Specific sputum markers, including higher sputum eosinophils, macrophages, and lymphocyte counts, were associated with remission after interleukin-5 (IL-5)–targeted therapy for patients with severe eosinophilic asthma. The finding was based on data from 52 individuals.
Although IL-5 therapies have been shown to be effective for improving asthma, patients’ responses vary, write Catherine Moermans, PhD, of Liege University, Belgium, and colleagues.
Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments, and reliable biomarkers for predicting treatment response are lacking, they say.
In an observational study published in the journal Chest, the researchers recruited 52 adults with severe asthma who began anti-IL-5 treatment at a single center. The primary outcome was remission of asthma.
Remission was defined as meting all of the following criteria 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire scores lower than 1.5 and/or asthma test greater than 19; forced expiratory volume in 1 second (FEV1) of at least 80% predicted; and/or improvement of FEV1 ≥ 10%, and a blood eosinophil count lower than 300 cells/mL.
Prior to treatment, the researchers measured eosinophil peroxidase (EPX), immunoglobulin E (IgE), IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP) and eotaxin-1 levels in the sputum of each patient.
At follow-up, 11 patients met the criteria for remission. These patients had significantly higher sputum eosinophil counts, sputum macrophage counts, and lymphocyte counts at baseline compared to those not in remission (P = .006, P = .02, and P = .04, respectively). Sputum neutrophil percentage levels were significantly lower in patients whose asthma was in remission compared to those whose asthma was not in remission (P = .007).
At the protein level, remission patients also showed higher baseline levels of sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein compared to patients who did not achieve remission (P = .046, P = .04, P = .002, P = .001, and P = .006, respectively).
Overall, EPX and IL-5 measures showed the best combination of sensitivity and specificity, as well as the best area under the curve, the researchers write.
Patients in remission were significantly more likely to be men (8 of 11 patients), a finding that reflected previous studies, the researchers write. The finding of eosinophilic inflammation associated with stronger response to anti-IL 5 therapy also reflected previous studies, but the current study showed that “with a comparable blood eosinophil level at baseline before biotherapy, the response can be highly variable.”
The study findings were limited by several factors, including the small sample size and the lack of a formal definition of remission. Other research needs include an analysis based on nonresponse or suboptimal response predictors, the researchers note.
The results suggest that sputum type 2 markers are potential predictors of remission after anti-IL-5 treatment in adults with severe eosinophilic asthma, although the results must be validated in a larger, multicenter cohort, they conclude.
The study was supported by GlaxoSmithKline and AstraZeneca. Several co-authors have relationships with these companies. Moermans has disclosed no relevant financial relationships.
Chest. Published online February 2, 2023. Full text
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