Specific Therapy for T2 Asthma

Abstract

Asthma is a disease with high incidence and prevalence, and its severe form accounts for approximately 10% of asthmatics. Over the last decade, the increasing knowledge of the mechanisms underlying the disease allowed the development of biological drugs capable of sufficiently controlling symptoms and reducing the use of systemic steroids. The best-known mechanisms are those pertaining to type 2 inflammation, for which drugs were developed and studied. Those biological treatments affect crucial points of bronchial inflammation. Among the mechanisms explored, there were IgE (Omalizumab), interleukin 5 (Mepolizumab and Reslizumab), interleukin 5 receptor alpha (Benralizumab) and interleukin 4/13 receptor (Dupilumab). Under investigation and expected to be soon commercialized is the monoclonal antibody blocking the thymic stromal lymphopoietin (Tezepelumab). Seemingly under study and promising, are anti-interleukin-33 (itepekimab) and anti-suppressor of tumorigenicity-2 (astegolimab). With this study, we want to provide an overview of these drugs, paying particular attention to their mechanism of action, the main endpoints reached in clinical trials, the main results obtained in real life and some unclear points regarding their usage.

The efficacy and safety of tezepelumab in the treatment of uncontrolled asthma: A systematic review and meta-analysis of randomized controlled trials

“…[3,4] Over the last decade, increased knowledge of the mechanisms underlying the pathogenesis of asthma has facilitated the development of modern biological therapy for the treatment of severe asthma. [5,6] Modern biological therapy targets the pro-inflammatory cytokines or mediators, including IL-5, IL-4, IL-13/IL4, IgE, and thymic stromal lymphopoietin (TSLP). [7][8][9] TSLP is an epithelial cell-derived cytokine in the airways, belonging to the group of alarmins, that plays a central role in the pathogenesis of asthma by activating and maintaining downstream inflammatory processes in response to multiple triggers, including viruses, bacteria, fungi, allergens, pollutants, smoke, other airborne irritants, and physical injury.…”

Mulberroside F improves airway hyperresponsiveness and inflammation in asthmatic mice

“…7 Excessive IL-13 secretion by airway Th2 cells stimulates AHR deterioration and increases airway mucus hypersecretion. 8 Therefore, in the respiratory system, reducing Th2-cell activation and increasing Th1-cell activation can potentially improve asthma attacks and relieve asthma symptoms.…”

“…12 The second category of asthma drugs is used to relieve and improve asthma attacks, and mainly comprises bronchodilators, including short-acting beta-agonists and anticholinergics. 8 Long-term use of oral or injectable steroids will produce a variety of side effects, and suppress immune system function, reducing the activities of Th1 cells and Th2 cells. 11 In recent years, many studies have shown that some natural products can regulate the activation of Th1 cells and Th2 cells, and improve the development of asthma symptoms.…”

“…IL‐4 can induce the activation of B cells into IgE‐secreting plasma cells, which enhances the activation of mast cells and eosinophils 7 . Excessive IL‐13 secretion by airway Th2 cells stimulates AHR deterioration and increases airway mucus hypersecretion 8 . Therefore, in the respiratory system, reducing Th2‐cell activation and increasing Th1‐cell activation can potentially improve asthma attacks and relieve asthma symptoms.…”

“…Clinical drugs include oral and inhaled steroids, leukotriene receptor antagonists, and long‐acting beta 2 agonists 12 . The second category of asthma drugs is used to relieve and improve asthma attacks, and mainly comprises bronchodilators, including short‐acting beta‐agonists and anticholinergics 8 . Long‐term use of oral or injectable steroids will produce a variety of side effects, and suppress immune system function, reducing the activities of Th1 cells and Th2 cells 11 .…”