Eosinophil subtypes in asthmatic patients treated with mepolizumab, omalizumab and dupilumab

Two eosinophil subtypes, resident (rEos) and inflammatory (iEos), have been identified, first in mice and later in asthmatic patients. The effects of different biologics on these subpopulations remain unclear. This study evaluates the impact of mepolizumab, dupilumab and omalizumab on the proportion of rEos and iEos in asthmatic patients over 52 weeks.

We conducted a prospective study with 1-year follow-up of 82 patients with severe asthma: 28 were not receiving biologic therapy, 24 were treated with mepolizumab, 20 with dupilumab and 10 with omalizumab. Clinical variables included Asthma Control Test, exacerbation history and lung function. Blood samples underwent flow cytometry to classify eosinophils into (Siglec-8⁺CD62L^lo+CD11b^hi) for iEos and (Siglec-8⁺CD62L^hi+CD11b^lo) for rEos. Interleukin (IL)-5 receptor expression and levels of free IL-5 and eotaxin I/II were also assessed.

Mepolizumab significantly reduced eosinophil concentrations compared with other groups (p<0.001). Patients without biologics had a high iEos proportion (23.4±13.7%), comparable with the omalizumab and dupilumab groups (31.3±12.8% and 27.6±10.1%). Mepolizumab-treated patients had markedly lower iEos proportions (2.4±4.0%, p<0.001). Stratifying iEos by quartiles, there was a significant relation between the highest quartile and lower FEV₁ % predicted (-15.6%, 95% CI 5.5-25.7) and a higher exacerbation rate (OR 2.24, 95% CI 1.02-4.91). After 1 year, iEos proportions correlated with higher systemic steroid use in mepolizumab and dupilumab groups. At 1-year follow-up, IL-5 levels were higher in omalizumab and dupilumab groups but lower in mepolizumab (p<0.01).

Biological therapies differentially affect eosinophil subtypes, correlating with lung function and steroid use. Monitoring iEos and rEos may serve as a marker of asthma control.