“The overarching goal of this research is to identify mechanisms associated with the recognition of fungi that contribute to the severity of fungal asthma,” said Chad Steele, Ph.D., professor in the Division of Pulmonary, Allergy and Critical Care Medicine and primary investigator of the new study. “We want to see how and why this immune response to fungi makes asthma worse.”Studies have shown that asthmatics who are sensitive to fungi are more likely to require hospitalization during asthma attacks and are more likely to require higher levels of therapeutic steroids during these episodes.
Steele, who has been examining the role of fungi on asthma for years, says that there are three or four common fungi that are most likely to affect asthma patients, including Aspergillus, commonly found on starchy foods like decaying bread and potatoes, or on plants and trees.
Steele will be looking at Aspergillus in particular, examining the components of the cell wall of the fungus, searching for molecules that seem to have the most effect on asthma responses. Much of the study’s focus will be on certain immune system proteins present in the lungs, particularly a family of cytokines that includes interleukin-22, among others. Previous studies by Steele’s laboratory have shown that IL-22 is required for the onset of allergic fungal asthma.
“Upon completion of the proposed studies, we expect to understand how IL-22 contributes to asthma severity and which components of the fungal cell wall drive asthma severity and to translate our results in human asthmatics who skin-test positive for fungi,” Steele said. “Data from these studies could possibly identify fungal cell wall allergens that may be targeted for controlling asthma severity in patients who test positive. If we can isolate those molecules that appear to be most associated with worsening asthma, we can look for anti-fungal drugs that may limit or curtail the allergic response and potentially lessen the effects on patients.”
Patients who test positive for fungi on skin tests tend to have much more severe asthma. In 2001, the NHLBI launched the Severe Asthma Research Program to develop a collaborative network approach to comprehensively characterize patients with asthma via clinical, physiologic, genomic and radiologic evaluations. During the past 10 years, the SARP network, which comprises seven sites throughout the United States, has enrolled more than 1,200 asthmatics, with more than a third of these individuals defined as severe asthmatics.
Information gleaned from the SARP findings in humans form the basis of Steele’s animal model studies. Steele says this makes the project a bit unusual, as it is taking clinical observations from patients back to the research laboratory with the intent to discover new knowledge that will ultimately be brought back to the clinical setting for patients’ benefit.
“We talk often of taking research from bench to bedside,” said Steele. “This aims to take research from bedside to bench and back again.”