Often considered an aggravating but otherwise benign component of
chronic obstructive pulmonary disease (
COPD), airway mucus hypersecretion is now recognised as a potential risk factor for an accelerated loss of lung function in
COPD and is a key pathophysiological feature in many patients, particularly those prone to
respiratory tract infection. Consequently, it is important to develop drugs that inhibit mucus hypersecretion in these susceptible patients. Conventional
therapy including
anticholinergics, beta2-adrenoceoptor agonists, alone or in combination with
corticosteroids,
mucolytics and
macrolide antibiotics are not entirely or consistently effective in inhibiting airway mucus hypersecretion in
COPD. Novel pharmacotherapeutic targets are being investigated, including inhibitors of nerve activity (e.g., BK(Ca) channel activators),
tachykinin receptor antagonists, epoxygenase inducers (e.g., benzafibrate), inhibitors of
mucin exocytosis (e.g., anti-MARCKS
peptide and Munc-18B blockers), inhibitors of
mucin synthesis and goblet cell
hyperplasia (e.g.,
EGF receptor tyrosine kinase inhibitors,
p38 MAP kinase inhibitors,
MEK/ERK inhibitors, hCACL2 blockers and
retinoic acid receptor-alpha antagonists), inducers of goblet cell apoptosis (e.g., Bax inducers or Bcl-2 inhibitors), and
purinoceptor P(2Y2) antagonists to inhibit
mucin secretion or P(2Y2) agonists to hydrate secretions. However, real and theoretical differences delineate the mucus hypersecretory phenotype in
COPD from that in other hypersecretory diseases of the airways. More information is required on these differences to identify therapeutic targets pertinent to
COPD which, in turn, should lead to rational design of anti-hypersecretory drugs for specific treatment of airway mucus hypersecretion in
COPD.