UA scientists working to identify traits that increase or decrease susceptibility to asthma

University of Arizona BIO5 Institute researchers are working to identify traits that increase or decrease a person’s susceptibility to asthma. This effort could some day lead to treatments – administered as early as in the womb – to prevent asthma and other diseases from occurring in people who have a tendency to get them.

Funded with a two-year, $958,544 National Institutes of Health grant, Donata Vercelli, is leading a study to identify epigenetic predictors of asthma in neonates. Asthma, a chronic inflammation of the lungs and air passages that affects the ability to breath, affects 15 percent of the population and is a growing health problem, Vercelli said.

The study is looking at the interaction of several factors, including genetics, environment and timing, to discover markers that are present in people who get asthma, and in people who are protected from the disease, said Vercelli, the project’s principal investigator and BIO5 member.

“We are trying to understand what it takes to become asthmatic. We really don’t know exactly which biological pathways are involved,” she said. “We think that if we look at children at birth, the ones who will develop asthma later on will be different in their genetic marks than children who will not become asthmatic. Did something happen in utero that marked their genes differently?”

An earlier University of Arizona research project showed that the presence of dogs during the first two years of a child’s life decreases the chance the child will develop asthma, proving that environmental factors play a role, said Vercelli, UA professor of cell biology, director of the Arizona Center for the Biology of Complex Diseases (ACBD) and director of the Functional Genomics Laboratory at the Arizona Respiratory Center.

Studies have also shown that children born and/or raised on farms in close proximity to livestock are less likely to develop asthma, she said.

“If a pregnant mother spends a lot of time in stables in contact with livestock, the child that is born is going to have a much lower risk for asthma. It is very possible that there is a prenatal affect,” she said.

“The fact that exposure to dogs or stables significantly reduces the risk of asthma tells you there is a lot of room for prevention,” she said.

The industrialized world has seen a move toward environmental cleanliness in the past half century that appears to have triggered an increase in the occurrence of complex diseases like asthma, allergies, ulcerative colitis, Alzheimer’s and others, she said.

“Over the past 50 years or so very profound changes have happened in the way we live that have to do with cleanliness, with immunization, with the use of antibiotics and things of that kind. We have reduced very dramatically the microbial burden, the amount of microbial products in the environment,” she said.

“The immune system hasn’t taken this lightly – in fact, the immune system does not work as well without these products around,” she said. “We have decreased the microbial burden so drastically that our immune systems has gone berserk.”

Children born of mothers with asthma are at greater risk to get the disease, said Marilyn Halonen, project co-investigator, UA professor of pharmacology and immunobiology and BIO5 member.

“An objective is to identify potential epigenetic changes that are detectable at birth in children born to mothers with asthma,” Halonen said. The study will look at genetic expression that can lead to asthma, and what can be done to prevent such expressions, she said.

By discovering the process that results in the altered pattern of gene expression that results in asthma, a way to interfere with that process could be developed, she said.

“There might be some way to treat the mother during pregnancy and prevent the child from getting asthma,” she said. “In the case of asthma we think the window is in the very young: probably asthma begins in the first year of life.”

The project is fortunate that data in the form of study of youngsters from birth to age 8 by the Arizona Respiratory Center are already available, Halonen said. Blood samples taken at birth and annually up to age five from almost 500 local children will allow researchers to see what elements change in the youngsters as related to the development of asthma.

“This capacity for one project to build off another one is wonderful,” she said. “Providing the samples and the follow up information on the children and the mothers makes it possible to do this kind of study.”

While the markers that lead to asthma are expected to be identified within two years, it will likely be many years down the road before a treatment is developed, tested and approved for use, Halonen said.