Asthma Exacerbations – The Focus For Treatment Of Severe Asthma?

European Respiratory and Pulmonary Diseases, 2015;1(1):18–9 DOI: http://doi.org/10.17925/ERPD.2015.01.01.18

Abstract:

Asthma exacerbations (worsening of symptoms requiring oral corticosteroid treatment) impair quality of life, interfere with normal activities and can lead to hospital admission or even death. Predicting and preventing exacerbations is therefore an important focus in asthma management. Good patient education and adherence with appropriate treatment are important, as is detection of when this is not achieved. Increasingly it is recognised that uncontrolled airway inflammation in a risk factor for exacerbation, and detection and control of untreated inflammation can reduce exacerbation rates. As specific biologics are available for asthma treatment it will be important to use biomarkers to select those subgroups that will benefit from each type of treatment.
Keywords: Asthma, biologics, adherence, inflammation
Disclosure: Therese M Bidder has no conflicts of interest to declare. Douglas Robinson has consulted for Roche and has received lecture fees from GlaxoSmithKline and Boehringer Ingelheim and support to attend a conference from Meda. No funding was received for the publication of this article.
Received: August 12, 2015 Accepted August 17, 2015
Correspondence: Douglas S Robinson, Severe Asthma Service, Respiratory Medicine, UCLH NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK. E: douglas.robinson@uclh.nhs.uk
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

Asthma is recognised by symptoms of cough, wheeze and breathlessness, which are characteristically variable and can be measured by reversible airflow obstruction. These affect the lives of asthmatics in numerous ways, including disturbed sleep, limitation of activity, the psychosocial impact of chronic disease and side effects (real and feared) of treatment.1 Asthma attacks (periodic worsening of symptoms) can range from mild increases in symptoms controlled by the patient by use of short-acting beta agonists (SABA), to more severe attacks not responding to bronchodilators requiring GP or A&E visits and oral steroid treatment, through to very severe life-threatening attacks. Indeed there are still over 1,000 deaths from asthma in the UK per year.2 A recent review of asthma deaths identified around 40 % of deaths that occurred in patients where the severity of their asthma had not been appreciated either by the patient or their healthcare professionals, and inhaled corticosteroids (ICS) were under-used.2

Conventionally, asthma worsening requiring oral corticosteroid treatment is termed an exacerbation.1 Usually this is associated with nocturnal waking, increased short-acting bronchodilator use and daytime symptoms over several days. What causes exacerbations of asthma? Most data suggest exposure to triggers including allergens, viral or bacterial infections (upper or lower airway), and less often emotional triggers, irritants, occupational agents, of food allergens as part of generalised anaphylaxis.1,3 Data from challenge studies and hospital admission studies suggest that the combination of viral infection on top of existing airway inflammation (often allergic but also non-atopic) is the most frequent cause of exacerbations.3

Who gets exacerbations? The strongest predictor of a future exacerbation of asthma is previous exacerbations, especially where these have required admission to hospital.4 Asthma that is poorly controlled in terms of symptoms has been used to guide increased treatment to avoid exacerbations, but increasingly it is recognised that airway inflammation even without symptoms is a risk factor for exacerbation. Indeed, cluster analysis of clinical features and inflammation markers suggest that there are several subtypes of asthma, including one with high levels of airway inflammation despite low levels of symptoms: these patients were at high risk of exacerbation, as were those with high levels of type 2 inflammation (atopy, total immunoglobulin [Ig]-E and/or eosinophilic inflammation driven by Th2-type cytokine including interleukin [IL]-4, IL-5 and IL-13).5–7 These data raise the possibility of using markers of airway inflammation to guide treatment to optimise asthma control and prevent exacerbations. In a landmark study, Ruth Green and colleagues at Leicester UK showed that adjusting corticosteroid treatment using an algorithm that included sputum eosinophil counts reduced exacerbation by 50 % compared with conventional practice guided by lung function and symptoms alone.8 Similar studies have also suggested a role for monitoring airway inflammation by exhaled nitric oxide (FeNO) and airway hyper-responsiveness.9,10

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Keywords: Asthma, biologics, adherence, inflammation