People with familial emphysema have a hereditary deficiency of a blood component called alpha-1-antitrypsin resulting in the loss of a lung structural protein, elastin.

In the general population, emphysema usually develops in older individuals with a long smoking history. However, there is also a form of emphysema that runs in families.

People with familial emphysema have a hereditary deficiency of a blood component, alpha-l-protease inhibitor, also called alpha-l-antitrypsin (AAT). The number of Americans with this genetic deficiency is quite small, probably no more than 70,000. It is estimated that 1 in 3,000 newborns have a genetic deficiency of AAT, and 1 to 3 percent of all cases of emphysema are due to AAT deficiency.

The destruction of elastin that occurs in emphysema is believed to result from an imbalance between two proteins in the lung -- an enzyme called elastase, which breaks down elastin, and AAT, which inhibits elastase.

In the normal individual, there is enough AAT to protect elastin so that abnormal elastin destruction does not occur. However, when there is a genetic deficiency of AAT, the activity of the elastase is not inhibited and elastin degradation occurs unchecked.

If individuals with a severe genetic deficiency of alpha-l-protease inhibitor smoke, they usually have symptoms of COPD by the time they reach early middle age. Deficiency of alpha-l-protease inhibitor can be detected by blood tests available through hospital laboratories. People from families in which relatives have developed emphysema in their 30s and 40s should be tested for AAT deficiency. If a deficiency is found, it is critical for these people not to smoke.

Some scientists believe that nonfamilial emphysema, usually called "smoker's emphysema," also results from an imbalance between elastin-degrading enzymes and their inhibitors. The elastase-AAT imbalance is thought to be a result of the effects of smoking, rather than inherited as in familial emphysema.

Some evidence for this theory comes from studies on the effect of tobacco smoke on lung cells. These studies showed that tobacco smoke stimulates excess release of elastase from cells normally found in the lung. The inhaled smoke also stimulates more elastase-producing cells to migrate to the lung which in turn causes the release of even more elastase. To make matters worse, oxidants found in cigarette smoke inactivate a significant portion of the elastase inhibitors that are present, thereby decreasing the amount of active antielastase available for protecting the lung and further upsetting the elastase-antielastase balance.

Scientists believe that, in addition to smoking-related processes, there must be other factors that cause emphysema in the general population since only 15 to 20 percent of smokers develop emphysema. The nature and role of these other factors in smokers' emphysema are not yet clear.

Source: Compiled by COPD-International Community Members from U.S.National Heart, Lung and Blood Institute (NHLB) information.

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