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Medical Journal Review

January 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.

Current opinions for the management of asthma associated with ear, nose and throat comorbidities

Tiotiu A, Plavec D, Novakova S et al.
European Respiratory Review 2018; 27(150): Published online ahead of print (Nov 21). DOI:

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Ear, nose and throat (ENT) comorbidities are common in patients with asthma and are frequently associated with poorer asthma outcomes. Identification and management of these comorbidities may reduce medication requirements, contribute to improved asthma control and quality of life, as well as decrease asthma exacerbation rates. This review examines recent data regarding the prevalence, clinical impact and treatment effects of ENT comorbidities in asthma including allergic rhinitis, chronic rhinosinusitis with and without nasal polyposis, aspirin-exacerbated respiratory disease, obstructive sleep apnea and vocal cord dysfunction. This review closes by discussing the potential utility of biologic therapies in severe asthma and its potential efficacy in some ENT diseases.

Theory-based digital interventions to improve asthma self-management outcomes: Systematic review

Lycett HJ, Raebel EM, Wildman EK et al
Journal of Medical Internet Research 2018; 20(12): e293. DOI:

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The aim of this study was to examine the use and application of “theory” in the development of digital interventions to enhance asthma self-management and to evaluate the effectiveness of theory-based interventions in improving adherence, self-management, and clinical outcomes. Guidelines for the development of interventions recommend the use of a theoretical framework or model of behavior change. Theory can be used in various ways, for example, to identify modifiable determinants of health behaviors to be addressed within interventions (e.g., illness perceptions), to select appropriate techniques to address behavioral determinants (e.g., motivational interviewing), or to select people who are most likely to benefit from the intervention (e.g., patients who have misconceptions about their illness or treatment). In this study, the authors performed a systematic analysis using predetermined terms. Those meeting inclusion criteria were assessed for risk of bias using the Cochrane Collaboration tool. The Theory Coding Scheme (TCS) was used to establish the extent to which each intervention had applied theory and which theoretical constructs or behavioral determinants were addressed.

Associations between TCS scores and asthma outcomes were described within a narrative synthesis. Fourteen studies evaluating 14 different digital interventions met criteria. The most commonly cited theories were Social Cognitive Theory, Health Belief Model, and Self-Efficacy Theory. A greater use of theory in the development of interventions was correlated with effective outcomes (r=.657; P=.01): only the 3 studies that met >60% of the different uses of theory assessed by the TCS were effective on all behavioral and clinical outcomes measured. None of the 11 studies that met ≤60% of the TCS criteria were fully effective; however, 3 interventions were partially effective (i.e., the intervention had a significant impact on some, but not all, of the outcomes measured). Most studies lacked detail regarding the theoretical constructs and how they were applied to the development and application of the intervention. The authors conclude that these findings suggest that greater use of theory in the development and application of digital self-management interventions for asthma may increase their effectiveness.

Human and computational models of atopic dermatitis: A review and perspectives by an expert panel of the International Eczema Council

Eyerich K, Brown SJ, Perez White BE et al
Journal of Allergy and Clinical Immunology 2019; 143(1): 36-45. DOI:

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Despite the high prevalence of atopic dermatitis (AD), there has been a lack of a good animal model for this illness. Not surprisingly, there has been increasing interest in developing experimental approaches to study the pathogenesis of human AD in vivo, in vitro, and in silico to better define pathophysiologic mechanisms and identify novel therapeutic targets and biomarkers that predict therapeutic response. In this review by Eyerich et al, the authors explore a range of models, including genetic mutations relevant to AD, experimental integration of ‘‘omics’’ data sets, and development of predictive computational models. They note that although no one model captures the complex AD pathophysiology, they show that several do provide insights into key elements of cutaneous biology, molecular pathways, and therapeutic target identification. Furthermore, recent developments in computational analysis, including application of machine learning and a systems approach to data integration and predictive modeling, highlight the applicability of these methods to AD subclassification (endotyping), therapy development, and precision medicine.

Paucigranulocytic asthma: Uncoupling of airway obstruction from inflammation

Tliba O, Panettieri RA Jr
Journal of Allergy and Clinical Immunology 2018; Published online ahead of print (June 19). DOI:

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It has been well established that there is significant heterogeneity in asthma regarding the pattern of airway inflammation and response to treatment, highlighting the necessity of recognizing specific phenotypes. Based on the analysis of inflammatory cell counts in induced sputum, asthmatic patients can be classified into 4 unique phenotypes: eosinophilic asthma, neutrophilic asthma, mixed granulocytic asthma, and paucigranulocytic asthma (PGA). In this Rostrum, Drs. Tilba and Panettieri explore the literature regarding PGA. PGA is an asthma phenotype with no evidence of increased numbers of eosinophils or neutrophils in sputum or blood and in which our present anti-inflammatory therapies are ineffective. Interestingly, despite a paucity of data, PGA is believed to be the most common asthma phenotype in patients with stable asthma. It appears that PGA manifests as an uncoupling of airway obstruction from airway inflammation that can be driven by structural changes within the airways, such as airway smooth muscle tissue hypertrophy. In trying to better understand this pathophysiology, animal models provide evidence that processes evoking airway hyperresponsiveness and airway smooth muscle thickening occur independent of inflammation and might be a consequence of a loss of negative homeostatic processes. In the end, better understanding of the pathophysiology of this asthma phenotype will likely be derived from animal studies, and it is hoped through this work that precision therapies will improve PGA clinical outcomes.

A comprehensive understanding of the gut mucosal immune system in allergic inflammation

Tokuhara D, Kurashima Y, Kamioka M et al
Allergology International 2019; 68(1): 17-25. DOI:

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The gut mucosal immune system is really rather amazing.  It protects the host from the invasion of infectious pathogens and eliminates harmful non-self antigens, while still allowing the cohabitation of commensal bacteria in the gut and the entry of dietary non-self antigens into the body via the mucosal surface. These physiological and immunological activities are regulated by the gut mucosal immune network, comprising such features as gut-associated lymphoid tissue, mucosal immune cells, cytokines, chemokines, antimicrobial peptides, secretory IgA, and commensal bacteria. Disruption of gut homeostasis results in persistent or severe gastrointestinal infection, inflammatory bowel disease, or allergic inflammation. In this review by Tokuhara and colleagues, the authors comprehensively examine our current knowledge of the gut mucosal immune system, focusing on its interaction with allergic inflammation.