Airway Remodeling: Effect of Current and Future Asthma Therapies

Abstract

Airway remodeling (the structural changes which occur in the airways) is one of the characteristic features of severe persistent asthma. These changes include thickening of the laminar reticularis, an increase in the bulk of the airway smooth muscle, thickening of the basement membrane and alterations in the profile of extracellular matrix proteins in the airway wall. The mechanisms leading to airway remodeling are not well understood. Current asthma therapies are effective at reducing airway inflammation and hyperresponsiveness but their effect on airway remodeling is not as evident. Inhaled glucocorticoids have been reported to reduce the thickness of the basement membrane but also to be ineffective at combating remodeling. Similarly, leukotriene receptor antagonists have been shown to prevent or reverse matrix protein deposition in some models of asthma but to be without effect or increase extracellular matrix protein deposition from airway smooth muscle cells. Less is known about the effects of 2 -agonists on airway remodeling.Another class of drugs that is currently being trialed as asthma therapeutics are the phosphodiesterase 4 inhibitors. Recent studies have indicated that this class of drugs may have a role to play in the prevention or reversal of airway remodeling.This review aims to discuss what is currently known about the effectiveness of current therapies for the management of airway remodeling in asthma and to summarize the recent advances that may represent valuable additions for the reversal or prevention of airway remodeling in asthma.