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Pathogenesis

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Only susceptible individuals develop emphysema but in most cases the factors governing susceptibility are poorly understood.

The alveolar wall destruction typical of emphysema may be explained by the protease-antiprotease theory. The pulmonary protease is elastase derived from neutrophils and macrophages; the principal anti-protease is alpha-1 antitrypsin.

The main elements of the theory are:

  • tobacco smoke and other irritants result in inflammation and the influx of neutrophils and macrophages into the alveoli and bronchioles
  • elastase is released which breaks down elastin fibres and other structural proteins
  • serine protein inhibitors, principally alpha-1 antitrypsin, down-regulate the tissue destruction
  • chronic inflammation eventually degrades alveolar walls
  • protease overactivity is favoured by:
    • inactivation of alpha-1 antitrypsin by oxidants in smoke and oxygen free radicals secreted by neutrophils
    • hereditary deficiency in alpha-1 antitrypsin activity

Heavy smoking alone causes emphysema around the 6th decade.

Homozygotes for alpha-1 AT deficiency develop severe emphysema around the 4th decade. This is accelerated in smokers.

Weight loss, which is a common feature of the illness, and which is associated with increased morbidity and mortality, is thought to result from the release of TNF-alpha from hypoxic tissues.


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