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World Allergy Organization
WAO's mission: To be a global resource and advocate in the field of allergy, advancing excellence in clinical care through education, research and training as a world-wide alliance of allergy and clinical immunology societies.

Medical Journal Reviews

August 2015

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, the WAO Reviews Editor.

1. Underuse of guideline-recommended long-term asthma management in children hospitalized to the intensive care unit: a multicenter observational study

Hasegawa K, Ahn J, Brown MA, Press VG, Gabriel S et al. Underuse of guideline-recommended long-term asthma management in children hospitalized to the intensive care unit: a multicenter observational study. Annals Allergy Asthma Immunology 2015; 115(1): 10-16.

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As noted in this study’s introduction, at least in the state of New Jersey, there was a reported 6-fold rise in the need for intensive care unit (ICU) use in the treatment of asthma exacerbations between 1992 and 2006.  As it is believed that hospitalizations for asthma exacerbations are a consequence of treatment or maintenance failure, it made sense to explore this knowledge gap, by performing a multicenter study of children hospitalized for asthma exacerbation to investigate the proportion and characteristics of children admitted to the ICU and the frequency of guideline-recommended outpatient management in the pre- and post-hospitalization periods. It was hoped that better understanding of these important issues in long-term asthma care will aid in the development of strategies to improve the long-term prevention-oriented management of these hospitalized children.

To do so, the authors performed a 14-center medical record review study of children aged 2 to 17 years hospitalized for asthma exacerbation during 2012-2013. The primary outcome was admission to the ICU.  Secondary outcomes were 2 preventive factors: use of inhaled corticosteroids (ICS) and evaluation by asthma specialists in the pre- and post-hospitalization periods.

They found that of the 385 children hospitalized for asthma, 130 (34%) were admitted to the ICU. The risk factors for ICU admission were female sex, having public insurance, a marker of chronic asthma severity (ICS use), and no prior evaluation by an asthma specialist. Among children with an ICU admission, guideline-recommended outpatient management was suboptimal, which included lack of use of an ICS as well as not having been seen by an asthma specialist. Sadly, at hospital discharge, among children with ICU admission who had not previously used controller medications only 85% were prescribed ICSs and only 62% were referred to an asthma specialist during the 3-month post-hospitalization period.

The authors go on to note that in conjunction with the earlier studies reporting that longitudinal outpatient care by a specialist is associated with fewer subsequent ED visits or hospitalizations and better asthma control, their results lend significant support to this guideline recommendation in the care of children with high-risk asthma.

2. Clinical Relevance of Cluster Analysis in Phenotyping Allergic Rhinitis in a Real-Life Study

Bousquet PJ, Devillier P, Tadmouri A, Mesbah K, Demoly P, Bousquet J. Clinical relevance of cluster analysis in phenotyping allergic rhinitis in a real-life study. International Archives of Allergy and Immunology 2015; 166(3): 231-240. (doi:10.1159/000381339)

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As pointed out by the authors, novel phenotypic characterization of allergic diseases is needed to distinguish groups of patients presenting with allergic rhinitis (AR). It is hoped that through the identification of phenotypes clinicians can improve management and AR control. Popular epidemiologic approaches, such as the unsupervised statistical techniques, have recently emerged to meet these needs. These approaches consist of applying unsupervised statistical methods to a population with a wide distribution of related symptoms, and then identifying the possible underlying phenotypes.

Ideally each of these phenotypes should be as homogeneous as possible and have as little overlap as possible with each of the other phenotypes. Phenotypes are not known a priori, and there are no predefined views about them. There are different types of clustering approaches such as hierarchical, partitioning and model-based clustering as well as network analysis. Many studies in asthma and allergic diseases have used various clustering methods to stratify patients; with one of the recommended methods being Ward’s hierarchical cluster analysis. Through this method patients in the same cluster are more similar to each other than those in different clusters.

A French observational prospective multicenter study (EVEIL: Echelle visuelle analogique dans la rhinite allergique) was carried out on 990 patients consulting general practitioners (GPs) for AR and treated as per clinical practice. In this study, changes in symptom scores, VAS and QoL were measured at baseline and after 14 days of treatment. The study involved a careful evaluation of demographic and clinical characteristics and was suitable for cluster analysis. In this paper, the authors performed a post hoc analysis using the dataset of the EVEIL study to identify clusters of patients with AR using Ward’s hierarchical method, and to define their clinical relevance at baseline and after 14 days of treatment. The cluster approach was compared to ARIA (Allergic Rhinitis and its Impact on Asthma), which is a hypothesis-driven approach largely used in clinical practice. Through use of the cluster approach, patients were clustered into 4 phenotypes which partly followed the ARIA classes. These phenotypes differed in their disease severity (symptoms and quality of life). It should be noted that physicians in “real-life practice” prescribed medication regardless of the phenotype and severity, except for patients with ocular symptoms, who more frequently were prescribed ocular antihistamines. Interestingly, they found that cluster analysis using demographic and clinical parameters did not appear to add relevant information for disease stratification in allergic rhinitis and prescribed treatments were comparable in hypothesis- and data-driven analyses.

In conclusion the authors note that insufficient numbers of primary care physicians stratify their patients in terms of severity, clinical parameters readily available in their offices are helpful in assessing the response to treatment in AR and cluster analysis did not add to disease stratification.

3. Mast Cells, Mastocytosis, and Related Disorders

Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. The New England Journal of Medicine 2015; 373(2): 163-172. (doi:10.1056/NEJMra1409760)


This article is a wonderful overview of recent developments regarding the physiology and pathobiology of mast cells. In this review, they examine the role of mast cells in human disease. To do so they explore our understanding of the mechanisms of mast cell activation and appropriate diagnostic testing and treatment, both at present and hopefully for the future.

I would encourage practicing allergists to read this paper and to keep it handy for your care of patients with suspected mast cell disease.