Role of the mucins in pathogenesis of COPD: implications for therapy

Bello, Federica Lo; Ieni, Antonio; Hansbro, Philip M.; Ruggeri, Paolo; Stefano, Antonino Di; Nucera, Francesco; Coppolino, Irene; Monaco, Francesco; Tuccari, Giovanni; Adcock, Ian M.; Caramori, Gaetano

doi:10.1080/17476348.2020.1739525

Cited by 15 publications

(3 citation statements)

References 148 publications

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“…Surprisingly, there is an absence of controlled clinical trials concerning the impact of LAMAs on mucin synthesis, production and rheology [72], while there are conflicting findings regarding airway mucociliary clearance [28,34,73]. TAGAYA et al [28] reported that TIO reduced the nasal clearance time in COPD patients, an effect that could be the result of a lower mucus hypersecretion and an increase in mucociliary clearance time in the airways.…”

Section: Discussionmentioning

confidence: 99%

The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

et al. 2022

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Patients suffering from chronic obstructive pulmonary disease (COPD) clinically manifest airway mucus hypersecretion as sputum expectoration and cough. Evidence accumulated in the past decade has shown that the cholinergic system not only regulates airway smooth muscle contraction but also the activity of inflammatory and airway epithelial cells, including goblet cells, and submucosal gland activity. Long-acting muscarinic antagonists (LAMAs) with the most favourable M3/M2 muscarinic acetylcholine (ACh) receptors residency properties are not only excellent bronchodilators but potentially also mucus-modifying agents, able to positively impact on mucus hypersecretion and cough. The aim of this systematic review was to investigate the impact of LAMAs on mucus hypersecretion and cough in COPD patients. The evidence confirmed that LAMAs, mainly tiotropium and aclidinium, improved sputum production and cough in moderate to severe COPD. Thus, LAMAs not only antagonise the ACh-induced bronchoconstriction of the airways but also appear to limit the production of mucus secreted in response to ACh by airway goblet cells and/or submucosal glands. Further clinical studies are necessary to evaluate the impact of LAMAs exclusively on sputum symptoms and cough as primary end-points and to investigate whether LAMAs have a modulatory action on the rheological properties of mucus.

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Section: Discussionmentioning

confidence: 99%

The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

et al. 2022

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“…However, the activation of EGFR, also leads to goblet cell hyperplasia, mucus hypersecretion, and overproduction of MUC5AC, which may exacerbate the pathological changes in respiratory diseases ( 76 – 79 ). Overproduction of the MUC5AC gene is a characteristic of many respiratory diseases including CF, asthma, and COPD ( 7 , 80 , 81 ), creating hyper-concentrated mucus, which is thicker, more adherent and prone to mucus plugging ( 82 ). Consequently, thicker and more adherent mucus may create further hypoxic niches within it.…”

Section: Hypoxia-epithelial Interactions: Consequences For the Host Dmentioning

confidence: 99%

Influence of Hypoxia on the Epithelial-Pathogen Interactions in the Lung: Implications for Respiratory Disease

et al. 2021

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Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies.

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“…Mucus hypersecretion may also result in airway obstruction as mucus occupies the airway lumen and inclines to be retained due to ciliary dysfunction [91,92]. Accumulating evidences have been revealed the tremendous complexity of the expression, interactions, and functions of mucins in patients with different severity of COPD, suggesting that modulating the synthesis, secretion, or structure of mucins in these patients might be a useful treatment for this disease [93]. Several natural compounds such as flavonoids have shown their potential effects on the expression and secretion of mucin [94].…”

Section: Expectorantmentioning

confidence: 99%

Evaluation of Naringenin as a Promising Treatment Option for COPD Based on Literature Review and Network Pharmacology

Chen

et al. 2020

Biomolecules

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Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incompletely reversible airflow limitation and seriously threatens the health of humans due to its high morbidity and mortality. Naringenin, as a natural flavanone, has shown various potential pharmacological activities against multiple pathological stages of COPD, but available studies are scattered and unsystematic. Thus, we combined literature review with network pharmacology analysis to evaluate the potential therapeutic effects of naringenin on COPD and predict its underlying mechanisms, expecting to provide a promising tactic for clinical treatment of COPD.

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Role of the mucins in pathogenesis of COPD: implications for therapy

Cited by 15 publications

References 148 publications

The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

The impact of long-acting muscarinic antagonists on mucus hypersecretion and cough in chronic obstructive pulmonary disease: a systematic review

Influence of Hypoxia on the Epithelial-Pathogen Interactions in the Lung: Implications for Respiratory Disease

Evaluation of Naringenin as a Promising Treatment Option for COPD Based on Literature Review and Network Pharmacology

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