Abstract
Asthma is now recognized as a heterogeneous disease, encompassing different phenotypes driven by distinct pathophysiological mechanisms called endotypes. Common phenotypes of asthma, referred to as eosinophilic asthma, are characterized by the presence of eosinophilia. Eosinophils are usually considered invariant, terminally differentiated effector cells and have become a primary therapeutic target in severe eosinophilic asthma (SEA) and other eosinophil-associated diseases (EADs). Biological treatments that target eosinophils reveal an unexpectedly complex role of eosinophils in asthma, including in SEA, suggesting that “not all eosinophils are equal”. In this review, we address our current understanding of the role of eosinophils in asthma with regard to asthma phenotypes and endotypes. We further address the possibility that different SEA phenotypes may involve differences in eosinophil biology. We discuss how these differences could arise through eosinophil “endotyping”, viz. adaptations of eosinophil function imprinted during their development, or through tissue-induced plasticity, viz. local adaptations of eosinophil function through interaction with their lung tissue niches. In doing so, we also discuss opportunities, technical challenges, and open questions that, if addressed, might provide considerable benefits in guiding the choice of the most efficient precision therapies of SEA and, by extension, other EADs.
Highlights
Asthma is a highly prevalent chronic respiratory disease responsible for a considerable health burden worldwide [1]
“eosinophil-associated” diseases (EADs) characterized by tissue eosinophilia remains a challenge [20,21]. This calls for a deeper understanding of eosinophil biology in eosinophil-associated diseases (EADs), including severe eosinophilic asthma (SEA), by addressing fundamental questions pertaining to the determinants of the pathogenic roles of eosinophils
We further address the possibility that different SEA phenotypes may be driven by differences in eosinophil biology through eosinophil “endotyping” or plasticity
Summary
Asthma is a highly prevalent chronic respiratory disease responsible for a considerable health burden worldwide [1]. Clinical findings with anti-eosinophil therapeutics thereby suggest that eosinophils, even when infiltrating the lungs in significant numbers, may have a variable impact on asthma manifestations, depending on the disease phenotype or endotype These notions are in line with the broader realization that predicting the role of eosinophils and their response to anti-eosinophil therapies in human “eosinophil-associated” diseases (EADs) characterized by tissue eosinophilia remains a challenge [20,21]. This calls for a deeper understanding of eosinophil biology in EADs, including SEA, by addressing fundamental questions pertaining to the determinants of the pathogenic roles of eosinophils. We discuss the technical challenges and open questions that, if addressed, could provide considerable benefits in guiding the choice of the most efficient precision therapies of SEA and, by extension, of other EADs
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