Abstract
Asthma is a common but complex chronic inflammatory heterogeneous lung disease, punctuated by the pathophysiological phenomenon of airway narrowing, coupled with symptoms of wheezing 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, and consequently, 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 in immunoglobulin 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 strategies for this condition focused on two drug classes: β2 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.
Highlights
BackgroundAsthma is a significant economic burden in the United States (US), based on morbidity, mortality, treatment, and lost productivity due to absenteeism from work and school
Findings from this study reported a rate of 2.4 patients per year experiencing clinically significant exacerbations within the placebo group, with the 75 mg, 250 mg, and 750 mg mepolizumab groups reporting rates of 1.24 (48% reduction, 95% CI 31 - 61%; p < 0.0001), 1.46 (39% reduction, 19 - 54%; p = 0.0005), and 1.15 (52% reduction, 36 - 64%; p < 0.0001) patients per year, respectively
Clinical trials evaluating the efficacy of new biologic agents, such as omalizumab (Xolair®), reslizumab (Cinqair®, US, Cinqaero®, EU), mepolizumab (Nucala®), benralizumab (Faserna®), and dupilumab (Dupixent®), have shown significant relative reductions in exacerbation rates, increases in forced expiratory volume in 1 second (FEV1), and occasionally reductions in inflammatory markers when used in patients with refractory asthma despite maximal usage of available β2-agonists and/or inhaled corticosteroids
Summary
Nathaniel Johnson 1 , Blessy Varughese 2 , Marianne A. 1. Pharmacy, Corpus Christi Medical Center, Corpus Christi, USA 2. Internal Medicine, Texas A&M Health Science Center, Temple, USA 4. Miscellaneous, Corpus Christi Cancer Center, Corpus Christi, USA
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