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      Acute Severe Asthma in Adolescent and Adult Patients: Current Perspectives on Assessment and Management

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          Abstract

          Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.

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          T-helper type 2-driven inflammation defines major subphenotypes of asthma.

          Prescott G Woodruff, Barmak Modrek, David F Choy … (2009)
          T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous. To determine whether this clinical heterogeneity reflects heterogeneity in underlying molecular mechanisms related to Th2 inflammation. Using microarray and polymerase chain reaction analyses of airway epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy control subjects, we classified subjects with asthma based on high or low expression of IL-13-inducible genes. We then validated this classification and investigated its clinical implications through analyses of cytokine expression in bronchial biopsies, markers of inflammation and remodeling, responsiveness to inhaled corticosteroids, and reproducibility on repeat examination. Gene expression analyses identified two evenly sized and distinct subgroups, "Th2-high" and "Th2-low" asthma (the latter indistinguishable from control subjects). These subgroups differed significantly in expression of IL-5 and IL-13 in bronchial biopsies and in airway hyperresponsiveness, serum IgE, blood and airway eosinophilia, subepithelial fibrosis, and airway mucin gene expression (all P < 0.03). The lung function improvements expected with inhaled corticosteroids were restricted to Th2-high asthma, and Th2 markers were reproducible on repeat evaluation. Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation. Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma. Furthermore, current models do not adequately explain non-Th2-driven asthma, which represents a significant proportion of patients and responds poorly to current therapies.
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            Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

            Arnav Agarwal, Claus Bachert, Sinthia Z Bosnic-Anticevich … (2018)
            Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update.
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              Asthma

              Alberto Papi, Christopher Brightling, Søren Pedersen … (2018)
              Asthma-one of the most common chronic, non-communicable diseases in children and adults-is characterised by variable respiratory symptoms and variable airflow limitation. Asthma is a consequence of complex gene-environment interactions, with heterogeneity in clinical presentation and the type and intensity of airway inflammation and remodelling. The goal of asthma treatment is to achieve good asthma control-ie, to minimise symptom burden and risk of exacerbations. Anti-inflammatory and bronchodilator treatments are the mainstay of asthma therapy and are used in a stepwise approach. Pharmacological treatment is based on a cycle of assessment and re-evaluation of symptom control, risk factors, comorbidities, side-effects, and patient satisfaction by means of shared decisions. Asthma is classed as severe when requiring high-intensity treatment to keep it under control, or if it remains uncontrolled despite treatment. New biological therapies for treatment of severe asthma, together with developments in biomarkers, present opportunities for phenotype-specific interventions and realisation of more personalised treatment. In this Seminar, we provide a clinically focused overview of asthma, including epidemiology, pathophysiology, clinical diagnosis, asthma phenotypes, severe asthma, acute exacerbations, and clinical management of disease in adults and children older than 5 years. Emerging therapies, controversies, and uncertainties in asthma management are also discussed.
              Article 0 comments Cited 516 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Clin Med
                Journal ID (iso-abbrev): J Clin Med
                Journal ID (publisher-id): jcm
                Title: Journal of Clinical Medicine
                Publisher: MDPI
                ISSN (Electronic): 2077-0383
                Publication date (Electronic): 22 August 2019
                Publication date Collection: September 2019
                Volume: 8
                Issue: 9
                Electronic Location Identifier: 1283
                Affiliations
                [1 ]ICU, 1st Department of Pulmonary Medicine, “Sotiria” Hospital, Athens School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
                [2 ]1st ICU, Evangelismos Hospital, Athens School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
                [3 ]Respiratory Outpatient Clinic, 71305 Heraklion, Greece
                Author notes
                [* ]Correspondence: nikrovina@ 123456med.uoa.gr
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-0138-5582
                Article
                Publisher ID: jcm-08-01283
                DOI: 10.3390/jcm8091283
                PMC ID: 6780340
                PubMed ID: 31443563
                SO-VID: 9b0e01dd-e966-446a-9126-96da5b87a197
                Copyright © © 2019 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 06 July 2019
                Date accepted : 19 August 2019
                Categories
                Subject: Review

                Keywords: acute severe asthma exacerbation,near fatal asthma
                Data availability:
                Keywords: acute severe asthma exacerbation, near fatal asthma

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