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Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations

Tricia McKeever, Kevin Mortimer, Andrew Wilson, et al.
N Engl J Med 2018;378:902–10
doi: 10.1056/NEJMoa1714257

Acute exacerbations of asthma can be alarming for patients, cause illness, can be fatal, and account for a large proportion of costs related to asthma. While asthma control has been shown to improve in patients with self-management plans, a previously recommended step of doubling the dose of inhaled glucocorticoids has been shown to be ineffective at preventing acute exacerbations. In 2016 a Cochrane review concluded that it is unlikely that increasing the dose of inhaled glucocorticoids reduces the odds of systemic glucocorticoid use or hospitalisation or shortens recovery time.

A randomised, unblinded, pragmatic, multicentre trial comprising 1,922 participants (adults and adolescents) was commissioned by the Heath Technology Assessment Programme of the National Institute for Health Research in the UK. McKeever, Mortimer and colleagues tested the hypothesis that, when asthma control started to deteriorate, a temporary increase in the dose of inhaled glucocorticoids by a factor of four would reduce the use of oral glucocorticoids for asthma compared with a plan that did not include this step. The quadrupling group showed (1) fewer severe asthma exacerbations (2) a higher frequency of treatment-related adverse events, such as oral candidiasis, but (3) no significant between-group differences in the incidence of pneumonia. Given the potential benefit with regard to preventing exacerbations and considering the established toxicity associated with inhaled glucocorticoids as well as the biases that may have been introduced in this study by the absence of blinding, the authors urge that individual practitioners, patients and guideline committees consider whether the magnitude of the reduction achieved is clinically meaningful.

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