Targeting airway mucus hypersecretion in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

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Characteristic comparison of three rat models induced by cigarette smoke or combined with LPS: To establish a suitable model for study of airway mucus hypersecretion in chronic obstructive pulmonary disease

Pulmonary Pharmacology & Therapeutics ◽

10.1016/j.pupt.2012.06.004 ◽

2012 ◽

Vol 25 (5) ◽

pp. 349-356 ◽

Cited By ~ 45

Author(s):

Yi-Chu Nie ◽

Hao Wu ◽

Pei-Bo Li ◽

Yu-Long Luo ◽

Chen-Chen Zhang ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Cigarette Smoke ◽

Chronic Obstructive ◽

Suitable Model ◽

Obstructive Pulmonary Disease ◽

Mucus Hypersecretion ◽

Rat Models ◽

Airway Mucus

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Clinical significance of airway mucus hypersecretion in chronic obstructive pulmonary disease

Journal of Translational Internal Medicine ◽

10.1515/jtim-2015-0013 ◽

2015 ◽

Vol 3 (3) ◽

pp. 89-92 ◽

Cited By ~ 7

Author(s):

Pan-wen Tian ◽

Fu-qiang Wen

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Pulmonary Disease ◽

Poor Quality ◽

High Rate ◽

Rapid Decline ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Mucus Hypersecretion ◽

Phosphodiesterase 4 Inhibitors ◽

Airway Mucus

Abstract Airway mucus hypersecretion is one of the most important features of chronic obstructive pulmonary disease (COPD). Airway mucus hypersecretion in COPD patients results in outcomes such as rapid decline of lung function, poor quality of life, and high rate of acute exacerbation, hospitalization and mortality. Nonpharmacologic treatments for airway mucus hypersecretion in COPD include smoking cessation and physical rehabilitation. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. Novel drugs with promising prospects are currently under clinical trials.

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The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

10.20944/preprints202008.0260.v1 ◽

2020 ◽

Author(s):

Jingyuan Li ◽

Zuguang Ye

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Signaling Pathways ◽

Pulmonary Disease ◽

Beat Frequency ◽

Ciliary Beat Frequency ◽

Chronic Obstructive ◽

High Morbidity ◽

Obstructive Pulmonary Disease ◽

Mucus Hypersecretion ◽

Airway Mucus

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [ nuclear factor-κB (NF-кB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

Download Full-text