Medical Health Encyclopedia

Smoking and Biologic Factors Leading to Emphysema. Emphysema caused by smoking most often occurs in the upper lobes of the lungs. Some experts believe that smoking causes an imbalance between AAT and proteases in the following way:

• Heavy smoking can over-stimulate the immune system so that proteases are overproduced.
• In addition, cigarette smoke triggers the release of damaging particles called oxygen-free radicals (or oxidants) that deactivate AAT and make it ineffective. Emphysema, then, can develop in smokers who have sufficient and even high amounts of AAT.

Only 15% to 20 all smokers develop emphysema, however. Other factors, such as genetic abnormalities, may need to be present to increase susceptibility to airway damage. Some genetic factors being investigated are the following:

• Researchers identified a group of patients who might have an inherited susceptibility to the effects of smoking, so that severe COLD develops at an earlier age than usual.
• Some people may have genetic factors that cause the lungs to be hyper-reactive to stimulants and allergens.
• Some evidence points to genetic abnormalities in an important enzyme called microsomal epoxide hydrolase, which is responsible for the breakdown of harmful oxidants found in cigarette smoke.
• Researchers are also studying a variant of the gene for tumor necrosis factor, an immune factor responsible for inflammatory damage in a number of diseases.

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Alpha 1-Antitrypsin (AAT) Deficiency. An estimated 70,000 people Americans have inherited condition called alpha 1-antitrypsin deficiency (AAT) deficiency that caused emphysema in between 20,000 to 40,000 of them. This disorder results in inadequate amounts of the protective enzyme AAT. Without adequate amounts of AAT, early and progressive damage occurs in both the walls of the alveoli and the airways leading to them. Because smoke is a major toxin and deactivates any residual amounts of AAT, smokers with AAT deficiency have almost no chance of escaping emphysema. Nonsmokers also are at high risk, however. The disease develops in people as young as 30 years old, who are usually of Northern European descent.