Utilizing Exhaled Breathe Condensate Collection to Study Ion Regulation in Cystic Fibrosis

Study Overview
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Brief Summary
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Our aims were to determine if exhaled breath condensate (EBC) could detect differences in ion regulation between cystic fibrosis (CF) and healthy and measure the effect of the albuterol on EBC ions in these populations. We hypothesized EBC chloride and sodium would be lower in CF patients at baseline and that albuterol would decrease EBC sodium and increase EBC chloride.

Official Title
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Modifying Genes in Cystic Fibrosis: The Beta-2 Adrenergic Receptors and Epithelial Na+ Channels

Conditions
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Cystic Fibrosis, Healthy

Intervention / Treatment
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* Drug: Albuterol
* Drug: Placebo saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects: no cardiovascular abnormalities not overweight BMI>25 18-55 years of age CF subjects: mild to moderate CF (FEV1>40% predicted) clinically diagnosed with positive sweat test (sweat Cl->60mmol/L) 10-55 years of age clinically stable Exclusion Criteria: Healthy subjects will be excluded if: If unable to consent for him/herself (cognitive impairment) Have a history or evidence of cardiovascular and/or pulmonary abnormalities. Have an abnormal 12-lead EKG Have an abnormal pulmonary function test Have a history of asthma Have a history of renal disease or estimated creatinine clearance < 55ml/min Women who are pregnant or planning to become pregnant during the study CF subjects: If unable to consent for him/herself (cognitive impairment) Physically unable to perform exercise or breathing tests Have a history of renal disease or estimated creatinine clearance < 55ml/min Women who are pregnant or planning to become pregnant during the study. Have an abnormal 12-lead EKG Cystic Fibrosis related diabetes is uncontrolled Forced Expiratory Volume after 1 second (FEV1) is less than 40% predicted Have a history of joint disease Have history of pulmonary exacerbation within the last two weeks Experienced pulmonary hemorrhage within 6 months resulting in greater than 50cc of blood in the sputum not currently enrolled in any other research study

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 55 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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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Albuterol<br>2.5 mg diluted in 3mL normal saline nebulized using a Power Neb2 nebulizer | Drug: Albuterol<br>* 2.5 mg diluted in 3mL normal saline nebulized using a Power Neb2 nebulizer<br>|
| Placebo Comparator: Saline (healthy only)<br>nebulized 3 ml normal saline using a Power Neb2 nebulizer | Drug: Placebo saline<br>* nebulized 3mL normal saline) using a Power Neb2 nebulizer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exhaled Sodium (mmol/L) | We collected exhaled breath condensate (EBC) samples, with subjects breathing on a Jaeger EcoScreen for 20 minutes. EBC samples were collected in cystic fibrosis and healthy subjects before and 30-, 60-, and 90-minutes following albuterol administration. | up to 90-minutes post albuterol | 
| Net Exhaled Chloride | The calculation of net chloride efflux was used to account for the paracellular reabsorption of Cl- that will follow the reabsorption of Na+ to maintain electroneutral ion flux. Thus, the net chloride efflux calculation used was the gross chloride concentration plus the absolute value of the percent change in sodium from baseline multiplied by the gross chloride concentration for each time point: Net Cl- efflux - [Cl- X-min post] + (([Na+ X-min post]-[Na+Baseline])/ [Na+Baseline]) x [Cl- X-min post]) | baseline to 90 minutes post albuterol administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diffusion Capacity of the Lungs for Carbon Monoxide | Using the rebreathe technique the diffusion capacity of the lungs for carbon monoxide and nitric oxide were measured, and this allowed for the determination of alveolar-capillary membrane conductance and pulmonary capillary blood volume. These measurements were made at baseline and 30-, 60- and 90-minutes post albuterol administration in cystic fibrosis and healthy subjects. | baseline, 30-, 60- and 90-minutes post albuterol administration | 
| Diffusion Capacity of the Lungs for Nitric Oxide | Using the rebreathe technique the diffusion capacity of the lungs for carbon monoxide and nitric oxide were measured, and this allowed for the determination of alveolar-capillary membrane conductance and pulmonary capillary blood volume. These measurements were made at baseline and 30-, 60- and 90-minutes post albuterol administration in cystic fibrosis and healthy subjects. | baseline, 30-, 60- and 90-minutes post albuterol administration | 
| Peripheral Oxygen Saturation | A finger pulse oximeter allowed for the measurement of peripheral oxygen saturation at baseline, 30-, 60- and 90-minutes post albuterol in cystic fibrosis and healthy subjects. | baseline, 30-, 60- and 90-minutes post albuterol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exhaled breath condensate, diffusion capacity of the lungs for carbon monoxide and nitric oxide, albuterol, peripheral oxygen saturation, ion regulation