Type 2 inflammation in asthma and other airway diseases

Abstract

Chronic inflammatory airway diseases, including asthma, chronic rhinosinusitis, eosinophilic COPD and allergic rhinitis are a global health concern. Despite the coexistence of these diseases and their common pathophysiology, they are often managed independently, resulting in poor asthma control, continued symptoms and poor quality of life. Understanding disease pathophysiology is important for best treatment practice, reduced disease burden and improved patient outcomes.The pathophysiology of type 2 inflammation is driven by both the innate immune system triggered by pollutants, viral or fungal infections involving type 2 innate lymphoid cells (ILC2) and the adaptive immune system, triggered by contact with an allergen involving type 2 T-helper (Th2) cells. Both ILC2 and Th2 cells produce the type-2 cytokines (interleukin (IL)-4, IL-5 and IL-13), each with several roles in the inflammation cascade. IL-4 and IL-13 cause B-cell class switching and IgE production, release of pro-inflammatory mediators, barrier disruption and tissue remodelling. In addition, IL-13 causes goblet-cell hyperplasia and mucus production. All three interleukins are involved in trafficking eosinophils to tissues, producing clinical symptoms characteristic of chronic inflammatory airway diseases.Asthma is a heterogenous disease; therefore, identification of biomarkers and early targeted treatment is critical for patients inadequately managed by inhaled corticosteroids and long-acting β-agonists alone. The Global Initiative for Asthma guidelines recommend add-on biological (anti IgE, IL-5/5R, IL-4R) treatments for those not responding to standard of care. Targeted therapies, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab, were developed on current understanding of the pathophysiology of type 2 inflammation. These therapies offer hope for improved management of type 2 inflammatory airway diseases.

Triple-tyrosine kinase inhibition by BIBF1000 attenuates airway and pulmonary arterial remodeling following chronic allergen challenges in mice

“…In the present study, treatment with BIBF1000 reduced allergen-induced inflammatory cell infiltration and cytokine expression (TNF-α, IL-1β) in the lung. Type 2 inflammation plays central roles in developing allergic asthma [ 27 ]. Each of the type-2 cytokines (interleukin (IL)-4, IL-5, and IL-13) exerts several roles in the airway inflammation cascade [ 27 – 30 ].…”

Role of Ezrin in Asthma-Related Airway Inflammation and Remodeling

“…As is known to all, the pathological mechanism of asthma is type 2 airway inflammation involving type 2 innate lymphoid cells (ILC2) and type 2 T-helper (Th2) cells. Allergens are the main triggers [ 91 ]. Airway epithelial cells are the first line of defense, releasing alarmins interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), ezrin, and initiating the immune cascade, leading to a release of interleukin-4 (IL-4) and interleukin-13 (IL-13) [ 92 ].…”

“…Airway epithelial cells are the first line of defense, releasing alarmins interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), ezrin, and initiating the immune cascade, leading to a release of interleukin-4 (IL-4) and interleukin-13 (IL-13) [ 92 ]. IL-4 and IL-13 are called prototypical type 2 cytokines, which can cause immunoglobulin E (IgE) production and eosinophils can transport to the airways [ 91 ], thus triggering an asthma attacks. Furthermore, IL-13 induces the phosphorylation of Janus Kinase 2 (JAK2), followed by increased nuclear translocation of phosphorylated signal transducers and activators of transcription 6 (STAT6), leading to downregulated ezrin expression, which is related to IL-13-induced epithelial injury [ 93 ].…”

Clinical Remission of Asthma and Allergic Rhinitis - in a Longitudinal Population Study

“…3,4 Both disorders are often associated with IgE sensitization and type-2 inflammation. 5 Although asthma and allergic rhinitis are chronic diseases, some patients experience periods of remission. Clinical remission of asthma occurred in 20-43% of patients followed during 10-30 years, [6][7][8][9] while remission of allergic rhinitis has occurred in up to 25% of the patients in previous studies.…”