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Medical Journal Review

March 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. Effect of 2 Years of Treatment with Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years among Patients with Moderate to Severe Seasonal Allergic Rhinitis, The GRASS Randomized Clinical Trial

Scadding GW, Calderon MA, Shamji MH, Eifan AO, Penagos M et al. JAMA 2017; 317(6):615-625. (doi:10.1001/jama.2016.21040)


It is well known that guidelines regarding immunotherapy recommend a minimum of 3 years of treatment to maintain long-term efficacy. Certainly, if similar efficacy could be seen with shorter duration of therapy this could be cost saving. To answer this question, the authors performed a randomized double-blind, placebo-controlled, 3–parallel-group study 2 years of treatment with grass pollen sublingual immunotherapy in adult patients with moderate-to-severe seasonal allergic rhinitis. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 μg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 μg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation).

The primary outcome was total nasal symptoms score (TNSS) comparing sublingual immunotherapy vs placebo at year 3. It should be noted that subcutaneous immunotherapy was included as a positive control and that the study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy.

Although secondary outcomes did show some clinical efficacy, the authors failed to demonstrate a positive effect in the primary outcomes. In the intent-to-treat population, mean TNSS for the sublingual immunotherapy group was 6.36 (95%CI, 5.76 to 6.96) at pretreatment and 4.73 (95%CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95%CI, 5.23 to 6.88) at pretreatment and 4.81 (95%CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95%CI, −1.25 to 0.90; [P = .75]).

2. Self-assessment of Allergic Rhinitis and Asthma (SACRA) Questionnaire-based Allergic Rhinitis Treatment Improves Asthma Control in Asthmatic Patients with Allergic Rhinitis

Yasuo M, Kitaguchi Y, Komatsu Y, Hama M, Koizumi T et al. Internal Medicine 2017; 56(1): 31-39 (

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In this study Yasuo and colleagues investigated whether add-on treatment for allergic rhinitis (AR) based on the Self-assessment of Allergic Rhinitis and Asthma (SACRA) questionnaire for assessing AR control improved both AR and asthma control in asthmatic patients with AR. The investigators enrolled 200 asthmatic patients and administered add-on AR treatments based upon the results of the SACRA questionnaire. After the first SACRA questionnaire, 67 asthmatic patients agreed to receive an add-on AR treatment (lacked control of their AR). Three months after the AR treatment, a second SACRA questionnaire, asthma control test (ACT), and pulmonary function tests were performed. They found that the administration of a SACRA questionnaire-based add-on AR treatment improved the asthma visual analog scale (VAS), the ACT score as well as pulmonary function in symptomatic AR patients. Thus, reinforcing the importance of the “one airway – one disease concept”.

3. Guidance on Completing a Written Allergy and Anaphylaxis Emergency Plan

Wang J, Sicherer SH, Section on Allergy and Immunology – American Academy of Pediatrics. Pediatrics 2017; 139(3): e20164005 (DOI:10.1542/peds.2016-4005)

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This article provides guidance to aid health care providers in the writing of a personalized allergy and anaphylaxis emergency plan. The authors are to be commended for their very thorough review of the topic. Issues discussed include: optimizing completing the form, understanding of treatment pathways, and even who to provide an emergency plan for. Lastly, they provide an actual suggested Allergy and Anaphylaxis Emergency Plan form. This is a wonderful resource for both allergists and our primary care colleagues.

4. Epinephrine for First-aid Management of Anaphylaxis

Sicherer SH, Simons FER, Section on Allergy and Immunology – American Academy of Pediatrics. Pediatrics 2017; 139(3): e20164006 (DOI:10.1542/peds.2016-4006)

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This is an American Academy of Pediatrics update regarding the acute care intervention of anaphylaxis.  It provides clinicians a wonderful resource to aid in identification and treatment of anaphylaxis. The authors stress several key points regarding this illness. These include: validated clinical criteria to facilitate in the prompt diagnosis, stress the prompt intramuscular administration of the epinephrine autoinjector, discussion of the conundrum of appropriate epinephrine dosing in infants/young children, effective management of anaphylaxis from a community perspective as well as approaches for prevention of anaphylaxis. 

5. Effect of Inhaled Corticosteroid Particle Size on Asthma Efficacy and Safety Outcomes: A Systematic Literature Review and Metaanalysis

El Baou C, Di Santostefano RL, Alfonso-Cristancho R, Suarez EA, Stepmel D et al. BMC Pulmonary Medicine 2017 (7 February); 17:31 (DOI:10.1186/s12890-016-0348-4)

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It is well known that currently available inhaled corticosteroids (ICS) differ in particle size. Several previous studies have demonstrated that particle size differences may impact on clinical outcomes. Thus, the intent of this paper was to perform a meta-analysis to determine the effect of small versus standard particle size ICS on asthma measures. 

The authors found 23 trials that met the eligibility criteria. Benefit-risk plots did not demonstrate any clinically meaningful differences across the efficacy endpoints considered and no appreciable differences were noted for most safety endpoints. Specifically, meta-analysis results, using a random-effects model, demonstrated no significant difference between standard and small size particle ICS medications in terms of effects on mean change from baseline FEV1 (L) (−0.011, 95% confidence interval [CI]: −0.037, 0.014 [N = 3524]), morning PEF (L/min) (medium/ low doses: −3.874, 95% CI: −10.915, 3.166 [N = 1911]; high/high-medium doses: 5.551, 95% CI: −1.948, 13.049 [N = 749]) and FEF25–75% predicted (−2.418, 95% CI: −6.400; 1.564 [N = 115]). The authors conclude that based on the available literature, no clinically significant differences in efficacy or safety were observed comparing small and standard particle size ICS medications for the treatment of asthma.