Weighted Breaths: Exploring Biologic and Non-Biologic Therapies for Co-Existing Asthma and Obesity

Abstract

Purpose of review: To discuss the effectiveness of biologics, some of which comprise the newest class of asthma controller medications, and non-biologics in the treatment of asthma co-existing with obesity.

Recent findings: Our review of recent preliminary and published data from clinical trials revealed that obese asthmatics respond favorably to dupilumab, mepolizumab, omalizumab, and tezepelumab, which are biologics currently indicated as add-on maintenance therapy for severe asthma. Furthermore, clinical trials are ongoing to assess the efficacy of non-biologics in the treatment of obese asthma, including a glucagon-like peptide-1 receptor agonist, a Janus kinase inhibitor, and probiotics. Although many biologics presently indicated as add-on maintenance therapy for severe asthma exhibit efficacy in obese asthmatics, other phenotypes of asthma co-existing with obesity may be refractory to these medications. Thus, to improve quality of life and asthma control, it is imperative to identify therapeutic options for all existing phenotypes of obese asthma.

Keywords: Asthma; Biologic; Clinical trial; Forced expiratory volume in one second; Obesity; Probiotic.

Fig. 1

Exposure of the luminal surface of the respiratory epithelium to injurious stimuli, including air pollutants, microbes, or enzymatically-active antigens leads to the release of alarmins [interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP)] from epithelial cells and the initiation of multiple inflammatory cascades, which are important in the pathogenesis of asthma. By engaging their respective receptors described in the body of this review, these alarmins stimulate the release of T-helper cell type-2 (T_H2) cytokines (IL-4, IL-5, and IL-13) from group 2 innate lymphoid cells (ILC2) and T_H2 cells. Once released into the extracellular space, these T_H2 cytokines subsequently bind their corresponding receptor subunits, which are part of a heterodimeric receptor complex located on the surface of various hematopoietic and non-hematopoietic cells. Immunoglobulin (Ig) E, which is released from B cells in response to IL-4 and IL-13, binds its high-affinity receptor, FcεRI, on the surface of basophils and mast cells. Following antigen cross-linking of IgE-FcεRI complexes on the surface of basophils and mast cells, deleterious mediators of allergic inflammation are secreted into the extracellular milieu. Activated dendritic cells and macrophages secrete IL-23, which stimulates the release of IL-17A from T_H17 cells. IL-17A, in turn, initiates the release of chemokine (C-X-C motif) ligand 1 (CXCL1), a chemotactic cytokine for neutrophils, from epithelial cells [99, 152], which leads to neutrophil migration to the air spaces. Finally, tumor necrosis factor (TNF)-α, which is increased in asthmatic airways, causes eosinophil and neutrophil chemotaxis [104]. The name of each biologic discussed in this review has been placed next to its molecular target, and those biologics in bold italicized red font are currently approved by the United States Food and Drug Administration as add-on maintenance therapy for severe asthma. Please note that this figure does not comprehensively illustrate (1) cytokine release from or (2) the presence of cytokine receptors on each cell type shown in this figure. This figure was created using BioRender (Toronto, Ontario, Canada)