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Medical Journal Review

February 2016

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 each month from Juan Carlos Ivancevich, MD, WAO Web Editor-in-Chief, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor.

1. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice.

Price D, Wilson AM, Chisholm A, Rigazio A, Burden A, Thomas M, King C. Predicting frequent asthma exacerbations using blood eosinophil count and other patient data routinely available in clinical practice.  Journal of Asthma and Allergy 2016; 2016; 9: 1-12. (doi:10.2147/JAA.S97973).

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As clinicians caring for asthmatic patients, our goal has always been to predict and prevent exacerbations. Unfortunately, predictors of asthma exacerbations are needed. In an attempt to determine which patients are likely to suffer an asthma exacerbation, Price and colleagues performed a medical record review of 130,547 asthma patients aged 12–80 years from the UK Optimum Patient Care Research Database and Clinical Practice Research Datalink, 1990–2013, examining one year before (baseline) and one year after (outcome) their most recent blood eosinophil count. They compared patients who had two or more exacerbations to those who had no exacerbations or only one exacerbation and found that a blood eosinophil count >400/μL (versus <400/μL) increased the likelihood of two or more exacerbations >1.4-fold (odds ratio [OR]: 1.48 (95% confidence interval [CI]: 1.39, 1.58); P<0.001). Other variables that significantly increased the odds of exacerbation included increasing age, female gender, being overweight or obese, being a smoker, having anxiety/depression, diabetes, eczema, gastroesophageal reflux disease, rhinitis, and prescription for acetaminophen or nonsteroidal anti-inflammatory drugs. Compared with treatment at British Thoracic Society step 2 (daily controller ± reliever), treatment at step 0 (none) or 1 (as-needed reliever) increased the odds by 1.2- and 1.6-fold, respectively, and treatment at step 3, 4, or 5 increased the odds by 1.3-, 1.9-, or 3.1-fold, respectively (all P<0.05). Acute OCS use was the single best predictor of two or more exacerbations, with even one course increasing the odds by more than threefold (OR: 3.75 [95% CI: 3.50, 4.01]; P<0.001), and three or more courses increasing the odds by >25-fold (OR: 25.7 [95% CI: 23.9, 27.6]; P<0.001).

2. Management of the polyallergic patient with allergy immunotherapy: a practice-based approach.

Demoly P, Passalacqua G, Pfaar O, Sastre J, Wahn U. Management of the polyallergic patient with allergy immunotherapy: a practice-based approach. Allergy, Asthma & Clinical Immunology 2016;12:2. (doi:10.1186/s13223-015-0109-6)

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It has long been known that a great majority of patients with allergic respiratory disease are polysensitized and thus may be potentially clinically polyallergic. Yet, the allergy immunotherapy (AIT) management of these patients are not standardized. To bring guidance, an international group of experts in the field met to develop recommendations for the treatment of these patients. The group concluded that AIT is safe and effective in polysensitized and polyallergic patients, and should always be based on the identification of one or more clinically relevant allergens (founded on the type and severity of symptoms, the duration of symptoms, the impact on quality of life and how difficult an allergen is to avoid). They noted that single-AIT is recommended in polyallergic patients in whom one of the relevant allergens is nevertheless clearly responsible for the most intense and/or bothersome. They further recommended that “mixed 2-allergen immunotherapy” is indicated in polyallergic patients in whom two causal relevant allergens have a marked clinical and QoL impact. In such cases, whether delivered via the subcutaneous or sublingual route, high-quality, standardized, single-allergen formulations must be administered with an interval of 30 minutes. Mixing of allergen extracts may be considered, as long as the mixture is technically feasible, is allowed from a regulatory standpoint, and the allergen doses are reduced in proportion to the number of components but are still at concentrations with demonstrated efficacy.

3. Serum allergen-specific IgE testing: How much is too much? The Choosing Wisely campaign and others advocate against indiscriminate IgE testing in evaluating allergy.

Lau CK and Naugler C. Serum allergen-specific IgE testing: How much is too much? The Choosing Wisely campaign and others advocate against indiscriminate IgE testing in evaluating allergy. Cleveland Clinic Journal of Medicine 2016;83(1):21-24 (doi:10.3949/ccjm.83a.14125)

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This is a wonderful primary care review, published in the Cleveland Clinic Journal of Medicine, which uses a case of a man with angioedema of the lips who seeks medical consultation with a primary care physician and as a consequence undergoes a plethora of specific IgE tests to foods to highlight the poor predictive value of allergy testing blindly (poor pre-test probability). As all allergists know, this situation occurs with far too great a frequency. The authors, through this case, illustrate the poor predictive value of such testing blindly and reinforce it with an exploration of the literature to determine the combined sensitivity and specificity of 89 allergens (foods, respiratory allergens and hymenoptera) available for immunocap testing and find that only seven are “clinically useful”, based upon a predetermined cut-off of 170. Through this case, the authors stress that a patient’s history should be the guide for testing and note that this is often best accomplished by involving an allergist. This may be an ideal article to give to your primary care colleagues.

4. Systematic review of the toxicity of short-course oral corticosteroids in children.

Aljebab F, Choonara I and Conroy S. Systematic review of the toxicity of short-course oral corticosteroids in children. Archives of Disease in Childhood 2016; published online ahead of print, January 14. (doi:10.1136/archdischild-2015-309522)

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Short-courses of oral corticosteroids are commonly used in children for the treatment of asthma exacerbation and are known to be associated with potential adverse drug reactions (ADRs). This review by Aljebab and colleagues examines the most common and serious ADRs and determines their relative risk levels. Through a very extensive literature review, the authors identified studies in which oral corticosteroids were administered to patients aged 28 days to 18 years of age, for up to and including 14 days of treatment. They found 38 studies (including 22 randomized controlled trials) involving a total of 3200 children in whom 850 ADRs were reported. The three most frequent ADRs were vomiting, behavioral changes and sleep disturbance, with respective incidence rates of 5.4%, 4.7% and 4.3% of patients assessed for these ADRs. Infection was one of the most serious ADRs, with one child dying after contracting varicella zoster. When measured, 144 of 369 patients showed increased blood pressure; 21 of 75 patients showed weight gain; and biochemical hypothalamic–pituitary–adrenal axis suppression was detected in 43 of 53 patients. In our care of asthmatic patients, this study reinforces our goals of preventing exacerbations with appropriate controller therapy.

5. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report.

Gibson P, Wang G, McGarvey L, Vertigan AE, Altman KW, Birring SS. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report. Chest 2016; 149(1):27-44. (doi:10.1378/chest.15-1496)

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A systematic review of randomized controlled trials (RCTs) examining the efficacy of treatment in patients with unexplained cough (UCC) was undertaken by the expert cough panel of the American College of Chest Physicians. They examined studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks’ duration that was unexplained after systematic investigation and treatment which were assessed for relevance and quality. Based upon this systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology.  The panel found 11 RCTs which reported data on 570 participants with chronic cough who received a variety of interventions. They found that overall, the evidence supporting the diagnosis and management of UCC is limited. They agreed that UCC requires further study to establish consensus terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. Although gabapentin and morphine both exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation by the panel. Esomeprazole was found to be ineffective for UCC without features of gastroesophageal acid reflux and studies addressing nonacid gastroesophageal reflux disease were not identified. This guideline highlights gaps in our knowledge as well as areas for future research.