Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment

Abstract

Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.

Figure 1

Model of airway mucus epithelium: goblet cells and submucosal glands secret mucin, which forms mucus on the surface of the airway. It contains an upper gel layer and lower sol layer, between which is a surfactant layer present which helps in lubrication and transfer of energy from beating cilia to propel out inhaled pathogens and particles by the process known as mucociliary clearance.

Figure 2

Pathways leading to mucus hypersecretion TNF-α interacts with cell surface receptors and stimulates the EGFR gene in airway epithelial cells. IκB kinase (IKK) activation is induced by receptor stimulation. The IκB subunit of intracellular NF-κB is then phosphorylated (P) by IKK at its regulatory site, allowing for transactivation and degradation. This, in turn, releases NF-κB dimers and causes free NF-κB to move into the nucleus, where it activates the expression of target genes MUC5AC. IL-13 activates Janus kinase 1 (Jak1) to phosphorylate (P) STAT6 after binding to IL-4Rα receptors. STAT6 activation increases the expression of SPDEF, which upregulates mucous metaplasia genes and reduces forkhead box A2 (Foxa2), which negatively regulates MUC5AC.