patients with severe asthma requires that clinicians use tests to assess asthma phenotype and treat based on the results of these tests. In this publication by Blaiss and colleagues, the authors provide a consensus on asthma phenotyping and guiding principles for newer biologic therapies as well as bronchial thermoplasty. The authors note that although several clinical practice guidelines exist, they do not provide guidance on a phenotype-specific approach to care, which has become increasingly important.  This is a wonderful document that will aid clinicians in a practical fashion regarding the optimal use of these new interventions.

Role of airway epithelial barrier dysfunction in pathogenesis of asthma

Gon Y, Hashimoto S
Allergology International 2018; 67(10): 12-17. doi:10.1016/j.alit.2017.08.11

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In this review, the authors explore the latest literature regarding the potential for development of asthma as a consequence of disruption of the airway epithelium. Studies have shown that epithelial barrier fragility is associated with the release of several pro-inflammatory cytokines, including: TSLP, IL-25, and IL-33. It would appear that functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single “immunopathological unit”, which appears to result in allergic airway inflammation. It is a very interesting review that lays the groundwork for hopeful future therapies in asthma.

Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts FcεRI interaction

Jabs F, Plum M, Laursen NS, Jensen RK, Mølgaard B et al
Nature Communications 2018; 9(1):7. doi:10.1038/s41467-017-02312-7

Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. In their study Jabs and colleagues demonstrate how the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc shows that antibody binding results in a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. The authors speculate that understanding this inhibitory mechanism might aid in the development of strategies for the future development of anti-IgE therapeutics for the treatment of allergic diseases.

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