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

NCT ID: NCT02866487

Last Updated: 2022-02-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 72 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2018-05-14

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

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Bronchoscopy

Intervention Type: 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

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.

Bronchoscopy

Intervention Type: 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

Interventions

Bronchoscopy

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

Intervention Type: PROCEDURE

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

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Willliam Gerald Teague

Ivy Foundation Distinguished Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William G Teague, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia Health System

Charlottesville, Virginia, United States

Countries

United States

Other Identifiers

NAIL-5

Identifier Type: -

Identifier Source: org_study_id