Cystic Fibrosis, Healthy
Conditions
Keywords
exhaled breath condensate, diffusion capacity of the lungs for carbon monoxide and nitric oxide, albuterol, peripheral oxygen saturation, ion regulation
Brief summary
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.
Interventions
DRUGAlbuterol
2.5 mg diluted in 3mL normal saline nebulized using a Power Neb2 nebulizer
DRUGPlacebo saline
nebulized 3mL normal saline) using a Power Neb2 nebulizer
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Arizona
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled Sodium (mmol/L) | up to 90-minutes post albuterol | 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. |
| Net Exhaled Chloride | baseline to 90 minutes post albuterol administration | 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 \[Cl- X-min post\]) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diffusion Capacity of the Lungs for Carbon Monoxide | baseline, 30-, 60- and 90-minutes post albuterol administration | 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. |
| Diffusion Capacity of the Lungs for Nitric Oxide | baseline, 30-, 60- and 90-minutes post albuterol administration | 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. |
| Peripheral Oxygen Saturation | baseline, 30-, 60- and 90-minutes post albuterol | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Healthy Control subjects | 16 |
| Cystic Fibrosis Patients diagnosed with cystic fibrosis | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Healthy | Cystic Fibrosis | Total |
|---|---|---|---|
| Age, Continuous | 25 years STANDARD_DEVIATION 6 | 22 years STANDARD_DEVIATION 8 | 24 years STANDARD_DEVIATION 7 |
| BMI (kg/m2) | 23 kg/m2 STANDARD_DEVIATION 3 | 22 kg/m2 STANDARD_DEVIATION 3 | 22 kg/m2 STANDARD_DEVIATION 3 |
| BSA (m2) | 1.7 m2 STANDARD_DEVIATION 0.1 | 1.7 m2 STANDARD_DEVIATION 0.2 | 1.7 m2 STANDARD_DEVIATION 0.1 |
| Height (cm) | 169 cm STANDARD_DEVIATION 8 | 166 cm STANDARD_DEVIATION 8 | 167 cm STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 20 Participants |
| VO2 peak (% predicted) | 108 percent predicted STANDARD_DEVIATION 35 | 54 percent predicted STANDARD_DEVIATION 24 | 85 percent predicted STANDARD_DEVIATION 39 |
| Weight (kg) | 64 kg STANDARD_DEVIATION 9 | 60 kg STANDARD_DEVIATION 9 | 62 kg STANDARD_DEVIATION 9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
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.
Time frame: up to 90-minutes post albuterol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy | Exhaled Sodium (mmol/L) | Baseline | 2.58 mmol/L | Standard Deviation 1.51 |
| Healthy | Exhaled Sodium (mmol/L) | 30 minutes post | 1.97 mmol/L | Standard Deviation 0.58 |
| Healthy | Exhaled Sodium (mmol/L) | 60 minutes post | 2.37 mmol/L | Standard Deviation 0.94 |
| Healthy | Exhaled Sodium (mmol/L) | 90 minutes post | 2.23 mmol/L | Standard Deviation 1.34 |
| Cystic Fibrosis | Exhaled Sodium (mmol/L) | 90 minutes post | 1.86 mmol/L | Standard Deviation 0.93 |
| Cystic Fibrosis | Exhaled Sodium (mmol/L) | Baseline | 2.24 mmol/L | Standard Deviation 1.09 |
| Cystic Fibrosis | Exhaled Sodium (mmol/L) | 60 minutes post | 1.73 mmol/L | Standard Deviation 0.85 |
| Cystic Fibrosis | Exhaled Sodium (mmol/L) | 30 minutes post | 2.11 mmol/L | Standard Deviation 0.93 |
Primary
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 \[Cl- X-min post\])
Time frame: baseline to 90 minutes post albuterol administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy | Net Exhaled Chloride | Baseline | 0.064 mmol/L | Standard Deviation 0.05 |
| Healthy | Net Exhaled Chloride | 30 minutes post | 0.078 mmol/L | Standard Deviation 0.143 |
| Healthy | Net Exhaled Chloride | 60 minutes post | 0.084 mmol/L | Standard Deviation 0.073 |
| Healthy | Net Exhaled Chloride | 90 minutes post | 0.077 mmol/L | Standard Deviation 0.06 |
| Cystic Fibrosis | Net Exhaled Chloride | 90 minutes post | 0.050 mmol/L | Standard Deviation 0.016 |
| Cystic Fibrosis | Net Exhaled Chloride | Baseline | 0.037 mmol/L | Standard Deviation 0.02 |
| Cystic Fibrosis | Net Exhaled Chloride | 60 minutes post | 0.057 mmol/L | Standard Deviation 0.038 |
| Cystic Fibrosis | Net Exhaled Chloride | 30 minutes post | 0.048 mmol/L | Standard Deviation 0.031 |
Secondary
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.
Time frame: baseline, 30-, 60- and 90-minutes post albuterol administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy | Diffusion Capacity of the Lungs for Carbon Monoxide | Baseline | 21.5 mL/min/mmHg | Standard Deviation 5.8 |
| Healthy | Diffusion Capacity of the Lungs for Carbon Monoxide | 30 minutes post | 21.6 mL/min/mmHg | Standard Deviation 5.3 |
| Healthy | Diffusion Capacity of the Lungs for Carbon Monoxide | 60 minutes post | 21.6 mL/min/mmHg | Standard Deviation 6.2 |
| Healthy | Diffusion Capacity of the Lungs for Carbon Monoxide | 90 minutes post | 21.2 mL/min/mmHg | Standard Deviation 5.5 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Carbon Monoxide | 90 minutes post | 17.1 mL/min/mmHg | Standard Deviation 4.9 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Carbon Monoxide | Baseline | 17.3 mL/min/mmHg | Standard Deviation 4.4 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Carbon Monoxide | 60 minutes post | 17.0 mL/min/mmHg | Standard Deviation 4.4 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Carbon Monoxide | 30 minutes post | 17.4 mL/min/mmHg | Standard Deviation 4.3 |
Secondary
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.
Time frame: baseline, 30-, 60- and 90-minutes post albuterol administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy | Diffusion Capacity of the Lungs for Nitric Oxide | Baseline | 70.3 mL/min/mmHg | Standard Deviation 18.9 |
| Healthy | Diffusion Capacity of the Lungs for Nitric Oxide | 30 minutes post | 70.8 mL/min/mmHg | Standard Deviation 16.7 |
| Healthy | Diffusion Capacity of the Lungs for Nitric Oxide | 60 minutes post | 72.1 mL/min/mmHg | Standard Deviation 19.2 |
| Healthy | Diffusion Capacity of the Lungs for Nitric Oxide | 90 minutes post | 73.0 mL/min/mmHg | Standard Deviation 20.6 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Nitric Oxide | 90 minutes post | 58.5 mL/min/mmHg | Standard Deviation 17.8 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Nitric Oxide | Baseline | 55.0 mL/min/mmHg | Standard Deviation 15 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Nitric Oxide | 60 minutes post | 56.2 mL/min/mmHg | Standard Deviation 16.6 |
| Cystic Fibrosis | Diffusion Capacity of the Lungs for Nitric Oxide | 30 minutes post | 56.4 mL/min/mmHg | Standard Deviation 15 |
Secondary
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.
Time frame: baseline, 30-, 60- and 90-minutes post albuterol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy | Peripheral Oxygen Saturation | Baseline | 99 percent of oxygenated hemoglobin | Standard Deviation 1 |
| Healthy | Peripheral Oxygen Saturation | 30 minutes post | 100 percent of oxygenated hemoglobin | Standard Deviation 0 |
| Healthy | Peripheral Oxygen Saturation | 60 minutes post | 99 percent of oxygenated hemoglobin | Standard Deviation 1 |
| Healthy | Peripheral Oxygen Saturation | 90 minutes post | 99 percent of oxygenated hemoglobin | Standard Deviation 1 |
| Cystic Fibrosis | Peripheral Oxygen Saturation | 90 minutes post | 99 percent of oxygenated hemoglobin | Standard Deviation 1 |
| Cystic Fibrosis | Peripheral Oxygen Saturation | Baseline | 98 percent of oxygenated hemoglobin | Standard Deviation 1 |
| Cystic Fibrosis | Peripheral Oxygen Saturation | 60 minutes post | 98 percent of oxygenated hemoglobin | Standard Deviation 1 |
| Cystic Fibrosis | Peripheral Oxygen Saturation | 30 minutes post | 98 percent of oxygenated hemoglobin | Standard Deviation 1 |