Mechanisms of Immune Tolerance and Inflammation in Patients With Cystic Fibrosis With ABPA (ABPA)

February 12, 2016 updated by: Jay Kolls, University of Pittsburgh

SCCOR in Host Factors in Chronic Lung Diseases: Mechanisms of Immune Tolerance and Inflammation in Allergic Bronchopulmonary Aspergillosis (ABPA) in Patients With Cystic Fibrosis

The goal of this study is to identify the immunological factors that influence a patient's response to the presence of the fungus Aspergillus fumigatus (A. fumigatus) in the lungs. In patients with cystic fibrosis (CF), this fungus is not known to cause damage to the lungs, but some patients respond with an allergic reaction that may cause wheeze, cough, or difficulty breathing. Approximately 230 patients will be enrolled with an additional 60 people who do not have CF and who do not have a history of asthma to serve as a comparison group.

Study Overview

Status

Completed

Conditions

Detailed Description

In this cohort the investigators will study blood T-cell responses to Aspergillus antigens to determine if patients with ABPA have greater type 2 responses as measured by IL-13 compared to CF or non-CF controls.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Pennsylvania
  - Pittsburgh, Pennsylvania, United States, 15213
    - Children's Hospital of Pittsburgh of UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Male and female subjects with CF who have A. fumigatus in cultures of airway flora and receive clinical care at the Antonio J. and Janet Palumbo Cystic Fibrosis Center at Children's Hospital of Pittsburgh. Age (± 1 year) and sex matched healthy, non CF controls will also be recruited.

Description

Inclusion Criteria:

(CF)

diagnosis of CF
age 6 years or older
presence of A. fumigatus in culture of airway flora, or the presence of one or more of the diagnostic criteria for ABPA (Control)
age and sex matched to CF population

Exclusion Criteria:

(CF)

uncontrolled CF-related diabetes mellitus
use of oral steroids at a dose ≥ 0.5 mg/kg/day
history of lung transplantation
pulmonary exacerbation as defined by requirement for use of intravenous antibiotics or need for hospitalization within the preceding 14 days.
patients who have a diagnosis of HIV and have a CD4+ Tcell count below 500 cells/ml will be excluded (control)
asthma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
CF (non-ABPA) cystic fibrosis and culture positive for A. fumigatus in airway cultures.
CF and ABPA cystic fibrosis and diagnosis of ABPA
healthy control healthy non-CF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To test the hypothesis that the white blood cells of CF patients with ABPA will demonstrate increased inflammatory cytokine expression in response to binding of A. fumigatus antigens compared to white blood cells from non-ABPA patients. Time Frame: baseline, 6 month follow-up, ABPA exacerbation	baseline, 6 month follow-up, ABPA exacerbation

Secondary Outcome Measures

Outcome Measure	Time Frame
To test the hypothesis that T cells from CF patients with ABPA will have decreased adaptive regulatory function Time Frame: baseline, 6 month follow-up, ABPA exacerbation	baseline, 6 month follow-up, ABPA exacerbation
To test the hypothesis that surface-bound TGF beta is critical for the development and maintenance of immune tolerance to A. fumigatus antigens Time Frame: baseline, 6 month follow-up, ABPA exacerbation	baseline, 6 month follow-up, ABPA exacerbation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator: Jay K Kolls, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

January 1, 2008

First Submitted That Met QC Criteria