Mucus pathophysiology in COPD: differences to asthma, and pharmacotherapy.

Patients with chronic obstructive pulmonary disease (COPD) exhibit characteristics of airway mucus hypersecretion, including sputum production, increased luminal mucus, goblet cell hyperplasia and submucosal gland hypertrophy. These features are not common to all patients and the impact of hypersecretion on morbidity and mortality is a matter for debate. However, current evidence indicates that airway hypersecretion has pathophysiological and clinical significance in COPD, particularly as patients age or are prone to respiratory tract infection. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients. A number of drugs are currently available that may be of therapeutic benefit in hypersecretory disorders of the airways, e.g. glucocorticosteroids and anticholinergics. Novel compounds are undergoing preclinical research, e.g. inhibitors of epidermal growth factor receptor tyrosine kinase and antisense oligomers. However, preliminary data indicate that the mucus in COPD differs to that in asthma in that: 1) it is less viscous and without marked plasma exudation, 2) the ratio of mucin (MUC) 5AC:MUC5B may be reduced, and 3) there is full release of mucin into the airway lumen rather than "tethering" of mucus as in asthma. Consequently, future research should determine whether there really is an intrinsic abnormality specific to mucus in chronic obstructive pulmonary disease. Based upon this information, appropriate suppressers of mucus hypersecretion in chronic obstructive pulmonary disease can be developed.