A Disease Often Misdiagnosed as Asthma
Emphysema is a lung disease that affects the walls of the alveoli, the small sacs in the lungs that exchange oxygen for carbon dioxide.
Emphysema causes the alveolar walls to lose their elasticity. This causes small pockets of dead air to remain in the lungs and makes it difficult to exhale air from the lungs. Most emphysema cases are caused by smoking, but about 3 percent of cases are caused by an inherited deficiency in a protein that normally protects the alveoli. This protein is alpha-1 antitrypsin (AAT). In emphysema caused by AAT deficiency, the small airways that lead to the alveoli are also damaged.
In the normal lung, chemicals called proteases are produced by the body's immune system to protect the lungs from infection. Two types of proteases are elastase and trypsin. If the concentration of proteases in the lungs is too great, they can attack healthy lung tissue, destroying elastin, a substance necessary to maintain the elasticity, or flexibility, of the alveoli. AAT neutralizes the proteases, the most important being elastase, and protects the elastin.
Produced in the liver
AAT is produced by the liver and released into the bloodstream.
In people with AAT deficiency, elastase attacks the walls of the alveoli, causing irreversible damage. If allowed to progress, lung tissue continues to be destroyed, and eventually fatal emphysema develops.
The first signs of AAT deficiency often appear between the ages of 20 and 40. The first symptoms are usually shortness of breath, wheezing following activity, and a decreased ability to exercise.
There is a key difference in this type of emphysema versus the common emphysema that many smokers battle. The AAT deficiency emphysema is found throughout the lungs. The smoker's emphysema is found in the central airway of the lungs, according to Robert J. Fallat, M.D., a lung specialist in San Francisco.
"In the early stages, patients with AAT have a pure emphysema without chronic bronchitis or coughing up sputum," he says. "These patients have pretty good oxygen levels until they exercise, and their carbon dioxide level is normal. A smoker with chronic bronchitis generally has high levels of carbon dioxide and low levels of oxygen in the blood."
As the disease becomes severe, both types of emphysema look very much the same. Both have low levels of oxygen and carbon dioxide retention.
Mistaken for asthma
If a patient with chronic obstructive airways disease responds well to bronchodilators, health care providers say they have an "asthmatic component," according to Dr. Fallat. "That doesn't mean they have asthma, but just that they respond to the bronchodilators," he says.
Patients with AAT deficiency-related emphysema respond to bronchodilators, and they are often relatively young when they see a doctor about their symptoms, so they are often diagnosed with asthma.
"Physicians frequently miss the fact that these patients are rapidly getting worse with time, something asthmatics don't usually do," Dr. Ballat says. "Asthmatics go up and down but usually come back to normal. Alpha-1s go down and down and down."
Diagnosis of AAT deficiency is suspected when emphysema develops at a young age and in a person with a family history of lung disease at a young age. A simple breathing test that measures how forcefully a person exhales can help make the diagnosis.
"This is the single most important test a doctor can do in the office," says Dr. Fallat. "The average number for most people who aren't very old is 75 percent or more of their total air out in one second. Young people will expire 85 percent in one second. If that test is done regularly—every six months to a year on a patient diagnosed with asthma—and there is a drop from say 2-1/2 liters to 2 liters in a year or two, it should raise a question.
"If a patient is young and does not smoke, no one else in the family has asthma, and the father died of emphysema, the doctor should test for alpha-1," Dr. Fallat says. Testing for AAT deficiency includes measuring the amount of AAT in the blood and testing for the type of AAT genes.
Once AAT is diagnosed, treatment will require weekly intravenous infusions of the proteins, which come from human plasma donors.
Patients also go through pulmonary rehabilitation. With pulmonary rehab, they will learn different techniques of clearing sputum, the proper use of medications, and how to increase their exercise for more efficient use of oxygen.
"Exercise is key," says Dr. Fallat. "Most people with lung disease stop exercising because they are short of breath and uncomfortable. They need to retrain their brain centers and realize that, yes, they are working harder, but it's okay. This is a new way they have to breathe, and it's not hurting them.
"It's important to push beyond what they would normally do," he says. "In that process they don't necessarily improve their lung function, but they improve the efficiency of their muscles to utilize oxygen so they don't need to breathe as much."
Replacement therapy is not entirely effective in all cases. "There is pretty good data showing the effectiveness of replacement therapy, but there are some people who—despite everything you do—continue to go downhill," warns Dr. Fallat. "There are obviously other genetic factors that control this, and we will probably find those in the next five to 10 years."
For those people, lung transplants offer hope. Approximately one fourth of all lung transplants are alpha-1 adults.
The Z gene
In the most common type of alpha-1, a person inherits one Z gene from each parent. In the United States there are an estimated 100,000 alpha-1 ZZs.
"There are probably over 20,000 people in this country with AAT-related lung disease," says Dr. Fallat. "We know of only 3,000 to 5,000, so it's grossly under diagnosed."