Department of Physiology and Medicine, Nabanji Medical Centre, Lusaka, ZambiaFulltext PDF
Asthma is a highly prevalent chronic airway disease, affecting more than 358 million individuals globally, and it is the most common chronic inflammatory respiratory disease in children. Approximately 10% of patients with asthma have severe uncontrolled disease, unresponsive to high-dose inhaled corticosteroids, and long-acting β-agonists. About 55% of patients with severe asthma have the eosinophilic phenotype. A smaller proportion of these patients respond favorably to monoclonal antibodies targeted at T helper type 2 Interleukins (IL), such as mepolizumab, reslizumab, benralizumab and dupilumab. Add-on biologics have been shown to reduce exacerbation rates, and improve asthma control, and lung function. However, the majority of patients with neutrophilic and other phenotypes of asthma do not respond to anti-eosinophilic asthma biologics. Epithelial “alarmin” cytokines, IL-25, IL-33, and Thymic Stromal Lymphopoietin (TSLP) seem attractive to inhibit, because they are upstream initiator cytokines. TSLP plays a key role in the pathophysiology of eosinophilic asthma, neutrophilic asthma, and airway remodeling. Tezepelumab is a first-in-class fully human IgGʎ2 mAb that bind to TSLP, and prevents it to interact with its receptor TSLPR, thus inhibiting multiple downstream immune pathways, and production of cytokines, and chemokines. Tezepelumab has been shown to attenuate the early and late asthmatic responses, reduce exacerbation rates by 71%, and to decrease biomarkers of eosinophilic inflammation (blood eosinophil counts, and Fractional Exhaled Nitric Oxide, [FeNO], IL-5, IL-13). The improvements were observed in all the phenotypes of asthma, and independent of baseline blood eosinophil counts, IgE levels, and FeNO concentration. Thus, targeting alarmin cytokines is a charismatic approach to treat severe uncontrolled asthma.
Severe asthma; “Alarmin cytokines”; Thymic stromal lymphopoietin; Tezepelumab
Syabbalo N. The Role of Alarmin Cytokines in the Pathogenesis and Treatment of Severe Uncontrolled Asthma. Ann Clin Med Res. 2021; 2(1): 1022..