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Pathophysiological mechanisms of asthma

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Title: Pathophysiological mechanisms of asthma
Authors: Bush, A
Item Type: Journal Article
Abstract: The recent Lancet commission has highlighted that "asthma" should be used to describe a clinical syndrome of wheeze, breathlessness, chest tightness, and sometimes cough. The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors. The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease). It is also important not to over-treat the untreatable, such as fixed airflow obstruction. These can all be determined using simple, non-invasive tests such as spirometry before and after acute administration of a bronchodilator (reversible airflow obstruction); peripheral blood eosinophil count, induced sputum, exhaled nitric oxide (airway eosinophilia); and sputum or cough swab culture (bacterial infection). Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma. Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals. Advances in -omics technology allow delineation of pathways, which will be particularly important in TH2 low eosinophilic asthma, and also pauci-inflammatory disease. It is very important to appreciate the difficulties of cluster analysis; a patient may have eosinophilic airway disease because of a steroid resistant endotype, because of non-adherence to basic treatment, and a surge in environmental allergen burden. Sophisticated -omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice. However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.
Issue Date: 19-Mar-2019
Date of Acceptance: 19-Feb-2019
URI: http://hdl.handle.net/10044/1/68697
DOI: https://dx.doi.org/10.3389/fped.2019.00068
ISSN: 2296-2360
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Pediatrics
Volume: 7
Copyright Statement: © 2019 Bush. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Asthma UK
Funder's Grant Number: R43065
Keywords: airway inflammation
asthma phenotype
biomarker
bronchial biopsy
bronchial brushings
endotype
induced sputum
transcriptomics
Publication Status: Published
Conference Place: Switzerland
Article Number: ARTN 68
Appears in Collections:National Heart and Lung Institute



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