Asthma’s increase in recent years is mystifying researchers. Theories of why asthma rates continue to rise despite improvement in outdoor air quality have led to some possible explanations but medical experts have little scientific data to prove them.

Studies have indicated that asthma is both a genetic and environmental disease. Multiple genes are thought to determine a person’s predisposition to asthma and exposure to materials in the surrounding environment determines whether these genes express themselves or not.

The rise in mortality and hospitalization from asthma has occurred as air quality, as defined by the Environmental Protection Agency, has improved, said Homer Boushey, director of the Asthma Clinical Research Center at UCSF. Thus, there is a problem with the theory that industrial air pollution is responsible for the rise in asthma’s prevalence in US cities. People who live in poverty, especially minorities in cities, have alarming rates of asthma. In San Francisco, 80 of the 280 students at a Hunters Point elementary school were diagnosed with asthma last year. Children in Bay View/Hunters Point (BVHP) were hospitalized at a rate of nearly 80 per 10,000 for asthma, as compared to the state average of 22 per 10,000, according to a report by Kevin Grumbach, assistant professor of family and community medicine. For adults in this section of the city, the rate of 46 was five times higher than the state’s, and for the elderly, the rate nearly tripled the state numbers.

Although BVHP has 700 hazardous waste material facilities, 325 petroleum-storage tanks and two Superfund cleanup sites located in the district, researchers believe it may be the indoor air that is to blame. Many people in BVHP are poor, and thus may live in buildings infested with cockroaches and other allergen producers, such as house dust mites and tobacco smoke. Moreover, a study of childhood asthma rates in the former East and West Germany has also suggested that outdoor air quality is not the prime agitator. Researchers found a higher rate of asthma in the west, where the levels of air pollutants, especially of sulfates and particulates, are substantially lower than in the east.

Most people spend 80 percent or more of their time indoors, and with the introduction of wall to wall carpeting, reduced turn-over of indoor air (to save on heating costs), and the rise in popularity of cats as indoor pets, the population of the developed world may be exposed to higher concentrations of sensitizing allergens than ever before. The “big three” of indoor allergens known to sensitize humans are house dust mite, cat dander and cockroach.

“In Europe and the United States, the prevalence of asthma is about five percent, but the rate of increase in some parts of the developing world is shocking,” Boushey said. In San Francisco, although outdoor air quality is “pretty good,” Boushey said, “we have lots of cats, a damp environment, older homes that have lots of sensitizing molds, and long, overlapping pollen seasons.”

“Migration from industrializing to industrialized countries has been identified as a risk factor for Asian children moving to the UK and for Pacific islanders moving to Australia and New Zealand,” stated the journal The Lancet in its asthma supplement. “The same phenomenon has been observed in within-country migration from rural to urban areas, in most, but not all, studies in industrializing countries.”

This pattern is taking place in the US, where asthma affects 14 to 15 million persons and kills more than 5,000 people annually. “Asthma is less common among African-Americans who live in rural Georgia than it is among those who have migrated to Atlanta,” Boushey said. “With the move to an urban environment, changes in the allergens inhaled are probably accompanied by changes in diet and exercise, and some experts speculate that these changes may somehow alter how people respond to allergens they inhale.”

The urban, modern lifestyle may also account for why children are getting asthma at such a high rate. “The peak of asthma is in children,” Boushey said. “There is a dramatic increase in children bringing inhalers to school, especially in Hunters Point.” This increase is evident in other parts of the world. “Urban areas in Southeast Asia have reported a four-fold increase in the number of children with asthma,” Boushey said. Some researchers have speculated that because children spend more time at home and play close to the ground, they are more exposed to allergens.

“Children receive greater exposure to environmental pollutants whether they be in the air, water, food, their homes or their schools,” said Lawrie Mott of the Natural Resources Defense Council at a recent Occupational and Environmental Medicine Grand Rounds at Mount Zion. “Likewise, people of color are disproportionately exposed to pollution present in their communities. The likely confluence of these two trends is that children of color are the subgroup of the population most exposed, and least protected, from environmental health threats.”

There is yet another theory of why asthma has increased in modern day Western civilization. Because vaccines and antibiotics have reduced the frequency and severity of infections of the respiratory tract, and because public health measures have reduced the prevalence of parasitic infections of the gut, some researchers believe that the balance is altered between Th1 lymphocytes, which fight infection, and Th2 lymphocytes, which are thought to defend against parasites. According to this theory, the decline in respiratory infections in early childhood means that the Th1 lymphocytes aren’t kept active enough to inhibit activity of Th2 lymphocytes in the lungs. The Th2 lymphocytes, no longer attracted to fight parasites in the gut, are free to act in the respiratory tract. “It is as if these Th2 lymphocytes are looking for a purpose, and, when they encounter an allergen, think it’s a parasite and attack it,” said Boushey, emphasizing that this theory is far from proven.

“It raises this caveat that in changing tremendously the usual childhood infections that we all get and our immune systems evolving...there may be some immune consequences that nobody factored in,” said Richard Locksley, professor of medicine and microbiology and immunology. “But nobody is suggesting that we stop childhood vaccinations. It is still at the level of being observational. The challenge is to find out if they [childhood vaccinations and asthma increase] are truly related.”

Many UCSF researchers are studying asthma, from its cellular functions to clinical studies of asthma treatments. At a recent Dean’s Research Seminar, Dean Sheppard, professor of medicine and director of the Lung Biology Center at SFGH, Locksley, and David Corry, assistant professor of medicine, presented their research on asthma. Corry and Locksley discussed studies of transgenic mice indicating a primary role for lymphocytic production of interleukin-4 in mediating the pulmonary response to allergic sensitization and challenge, while Sheppard showed results from other studies of transgenic mice indicating that a disorder in the expression or function of adhesion molecules on airway epithelial cells may play a fundamental role in asthma’s pathogenesis.

“We’re just beginning to solve this conundrum,” Sheppard said. “It will take considerably more effort to understand this common and increasingly morbid disease.”

Although advances have been made in asthma therapies in recent years, Boushey said there is room for improvement in asthma’s diagnosis and treatment. “Where we need to improve is in making an objective assessment of severity,” Boushey said. “Retrospective studies of people who die from asthma show that 15 to 30 percent were thought to have had mild asthma prior to their last attack. A first step is to be sure that all patients with asthma know they are at risk, albeit a very low one for people with mild disease, and are taught how to recognize when they are getting into trouble and what to do if this occurs.”

UCSF’s asthma education program teaches asthmatics about their disease and how to avoid exacerbations of it. “It’s important to have a close connection and partnership with the clinician who is caring for the asthma for a correct assessment of the severity,” said Susan Janson, a nurse educator who directs the program. She says the goal of asthma management is to be symptom-free and able to engage in any activity, such as sports or work, without interruption.

“Be an advocate for yourself,” Janson said. “Nobody should be having daily symptoms. If they do, they have very severe asthma or their treatment is not adequate and they should go back to their physician for a change in treatment.”

By Paula Murphy

First appeared 12/22/97

The Asthma Center needs the help of just about anyone interested in becoming a research volunteer. Researchers usually conduct several studies simultaneously, so people with all types of asthma are needed -- allergic and non-allergic; occasional, intermittent, or persistent; very mild, mild, moderate, or severe.
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