PUBLICATION IN CHEST

Sputum as a monitoring tool for patients with severe asthma



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Asthma is a chronic respiratory disease with a high prevalence worldwide and severe asthma is the most costly type of asthma for the health care system. The targeted therapy mepolizumab, an antibody against interleukin 5, was introduced a few years ago and has revolutionized the management of severe eosinophilic asthma. However, not all patients respond in the same way to these treatments, which have a very high cost for society.

The level of eosinophils in the blood seems to be associated with a reduction in exacerbations, but they are not markers that reflect what is happening locally. So the GIGA and CHU team wanted to see if there were markers of response to mepolizumab in the induced sputum (a non-invasive tool for analyzing airway inflammation) of asthma patients before treatment. The investigators defined response to treatment after one year or "remission" as no use of systemic corticosteroids and no exacerbations, good symptomatic control of asthma disease (as assessed by questionnaires), improved lung function (defined as FEV1 increased by 10% or more than 80% of predicted values), and a blood eosinophil count of less than 300/microliter.

Of the 52 patients included in the study, 11 were diagnosed in remission at 1 year. The team then assessed the different populations of inflammatory cells in the induced sputum of these patients and determined inflammatory mediators involved in the patients' eosinophilia in the supernatant by ELISA. 

Patients in remission at 1 year were characterized before therapy by a higher proportion of males, a higher number of sputum eosinophils and a lower number of neutrophils compared to other patients. Regarding mediators, patients in remission had increased levels of TSLP, IL-5, EPX, eotaxin-1 and IgE in sputum compared to patients not reaching remission status. All these markers showed by ROC analysis a significant ability to discriminate patients in remission from other patients. The predictive value of blood eosinophils was not significant in our analysis. These results were confirmed by logistic regression, which showed that male sex, sputum neutrophil level, eotaxin-1, IL-5 and EPX levels were potential predictors of remission one year after the introduction of mepolizumab.

Although these results need to be validated in a larger cohort of patients and in a multicenter study, they show us that for detecting markers of response to mepolizumab, the use of sputum is more suitable than the use of blood. The use of induced sputum is now recommended by the European guidelines for the follow-up of asthma patients and the generalization of its use in clinical routine would thus be positive for the management of patients with severe asthma.

Reference

Sputum Type 2 markers could predict remission in severe asthma treated with anti-Interleukin-5.
Moermans C, Brion C, Bock G, Graff S, Gerday S, Nekoee H, Poulet C, Bricmont N, Henket M, Paulus V, Guissard F, Louis R, Schleich F. 
Chest. 2023 Feb 3:S0012-3692(23)00169-1. doi: 10.1016/j.chest.2023.01.037.

Contact

Catherine Moermans
cmoermans@chuliege.be

Florence Schleich

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