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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Cystic Fibrosis
• Intervention / Treatment: Drug: Albuterol; Drug: Placebo saline

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Wayne J Morgan, MD, Department of Pediatrics- Pulmonology, Allergy and Immunology, University of Arizona, Tucson, Arizona; Principal Investigator: Cori M Daines, MD, Department of Pediatrics- Pulmonology, Allergy and Immunology, University of Arizona, Tucson, Arizona; Principal Investigator: Eric M Snyder, PhD, Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona; Principal Investigator: Hanna Phan, PharmD, Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona; Principal Investigator: Asad Patanwalla, PharmD, Department of Pharmacy Practice and Science, University of Arizona, Tucson, Arizona

Publications and helpful links

General Publications

• Foxx-Lupo WT, Wheatley CM, Baker SE, Cassuto NA, Delamere NA, Snyder EM. Genetic variation of the alpha subunit of the epithelial Na+ channel influences exhaled Na+ in healthy humans. Respir Physiol Neurobiol. 2011 Dec 15;179(2-3):205-11. doi: 10.1016/j.resp.2011.08.008. Epub 2011 Aug 26.
• Baker SE, Wheatley CM, Cassuto NA, Foxx-Lupo WT, Sprissler R, Snyder EM. Genetic variation of alphaENaC influences lung diffusion during exercise in humans. Respir Physiol Neurobiol. 2011 Dec 15;179(2-3):212-8. doi: 10.1016/j.resp.2011.08.007. Epub 2011 Aug 26.
• Wheatley CM, Foxx-Lupo WT, Cassuto NA, Wong EC, Daines CL, Morgan WJ, Snyder EM. Impaired lung diffusing capacity for nitric oxide and alveolar-capillary membrane conductance results in oxygen desaturation during exercise in patients with cystic fibrosis. J Cyst Fibros. 2011 Jan;10(1):45-53. doi: 10.1016/j.jcf.2010.09.006. Epub 2010 Nov 2.
• Traylor BR, Wheatley CM, Skrentny TT Jr, Foxx-Lupo WT, Phan H, Patanwala AE, Morgan WJ, Daines CL, Sprissler R, Snyder EM. Influence of genetic variation of the beta2-adrenergic receptor on lung diffusion in patients with cystic fibrosis. Pulm Pharmacol Ther. 2011 Oct;24(5):610-6. doi: 10.1016/j.pupt.2011.06.001. Epub 2011 Jun 15.
• Snyder EM, Wong EC, Foxx-Lupo WT, Wheatley CM, Cassuto NA, Patanwala AE. Effects of an inhaled beta2-agonist on cardiovascular function and sympathetic activity in healthy subjects. Pharmacotherapy. 2011 Aug;31(8):748-56. doi: 10.1592/phco.31.8.748.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: June 15, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (Estimated): June 19, 2013

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: peripheral oxygen saturation; albuterol; exhaled breath condensate; diffusion capacity of the lungs for carbon monoxide and nitric oxide; ion regulation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: 08-1123-01; 1R01HL108962-01 (U.S. NIH Grant/Contract)