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#Allergy and Immunology
Mucus in the airways is essential to trap pathogens and inhaled particles for airway clearance through the mucociliary escalator towards the pharynx, where these get either swallowed or expectorated. Pathophysiology dictates that exposure to irritants and pathogens caused due to conditions such as bacterial or viral infections, asthma or chronic bronchitis cause leucocyte activation and release of inflammatory mediator, which increase mucus production and promotes clearance of the provocative stimuli. The balance between mucus production and clearance, however, is dependent on optimal mucus quantities and hydration state, and periciliary fluid depth. These rheological changes along with altered ciliary beating or uncoupling from the ciliary movement due to changes in liquid layer depth leads to defective mucociliary clearance and airway mucus accumulation, which in turn, can cause coughing. Thus, this discomfort warrants the need for therapeutic agents with the ability to improve mucociliary function and clear mucus hypersecretion. The therapeutic intervention reduction of MUC5AC, a major gel-forming mucins secreted by goblet cells of the human upper respiratory tract. Evidences support that guaifenesin can reduce the cellular content and secretion of MUC5AC, modify the viscoelastic properties of the secretions, and improve mucociliary transport rates.
The current study evaluated the effects of guaifenesin (an expectorant) and ambroxol that has anti-inflammatory, antioxidant and anaesthetic potential, on MUC5AC content and their ability to improve mucus rheology, which in turn, can ameliorate mucociliary transport rates in human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC. The study included the cultures were treated with guaifenesin and ambroxol in the continued presence of IL-13, post IL-13 pre-treatment for 3 days. The analysis was done on the parameters of cellular and secreted MUC5AC, mucociliary transport rates, mucus rheology at several time points.
The outcome revealed that IL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and reduced mucociliary transport rates with slight effects on the G’ (elastic) or G” (viscous) moduli of the secretions. Guaifenesin significantly impeded MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner. Ambroxol also showed mildly significant beneficial effects. Moreover, all analysed drugs increased mucociliary transport rates and decreased G’ and G” relative to IL-13 alone.
Based on these observations, it can be concluded that guaifenesin can successfully reduce cellular content and secretion of MUC5AC, increase mucociliary transport rates, and modify mucus rheology. Therefore, it can be used in the treatment of airway mucus hypersecretion and mucostasis in airway diseases, relieving productive cough.
Source: Seagrave J, Albrecht HH, Hill DB, Rogers DF, Solomon G. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells. Respir Res. 2012;13(1):98. Published 2012 Oct 31.