Are specialized pro-resolving mediators promising therapeutic agents for severe bronchial asthma?

In Japan, although the number of patients with asthma has increased, the number of patients who die from asthma has decreased (1.2 per 100,000 patients in 2015) (1). Currently, although the majority of asthma patients can be effectively treated with available medications, such as inhaled corticosteroids (ICS) or ICS/long-acting β2 agonists (ICS/LABA), options remain to be established for difficult-to-treat asthma (severe asthma), which can be considered an unmet need. Patients with severe asthma (presumably less than 10% of all asthma cases) who experience exacerbations consume considerable healthcare resources (2). According to data from a U.S. study by Chastek et al., in 2013, the total adjusted asthma-related costs among patients with severe asthma were $5,112 per year, or 2.9-fold higher than that among patients with persistent asthma (3). Adjusted asthma medication costs were $4,020 per year, which was triple the asthma medication costs for patients with persistent asthma. Much remains unclear regarding the optimal approach for the management of these patients and the underlying mechanisms driving this disease. Asthma is characterized by airway hyperresponsiveness and chronic airway inflammation. Numerous inflammatory cells, including eosinophils and lymphocytes, infiltrate the peribronchial tissue in patients with asthma. Long-standing asthma induces airway remodeling, leading to intractable asthma. Asthma patients are characterized by widely variable clinical pictures; asthma is thus often recognized as a syndrome and is classified into several phenotypes. Recent progress in genetics and molecular biology has led to the etiological and/or pathogenetic classification of the condition into endotypes (4). Recent studies have uncovered the actions and clinical potential of specialized pro-resolving mediators (SPMs), namely, the superfamily of pro-resolving mediators that includes the resolvin (E-series, D-series, and DPA-derived), protectin, and maresin families, as well as arachidonic-acid-derived lipoxins (5). Resolvin E1 (RvE1) is an anti-inflammatory lipid mediator derived from the omega-3 fatty acid, eicosapentaenoic acid (EPA), and has been recently shown to be involved in resolving inflammation (6). Although little is known about the actions of RvE1 in the resolution of asthma-induced inflammation, recent studies using a mouse model have shown the potential of RvE1 in treating asthma (7-9). In this editorial, we assess SPMs as possible candidates for asthma (particularly severe asthma) treatment, and review the current understanding of their