...not all cases of emphysema are caused by smoking?
The first comprehensive report describing emphysema was presented by Watson in 1764 . His 28 year-old patient complained of "chronic shortness of breath and productive cough" and died 10 days later. On autopsy, Watson observed, "greatly distended lungs, and large bladders filled with air, which no pressure on the surface of the lung could force back." On the right lung, he found "ruptured blebs filled with bloody fluid" . Today emphysema is characterized by enlargement of the respiratory airspaces without obvious fibrosis . The accompanying destruction of alveolar walls and decreased elastic recoil, reduces exhalation capacity. While many cases of emphysema are related to cigarette smoking, a genetic risk factor has also been identified [2, 3].
Indeed, in 1838 Louis reported the findings of a young pulmonologist, James Jackson Jr, who died of typhus in 1834. Jackson had observed a hereditary link to emphysema . Budd, in 1839, proposed that loss of pulmonary elasticity and dilation of air spaces in horses could have a hereditary component and be comparable to human emphysema . However, it was not until 1963 that Laurel and Eriksson linked inherited alpha1-antitrypsin (AAT) deficiency to premature emphysema . AAT is a protease inhibitor, which blocks proteases such as neutrophil elastase, from proteolytically degrading elastin, the lung matrix component responsible for elastic recoil. In the 1960s, observations by Janoff and Scerer and others led to the development of the proteinase-antiproteinase imbalance hypothesis . This hypothesis is based on four observations: (1) elastin is degraded by elastase, (2) in an animal model, a protease can induce alveolar damage similar to emphysema in humans, (3) AAT is a specific inhibitor of neutrophil elastase, (4) deficiency of AAT is associated with the development of pulmonary emphysema in both smokers and nonsmokers . While neutrophil elastase has been implicated in alveolar destruction in pulmonary emphysema, it is still unclear whether other proteases are implicated in disease progression. However, the arena is set for development of therapies to counteract matrix degradation while promoting protection of the remaining pulmonary matrix, specifically elastin.
Although genetic predisposition plays a critical role in the development of emphysema, the single most preventable risk factor is smoking, accounting for 90% of emphysema cases in the U.S.  Other preventable risk factors include air pollution, poor diet, and occupational hazards . While genetic predisposition alone can lead to early onset emphysema, genetic predisposition in association with preventable risk factors exacerbates disease progression. A greater understanding of the pathophysiology of pulmonary emphysema, whether related to genetic or preventable risk factors, will offer greater opportunities for targeted drug therapy and/or disease prevention.
This article written by Dr. Natavia Middleton, Feb. 2009.
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