Can Inhaled Corticosteroids Prevent Asthma Exacerbations?

Dhananjay Desai; Salman Siddiqui; Christopher Brightling

Disclosures

Curr Opin Pulm Med. 2011;17(1):16-22. 

In This Article

Asthma Exacerbations: Defining the Problem

Asthma exacerbations are an acute persistent deterioration in control. Exacerbations can be defined in terms of patient-reported outcomes, lung function or the clinical consequences of this loss of control in terms of healthcare utilization such as hospital admissions and courses of systemic corticosteroids. Asthma control is defined as the extent to which the various manifestations of asthma are reduced or removed by treatment.[3] Control is typically measured using parameters of lung function, and symptoms and can be assessed using validated tools such as the Juniper Asthma Control Questionnaire (ACQ).[6] Poor control is the persistence of symptoms often in spite of therapy and differs from an exacerbation whereby there is an acute worsening. Moreover, in contrast to poor control peak flow variability is not increased during exacerbations and there is typically loss of beta-agonist response.[7] However, the use of patient-reported outcomes does present challenges in distinguishing between poor control and exacerbations. Importantly, both poor control and exacerbations themselves are predictors of 'future risk' of exacerbations.[8]

Over the last decade there has been considerable progress to improve the definition of exacerbations towards greater uniformity, which is critical to interpret clinical research. Among the first studies that sought to address this was the 'Formoterol and Corticosteroid Establishing Therapy' (FACET)[9] study, which incorporated both subjective (symptoms) and objective (peak flow) definitions. That is the first trial that aimed to standardize definition of asthma exacerbations and effect of ICSs on many clinical aspects of asthma control. However, importantly, a reduction in peak flow often went unnoticed by both patients and physicians as it did not translate into symptoms and therefore was only uncovered after retrospective data analysis.[10] Most recently, an American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus report aiming to standardize definitions of exacerbations for clinical trials has defined severe exacerbations as events that usually require hospitalization/emergency room visits and/or the use of systemic corticosteroids for at least 3 days.[11] In contrast, a moderate exacerbation has been defined as an event that leads to an increase in existing asthma therapy not including systemic corticosteroids or a change in asthma symptoms/lung function over a period of at least 2 days, not warranting hospital admission.[11]

These standardized definitions will allow for comparisons between studies and will inform study design and powering. However, the major shortcoming of this focus upon healthcare utilization to define exacerbations is the potential for bias towards patients who have a greater tendency to self-report symptoms and have access to healthcare. It also does not consider the underlying pathogenesis of the exacerbation event. Therefore future definitions that embrace the aetiology, pathogenesis and clinical consequences of an exacerbation may be preferable and necessary to direct clinical care.

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