Asthma exacerbations: the Achilles heel of asthma care. Issue 12 (December 2022)

• Record Type: Journal Article
• Authors: McIntyre, Amanda; Busse, William W.
• Is Part Of: Trends in molecular medicine. Volume 28:Issue 12(2022)
• Page Start: 1112
• Page End: 1127
• Publication Date: 2022-12
• Subjects: asthma exacerbations -- airway inflammation -- T2 inflammation -- rhinovirus infections -- biologics; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2022.09.001
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : Asthma exacerbations significantly impact millions of patients worldwide to pose large disease burdens on affected patients, families, and health-care systems. Although numerous environmental factors cause asthma exacerbations, viral respiratory infections are the principal triggers. Advances in the pathophysiology of asthma have elucidated dysregulated protective immune responses and upregulated inflammation that create susceptibility and risks for exacerbation. Biologics for the treatment of severe asthma reduce rates of exacerbations and identify specific pathways of inflammation that contribute to altered pathophysiology, novel therapeutic targets, and informative biomarkers. Major steps to prevent exacerbations include the identification of molecular pathways whose blockage will prevent asthma attacks safely, predictably, and effectively. Highlights: Asthma affects 10% of the world's population but is a heterogeneous disease in terms of clinical manifestations and underlying molecular control of airway inflammation. In most asthma patients, a type 2 (T2) inflammatory pattern of inflammation drives clinical characteristics and susceptibility to exacerbations and forms the target for therapy. Asthma causes major health-care burdens for many patients and exacerbations are principal contributors to these disease burdens. The majority of asthma exacerbations are provoked by viral respiratory infections, with the common cold virus, rhinovirus (RV), the major infectious cause. RVs infect the airway epithelium to activate inflammation and increase the eosinophilic response to contribute to greater airflow obstruction and symptoms. Although inhaled corticosteroids are the primary treatment in asthma, they do not always prevent exacerbations in patients, particularly with severe disease. The development of monoclonal biologics directed towards components of T2 inflammation have begun to revolutionize the treatment of severe asthma and more effectively prevent exacerbations in asthma and reduce the need for systemic corticosteroids.