Utility of CD64 and TLR2 Assays to Diagnose Acute Pulmonary Exacerbations in Cystic Fibrosis

Study Overview
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Brief Summary
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Cystic fibrosis (CF) is the most common inherited disease in the western world. On a yearly basis, 56% of CF patients, or nearly 17,000 individuals in the US, suffer from acute pulmonary exacerbations (APE). The purpose of this study is to test a candidate assay for its ability to diagnose APE, the most important disease event in CF. While previous studies have been able to identify biomarkers of CF prognosis and risk stratification, three markers have demonstrated characteristics ideal for APE diagnosis: CD64, TLR2, and GILT. CD64 is a cellular receptor, expressed on numerous cells of the immune system, whose role is to bind antibodies which are attached to infected cells or pathogens. TLR2 plays a major role in early host-microbial interactions. GILT has been shown to be more precise in targeting immune responses against antigens and influences T lymphocyte response. This study looks to identify the differences in the expression of neutrophil CD64 and CD4+ T cell TLR2 and GILT between acute illness and baseline health as a sensitive marker of acute pulmonary exacerbation so that it may facilitate rapid hematologic diagnosis of the condition. The study also looks to compare sensitivity and specificity of the assays above to standard measures, such as health related quality of life scores (CFQ-R), loss of lung function, white blood cell counts and CRP, for diagnosing acute exacerbations.

Official Title
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Utility of CD64 and TLR2 Assays to Diagnose Acute Pulmonary Exacerbations in Cystic Fibrosis

Conditions
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Cystic Fibrosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of CF. Age 18 years old or greater. Presentation at baseline health OR at the start of treatment for a pulmonary exacerbation of CF. Ability to perform reproducible Pulmonary Function Tests Ability to produce sputum. Willingness to complete a health-related quality of life questionnaire Willingness to comply with study procedure and provide written consent. Exclusion Criteria: • Presence of a condition or abnormality that, in the opinion of the Principal Investigator (PI), would compromise the safety of the patient or the quality of the data.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute Pulmonary Exacerbation (APE)<br>Those subjects presenting with APE will be treated with at least two pathogen specific I.V. antibiotics, as dictated by their treating physician and compliant with standard guidelines for care of an APE. | |
| Baseline Health<br>Those subjects presenting at baseline health will be identified by their treating physician as such and will not be starting on any treatments for APE. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in neutrophil CD64 expression | The primary outcome measure is the difference in expression of neutrophil CD64 as measured by flow cytometry from circulating blood between the two groups (APE and baseline). | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Difference in CD4+ T cell TLR2 expression | The primary outcome measure is the difference in expression of CD4+ T cell TLR2 as measured by flow cytometry from circulating blood between the two groups (APE and baseline). | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Difference in GILT expression | The primary outcome measure is the difference in expression of GILT as measured by flow cytometry from circulating blood between the two groups (APE and baseline). | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of primary outcome measurements with lung function tests | A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with changes in FEV1 as measured by spirometry. | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Correlation of primary outcome measurements with C-Reactive Protein | A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in C-Reactive Protein (CRP) | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Correlation of primary outcome measurements with total white blood cell counts | A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in total white blood cell counts (WBC). | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Correlation of primary outcome measurements with sputum inflammatory markers | A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in sputum inflammatory markers as measured by sputum neutrophil counts and neutrophil elastase expression. | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Correlation of primary outcome measurements with phagocytosis | A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in the percentage of phagocytosis by isolated neutrophils. | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health | 
| Correlation of primary outcome measurements with quality of life questionnaire score | A secondary outcome measure is the correlation of the differences in expression of neutrophil CD64, CD4+ T cell TLR2, and GILT with differences in patient reported health related quality of life scores as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R). | Within 24 hours of initiation of IV antibiotic treatment for CF pulmonary exacerbation or at Baseline health |