Causes

Cigarette smoke accounts for over 80% of all cases of chronic obstructive lung disease. It contains irritants that inflame the air passages, setting off a cascade of biochemical events that damage cells in the lung, increasing the risk both for COLD and lung cancer. Different effects of smoking can lead to emphysema or chronic bronchitis, but smokers generally have signs of both conditions. The diagnosis of a specific type of COLD depends on which disease process predominates.

Causes of Emphysema

Smoking is the major cause of emphysema. In some rare inherited disorders, emphysema can develop even in nonsmokers.

The Disease Process Leading to Emphysema. The key process leading to emphysema is destruction of a protein in the lung called elastin, which is essential for the "springy" quality of many tissues in the body. This protein is specifically important in the lungs for maintaining flexibility in the alveoli -- the tiny sacs at the end of the airways.

An imbalance in the following chemicals may be important in this process:

• Proteases, particularly those known as elastase and trypsin. Proteases are enzymes released by white blood cells called neutrophils. Under normal circumstances, these enzymes are important for fighting infection and injury. In excess, however, these enzymes can degrade or destroy elastin.
• Alpha 1-antitrypsin (AAT). The AAT protein neutralizes proteases and therefore protects elastin from destruction.

An excess of protease coupled with impaired or deficient AAT can lead to emphysema. Eventually, the imbalance in these factors produces the inelastic walls of the alveoli and the pockets of dead air characteristic of emphysema. Any condition that causes an imbalance in any of these substances may trigger emphysema. Smoking is the major culprit, but genetic factors can also cause this imbalance.

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 - 20% of 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.

Alpha 1-Antitrypsin (AAT) Deficiency. An estimated 70,000 Americans have an inherited condition called alpha 1-antitrypsin deficiency (A1AD), which causes emphysema in 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 are also at high risk, however. Emphysema in people with A1AD develops in people as young as 30 years old, who are usually of Northern European descent.

Screening tests are now available to detect the genetic defect that causes A1AD. Couples in which one or both partners have a family history of the disease may wish to be tested for the deficiency, so they may take protective measures for themselves and any future children they may have. If the condition is present in the family, testing the children is important.

Causes of Chronic Bronchitis

Biologic Factors and Smoking in Chronic Bronchitis. In chronic bronchitis, smoking triggers inflammation that causes damage in the airways. The processes involved are less clearly understood than those in emphysema, but most likely include the following:

• Damage to the cilia, the hair-like waving projections that move bacteria and foreign particles out of the lungs -- when cilia are injured, such agents become trapped in the lungs and can cause infections that lead to chronic bronchitis.
• Enlargement of the mucus glands in the large airways of the lungs is also involved in the disease process.
• Overgrowth in the smooth muscle cells in the airway.

Bacteria and Viruses. Certain bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, are common in the lower airways of nearly half of chronic bronchitis patients. However, the role of bacteria, viruses, and other organisms in causing chronic symptoms, and inflammation is unclear. Some experts believe that a low-level infection in the lungs may trigger an inflammatory reaction that continues to produce subsequent acute attacks.