Arizona Respiratory Center Receives Nearly $7 Million
NIH SCOR Grant for Study of Asthma
Jan. 14, 2002
Contact: Jean Spinelli or George Humphrey, (520)626-7301
Gasping for air, wheezing and coughing -- these symptoms of the chronic lung disease asthma affect an estimated 17 million Americans, according to the Centers for Disease Control and Prevention (CDC).
To better understand the role of genetic and environmental factors in the development of this increasingly prevalent and often life-long disease, the Arizona Respiratory Center has been awarded a National Institutes of Health (NIH) Specialized Center of Research (SCOR) grant of nearly $7 million for a five year study. The Arizona Respiratory Center is a Center of Excellence at the University of Arizona College of Medicine in Tucson.
The study, "SCOR in Cellular and Molecular Mechanisms of Asthma," will examine the interactions between environment and genes, their effect on immune system development and on the onset of this common childhood illness.
"Most cases of asthma begin during the first years of life, which suggests that complex gene-by-environment interactions during these early years contribute significantly to the risk for the development of asthma," says Fernando Martinez, MD, director of the Arizona Respiratory Center and principal investigator for the study. "Understanding the early alterations of the immune system that are associated with the subsequent development of asthma is essential for designing a strategy for preventing the disease. This grant provides a unique opportunity to study how environmental factors and genetic background influence the maturation of the immune system during the initial phases of asthma."
The SCOR study will consist of three projects. The first, led by Dr. Martinez, will explore gene-by-environment interactions that may be involved in the apparent protective effect of early exposure to microbes on the development of asthma. Recent European studies indicate that environmental factors associated with a farming lifestyle hinder asthma development. The project will use a population sample of children living in a rural farming area of Germany who were studied for exposure to indoor markers of microbial exposure and showed few cases of asthma.
"The genetic data will be analyzed to determine why these children were less susceptible to developing asthma despite microbial exposure," says Dr. Martinez. "This is the first time that genetic and environmental factors will be studied together in an extensive manner for a general population sample of children."
Project co-investigators include Walter Klimecki, DVM, PhD, associate research scientist, Arizona Respiratory Center; Catharine Holberg, PhD, research associate professor, pediatrics, Arizona Respiratory Center; Penelope Graves, ScD, assistant research scientist, Arizona Respiratory Center; and Erika von Mutius, MD, MSc, head, Department of Asthma and Allergy, Children's Hospital, University of Munich, Germany.
The second project will explore genetic and immune factors that may explain the strong relationship between the presence of atopic dermatitis (eczema) in early life and the development of asthma.
"Eczema is the first allergic disease we can detect, and 60 percent of children with eczema develop asthma," says Dr. Martinez. "Most children who develop asthma show responses to local airborne allergens very early in life, but not all children who show such responses develop asthma. We will look at factors connecting eczema and asthma to understand the cause and effect on the way the immune systems develops." Project leader will be Marilyn Halonen, PhD, deputy director, Arizona Respiratory Center; professor, pharmacology, microbiology and immunology; and research professor, medicine. Ann Wright, PhD, assistant director, Arizona Respiratory Center, and research professor, pediatrics, will serve as project co-investigator.
The third project, led by Donata Vercelli, MD, associate research scientist, Arizona Respiratory Center, and associate professor, cell biology and anatomy, will explore the complex molecular mechanisms involved in gene regulation in the immune system and their impact on asthma. "Research has shown that in both allergy and asthma the normal process by which cells become specialized to produce antibodies against allergens is altered in such a way that the antibody response itself causes disease," says Dr. Vercelli. "However, our work suggests that this response is more complex than initially thought, and a component of it may actually protect against the development of asthma. Understanding how the nature of the allergen and the genetic background of the individual influence the antibody response may lead to a new approach to treating and preventing asthma by regulating immune responses to allergens."
The Arizona Respiratory Center received its first NIH SCOR grant in 1971, when the NIH established five "specialized centers of research" throughout the country. That SCOR grant is the longest running study at the University. Research results have led to other studies, including three population studies, a physiology study, four basic science projects, and the Children's Respiratory Study. The findings of the Arizona Respiratory Center SCOR study and other SCOR grants throughout the nation have contributed greatly to a better understanding of asthma, including the knowledge that smoking, environmental dusts, pollen, air pollution and allergens effect the lungs and airways.
The Arizona Respiratory Center is internationally known for its research into the causes and modes of development of asthma, chronic obstructive lung disease and sleep apnea. The 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.