The pathogenesis of emphysema.
Emphysema is an increase in size of the air spaces distal to the terminal bronchioles, and can thus only be diagnosed pathologically, but new quantitative CT methods hold promise, diagnosing, quantitating and locating the lesions in man, in life, non-invasively. The protease/antiprotease theory of the pathogenesis of emphysema proposes that cigarette smoke attracts alveolar macrophages to distal terminal bronchioles, these in turn releasing neutrophil chemotactic factors which attract circulating polymorphonuclear leucocytes, to release potent proteolytic enzymes (serine protease) in addition to the alveolar macrophage protease. These enzymes, which can cleave all the macromolecules of the lung interstitium, are antagonized (at least the serine elastase) in health by alpha 1-antitrypsin, a normal constituent of lung lining fluid. However, this can be oxidized by oxidants in cigarette smoke, and oxidants released by polymorphonuclear leucocytes in microbial killing. The role of these actions, and of antioxidants (both natural and therapeutic) and antielastases are reviewed, as well as the activities of lung defence cells in this process. Despite this explosion of recent knowledge, we are still unable to answer the all important question "Why don't all smokers develop emphysema?", and further research is needed into variability in these multiple factors involved in this important new theory of the pathogenesis of this, possibly the commonest of all respiratory disorders of a chronic disabling nature.
D002630:Chemotactic Factors / Q000502:physiology; D006801:Humans; D016209:Interleukin-8; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*; D015843:Serpins
D002630:Chemotactic Factors; D016209:Interleukin-8; D011480:Protease Inhibitors; D011506:Proteins; D015843:Serpins; D010447:Peptide Hydrolases