Yearning to Breathe Free - With new drugs and devices, asthmatics avoid attacks--and even play soccer

May 26, 1997

Back in the dark ages of asthma care--like five or so years ago--"managing" one's asthma meant scrambling for a puff of bronchodilator as breathing suddenly became as arduous as sucking peanut butter through a straw. But lately doctors have been abandoning this "treat as needed" approach in favor of a preventive one. "The paradigm has shifted from being reactive to being proactive," says Dr. Stan Szeffler of National Jewish Medical Center in Denver. And while today's "preventive" treatments still target the symptoms of asthma (inflammation and constriction of the bronchial tubes), scientists are in hot pursuit of drugs that target the causes: the hyperreactivity of those airways. Until the new drugs arrive, physicians are trying to educate patients to do the most with existing therapies.

The first step in preventing attacks is to eliminate "asthma triggers". To identify what triggers inflammation and bronchial constriction in a patient, doctors can perform a simple skin test for allergic reaction. The next step is to determine how severe the disease is. Someone who experiences no symptoms other than tightness in the chest after, say, sprinting for the schoolbus has a mild case and can usually get away with just a puff of a bronchodilator before exercise. But an asthmatic who regularly wheezes needs a veritable toolbox of drugs and devices, starting with the inhaler. Now almost as common in kids' backpacks as lunch money, inhalers hold a cartridge that, when pressed, releases a mist of medication. Another gadget is a "peak flow meter" that measures the rate at which the lungs expel air into a tube. That figure reveals how open the airways are and thus whether the patient needs a dose of medicine, and if so which one. (Depending on the severity of the disease, an asthmatic might use the monitor up to three times a day.) In some models a memory chip records the readings, and every month the patient downloads the numbers into a doctor's computer via a phone jack. By monitoring the data, physicians can fine-tune treatment.

The drugs they prescribe include controllers and relievers. Relievers, such as the inhalant albuterol, sold as Ventolin and Proventil, relax smooth muscles in the airways within seconds. They're emergency measures.

Controllers include antiinflammatories, such as corticosteroids, marketed as Vanceril, Azmacort and Flovent. Inhaled corticosteroids reduce inflammation in several ways, including by interference with lung cells' secretion of "cytokines." These substances inflame the airways, causing swelling and hence troubled breathing. Another anti-inflammatory, cromolyn sodium (marketed as Intal), is less effective than steroids but is often prescribed for children because it is so safe. The other class of controllers is bronchodilators, like salmeterol and theophylline. They relax the lungs' smooth muscle cells and keep airways open.

A new controller acts before a patient senses that an asthma attack is imminent. Leukotriene pathway inhibitors block the action of molecules that cause inflammation and constriction of the airways. Accolate and Zyflo, approved in 1996, are the first offerings in this new category; both are taken orally.

Given a choice, asthmatics would just as soon decline the honor of having a newly fascinating disease. But the mysterious rise in the number of asthmatics may have a silver lining: it has set off a race to bring new asthma treatments to market. The biotech firm Genentech is testing a molecule that blocks the action of immunoglobulin E (IgE), an antibody produced in response to asthma triggers. As any ragweed sufferer knows, IgE may be trying valiantly to fight off these invaders, but the collateral damage is huge: IgE binds to mast cells in the lungs and causes them to burst, releasing histamine and other inflammatory molecules. Genentech's IgE inactivator is probably two years from market.

Fast-acting relievers are being improved, too. The leading one, albuterol, is a mix of two mirror-image molecules. The good twin opens up breathing passages. The evil twin can make kids hyper or nervous, or cause irregular heartbeat or insomnia. One way to avoid the effects of the bad twin is to use a "spacer" device in the inhaler to send the medicine to the back of the throat and lungs, keeping it away from the tongue, where it can be swallowed and enter the bloodstream. Sepracor Inc. has another idea. It is trying to chemically separate out the bad twin, leaving the molecule that dilates airways. The drug could reach the market in 1998.

Even with imperfect drugs, most asthmatics can lead pretty normal lives. Although some patients avoid anything more vigorous than aiming the remote control, most need not. The problem is not exercise itself but breathing through the mouth. When air bypasses the nasal passages, which warm and moisten it, the lungs get walloped with cold, dry air, explains Dr. William Busse of the University of Wisconsin. That makes the airways contract. But most asthmatics can safely swim (lots of warm, moist air to breathe). Even gymnastics are usually OK (lots of stops and starts). Track and basketball are riskier, since constant running can induce through-the-mouth breathing. Soccer is fine for kids whose symptoms are controlled by a puff of Ventolin before kickoff; for more severe cases, playing fullback or goalie is safer than forward. But asthmatics should get an OK from their doctor before starting any exercise regimen.

Today's asthma therapies are more effective than the number of asthma deaths suggests. The drugs, devices and precautions work. But many patients--or, in the case of children, their parents--don't. "Only about 50 percent of inhaled medication is taken as prescribed," Dr. Henry Milgrom of National Jewish wrote. With such patients in mind, Jonathan Nyce of East Carolina University has created a molecule that strikes at the very core of asthma: the hyperreactivity of the airways. This exaggerated reactivity makes an asthmatic's airways inflame and constrict in response to triggers that don't bother a nonasthmatic's lungs at all. Nyce's "antisense molecule" deactivates the gene that produces the protein responsible for the hyperreactivity. "This could be the first once-a-day asthma medication to treat the underlying cause of the disease," says Nyce. If he's right, managing asthma will give way to curing it.

By Sharon Begley
With Anne Underwood in New York and Daniel Glick in Denver

Newsweek 5/26/97 Lifestyle/ Health: Yearning to Breathe Free