The Role of Biologics in Reducing Mucous Plug Burden in Asthma

Abstract

Asthma is a chronic inflammatory respiratory disease, affecting hundreds of millions of individuals worldwide. Mucous hypersecretion, which leads to the formation of mucous plugs within the airways, is a key pathophysiological feature associated with severe asthma and airway remodeling. Persistent airflow obstruction due to mucous plugging has been recognized as a contributor to poor symptom control in patients with asthma. This phenomenon is driven by type 2 inflammation, mediated by elevated levels of IL-5 and IL-13, as well as eosinophilic infiltration, which collectively promote the formation and persistence of mucous plugs. The presence of mucous plugging has been linked to the frequency and severity of exacerbations, as well as airflow obstruction. Imaging modalities such as high-resolution computed tomography (HRCT), hyperpolarized 129Xe MRI, and optical coherence tomography (OCT) have provided insights into the extent of mucous plugging and its association with airflow limitation. Over the past decade, biological therapies targeting specific pathways of type 2 inflammation have emerged as highly effective treatment options for patients with severe asthma. These therapies have conferred substantial improvements in lung function, reduction in exacerbation rates, and decreased oral glucocorticoid use. One of their mechanisms of action might be due to removal of persistent mucous plugs not achieved by conventional anti-asthmatic therapies such as inhaled corticosteroids (ICS) and oral corticosteroids (OCS). This comprehensive review summarizes the effects of biologics on mucous plugging in severe asthma, focusing on their mechanisms of action, clinical efficacy, and potential implications for optimizing treatment strategies.