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      Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma

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          Abstract

          Background

          Severe asthma is a largely heterogeneous disease with varying phenotypic profiles. The relationship between specific allergen sensitization and asthma severity, particularly in Asia, remains unclear. We aim to study the prevalence of specific allergen sensitization patterns and investigate their association with outcomes in a severe asthma cohort in an Asian setting.

          Methods

          We conducted a cross-sectional study of patients receiving step 4 or 5 Global Initiative for Asthma treatment. Univariate and multivariate analyses were performed to assess the association between sensitization to a specific identifiable allergen by skin prick test (SPT) and uncontrolled asthma (defined in our study as the use of ≥2 steroid bursts or hospitalization in the past year, a history of near-fatal asthma or evidence of airflow obstruction on spirometry).

          Results

          Two hundred and six severe asthma patients (mean age 45±17 years, 99 [48.1%] male) were evaluated. Of them, 78.2% had a positive SPT to one or more allergens. The most common allergen to which patients were sensitized was house dust mites ( Blomia tropicalis, Dermatophagoides pteronyssinus and Dermatophagoides farinae). Also, 11.7% were sensitized to Aspergillus species. On multivariate analysis, Aspergillus sensitization was associated with uncontrolled asthma (odds ratio 6.07, 95% confidence interval 1.80–20.51). In particular, Aspergillus sensitization was independently associated with the use of ≥2 steroid bursts in the past year (odds ratio 3.05, 95% confidence interval 1.04–8.95). No similar associations of uncontrolled asthma with sensitization to any other allergens were found.

          Conclusion

          High allergen, specifically Aspergillus sensitization was observed in the Asian population with severe asthma by SPT. Aspergillus sensitization was specifically associated with frequent exacerbations and a greater corticosteroid requirement. An improved understanding of the severe asthma with Aspergillus sensitization phenotype is warranted, which is likely a subgroup of severe asthma with fungal sensitization.

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          Most cited references35

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          Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program.

          Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P or = 12 years) was associated with lower lung function and sinopulmonary infections (P < or = .02). Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.
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            The link between fungi and severe asthma: a summary of the evidence.

            There is current evidence to demonstrate a close association between fungal sensitisation and asthma severity. Whether such an association is causal remains to be confirmed, but this is explored by means of a detailed literature review. There is evidence from two randomised controlled trials that, in the example of allergic bronchopulmonary aspergillosis (ABPA), treatment with systemic antifungal therapy can offer a therapeutic benefit to approximately 60% of patients. ABPA is only diagnosed if a combination of clinical and immunological criteria is achieved. It is not known whether such cases are a discrete clinical entity or part of a spectrum of the pulmonary allergic response to fungi or fungal products. This paper describes the epidemiological evidence that associates severity of asthma with fungi and discusses possible pathogenetic mechanisms. Many airborne fungi are involved, including species of Alternaria, Aspergillus, Cladosporium and Penicillium, and exposure may be indoors, outdoors or both. The potential for a therapeutic role of antifungal agents for patients with severe asthma and fungal sensitisation is also explored. Not only are many patients with severe asthma desperately disabled by their disease, but, in the UK alone, asthma accounts for 1,500 deaths per yr. The healthcare costs of these patients are enormous and any treatment option merits close scrutiny. Within this report, the case for the consideration of a new term related to this association is put forward. The current authors propose the term "severe asthma with fungal sensitisation". However, it is recognised that enhanced and precise definition of fungal sensitisation will require improvements in diagnostic testing.
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              Respiratory allergy caused by house dust mites: What do we really know?

              The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic rhinitis and allergic asthma. However, awareness of the condition remains generally low. This review assesses the links between exposure to HDM, development of the allergic response, and pathologic consequences in patients with respiratory allergic diseases. We investigate the epidemiology of HDM allergy to explore the interaction between mites and human subjects at the population, individual, and molecular levels. Core and recent publications were identified by using "house dust mite" as a key search term to evaluate the current knowledge of HDM epidemiology and pathophysiology. Prevalence data for HDM allergen sensitization vary from 65 to 130 million persons in the general population worldwide to as many as 50% among asthmatic patients. Heterogeneity of populations, terminology, and end points in the literature confound estimates, indicating the need for greater standardization in epidemiologic research. Exposure to allergens depends on multiple ecological strata, including climate and mite microhabitats within the domestic environment, with the latter providing opportunity for intervention measures to reduce allergen load. Inhaled mite aeroallergens are unusually virulent: they are able to activate both the adaptive and innate immune responses, potentially offering new avenues for intervention. The role of HDM allergens is crucial in the development of allergic rhinitis and asthma, but the translation of silent sensitization into symptomatic disease is still incompletely understood. Improved understanding of HDMs, their allergens, and their microhabitats will enable development of more effective outcomes for patients with HDM allergy.
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                Author and article information

                Journal
                J Asthma Allergy
                J Asthma Allergy
                Journal of Asthma and Allergy
                Journal of Asthma and Allergy
                Dove Medical Press
                1178-6965
                2017
                21 April 2017
                : 10
                : 131-140
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, Singapore General Hospital
                [2 ]Duke-National University of Singapore Medical School
                [3 ]Allergy Centre, Singapore General Hospital
                [4 ]Department of Biological Sciences, Faculty of Science, National University of Singapore
                [5 ]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                Author notes
                Correspondence: Sanjay H Chotirmall, Lee Kong Chian School of Medicine, Level 12 Clinical Sciences Building (CSB), 11 Mandalay Road, 308232 Singapore, Email schotirmall@ 123456ntu.edu.sg
                [*]

                These authors contributed equally to this work

                Article
                jaa-10-131
                10.2147/JAA.S130459
                5407445
                28461762
                e03d01b5-80fb-4ba9-bffb-a04c19db27b6
                © 2017 Goh et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Immunology
                atopy,airway,fungus,aspergillus,outcomes,prognosis
                Immunology
                atopy, airway, fungus, aspergillus, outcomes, prognosis

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