The asthma riddle - Scientists are still struggling to understand the epidemic

By Stephen Smith, Globe Staff, 4/13/2004

There's no disputing that the United States is in the midst of an unparalleled asthma attack: A pair of federal reports recently announced that 16 million adults and 9 million children now suffer from the respiratory illness, wringing $13 billion from the nation's annual health-care bill.

It is the cause of all this misery that remains murky.

Maybe it's the way we seal ourselves into our newly built houses. Or maybe how obsessed we are with keeping ourselves free of germs and disease. Or maybe even that we now cure our children's fevers with Tylenol instead of aspirin. Or perhaps it's all of the above and more.

"I don't think there will ever be a silver bullet for asthma," said Dr. Megan Sandel, a pediatrician at Boston University Medical Center who has studied the interplay between housing conditions and respiratory illnesses. "I don't think we're going to end up saying, `This is the one thing going on with asthma and this is how we fix it.' "

Bringing the disease under control will never be as simple as writing the same prescription for 25 million Americans, researchers say. A medicine used to treat youngsters suffering from exercise-induced asthma, for instance, doesn't do much good for older adults with a more chronic version of the disease. Asthma scientists now hope to develop drugs that will intervene at different stages of the disease. Ultimately, by using the tools of genetic science, doctors expect to tailor asthma treatments to the needs of each patient.

If the first mystery of asthma is its root cause and the second is how to treat it, then the third is why it has increased so quickly and so furiously.

As recently as 1980, medical surveys showed that barely 6.8 million Americans -- both children and adults -- had been diagnosed with the illness.

"If you speak to pediatricians who trained 20 or 30 years ago, they will tell you that asthma was a disease you saw only occasionally," Sandel said. "And if you were to ask a classroom of kids to raise their hands to show how many had asthma or carried an inhaler, maybe one or two would. Now, you ask and in some classes you will find one-third of the kids have asthma."

One tempting explanation is to blame the reported increase on either better tracking of the disease or more thorough diagnosing. While conceding that these factors have contributed somewhat, specialists note that steep increases in both the number of children hospitalized for asthma and those treated in emergency rooms show that a true health crisis has emerged.

So what happened in the blink of two decades?

Genetics clearly play a role in who gets asthma -- scientists know that children born to asthmatic parents are substantially more likely to develop the illness -- but genes don't change fast enough to create a 20-year jump in cases.

"Probably, the population was just as susceptible 25 years ago but somehow that susceptibility has now been converted into disease," said Dr. Stephen Redd, chief of the air pollution and respiratory health branch at the US Centers for Disease Control and Prevention.

So, something in the outside world must have changed to change what is happening at the molecular level in humans.

Among the more popular -- albeit controversial -- theories is the hygiene hypothesis, which suggests that we're simply too clean, too free of the bacteria and viruses responsible for illnesses such as measles and mumps.

According to this theory, soldiers of the immune system essentially become bored as their old enemies are vanquished by vaccines. So they instead train their radar on otherwise harmless agents -- maybe dust mites -- and misidentify them as dangerous invaders, mounting a response that incites inflammation in the lungs and constriction of the smooth muscle in airways.

European studies have shown that children who grow up on farms exposed to livestock are less likely to suffer from asthma. An American study reported that children living in homes swarming with cats were less likely to develop asthma than children in houses with just a single cat. All those exposures, the scientists argue, have the effect of teaching the immune system not to respond in a harmful way to what might otherwise trigger attacks.

But here's the rub: Children in crowded, dilapidated urban environments would seem to be exposed to all manner of infectious agents, which, in turn, would seem to confer protection against asthma. But when researchers in New York surveyed homeless camps, they found 50 percent of children had asthma.

"The hygiene hypothesis is a nice tidy hypothesis, and there are data to support it and data not to support it," said Ken Adams, who recently retired as chief of the asthma and inflammation section at the National Institute of Allergy and Infectious Diseases. "I think it's overly simplistic. Like every grand hypothesis, there's some truth to it, and there's some holes to it."

Other scientists are investigating how changes in home-building and in Western lifestyles might be influencing the increase in asthma. Although air pollution -- particularly diesel emissions -- has been implicated in asthma, research suggests that the air we breathe inside may be even more important than the air we inhale outside.

In the years following the energy crisis of the 1970s, houses were turned into sealed vaults, with measures taken to prevent inside air from leaking out and outside air from seeping in. The result is that well-known asthma triggers such as cockroach droppings, dust mites, and pet dander get trapped inside. And so do children, held hostage to their homes either because of parental concerns about safety or because the kids are riveted to the TV or computer.

"When I grew up, we were outside until our parents dragged us inside after roaming the neighborhood looking for us," said Dr. George O'Connor, a pulmonologist and asthma researcher at the BU School of Medicine. "That's not true anymore."

Another change that researchers suspect could have something to do with the epidemic: A shift away from using aspirin for children's illnesses. A team of Wisconsin scientists argued in a 1998 medical journal article that increasing use of pain relievers containing acetaminophen -- the key ingredient in Tylenol -- produces a complex chemical interaction that affects the immune system. The resulting change, they wrote, may make children more sensitive to allergens that trigger asthma.

The complexity of the illness and its causes leaves the future of asthma control looking a lot like cancer treatment.

"Cancer isn't one disease, it's many diseases," said Dr. Richard Schwartzstein , clinical director in the Division of Pulmonary and Critical Care Medicine at Beth Israel Deaconess Medical Center. "It's the same way with asthma."