by Joanne Shaw
John A. Mangos, M.D., says he's participating in a quiet revolution. The revolution centers around changing the public's perception of asthma and advocating new drug therapies for patients with the disease.
"Usually, people think asthma is about bronchial constriction," said Dr. Mangos, professor of pediatrics and the Eloise Alexander Distinguished Chair in Pediatric Pulmonology. "Yes, there is bronchial constriction in asthma; however, this represents a small component of the disease process.
In the last 10 years we have changed our thoughts about the nature of asthma and, consequently, the therapy for the disease."
From the mid-1930s to the mid-1980s asthma was treated with bronchodilators--often injections of epinephrine, added Dr. Mangos. "Those injections made the patient feel terrible, giving him or her a tightness of the chest and a feeling of pending doom. Then we started using theophylline--the stimulant found in tea which is related to the caffeine found in coffee. Theophylline, though, is a very capricious drug with a very narrow therapeutic range. If you use less than the required amount, it doesn't work. If you use more, the result can be very serious toxic effects."
In the 1960s, hand-held inhalers delivering medications for bronchodilation were introduced. "An epidemic of deaths occurred in the late 1960s, because the first inhalers contained rather crude medications, and they would only last about 20 minutes," said Dr. Mangos. "They would cause the airway to open a little, and the patient would breathe easier. However, there's a limit to the amount of airway dilation.
"Sometimes we succeeded with these treatments, and many times we failed. We didn't know why," said Dr. Mangos. "Now we know why."
The same substances that cause bronchial constriction cause inflammation
and swelling of the wall of the bronchi, explained Dr. Mangos.
(See illustrations.) Inflammation in the bronchi causes swelling of the mucosa, the mucous membranes of the lungs, and increases the secretionary activity of the bronchial glands. Also, the secretions during an asthma attack are thick and sticky.
"So the main cause of airway obstruction is inflammation," said Dr. Mangos. "It has been estimated that only about 20 percent of the obstruction of the airways during an asthma attack is due to bronchial constriction."
In the mid-1980s, physicians and researchers began to realize the role of inflammation in asthma. During the early and mid-1990s, the National Institutes of Health created a Consensus Report emphasizing the new knowledge about inflammation and the treatment of asthma.
"We have reversed the order of medications," said Dr. Mangos. "In the past we used mainly bronchodilators, and to support the effect of the bronchodilators we gave anti-inflammatory drugs. Now, most patients have their asthma controlled with antiinflammatory drugs, and when they get into trouble we use bronchodilators to give them additional relief.
"It's very hard to change the thinking of patients and health professionals who have viewed asthma as a bronchoconstrictive state," he added. "We need to transmit to our students and to our residents the new understanding of the nature of the disease asthma."
The new understanding of the disease has promoted treatment with
antiinflammatory drugs such as cromolyn sodium, nedocromil and
corticosteroids. "We can easily administer these drugs in many ways," said Dr. Mangos. "The important thing is not to forget the inflammation."
The next generation of drugs for asthma will target the causes of the
inflammation and bronchoconstriction. Substances in the body called
cytokines, secreted by cells of the immune system, cause the inflammation
and bronchoconstriction in the airways. "Reducing the substances
that trigger inflammation is vital," explained Dr. Mangos. "Cytokines target cells in different organs. The new drugs will act as blockers--when a cytokine tries to hit the target cell, the blocker will cause the cytokine to bounce
off the cell so the cytokine doesn't cause any problem. The cytokines are metabolized."
Dr. Mangos is prescribing some of the new drugs. "They have been so successful that some of our patients require only one pill a day to take care of their asthma," said Dr. Mangos. "Rarely do they need bronchodilators.
"There also is a new steroidal solution, soon to be released in the
market, that can be used with a nebulizer to block the inflammatory
response of the airways," said the physician. "The reason
we're using many of these agents as inhaled drugs is to avoid the drugs'
marked effects on other parts of the body. Recently, newspapers carried a story saying the use of inhaled steroids can stunt the growth of children. That's true, but asthma can stunt their growth even more.
"Also, the new generation of inhalable steroids has markedly reduced systemic effects. Properly used, these medications are remarkably safe, and they work."
Dr. Mangos also described the progressive nature of the disease and preventive measures. "In the past five years we have realized that pediatric asthma is a progressive disease that starts early in life with mild symptoms and gradually progresses into a severe and, at times, life-threatening disease. Preliminary studies have demonstrated that early recognition of asthma and 'preventive' treatment may stop the progression of the disease, so that it may never progress to its severe form," Dr. Mangos explained.
"Today, we have at least two types of medications that allow us to
use this 'preventive' approach to the management of asthma in
children," he said.