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

NCT02866487 | Completed

• 1 other identifier: NAIL-5
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Percent neutrophils bearing surface markers for IL-5 Receptor

  The percentage of neutrophils which bear surface markers for the IL5-R in lung fluid and peripheral blood will be compared in children with different asthma phenotypes

  6+ months post bronchoscopy

Secondary Outcomes (4)

• 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

  48-72 hours post bronchoscopy

• Measurement of neutrophil degranulation and inflammatory mediator production following IL-5 binding to its receptor on neutrophils isolated from the BAL

  48-72 hours post bronchoscopy

• Production of Reactive Oxygen Species following IL-5 R engagement

  48-72 hours post bronchoscopy

• Measurement of neutrophil survival in culture upon IL-5 R engagement in vitro

  48-72 hours post bronchoscopy

Study Arms (2)

Asthmatics

0-5 years of age: Intermittent cough, wheeze, chest symptoms AND one or more of the following: Eczema Eosinophilia Elevated total IgE Positive family history 6-17 years of age: Physician diagnosis Current treatment with one or more asthma medications Recurrent episodes of cough, wheeze, chest discomfort, pain

Procedure: Bronchoscopy

Age-Similar Non-asthmatic Controls

Age-similar controls will undergo diagnostic bronchoscopy for clinical indications in the absence of known asthma, including recurrent pneumonia, congenital lung anomalies, prolonged cough, suspected laryngeal abnormalities, and suspected aspiration syndromes. Inclusion in the final set to be determined post-procedure based on BAL granulocyte profiles. To be included as a control, participants must have pauci-granular BAL counts (less than 2 percent eosinophils and less than 4 percent PMN), no positive allergen sensitization, and no positive viral or bacterial studies from analysis of BAL fluid.

Procedure: Bronchoscopy

Interventions

Bronchoscopy PROCEDURE

A diagnostic bronchoscopy will be conducted for clinical indications in children referred to the University of Virginia Children's Hospital for evaluation of respiratory symptoms

Age-Similar Non-asthmatic Controls; Asthmatics

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood, bronchoalveolar (BAL) fluid, nasal wash/absorbent pad fluid, and nasal scraping epithelial cells will be collected for study analyses with leftover samples banked for future research

MeSH Terms

Conditions

Asthma

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• William G Teague, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ivy Foundation Distinguished Professor of Pediatrics

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 15, 2016
• Study Start: August 1, 2016
• Primary Completion: May 14, 2018
• Study Completion: May 14, 2018
• Last Updated: February 7, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)