Family History of COPD

The only concretely identified genetic factor involved in risk of COPD is AAT deficiency. AAT is an enzyme that normally prevents loss of the lungs’ elastic fibers. People with this deficiency do not produce a sufficient amount of this enzyme.

The discovery of a relationship between AAT deficiency and the development of early-onset emphysema led to the knowledge that the destruction of lung elastin played a major role in the changes in the physiology of the lung that occur with emphysema. Subsequently, it was shown that an enzyme (neutrophil elastase) which is inactivated by AAT causes structural damage in the lung, mucus gland hyperplasia, mucus secretion, and an impairment of mucociliary clearance. Another inhibitor of neutrophil elastase, known as secretory leukoprotease inhibitor (or SLPI), is released by airways cells and mucus glands. Neutrophil elastase also affects the epithelial cells, causing changes that further impair the host defenses and ultimately lead to an increase in bacterial colonization.

Liou and Campbell studied the processes in which neutrophils degrade the connective tissue after neutrophil elastase is released. They found a correlation between the tissue destruction and the concentration of the surrounding AAT inhibitors. From their work, it became evident that neutrophil migration into the lung produced an area of neutrophil elastase-changes in the cells. The cell damage increases as the numbers of cells that migrate increase.

Because the concentration of the AAT was less in people with this deficiency, the tissue destruction process was enhanced and led to an earlier development of COPD. In addition, Sallenave, et al found that the release of elastase from the neutrophil inhibits the production of SLPI in the airways, thus providing a greater opportunity for the enzyme to affect structural changes.

People with this deficiency can develop airflow obstruction by their early 40s, with this rate accelerated by 10 to 15 years among smokers with this deficiency. Smokers with some forms of AAT deficiency are 10 times more likely to develop COPD almost 19 years earlier than nonsmoking relatives who are also deficient in the enzyme.

This deficiency accounts for only a small proportion of COPD cases (less than 1% in the US), and there is a wide variety in the severity of lung disease associated with it. In the largest available screening study of 200 000 Swedish newborns, AAT deficiency was documented in 1 of 1,575 newborns (0.0635%). In the largest available American screening study of 107 038 newborns in Oregon, this deficiency was noted in 1 of 5,097 (0.0196%). These figures correlate with a prevalence of 1:3,000 Americans.

It has also been established that chronic bronchitis is prevalent among some families. While genetics may play a role in this prevalence, it may also be due to environmental factors, such as indoor pollutants (eg, natural gas). It has also been found that all members of a family in which at least 1 member smokes are at greater risk for developing chronic bronchitis.

Research has also found that first-degree smoking or ex-smoking relatives of patients with early-onset COPD, that is not attributable to AAT, have significantly greater lung function loss than either nonsmoking relatives or heavy smokers in general. The data suggest that other genetic factors may sometimes be at work besides AAT deficiency.

In Summary heredity is;

• only concretely identified genetic factor is AAT deficiency
• AAT is an enzyme that normally prevents loss of the lungs’ elastic fibers
• AAT accounts for less than 1% of all cases of COPD in the US
• people with AAT generally develop airflow obstruction by their early 40s