Loosening the stranglehold of a chronic disease.
In William Golding's Lord of the Flies, the Cassandra-like character called Piggy has asthma that renders him breathless, helpless ("'My auntie told me not to run,' he explained, 'on account of my asthma'"), and ridiculed. But as sufferers know, asthma is no laughing matter. At least 15 million Americans have the disease, and each year 5,000 die as a result of acute asthma attacks, with the highest mortality rate among blacks aged 15 to 24.
Although we often think of asthma as a minor annoyance that the Teddy Roosevelts of the world valiantly overcome, the suffering of asthmatics is real. Specialists think it's time both doctors and patients began taking the disease more seriously, starting with more aggressive management. As Jeffrey Drazen, M.D. '72, points out, today's doctors have many more weapons at their disposal than he did when he took care of his first asthma patient, a 12-year-old girl, in 1968.
"Clearly it was a devastating illness for the girl and her family," he recalls. "She would try activities and then, as the family perceived it, she would feel--for no apparent reason--like she had a rope around her neck. They had her on the best medications available, but when those weren't effective, they had to pack up the whole family and take her for emergency treatment. That often took half a day, and was quite disruptive."
At that time, people who suffered from acute asthma went nowhere without an inhaler--a small cartridge filled with a bronchodilator that quickly opens constricted airways. This continues to be good short-term treatment for asthma attacks, but more recently researchers have begun to realize that these attacks have an underlying cause--inflammation--that needs to be managed on a long-term basis.
"The airway is surrounded by smooth muscle, kind of like a Slinky coiled around a tube," says Drazen, now Francis professor of medicine at Harvard Medical School and chief of pulmonary critical care at Brigham and Women's Hospital. "In people with asthma, the muscles intermittently constrict and narrow the breathing passage. Why this happens isn't clear, but bronchodilators relax the muscles and relieve this short-term constriction." (Asthmatic children who outgrow the disease in puberty apparently benefit from a similar, but in their case developmental, widening of the bronchial openings.)
What's become increasingly apparent is that these acute asthma attacks are the result of an airway that is chronically inflamed. As a result, bronchial tissue can be easily provoked into spasm, either by exertion or by environmental allergens, such as those produced by cockroaches and dust mites; psychological stress can also stimulate wheezing and other symptoms in patients. "Bronchodilators don't relieve the long-term problem of the inflammation that leaves the airway hyperresponsive to irritation," Drazen continues. "It's sort of like having a very good fire extinguisher, without having any way to prevent fires in the first place."
Today, the inhalers so emblematic of asthma and its intrusiveness are giving way to new, longer-term anti-inflammatory therapies that prevent asthma attacks before they flare up. Asthma specialists, for instance, are recommending that doctors start their patients with a stiff dose of oral steroids in order to get airway inflammation under control as quickly as possible.
One of Drazen's patients is Joe Gannon, a laboratory technician at Brigham and Women's. Four years ago, Gannon's children tried to convince him to quit smoking--they stole his cigarettes, crushed them, flushed them down the toilet, and grimaced and griped each time he lit up. When he did stop smoking for a few days to get over a flu, Gannon figured it was time to quit cold turkey.
But he grew concerned when he continued to have difficulty breathing. At first, it felt like left-over flu, but soon he found himself unable to carry his children upstairs without wheezing, and coaching his two soccer teams became unbearable. "When I lay in bed at night, it was like listening to musical notes," he recalls. "It was the sound of my own wheezing." Gannon was surprised and somewhat relieved to find out that he was suffering from asthma; a short course of steroids allowed him to begin breathing easily again.
Recently, the National Heart, Lung, and Blood Institute amended its guidelines to recommend that even patients with mild to moderate asthma receive such strong anti-inflammatory therapy. Unfortunately, according to Drazen, many asthma patients don't get it. "The problem is that a lot of doctors still treat asthma on an only-when-it's-bothering-you basis," he says. "And there are many patients who don't want to use steroids or brand-new drugs, because they're afraid something terrible will happen to them."
Fears about steroids are understandable: when taken over long stretches of time in high doses, these drugs cause hair thinning, bone loss, weight gain, emotional changes, and a wide variety of other side effects. Joe Gannon recalls experiencing some swelling and mood swings after only a 10-day course of steroids. And doctors aren't even sure exactly why steroids work. "I can think of about eight or nine ways that steroids could affect lung function, and I don't have any idea which of them might be right," Drazen says. "It's very difficult to use a treatment without knowing the biological basis of what you're doing."
Fortunately, there are now more options for asthma treatment. New, longer-acting bronchodilators are particularly useful in helping patients sleep through the night. Two new drugs--zafirlukast and zileuton--interfere with the production and activity of leukotrienes, substances produced by the body that stimulate the inflammatory process. Some patients, like Joe Gannon, are flooded with leukotrienes that set off frequent, severe attacks. Gannon began taking zileuton while it was still in the experimental stage; the drug, which he continues to take four times daily, now has FDA approval. "These drugs resulted from research into understanding the basic biology of asthma," says Drazen. "It's good news for those whose asthma is due to leukotriene excess. That's probably about half the patient population."
"Now that we recognize that asthma is chronic," Drazen continues, "I'm hoping that we can get more patients and physicians to buy into tighter control." That means regular management: daily monitoring of patients' lung capacity, careful control of their environment, regular doses of medication to prevent attacks, and strong short-term therapy to head off acute episodes of breathlessness. Like diabetes, another chronic disease, asthma requires significant patient education.
"We're lucky in some ways," Drazan notes, "because some of our new treatments are easier to take and have fewer side effects. It's easier to take a pill than to use an inhaler, for example. But now we have to teach asthma patients to take their drugs even when they don't have any symptoms. It's going to take a big educational effort to change people's view of asthma, but the sooner we get started, the better off we'll all be."
Freelance writer John F. Lauerman, who lives in Brookline, Massachusetts, is coauthor, with Dr. David M. Nathan, of Diabetes (Times Books).
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