Carol Considine, the 63-year-old matriarch of a family of six children and 11 grandchildren, walks into the Partners Asthma Center at Boston's Brigham and Women's Hospital on a rainy Wednesday for a check-up she undergoes every few months. She is cheery and soft-spoken--and sometimes horribly desperate to breathe. "The shortness of breath comes first," says Considine. "Then I start wheezing, and it blows up into a full attack."

Considine battles asthma, a disease with which she was not diagnosed until age 45 when she fell ill with a cough that brought up greenish phlegm from her labored lungs. She was hospitalized 25 times over the next five years and took a permanent leave of absence from her job. She began using a powerful steroid medication that calmed her inflamed lungs but also left her with osteoporosis, diabetes, and skin that tears easily. "The frustrating part is that you look around and want to do something like gardening or cleaning or decorating," notes Considine, "and I don't do any of that anymore."

In her daily struggle to breathe, Considine is not alone. She is one of 17 million Americans who suffer from asthma, a chronic respiratory disease that defies easy profiling. Suspected causes, risk factors, and treatments are astonishingly varied, while fundamental aspects of the disease remain unknown. It's the perfect target for researchers at the Harvard School of Public Health, where a de facto asthma center has emerged that represents the best hope for people like Considine.

At the School, the approach is to attack the asthma epidemic on many levels and then share the results among researchers. Experts believe this may be the smartest way to curtail the disease because asthma probably results not from a single contagion but from a confluence of environmental and genetic factors, each requiring its own investigation. "There is no common story," says Joseph Brain, the Cecil K. and Philip Drinker Professor of Environmental Physiology and chair of the Department of Environmental Health, "so we are coming at it from many different ways."

Some asthmatics may be born genetically susceptible to the disease. To investigate this possibility, researchers from the School and the Channing Laboratory are collaborating on studies in three countries to uncover the genetic basis of asthma. Xiping Xu, associate professor of occupational epidemiology in the Department of Environmental Health, runs the Program for Population Genetics, which analyzes genetic information from large groups of people to find associations with several common conditions. A Chinese native, Xu began looking at the relationship between genetics and asthma in his home country in the mid-90s, querying families about their lifestyles and analyzing their blood samples to correlate dna to asthma incidence. In particular, he tracked pairs of siblings when one has asthma and the other does not. "Our eventual goal is to use this study to improve the diagnosis and treatment strategies of asthma," said Xu.

Xu is joined by Scott Weiss, professor in the Department of Environmental Health and Channing Laboratory researcher, who is conducting a similar study of families in the United States and a pilot study in Costa Rica. Weiss says he is unsure how much of a role genes play in asthma but hopes that his investigation will contribute needed pieces to solving the asthma puzzle. "Now we can look at genes and environment together," he remarks, "and this combination will bring about new study designs and ideas about disease causation."

For Carol Considine, genealogy does not seem to play a role in her affliction. No one else in her immediate family has the disease. She suspects that an air conditioning unit at her work somehow triggered her first attack but is unsure. The basis for her suspicions is a huge part of the asthma investigation that looks into environmental factors of the epidemic.

Surprisingly, asthma is a disease of wealthy countries with well-established health care systems, and rates are high in nations such as the United States, Sweden, Australia, England, and New Zealand. Genetics is not enough to explain the phenomenon, and some experts are beginning to think that asthma--even adult-onset asthma--may start to develop very early in life, perhaps even in utero. One theory is that people in developed countries just may be too clean for their own health. Researchers call this idea the "hygiene hypothesis," which suggests that people who are not exposed to enough infections when they are very young develop twitchy immune systems that may overreact to mild irritants. Allergies and asthma ensue.

Donald Milton, associate professor of occupational and environmental health in the Department of Environmental Health, knows all about the hygiene hypothesis because he has seen its possible effects in common households. Milton and his colleagues Diane Gold, assistant professor, and Harriet Burge, associate professor, both in the Department of Environmental Health, have been measuring levels of air particles called endotoxins in homes. Endotoxins are released from bacteria when they disintegrate and are known to inflame airways and produce an asthma-like syndrome at high levels. Yet Milton and his colleagues have confirmed an intriguing relationship between dogs, endotoxins, and asthma: families with dogs have higher endotoxin levels in their homes than those without man's best friend--and they also have lower rates of asthma. Although still unclear, the link between dogs and household endotoxins may be related to the dirt that dogs introduce, which may provide some protective effect. "Some aspect of this is reflected in what my grandfather used to say, 'You have to eat a peck of dirt in your life'," notes Milton. "He was a farmer in the Ohio Valley and thought we were too worried about cleanliness, and perhaps this is true. What he wasn't focused on is that you have to get this dirt early in your life."

The hygiene hypothesis is just one potential explanation for high asthma rates in developed nations. Some alternate theories being studied at the School suggest that these countries have more carpeting that traps dust mites, dander, and other irritants and better insulated homes that prevent irritants from blowing away. Others postulate that people in developed countries may be exposed to more air pollutants produced by diesel trucks and industry that exacerbate asthma susceptibilities.

The recent efforts of School researchers, who have identified not only a link between obesity and asthma but also a possible biological explanation for the disease, exemplify the kind of cooperation necessary to allay this multivariate condition. While sifting through data from the Nurses' Health Study in 1997, Channing Laboratory researcher Carlos Camargo, D.P.H.'96, observed that women with high body mass index--a more accurate measurement of obesity than weight alone--were at a significantly increased risk of developing asthma. Camargo, Scott Weiss, and their colleagues were unsure of the biology behind the link, so Weiss called Jeffrey Fredberg, professor of bioengineering and physiology in the Department of Environmental Health, to see if he could offer a hypothesis.

Fredberg thought the answer could be found in the work of Stephanie Shore, an associate professor in his department. Shore devised an experiment in which she exposed skinny and fat mice to ozone, which inflames the lungs. She expected the heavier mice to have worse inflammation, but the obese mice didn't seem to be affected in the least. Instead, their skinny counterparts showed inflammation. When Shore compared the two kinds of mice, she noted that the obese mice had been genetically modified to lack a hormone called leptin, which is found in both mice and humans. In obese people, leptin runs through the blood at high levels. Perhaps, theorized Shore, it is the hormone--and not the obesity--that makes heavier people more susceptible to asthma attacks. The work seemed to offer the biological explanation Camargo and Weiss sought. "Here are two big public health problemsÑobesity and asthma--and we may have found a key factor to link them," says Fredberg.

As for Carol Considine, she considers herself lucky to have a close-knit family nearby who visits her Natick home frequently to check on her. She hopes someday soon that their concern may become unnecessary. Comments Weiss, "The therapeutic solution that will come from this research is hard to predict, but I think that we will reach a point at which we will understand the disease in much more intimate detail, and I don't think it's going to take a hundred years to do that."

Christina Roache