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Medical Journal Review

May 2019

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.

European S2k Guideline on Chronic Pruritus
Weisshaar E, Szepietowski JC, Dalgard FJ, Garcovich S, Gieler U et al.
Acta Dermato Venereologica 2019;99(5):469-506. doi: 10.2340/00015555-3164.
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Pruritus is a very common problem, with studies demonstrating that every fifth person in the general population has suffered from chronic pruritus at least once in their lifetime with a 12-month incidence of 7%. Pruritus may be the result of a dermatological or non-dermatological disease. Especially in non-diseased skin it may be caused by systemic, neurological or psychiatric diseases, as well as being a side effect of medications. In a number of cases chronic pruritus may be of multifactorial origin. In light of its multiple potential causes, pruritus needs a precise diagnostic work-up. Furthermore, treating chronic pruritus needs to be targeted, multimodal and performed in a step-wise fashion, often requiring an interdisciplinary approach. This guideline is the updated and consensus-based (S2k) European guideline on chronic pruritus, developed by a team of European pruritus experts from multiple disciplines.

Serum levels of eosinophil-derived neurotoxin: A biomarker for asthma severity in adult asthmatics
Lee Y, Lee JH, Yang EM, Kwon E, Jung CG et al
Allergy Asthma & Immunology Research 2019;11(3):394-405. doi: 10.4168/aair.2019.11.3.394.
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Although eosinophilic inflammation can be a key component of severe asthma (SA), there has been no reliable serum biomarker for the eosinophilic inflammation of SA. In this study, the authors explored the use of serum eosinophil-derived neurotoxin (EDN) as a predictor of eosinophilic inflammation of SA in adult asthmatics. The authors examined serum levels of EDN and periostin, comparing SA (n=235), to non-severe asthmatics (n=898) to healthy controls (n=125). Overall, the SA were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 compared to non-severe asthmatics. They found that serum levels of EDN and periostin were significantly higher in severe asthmatics versus non-severe asthmatics and healthy controls (all P < 0.05).   The authors concluded that the results of this study suggest that the serum EDN level can help identify SA in adult asthmatics. As SA is a heterogeneous phenotype, further studies are needed to identify useful biomarkers for assessing subtypes and long-term clinical outcome of SA.

Management of ocular allergy itch with an antihistamine-releasing contact lens
Pall B, Gomes P, Yi F, Torkildsen G
Cornea 2019;38(6):713-717. doi: 10.1097/ICO.0000000000001911.
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In this article by Pall et al., the authors present data regarding a contact lens (CL)-based drug delivery system for therapeutic delivery of the antihistamine ketotifen which was tested in 2 parallel, conjunctival allergen challenge-based trials. In these studies, subjects were randomized into 3 treatment groups. Group 1 received test lens in one eye and control lens in the contralateral eye; the eye chosen to receive test lens was randomly selected in a 1:1 ratio. Group 2 received test lenses bilaterally, and group 3 received control lenses bilaterally. Allergen challenges were conducted on 2 separate visits: following lens insertion, the subjects were challenged at 15 minutes (to test onset) and 12 hours (to test duration). The primary endpoint was ocular itching measured using a 0 to 4 scale with half-unit steps. Secondary endpoints included ciliary, conjunctival, and episcleral hyperemia. The researchers found that the mean itching scores were lower for those wearing the test lens as compared to those that received control lenses without ketotifen, indicating that the test lens effectively reduced allergic responses. Mean differences in itching were statistically and clinically significant (mean score difference > 1) at both onset and duration for both trials. This is the first demonstration of efficacy for CL delivery system for ocular allergy.

Global, national, and urban burdens of paediatric asthma incidence attributable to ambient NO2 pollution: Estimates from global datasets
Achakulwisut P, Brauer M, Hystad P, Anenberg SC
Lancet Planet Health 2019;3(4):e166-e178. doi: 10.1016/S2542-5196(19)30046-4.
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Pediatric asthma incidence is associated with exposure to traffic-related air pollution (TRAP), but the TRAP-attributable burden remains poorly quantified. Nitrogen dioxide (NO2) is a major component and common proxy of TRAP. In this study, the authors estimated the annual global number of new pediatric asthma cases attributable to NO2 exposure at a resolution sufficient to resolve intra-urban exposure gradients. To do so, they examined 2015 country-specific and age-group-specific asthma incidence rates from the Institute for Health Metrics and Evaluation for 194 countries and 2015 population counts at a spatial resolution of 250×250 m from the Global Human Settlement population grid. They used 2010–12 annual average surface NO2 concentrations derived from land-use regression at a resolution of 100×100 m, and derived concentration-response functions from relative risk estimates reported in a multinational meta-analysis.

From this data they were able to estimate the NO2-attributable burden of asthma incidence in children aged 1–18 years in 194 countries and 125 major cities at a resolution of 250×250 m. They estimated that 40 million (95% uncertainty interval [UI] 1·8–5·2) new pediatric asthma cases could be attributable to NO₂ pollution annually; 64% of these occur in urban centers. This burden accounted for 13% (6–16) of global incidence. Regionally, the greatest burdens of new asthma cases associated with NO2 exposure per 100,000 children were estimated for Andean Latin America (340 cases per year, 95% UI 150–440), high-income North America (310, 140–400), and high-income Asia Pacific (300, 140–370). Within cities, the greatest burdens of new asthma cases associated with NO2 exposure per 100,000 children were estimated for Lima, Peru (690 cases per year, 95% UI 330–870); Shanghai, China (650, 340–770); and Bogota, Colombia (580, 270–730). Among 125 major cities, the percentage of new asthma cases attributable to NO2 pollution ranged from 5·6% (95% UI 2·4–7·4) in Orlu, Nigeria, to 48% (25–57) in Shanghai, China. The authors stress that their data indicate that efforts to reduce NO2 exposure could help prevent a substantial portion of new pediatric asthma cases in both developed and developing countries, especially in urban areas, and that traffic emissions should be a target for these exposure-mitigation strategies.

Stepwise approach towards adoption of allergen immunotherapy for allergic rhinitis and asthma patients in daily practice in Belgium: A BelSACI-Abeforcal-EUFOREA statement
Hellings PW, Pugin B, Mariën G, Bachert C, Breynaert C et al.
Clinical and Translational Allergy 2019;9:1: (Feb 4) doi: 10.1186/s13601-019-0243-1
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In this review, the authors explore the literature regarding the use of allergy immunotherapy (AIT) for allergic rhinitis (AR). AR affects 23–30% of the European population with equal prevalence reported in Belgium. Even with evidence-based guideline therapy, up to 40% of AR patients remain uncontrolled. AIT has been shown to improve the level of control in up to 84% of patients being treated with AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products. Furthermore, AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues, as well as several patient- and physician-related factors. To overcome these hurdles, patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT, and physicians dealing with AR patients should inform them about the potential tolerance-inducing effects of AIT. Also, clinicians need to select appropriate patients for AIT, choosing evidence-based AIT products and following treatment protocols with proven efficacy.