A Review of Respiratory Biologic Agents in Severe Asthma.
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abstract
Asthma is a common but complex chronic inflammatory heterogeneous lung disease, punctuated bythe pathophysiological phenomenon ofairway narrowing, coupled withsymptoms ofwheezing and coughing. The mechanism behind these symptoms is due to migration of eosinophils, mast cells, and CD4 T-helper cells into the submucosa of the airway, leading to hyperresponsiveness to common allergens, microorganisms, oxidants, pollutants, andconsequently, airway remodeling. There is evidence that this migration is mediated by inflammatory cytokines derived from T-helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2), such as interleukins 4, 5, and 13. These cytokines lead to an increase inimmunoglobulin E (IgE) production. Additionally, thymic stromal lymphopoietin (TSLP) released from airway epithelium can activate Th2 cells, innate lymphoid cells, or both. All have proven significant in the promotion of chronic airway inflammation and remodeling. In the past,most treatment strategiesfor this condition focused on two drug classes: 2 agonists (both short- and long-acting), and inhaled corticosteroids. Other treatments have included maintenance drugs, such as leukotriene receptor antagonists, long-acting anticholinergic agents, and theophylline. None of these, however, directly impact the interleukin or IgE pathways in a meaningful manner. Clinical trials of novel agents impacting these pathways have demonstrated efficacy and improved outcomes in asthma exacerbations, control, and forced expiratory volume in 1 second (FEV1) in patients with severe asthma. Future treatments in asthma will focus on drugs that target these aforementioned cytokines.
