Lung Fluid and Peripheral Blood Neutrophil IL-5 Surface Receptor in Children With Asthma

The pattern of lower airway inflammation in asthma is heterogeneous, but in many patients,
the polymorphonuclear neutrophil (PMN) is the predominant granulocyte infiltrating the
airspaces. Although it is known to have an important function in innate immune defense, the
role of the PMN in asthma has not been well elucidated. In work in progress, the
investigators have identified the receptor for IL-5 on the surface of bronchoalveolar lavage
(BAL) PMNs in a subset of children with severe, treatment-resistant asthma, a characteristic
that is not found in peripheral blood neutrophils. While the function of this IL-5 receptor
has yet to be determined, preliminary evidence strongly supports a mechanism linking
neutrophilic with type 2 inflammation in the lower airways of children with asthma, a
discovery that has exciting potential to modify the treatment of asthma.

The primary objective of this observational cross-sectional study is to test the overall
hypothesis that therapeutic intervention directed against the IL-5R on lung PMNs will
decrease inflammation and improve clinical outcomes in patients with poorly controlled
asthma. The secondary study objective is to demonstrate that IL-5R expression on
lung-infiltrating PMNs is functional, will activate known IL-5R-induced signaling pathways,
and will lead to enhanced PMN pro-inflammatory activity including increased PMN recruitment,
prolonged survival, degranulation, and release of reactive oxygen species.