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Airway Remodeling: A Review of its Pathophysiology and Drug Treatment Challenges

Sakagami M.

Respiratory Drug Delivery 2020. Volume 1, 2020: 47-56.

Abstract:

Our present ‘one size fits all’ drug treatment strategy using inhaled corticosteroids (ICS) and long-acting beta adrenergic bronchodilators (LABA) fails in severe and uncontrolled asthma, which are responsible for a large proportion of asthma-related health costs. In this subset of patients, a cluster of different structural changes in the large and small airways are often seen, and referred to as ‘airway remodeling’ (AR). AR is pathophysiologically characterized by the presence of chronic T-helper 2 (Th2) cell-type and eosinophilic inflammation alongside allergic immunoglobulin E (IgE) induction and release in the airways. Monoclonal antibody (mAb) biologics targeting Th2/eosinophilic cytokines (IL-4 and IL-5) and IgE have recently shown effectiveness as add-on therapies to ICS and LABA in severe/uncontrolled asthma in addition to anti-leukotriene (LT) drugs. Nevertheless, their true clinical merits will likely be proven only upon identification of critical pathogenetic asthma endotypes, and to date, their impact on AR remains uncertain in patients due to the absence of confirmatory diagnostic tools. More new molecules are being investigated, focused on different pathogenetic mechanisms of AR. Even so, drug delivery to the small airways is still a formidable challenge, irrespective of the use of systemic or local inhaled routes of administration.