COPD; Alpha-1 antitrypsin deficiency; Bronchitis - chronic; Chronic bronchitis; Emphysema
Cigarette smoke accounts for more than 80% of chronic obstructive lung disease cases. It contains irritants that inflame the air passages, setting off a chain of events that damage cells in the lung, increasing the risk for both COPD and lung cancer.
Different effects of smoking can lead to emphysema or chronic bronchitis, but smokers generally have signs of both conditions.
Smoking is the major cause of emphysema. In some rare inherited disorders, emphysema can develop in nonsmokers.
The key process leading to emphysema is not well understood. It appears that inflammatory cells (T lymphocytes, neutrophils, and alveolar macrophages) release chemicals called enzymes that attack the tissue in the deepest part of the lung where oxygen and carbon dioxide are exchanged. As a result, the bronchioles detach from the alveoli, and holes appear. Airways become narrowed, and breathing out becomes difficult.
The typical COPD patient is a current or former smoker, over age 50, with a pack-a-day habit of more than 20 years. Lung function continues to get worse as the person ages.
Smoking is the major cause of COPD worldwide. In underdeveloped countries, smoke, exposure to industrial pollutants in poorly ventilated work areas, and cooking over wood and coal fires are also major contributors. As smoking has become more widespread among women, the incidence of COPD in women has grown proportionally. What was once considered a man's disease now affects a greater number of women. Moreover, women appear to be more susceptible to the effects of smoking and pollution than men.
On the positive side, smoking rates in the U.S. are dropping, and the proportion of adults under 55 with COPD is gradually declining. This indicates that the high death rate will eventually level out. In particular, the rate of COPD in young African-Americans is declining significantly. The rate in younger Caucasians is not decreasing as dramatically.
More than 80% of people who die from COPD are current or former smokers. The longer a person smokes, the higher the risk for emphysema. Most patients have smoked the equivalent of one pack a year for 20 years, and many have smoked for up to the equivalent of 40 years. Once a smoker quits, the rate of lung function loss becomes the same as in a nonsmoker; however, much of the lung damage that occurred during smoking may not be reversible.
Emphysema caused by smoking most often occurs in the upper lobes of the lungs.
In chronic bronchitis, smoking triggers inflammation that causes damage in the airways. The processes involved include:
Generally, about a quarter of all smokers develop COPD. Other factors, such as genetic abnormalities, may be necessary for people to develop the airway damage that leads to COPD. The link may be a gene called ADAM33, which researchers have discovered is more common in smokers with COPD than in those who don't have the disease. Other genetic variants linked to the disease have been discovered on chromosome 4, as well as in the gene for the a-nicotinic acetylcholine receptor, CHRNA 3/5 (a chemical messenger that has also been linked to smoking and lung cancer).
Alpha-1 antitrypsin deficiency (A1AD) is the only known genetic risk factor that has been associated with the emphysema type of COPD. About 1% to 2% of people with emphysema have this disorder, which prevents their bodies from making enough of the protective enzyme, AAT. Without enough AAT, damage occurs in both the walls of the alveoli and the airways leading to them.
Because smoke is a major toxin and deactivates any amounts of AAT that do remain, 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 with a family history of the disease may want 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 already in the family, testing the children is important.
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 acute attacks. Viruses may also exaggerate the lung response to infections, leading to exacerbations of COPD.
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