Clinical trial NCT02866487: Lung Fluid and Peripheral Blood Neutrophil IL-5 Surface Receptor in Children With Asthma
Official title: Lung Fluid and Peripheral Blood Neutrophil IL-5 Surface Receptor in Children With Asthma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 72
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population includes children with refractory respiratory symptoms, most who will have poorly-controlled asthma. An age similar comparison group with structural lung anomalies who undergo diagnostic bronchoscopy will serve as controls.

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Ages 0-17
* Treatment-resistant, refractory respiratory symptoms
* Scheduled for a clinical diagnostic bronchoscopy

Exclusion Criteria:

* Known lower respiratory tract infection within 60 days of scheduled bronchoscopy
* Systemic disorders involving the heart, respiratory system, CNS, renal, and endocrine systems

Primary outcomes:
measure: Percent neutrophils bearing surface markers for IL-5 Receptor
timeFrame: 6+ months post bronchoscopy
Secondary outcomes:
measure: In vitro analysis of IL-5 Receptor (IL-5 R) function: Signaling via the IL-5 R displayed on neutrophils from the BAL (and if necessary, peripheral blood) following ligand (IL-5) binding
timeFrame: 48-72 hours post bronchoscopy
measure: Measurement of neutrophil degranulation and inflammatory mediator production following IL-5 binding to its receptor on neutrophils isolated from the BAL
timeFrame: 48-72 hours post bronchoscopy
measure: Production of Reactive Oxygen Species following IL-5 R engagement
timeFrame: 48-72 hours post bronchoscopy
measure: Measurement of neutrophil survival in culture upon IL-5 R engagement in vitro
timeFrame: 48-72 hours post bronchoscopy
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Virginia
name: William G Teague, MD
role: PRINCIPAL_INVESTIGATOR
References: