Real-Time Assessment of Lung Structure and Function in Children and Young Adults With CF Using Electrical Impedance Tomography

Study Overview
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Brief Summary
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The purpose of this study is to determine the ability of electrical impedance tomography (EIT) to identify structural and functional physiological changes that occur with disease progression in cystic fibrosis patients. The investigators also aim to determine whether EIT can serve as an alternative for CT to identify regions of air trapping and consolidation, whether EIT can provide clinically useful information about response to treatment for an acute PE, and whether EIT can provide longitudinal information about structural changes in the lung.

Official Title
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Real-Time Assessment of Lung Structure and Function in Children and Young Adults With CF Using Electrical Impedance Tomography

Conditions
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Cystic Fibrosis, Healthy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1: Age 3-21 years Male or female Healthy subjects with no known or suspected chronic or temporary lung disease Cohort 2: Age 3-21 years Male or female CF as diagnosed based on sweat chloride value(>60 mmol/L) or two known disease causing mutations Cohort 3: Age 3-21 years Male or female CF as diagnosed based on sweat chloride value (>60 mmol/L) or two known disease causing mutations Experiencing a protocol defined pulmonary exacerbation and being started on oral or intravenous antibiotics Exclusion Criteria: Unwilling/refusal to sign consent Known congenital heart disease, arrhythmia, or history of heart failure Wearing a pacemaker or a metallic surgical implant in the chest History of infection with Burkholderia cepacia Developmental delays that could result in an inability to complete study procedures

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 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 |
| --- | --- |
| Cohort 1 - Healthy Controls<br>Persons, male or female, between the ages of 3 and 21 (inclusive) with healthy lungs, defined by no known or suspected chronic or temporary lung disease. A single study visit | |
| Cohort 2 - CF Longitudinal<br>Persons, male or female, with CF, defined by two known disease-causing mutations and/or a sweat chloride value of >60mmol/L, between the ages of 3 and 21 (inclusive). | |
| Cohort 3 - CF Exacerbation<br>Persons, male or female, with CF, defined by two known disease-causing mutations and/or a sweat chloride value of >60mmol/L, between the ages of 3 and 21 (inclusive), experiencing a pulmonary exacerbation requiring antibiotics. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of air trapping and consolidation by EIT | The detection task for identifying air trapping and consolidation is to determine by inspection regions of EIT VQ index significantly lower than the surrounding lung region, with actual numbers or relative differences to be determined as part of this study in the correlation analysis to CT scans. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determining utility of EIT information in response to treatment for a pulmonary exacerbation | Individual outcome measures (CFCS, LCI , PFT, and EIT measures) will be evaluated using paired t-tests, and the corresponding t-statistics from each of the tests will be used as measures of effect size for comparison. In addition, all of the clinical outcomes can be compared statistically using a joint model approach (this is the same model that is referenced in Q3 below). | 36 months | 
| Determination of structural changes in the lung by EIT | The EIT-derived global VQ indices, FEV1, FEV1/FVC, FVC, and extent of air trapping and consolidation will be studied longitudinally and compared to LCIs, PFTs, and CT scans when available to assess the ability of EIT to identify structural and reversible physiological changes that occur with disease progression. To estimate the change in the EIT measures of global VQ, air trapping and consolidation, and EIT-derived PFT outputs over time, a random coefficient model with an intercept and slope fit for each subject with at least two measurements over the 3 years will be used. A bivariate version of the random coefficients model will be fit to address whether the EIT outcome variable is associated with the spirometer PFT outputs, LCI, and CFCS while accounting for repeated measures. | 36 months |