Poor outcomes and asthma hospitalisations: How important is asthma severity and how do we measure it?

Asthma hospitalisations may be largely preventable but are often associated with serious adverse outcomes, including death or respiratory failure necessitating mechanical ventilation. Risk stratification of patients at highest risk of hospitalisation and poor outcomes is important for both epidemiologic research and for the identification of patients for targeted intervention. Intuitively, the severity of a patient’s underlying asthma is a factor that could be used in such risk stratification. However, the importance of asthma severity in determining asthma outcomes, such as death, has not been conclusively determined. Indeed, at least in children, the risk of asthma death may even be independent of the underlying severity of disease. Part of the uncertainty stems from the fact that there is no agreed upon ‘‘gold standard’’ for categorising asthma severity. In the United States, the National Asthma Education and Prevention Program (NAEPP) Expert Panel III recommends the use of asthma symptoms, limitation of activity, lung function, and requirement for short-acting b-agonists. Consistent with this recommendation, FEV1 and peak flow do appear to be predictive of asthma death. For example, one study found that for every 25% decline in FEV1 below that predicted, the risk of all-cause mortality in asthma approximately doubled. Even in the absence of spirometry information, however, an asthma severity score, determined by dyspnoea symptoms, asthma medication usage (including frequency of prior systemic corticosteroid usage), and prior asthma hospitalisations and intubations, is prospectively associated with mortality in patients who have previously been hospitalised with asthma. Nonetheless, although the NAEPP acknowledges the importance of short-acting b-agonist frequency in measuring asthma severity, it concludes that, for treatment purposes, the prior requirement for oral systemic corticosteroids should not be used to distinguish asthma severity in patients who otherwise meet criteria for persistent asthma based on the factors mentioned above. In the present issue of Allergologia et Immunopathologia, the EAGLE investigators report the results of a study comparing the characteristics of hospitalised severe asthma patients to the characteristics of hospitalised patients with less severe asthma, retrospectively utilising a cohort of patients from Spain and Latin America. The major characteristics examined were age, gender, pre-hospitalisation FEV1, atopic status, prevalence of prior hospitalisation, and change in FEV1 or peak flow associated with the index of hospitalisation. Of note, the authors categorised patients as having severe asthma based on their treatment regimen. In particular, patients were categorised as having ‘‘severe asthma’’ if their outpatient therapeutic regimen at the time of hospitalisation was the equivalent of Steps 4 or 5 of the Global Initiative for Asthma (GINA) management and prevention guidelines. Based on the GINA guidelines, for the majority of patients in the time periods under consideration, this would generally correspond to the prescription of at least medium-dose inhaled corticosteroids (Step 4) or systemic corticosteroids (Step 5). The study found that patients admitted to the hospital for asthma exacerbations, who had been placed on Steps 4 or 5 outpatient asthma therapies, were at greater risk of requiring mechanical ventilation, on average required longer hospital stays, and were at greater risk of in-hospital allcause mortality as compared with patients on less intensive outpatient therapies. Although the causal relationship between asthma therapies and outcomes was not assessed in this study, it appears unlikely that asthma therapies were responsible for poor outcomes. Indeed, prior research has demonstrated that the failure to prescribe inhaled corticosteroids, upon discharge from an asthma hospitalisation, is associated with increased risk of subsequent mortality. Therefore, more intensive outpatient asthma therapy is an indicator of more severe asthma, and patients on higher doses of inhaled corticosteroids or systemic corticosteroids are likely to have worse morbidity and mortality outcomes, associated with an asthma hospitalisation, than patients on less intensive therapies because they have more severe asthma. In the current study, the in-hospital FEV1 (or peak flow) among patients with severe asthma was lower than among those with less severe asthma. Of note, however, the amount by which FEV1 declined, as compared with pre-hospitalisation ARTICLE IN PRESS