ABSTRACT
Patients with COPD usually exhibit characteristics of airway mucus hypersecretion, namely chronic sputum production (1), increased mucus in the airway lumen (2) submucosal gland hypertrophy (2), and goblet cell hyperplasia (3). Theoretically, the clinical consequences of hypersecretion are ventilation-perfusion mismatch, with impairment of gas exchange, and compromised mucociliary clearance, which encourages bacterial colonisation and leads to a vicious cycle of exacerbations. Consequently, inhibition of mucus hypersecretion would appear a reasonable therapeutic aim. However, the extent of the contribution of mucus to pathophysiology and clinical symptoms in COPD is controversial. For example, a number of influential epidemiological studies in the late 1970s and ’80s, found little or no evidence for the involvement of mucus in either the age-related decline in lung function (forced expiratory volume in one second; FEV1) or mortality associated with COPD (4-8). The general consensus of these studies was that chronic airflow obstruction and mucus hypersecretion were independent disease processes. In contrast, a number of studies in the late 1980s and ’90s found positive associations between cough and phlegm production and decline in lung function, hospitalisation and death (9-13). It should be noted that in a number of the latter studies, although statistically significant, the
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associations for mucus were less impressive than for other measures, for example between mortality and the FEV1/VC (vital capacity) ratio (9). The reason(s) for the contradictory observations of the two groups of publications are unclear. Use of occupational cohorts exposed to high levels of industrial pollution in some studies may not equate with the general population. Use of FEV1 and mortality, at either end of the disease spectrum, as primary outcome measures may be less relevant than intermediate measures such as hospitalization. For all of the above studies, the relationship between sputum production and mucus hypersecretion, particularly in the small airways, the main site of obstruction (14), is unknown. Furthermore, not all patients expectorate and there is an overlap in gland size, not only with healthy nonsmokers but also between sputum producers and nonproducers (15,16). Goblet cell hyperplasia is not a consistent observation (2). Nevertheless, although not diagnostic for the condition, mucus hypersecretion clearly contributes to morbidity and mortality in certain groups of patients with COPD. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients without affecting normal mucus secretion and mucociliary clearance.
