Asthma is a common chronic lung disease affecting approximately 1 in 13 adults in the U.S., with rates of asthma in the U.S. increasing yearly. Scientists are working hard to understand the disease and test potential treatments. The Inhalation Exposure Core at the California National Primate Research Center (CNPRC) is one of the few facilities worldwide that can research environmental effects on asthma development.
Modeling Asthma
Perfectly paired with naturally occurring conditions in Northern California like wildfire smoke and roadway air pollution, the Inhalation Exposure Core is a critical resource for mechanistic and therapeutic studies of lung disease. Together with expertise from scientists in the CNPRC Cardiorespiratory Diseases Unit, the science of how children and adults develop asthma is an important question that must be addressed when considering strategies to ameliorate symptoms.
There is currently no cure for asthma. While the disease can usually be managed with the right treatments, medications are costly, and researchers are still looking for answers. The head of CNPRC’s Inhalation Exposure Core, Lisa Miller, explains, “the nonhuman primate is the ideal laboratory animal model for the study of asthma across the lifespan”.
Unanswered Questions
Asthma is a condition in which the lungs are sensitive to triggers in the air. Pollutants or allergens lead the airway to restrict causing difficulty breathing and if left untreated, death. The disease is can also vary between patients. For example, a subset of patients, primarily adult females, develop a perplexing non-atopic or non-allergen induced asthma that unresponsive to current treatments.
A newly established nonhuman primate model of non-atopic asthma could potentially benefit up to 7.5 million Americans[1]. Like humans, rhesus macaques can naturally develop a form of airway hyperreactivity matching non-atopic asthma or non-allergen asthma. The model is also “astonishingly reproducible” Miller remarks.
Infant Behavior and Asthma
Through data collected from a unique longitudinal research project, the biobehavioral assessment program (BBA), CNPRC researchers found a compelling relationship. Behavioral inhibition, a temperament defined by fearful responses to novelty, during infancy was associated with airway hyperreactivity later in development in a 2013 study published in PLoS One.
After realizing the surprising connection between behavioral inhibition and the development of asthma phenotypes, researchers combined available resources from the BBA and Inhalation Exposure Core to follow the development of 49 rhesus macaque monkeys from infancy to yearling status. Of these 49 animals, 24 were classified as behaviorally inhibited during infancy and subsequently illustrated airway hyperresponsivity as yearlings.
The Right Resources for the Research
The CNPRC’s Inhalation Exposure Core consisting of expert scientists, veterinarians, and advanced facilities is well-positioned to test the efficacy of possible treatments for airway hyperreactivity, either naturally in non-atopic asthma or in response to toxic inhalants such as pollutant ozone (O3).
Notably, the Inhalation Exposure Core played a key role in a study published through the Journal of Allergy and Clinical Immunology in 2020. The study involved a promising new drug derived from flaxseed to assess whether the non-atopic asthma monkey model would be sensitive to novel antioxidant compounds.
Indeed, the research identified specific immune changes resulting from O3 exposure and showed the treatment was able to prevent the immune changes related to asthma symptoms. The drug that was tested in the rhesus macaque model of non-atopic asthma is now planned for clinical trial in human asthmatics.
Next Steps
The varied forms, causes, and developmental onsets of asthma make the disease particularly difficult to model in simpler organisms. The rhesus monkey model of asthma continues to be critical in developing and testing new therapies for asthma phenotypes.
“The CNPRC Inhalation Exposure Core is a state-of-the-art facility with unique expertise that cannot be found anywhere outside of UC Davis; it is a critical resource for translational cardiorespiratory disease research with global impact for the scientific community,” says Miller.
There is an urgent need to better understand the chronic lung disease as doctors continue to report increased prevalence of asthma in their patients. CNPRC researchers are hopeful that their science can help. These findings from CNPRC scientists not only illustrate a reproducible and naturally occurring animal model of asthma, but they also open the door to many more questions about how behavior and personality interact with health.
[1] Calculated by applying a 30% estimate from https://www.medicalnewstoday.com/articles/325536#intrinsic-vs-extrinsic to current U.S. statistics of asthma prevalence (https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm)
Written by Logan Savidge
Inhalation and Exposure Core Contact:
Lisa Miller | lmiller@ucdavis.edu
