Asthma

Two distinct types of asthma exacerbation in patients on mepolizumab


Exacerbations in patients with severe asthma who are being treated with mepolizumab can be categorised into two distinct types, UK researchers have reported.

The results suggest that a more precision medicine approach may be useful in treating acute wheezing episodes in this group of patients.

Data from a study at four specialist severe asthma centres showed that patients with non-eosinophilic events are driven by infection and present with low fractional exhaled nitric oxide (FeNO) and high C-reactive protein concentration.

By contrast patients with high eosinophil counts when they had exacerbations also have high FeNO.

The researchers said that the two distinct entities shown in their analysis of 140 participants with severe eosinophilic asthma eligible for mepolizumab therapy could largely be differentiated using FeNO.

It challenges the routine use of oral corticosteroids for the treatment of all asthma exacerbation events in patients taking mepolizumab, they concluded in The Lancet Respiratory Medicinee.

And raises questions about switching of biological therapies for treatment failure without first profiling the inflammatory phenotype of ongoing asthma exacerbations.

The MEX study analysis also shows that there are clinically available tools that can be used to ‘profile’ exacerbations in patients treated with mepolizumab, the researchers added.

Over the 18-month study there were 172 exacerbations with 96 assessed before rescue treatment was started.

Patients who had exacerbations had a higher exacerbation rate and more emergency department attendances in the year before beginning treatment with mepolizumab, the researchers reported.

When comparing exacerbations with a high sputum eosinophil count (≥2%) with those with a low sputum eosinophil count (<2%), they had high FeNO, lower FEV1 to forced vital capacity ratios and higher blood eosinophil counts.

Exacerbations with a low sputum eosinophil count had higher C-reactive protein concentrations, higher sputum neutrophil counts and were more likely to be treated with antibiotics.

In all, FeNO less than 20 or higher than 50 ppb was the most useful discriminator of inflammatory type exacerbations, they concluded.

The goal of the research was to look in more detail at the inflammatory and physiological characteristics of exacerbation events in patients treated with mepolizumab given that in general those patients report fewer symptoms, have a lower sputum eosinophil count, and smaller fall in peak expiratory flow, the researchers said.

Study co-author Professor Ian Pavord, professor of respiratory medicine at the University of Oxford, said: “This heterogeneity in triggers and inflammatory mechanism suggests that a precision medicine, biomarker directed approach might result in more effective and economical treatment of acute wheezing illnesses. More studies are needed to investigate this.”

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