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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Cystic Fibrosis, Allergic Bronchopulmonary Aspergillosis

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CF (non-ABPA)<br>cystic fibrosis and culture positive for A. fumigatus in airway cultures. | |
| CF and ABPA<br>cystic fibrosis and diagnosis of ABPA | |
| healthy control<br>healthy non-CF | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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. |  | baseline, 6 month follow-up, ABPA exacerbation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To test the hypothesis that T cells from CF patients with ABPA will have decreased adaptive regulatory function |  | 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 |  | baseline, 6 month follow-up, ABPA exacerbation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic Bronchopulmonary Aspergillosis, Aspergillus fumigatus, cytokine expression