Exacerbation frequency linked to lung function decline in severe eosinophilic asthma
medwireNews: Repeated exacerbations in patients with severe eosinophilic asthma may be associated with accelerated deterioration of lung function, study findings show.
The researchers found a direct relationship between the number of exacerbations experienced by such patients and a decline in lung function in a combined post-hoc analysis of the DREAM and MENSA studies.
Indeed, the team estimated from a linear regression model that a patient’s forced expiratory volume in 1 second (FEV1) decreased by 50 mL (p<0.001) for every additional exacerbation. This was after accounting for multiple factors, including exacerbation category, treatment, and baseline lung function.
“Preventing exacerbations should be one of the most important treatment goals and therefore disease management approaches, including step-down of controller therapy, should be carefully considered in patients with severe disease who are prone to exacerbations,” say Hector Ortega (Respiratory US Medical Affairs, GlaxoSmithKline, La Jolla, California) and colleagues.
The DREAM and MENSA studies involved a total of 1192 patients with severe asthma, aged an average of 49 years, who were treated with mepolizumab or placebo over a period of 12 and 8 months, respectively. The patients, the majority of whom were nonsmokers, had an average disease duration of 20 years and despite receiving current therapy had experienced exacerbations in the 12 months prior to the start of the trials, and had direct or indirect evidence of eosinophilic inflammation.
Analysis of the two studies combined showed that the 572 patients who did not experience exacerbations had a 143 mL improvement in postbronchodilator FEV1, from a baseline value of 1848 mL.
This compared with an FEV1 decrease of 77 mL for the 90 patients who experienced three or more exacerbations.
Exacerbations were defined as disease worsening requiring the use of systemic corticosteroids for 3 or more days and/or hospitalization, or for the 28% of patients on maintenance oral corticosteroids (OCS), a doubling of the OCS dose for at least 3 days and/or hospitalization.
Similar results were seen for the two studies individually and for changes in postbronchodilator forced vital capacity, the team reports in The Journal of Allergy and Clinical Immunology: In Practice.
They suggest that exacerbations and declines in FEV1 may both be manifestations of a more severe disease phenotype, noting that affected patients tended to have poorer lung function at baseline, a more pronounced history of smoking, a higher use of maintenance OCS, and a higher level of uncontrolled disease.
The researchers conducted an exploratory analysis on the effects of treatment, which improved FEV1 relative to placebo in those without exacerbations but not in those experiencing three or more.
They suggest that in these patients “other noneosinophilic mechanisms (eg, noneosinophilic type 2 inflammation) are involved in the pathogenesis of these exacerbations.”
By Lucy Piper
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group