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Medical Journal Review

September 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.

Optimal cut-off value and clinical usefulness of the Adherence Starts with Knowledge-12 in patients with asthma taking inhaled corticosteroids
Takemura M, Nishio M, Fukumitsu K, Takeda N, Ichikawa H et al
Journal of Thoracic Disease 2017; 9(8): 2350-2359  DOI: 10.21037/jtd.2017.06.115


We have long known that non-adherence to inhalation therapy is sadly quite common in our asthmatic patients. The Adherence Starts with Knowledge-12 (ASK-12) survey was developed to in attempt to detect patient-specific barriers to medication adherence. The ASK-12, a shorter form of the ASK-20, is a 12-item questionnaire consisting of three domains related to medication adherence: inconvenience/forgetfulness, treatment beliefs, and behavior. Responses for each item are scored on a 5-point scale. Scores can range from 12 to 60 with higher scores representing greater barriers to adherence. In this study, Takemura and colleagues investigated the clinical usefulness of the ASK-12 in asthmatic patients in whom pharmacy-refill data were available in order to determine a cut-off value for the ASK-12 for non-adherence to inhalational therapy and with this information identified factors associated with non-adherence. The authors found a significant correlation between pharmacy-refill rates and the ASK-12 total score (r=−0.55, P<0.0001). The optimal cut-off value of the ASK-12 total score to discriminate non-adherent patients (defined by pharmacy-refill rate <80%) was 23, with 71.4% specificity and 93.3% sensitivity. Using this value, 52 (45.6%) patients were classified as non-adherent. Univariate followed by multivariate analysis identified younger age as a predictor of non-adherence to inhalation regimens (odds ratio, 2.67; 95% CI, −0.95 to −0.06; P=0.027).

Management of chronic spontaneous urticaria (CSU): a treat to target approach using a patient reported outcome
Lima H, Gooderham M, Dutz J, Lynde C, Chapdelaine H et al.
Allergy, Asthma & Clinical Immunology 2017: 13:38  DOI: 10.1186/s13223-017-0210-0


Treat-to-target (T2T) treatment strategy aims to achieve complete symptom control and improve the patient’s quality of life (QoL). When compared to the traditional symptom-based approach, target-based strategies have been shown to lead to better treatment and patient outcomes in diseases with complex clinical presentations and a paucity of overt symptoms such as diabetes, hypertension, and rheumatoid arthritis. In this article, Lima and colleagues propose a T2T approach for the management of patients with chronic spontaneous urticaria (CSU) via a Canadian task force consisting of dermatologists, immunologists, and allergists. The experts suggest that key T2T/CSU recommendations are the use of a patient reported outcome as the principal target; suggesting the assessment of symptom control be measured by the Urticaria Activity Score 7 (UAS7 ≤ 6), targeting symptom remission (UAS7 = 0).

Early probiotic supplementation for eczema and asthma prevention: A Randomized controlled trial
Cabana MD, McKean M, Caughey AB, Fong L, Lynch S et al.
Pediatrics 2017; 140(3): e20163000  DOI: 10.1542/peds.2016-3000


Some theorize that in light of the hygiene hypothesis, probiotic exposure could theoretically affect immune system development and reduce the subsequent risk for the development of allergic illnesses. Thus, the purpose of this study by Cabana et al. was to determine if probiotic administration during the first 6 months of life decreases childhood allergic illness through the performance of a randomized, double-blind controlled trial of Lactobacillus rhamnosus GG (LGG) supplementation examining the cumulative incidence of eczema (primary end point) and asthma and rhinitis (secondary end points) in high-risk infants. For the first 6 months of life, intervention infants (n = 92) received a daily dose LGG and inulin, while control infants (n = 92) received inulin alone. Infants were accrued over a 6-year period (median follow-up: 4.6 years; 95% retention rate at 2 years). At age 2, the estimated cumulative incidence of eczema was 30.9% (95% confidence interval [CI], 21.4%–40.4%) in the control arm and 28.7% (95% CI, 19.4%–38.0%) in the LGG arm, for a hazard ratio of 0.95 (95% CI, 0.59–1.53) (log-rank P = .83). At 5 years of age, the cumulative incidence of asthma was 17.4% (95%CI, 7.6%–27.1%) in the control arm and 9.7% (95% CI, 2.7%–16.6%) in the LGG arm, for a hazard ratio of 0.88 (95% CI, 0.41–1.87) (log-rank P = .25). Overall the indication is that in high-risk infants, early LGG supplementation for the first 6 months of life does not appear to prevent the development of eczema or asthma at 2 years of age.

A systematic review of adverse drug events associated with administration of common asthma medications in children
Leung JS, Johnson DW, Sperou AJ, Crotts J, Saude E et al.
PLoS ONE 2017; 12(8): e0182738   DOI: 10.1371/journal.pone.0182738


In this report, Leung and colleagues systematically review the literature to determine frequencies of adverse drug events (ADE) associated with pediatric asthma medications. Their systematic review identified 14,540 citations. 46 studies were included: 24 RCT, 15 cohort, 4 RCT pooled analyses, 1 case-control, 1 open-label trial and 1 quasi-experimental study. Studies examined the following drug classes: inhaled corticosteroids (ICS) (n = 24), short-acting beta-agonists (n = 10), long-acting beta-agonists (LABA) (n = 3), ICS + LABA (n = 3), Leukotriene Receptor Antagonists (n = 3) and others (n = 3). Through this analysis, the authors were able to identify a detailed index of 406 ADE descriptions and frequencies organized by drug class. The majority of data was related to ICS, with 174 ADE affecting 13 organ systems including adrenal and growth suppression. Furthermore, although rare, serious ADE demonstrated a frequency ranging between 0.9±6% per drug. There were no confirmed pediatric deaths, but 13 potential deaths were identified in a LABA study which included combined adult and pediatric subjects. The authors noted substantial methodological concerns, particularly with identifying ADE and determining severity, highlighting the need for standardization in future research examining pediatric asthma medication safety

Better recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy: iMAP–an international interpretation of the MAP (Milk Allergy in Primary Care) guideline
Venter C, Brown T, Meyer R, Walsh J, Shah N et al.
Clinical and Translational Allergy 2017; 7:26   DOI: 10.1186/s13601-017-0162-7


Cow’s milk allergy (CMA) is one of the most complex food allergies implicated in IgE-mediated food allergy, but can also present with diverse manifestations of non-IgE-mediated food allergy, such as food protein induced enteropathy, enterocolitis or proctocolitis. In light of concern regarding the early and timely diagnosis of CMA, multiple guidelines have been developed. The UK guideline, “Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy—a UK primary care practical guide”, was published in 2013. This Milk Allergy in Primary Care (MAP) guideline outlines in simple algorithmic form, not only the varying presentations of cow’s milk allergy, but also focuses on the practical management of mild-to-moderate non-IgE-mediated allergy. Based on the international uptake of the MAP guideline, it became clear that there was a need for practical guidance beyond the UK. In light of this need, the authors published this international update, which incorporates further data, feedback from UK healthcare professionals and affected families and, as well as the inclusion of international experts on their updated guideline panel.