Diagnosis and management of eosinophilic asthma: a US perspective

Abstract

Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma.

Keywords: IL-13; IL-4; Th2; allergy; asthma; eosinophil.

Figure 1

Schematic of eosinophils in airway inflammation and therapeutic targets. In response to allergens, viruses, or mucosal injury, airway epithelial cells produce cytokines, including IL-25, IL-33, and TSLP, which promote differentiation of Th2 cells, as well as activation of mast cells, macrophages, and type 2 innate lymphoid cells. IL-4 and IL-13 produced by Th2 and other cells results in eotaxin production, B-cell IgE class switching, airway hyperresponsiveness, and mucus secretion. IL-5 stimulates bone marrow eosinophil generation, and mediates recruitment, activation, and survival of eosinophils. GM-CSF produced by alveolar macrophages and eosinophils contributes to maturation and survival of eosinophils. Eosinophils release major basic protein, ROS, and enzymes, as well as Th2 cytokines and inflammatory lipid mediators including cysteinyl leukotrienes and prostaglandin D2. These products result in recruitment and activation of immune and structural cells. Further, production of Th2 cytokines and growth factors, such as TGF-β, contribute to features of airway remodeling in chronic asthma. A number of therapeutic targets (depicted by bullseyes) have been identified for eosinophilic asthma and are currently under investigation. Abbreviations: CRTH2, chemoattractant receptor homologous Th2; CystLTs, cysteinyl leukotrienes; GM-CSF, granulocyte macrophage-colony stimulating factor; IL, interleukin; ILC2, innate lymphoid cell type 2; IgE, immunoglobulin E; PGD2, prostaglandin D2; ROS, reactive oxygen species; Siglec-8, sialic acid binding Ig-like lectin 8; Th2, T-helper type 2; TGF-β, transforming growth factor beta; TSLP, thymic stromal lymphoprotein.