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

ABSTRACT

Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different mucins present in the different compartments of the human lower airways. This occurs both in normal subjects and in COPD patients in different clinical phases and stages of severity.

Areas covered: We review the known physiological mechanisms that regulate mucin production in human lower airways of normal subjects, the changes in mucin synthesis/secretion in COPD patients and the clinical efficacy of drugs that modulate mucin synthesis/secretion.

Expert opinion: It is evident that the old simplistic concept that mucus hypersecretion in COPD patients is associated with negative clinical outcomes is not valid and that the therapeutic potential of ‘mucolytic drugs’ is under-appreciated due to the complexity of the associated molecular network(s). Likewise, our current knowledge of the effects of the drugs already available on the market that target mucin synthesis/secretion/structure in the lower airways is extremely limited and often indirect and more well-controlled clinical trials are needed in this area.

KEYWORDS:

• MUC5AC
• MUC5B
• mucoactive drugs

Article Highlights

• Changes in mucin gene expression and production, mucin degradation and dehydration of the mucus layer alter the physiological function of mucins in the human lower airways.

• Different pathogens, such as respiratory viruses and bacteria, may upregulate or down-regulate mucin-secreting cell differentiation and mucin secretion.

• The large number of different mucins in the different compartments of the human lower airways are characterised by an enormous complexity of expression, interactions and functions both in normal subjects and in patients with COPD of different clinical phases and stages of severity.

• The pathogenic role of changes in mucin gene expression and production observed in the blood and/or lower airways of COPD patients requires more translational studies.

• The efficacy of mucin synthesis/secretion/structure modulators in the treatment of COPD remains controversial.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

PMH is funded by a Fellowship and grants from the NHMRC [1079187, 1175134].