"Unfortunately, asthma is a very complex disease," says Fernando Martinez, MD, director of the Center. "It is not caused by a single gene or environmental factor, but by a variety of these components and their complex interactions." Understanding all the forces at work in the development of asthma is essential for designing a strategy for defeating the disease.
A Center of Excellence at the University of Arizona College of Medicine in Tucson, the Arizona Respiratory Center brings together experts in immunology, pathology, radiology, internal medicine, pediatrics, pharmacology, epidemiology, molecular genetics, computer science and many other disciplines to attack respiratory disease in children and adults. Following is some of the research involved in the Center's campaign against asthma:
"Only when we know which genes are involved in causing lung and heart disease can we develop cures for them," says Walter Klimecki, DVM, PhD, associate research scientist at the Arizona Respiratory Center and an investigator for one of the Center's largest genetics studies.
"Genomic Applications for Heart, Lung, and Blood Research" seeks to discover the variations in genes involved in the immune system that contribute to asthma, chronic obstructive pulmonary disease (COPD), myocardial infarction (heart attack), and deep venous thrombosis (DVT). Among the most common diseases of the lung, heart and blood, they are responsible for close to $100 billion per year in health care costs, Dr. Klimecki says.
"We believe these diseases share an important common feature: they are influenced by the immune system and inflammation. Using all of the available scientific information, including the recent work of the human genome project, we will choose 50 immune system genes that may play a major role in this process," explains Dr. Klimecki. "These genes will be analyzed in 90 people to compare the sequences, one person to the next, to find variations. Then we will test populations of people with asthma, COPD, myocardial infarction and DVT against healthy populations to determine whether these gene variations are associated with these diseases. This will be the first step to finding the genes that cause, or cause susceptibility to, these diseases."
Arizona Respiratory Center members involved in the study include Center director Fernando Martinez, MD, principal investigator for the overall project; Dr. Klimecki, principal investigator, Analytical Genomics Center and Bioinformatics Center-Tucson; and Donata Vercelli, MD, principal investigator, Functional Genomics Center. The research team also includes Harvard University investigators from the Bioinformatics Program at Children's Hospital Boston and the Department of Medicine at Brigham and Women's Hospital, both teaching hospitals of Harvard Medical School.
The four-year study is funded by the National Institutes of Health, National Heart, Lung and Blood Institute, part of the NIH.
"Tucson is one of seven sites in the country for the study, which is focusing on underserved, primarily minority 'inner-city' children and the indoor environmental factors involved in asthma," says principal investigator Wayne Morgan, MD, associate director of the Arizona Respiratory Center, UA professor of pediatrics and physiology, and chief of pediatric pulmonary medicine. "Our effort is directed at determining which factors, such as mold, dust and cockroach eggs, are most likely to trigger asthma attacks in inner city children, as well as the role of physicians in identifying and monitoring asthma patients."
The four-year study is part of a multicenter, nationwide program funded by the National Institute of Allergy and Infectious Disease and the National Institute of Environmental Health Science, both part of the National Institutes of Health (NIH). Other study sites are Chicago, New York (Manhattan and the Bronx), Dallas, Seattle and Boston.
Co-investigators on the $1.9 million Tucson grant are Paul Enright, MD, associate professor in the UA Department of Medicine, and Anne Wright, PhD, Arizona Respiratory Center assistant director and research professor of pediatrics. Collaborating with UA researchers are physicians with El Rio/Mercy Care Health Plan and Kino Community Hospital/Pima Health Systems.
Approximately 140 Tucson children ages 6-12 with moderate to severe asthma from families living in census tracts with a high poverty level are participating in the study, which has enrolled more than 900 children nationwide.
Participants receive an in-depth clinical evaluation, including an assessment of the factors affecting their asthma, allergy skin testing and a lung function exam. Participants also receive an extensive evaluation of their environment to determine if factors in the home, including common indoor allergens and tobacco smoke, are contributing to the child's asthma, along with recommendations on how to make improvements.
Some study participants, chosen randomly, also receive at no cost a comprehensive environmental intervention that could include professional cockroach extermination, repair of cracks and pest entry points, encasing mattress and pillows, and installing filters to reduce airborne cat, dog and fungal allergens. In addition, the family is given information about indoor allergens in the home and how to reduce the child's exposure to these allergens.
"This study will help determine the most efficient manner to improve the health of low-income children with asthma who need an aggressive program to manage their asthma," Dr. Morgan says. "It will provide valuable insights regarding control of the inner-city asthma epidemic."
However, the extent to which this major advance in asthma management succeeds in preventing or diminishing the severity of the disease depends in large part on patient behavior. "Research shows that medicine-taking behavior is motivated by patient perceptions about the cause and symptoms of their illness and how medications work. Yet, little is known about the perceptions of asthmatic children and their parents and how these beliefs influence management of the disease," says Anne Wright, PhD, assistant director of the Arizona Respiratory Center and research professor of pediatrics.
Because few studies have investigated the perceptions of the disease by Native Americans, among whom the incidence of asthma is increasing, Dr. Wright and David Van Sickle, MA, a UA doctoral candidate in anthropology, collaborated on a study, "Navajo Perceptions of Asthma and Asthma Medications: Clinical Implications."
UA researchers worked with colleagues from Diné College and Northern Navajo Medical Center in Shiprock, N.M., on the project, which was supported by the National Institute of Allergy and Infectious Diseases. Study results were published in the July 2001 edition of the journal Pediatrics.
The study found that a combination of factors influenced participants' hesitancy to use inhaled anti-inflammatory medication on a long-term basis, particularly in the absence of symptoms.
Parents viewed asthma not as a chronic disease but as temporary symptoms that children would outgrow or that would disappear if the body was allowed to heal itself. They also expressed concerns about asthma medication side effects and dependence. Because bronchodilators were seen as being immediately effective, they were used more frequently than inhaled steroids or other anti-inflammatories.
While severity of an asthma attack was the main reason to seek emergency department (ED) treatment, the nebulized medicines given in the ED were perceived by many as the most effective medicine. Trying to control symptoms at home with prescription medication sometimes was perceived as prolonging suffering. In addition, medicine use and medical attention often were delayed because symptoms had not yet approached the remembered severity of previous attacks requiring ED treatment.
The study also found that children older than age 7 had a significant level of responsibility for their medications, consistent with the value placed on individual autonomy in Navajo culture.
"This finding underscores the importance of identifying who is responsible for supervising medication use within the family, so that educational messages about the medications can be targeted to the appropriate persons, in many cases the child as well as the parent," says Dr. Wright.
"Ethnographic research such as this provides valuable information about how medicines are used," notes Dr. Wright. "Understanding perceptions that discourage use of inhaled anti-inflammatory medication by Navajo asthmatics should lead to the development of appropriate educational materials, improved management, and a substantial reduction in costs of care."
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