University of Virginia School of Medicine
Targeting Neutrophils in Severe Childhood Asthma
Childhood asthma is a chronic inflammatory lung disorder affecting 9 percent of children in the United States. Some children with asthma have severe or treatment-resistant disease that results in significant healthcare expenditures, missed school and impaired quality of life. Severe asthma is frequently characterized by the presence of neutrophils, an inflammatory cell type, in the lower airways. However, there are currently no therapies specifically designed to target neutrophilic asthma. We will examine the expression and function of the receptor for a protein called interleukin-5 (IL-5R) on the surface of airway neutrophils. The results of this study could have major impacts on the treatment of severe neutrophilic asthma, by advancing our understanding of how therapies that target the IL-5 pathway might be effective in this disease.
Update: To date, we have enrolled 86 children with treatment-refractory asthma. We have gained insights into the expression of the IL-5 receptor (CD125) on the surface of airway neutrophils, and how it may lead to inflammation in the asthmatic lung. We have also found that neutrophilic inflammation is important in children with severe asthma, highlighting the need for treatment strategies targeting neutrophils. Additional work to be completed in the next year will better explain how CD125 neutrophils contribute to airway inflammation and tissue damage, and define what factors lead to increased activity of CD125 on neutrophils. This work has the exciting potential to advance of our understanding of the disease process of severe childhood asthma.