Revisited role for mucus hypersecretion in the pathogenesis of COPD

Abstract

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease of which the basic pathophysiological mechanisms remain largely unknown. On the basis of recent results from pathological studies and large clinical trials, the presence of airway inflammation does not seem to be sufficient to explain the complexity of the disease and the relatively poor response to treatment. It is probably time to abandon the concept of COPD as a unique disease and define, identify and treat the various aspects, which may differ between individuals. Among the different phenotypic distinctions, the classical distinction "chronic bronchitis" has mucus hypersecretion as the key presenting symptom. Its role in COPD has been the subject of an ongoing debate; however, it now appears to be being re-evaluated due to findings from recent epidemiological and pathological studies. In this context, the view that chronic mucus hypersecretion plays a secondary role in the pathogenesis of COPD should be abandoned and instead, drugs targeting mucus hypersecretion should be considered as a treatment option.

FIGURE 1.

Pathological changes of the central airways in chronic obstructive pulmonary disease. a) A central bronchus from the lung of a cigarette smoker with normal pulmonary function. Only small amounts of bronchial smooth muscle are present and the epithelial glands are small. b) In contrast, a subject with chronic bronchitis has bronchial smooth muscle that appears as a thick bundle and enlarged bronchial glands. c) The enlarged bronchial glands at a higher magnification. A chronic inflammatory process involving polymorphonuclear leukocytes (arrowhead) and mononuclear cells, including plasma cells (arrows) can also be seen. Reproduced from [11], with permission from the publisher.

FIGURE 2.

Incidence of chronic obstructive pulmonary disease according to the history of chronic cough/phlegm. The statistically significant incidence rate ratio (persistence versus absence) was 4.04 (95% CI 2.29–7.11). ECRHS: European Community Respiratory Health Survey. Reproduced from [23] with permission from the publisher.

FIGURE 3.

Kaplan–Meier survival plot of 101 cases of severe (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3) and very severe (GOLD stage 4) chronic obstructive pulmonary disease following lung volume reduction surgery. The median survival was shortened in the quartile with the most severe occlusion by mucous exudate on the fully expanded lumen (HR 3.28, 95% CI 1.55–6.92; p = 0.002) after adjustment for several factors. ––––: quartile 1 (smallest); ········: quartile 2; ·-·-·-: quartile 3; - - - -: quartile 4 (largest). Reproduced from [25] with permission from the publisher.