The biochemical pathogenesis of chronic obstructive pulmonary diseases: protease-antiprotease imbalance in emphysema and diseases of the airways

Emphysema is believed to result from destruction of elastic fibers due to an imbalance between proteases and their inhibitors in the lung. The imbalance can arise from a primary failure of secretion of the inhibitors, as occurs in hereditary alpha-1-protease inhibitor deficiency, or as the result of complex interactions of environmental agents with the lung. Environmental agents may produce their effects by stimulating degradation of elastic fibers by neutrophils and macrophages, damaging protease inhibitors by oxidative or proteolytic mechanisms or by impairing the biosynthetic repair of damage to the connective tissue. Protease excess has also been consistently observed in purulent sputum. Since experimentally administered proteases stimulate secretion of mucus and damage mucociliary clearance, protease-antiprotease imbalance might be involved in the pathogenesis of bronchitis and bronchiectasis as well as emphysema. Because the protease inhibitors of bronchial mucus are distinct from those of the acinar units, and no hereditary deficiencies are known, there is no direct proof of this hypothesis in man.