Healthy Volunteers
Conditions
Keywords
airway blood flow, albuterol, acidosis, alkalosis
Brief summary
The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. Methods: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation
Detailed description
The lungs provide a unique absorptive surface for drug delivery. Many inhaled drugs are rapidly absorbed into the airway because of their lipophilic chemical characteristics. However, the majority of the currently used β2-adrenergic bronchodilators cannot freely diffuse across the epithelial cell membrane because of their transient or permanent positive charge at physiological pH. Inhaled albuterol, a β2-adrenergic agonist used widely for the treatment of obstructive airway disease, is charged positively in neutral or acidic conditions and thus requires active transport across the airway epithelium. Previous studies in the lab have shown that albuterol uptake into airway epithelia occurs via a pH sensitive cation transporter (OCTN2). The vasodilator response to an inhaled β2-adrenergic agonist could be an expression of epithelial cation transport. The investigators propose that the magnitude and duration of vasodilation in the airway caused by an inhaled hydrophilic β2-adrenergic agonist such as albuterol may be altered by changes in airway pH. The purpose of this protocol is to determine the effect of ASL pH on the response of Qaw to inhaled albuterol by manipulating airway pH through ventilatory maneuvers in health subjects: hyperventilation to raise pH and ventilation with CO2 bleed-in to lower pH.
Interventions
OTHERquiet breathing
Subjects were instructed to breath normally at room air.
OTHERHypocapnic Hyperventilation
hypocapnic hyperventilation, the subjects were instructed to breathe fast and deep until their end-tidal pCO2 fell to 30 mmHg, corresponding to a systemic pH increase of about 0.1 pH units.
OTHERHypercapnic Hyperventilation
For hypercapnic hyperventilation, a modification of a previously described procedure (15). While monitoring SaO2 using pulse oximetry and end-tidal CO2 by mass-spectrometry on a breath by breath basis, CO2 was bled into the inspired air to achieve an end-tidal pCO2 of at least 55 mmHg
OTHEReucapnic hyperventilation
For eucapnic hyperventilation, the subjects were instructed to increase their ventilation to the highest level of ventilation recorded in the previous two hyperventilation maneuvers, while CO2 was bled into the inspired air to maintain end-tidal pCO2 at 40 mmHg.
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Lifetime non-smokers * FEV1 \> 80% predicted value and FEV1/FVC \> 0.75
Exclusion criteria
* Cardiovascular disease or use of cardiovascular or vasoactive drugs; * Lung disease or use of airway drugs (i.e. inhaled corticosteroids, β adrenergic agonists); * Respiratory infection during the 4 weeks preceding the study * Use of systemic glucocorticoids within 4 weeks of the study * Pregnant or nursing females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline | 15 minutes after albuterol inhalation | Effect of airway pH on albuterol responsiveness as reflected by the change in airway blood flow after 180μg albuterol by inhalation (ΔQaw) vs baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled Breath Condensate (EBC) pH Variation | 10 minutes after each respiratory manouver. | EBC samples were collected at each respiratory maneuver by directing the subject's exhaled breath into a pre-cooled (-10C) tube for 10 min. pH was measured immediately after collection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Controls health-lifetime non-smokers were enrolled | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Controls |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 45 years |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline
Effect of airway pH on albuterol responsiveness as reflected by the change in airway blood flow after 180μg albuterol by inhalation (ΔQaw) vs baseline.
Time frame: 15 minutes after albuterol inhalation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Health Controls | Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline | quiet breathing | 16.8 changes from baseline in μl.min-1.ml-1 | Standard Error 1.9 |
| Health Controls | Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline | eucapnic hyperventilation | 14.5 changes from baseline in μl.min-1.ml-1 | Standard Error 2.4 |
| Health Controls | Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline | hypocapnic hyperventilation | -0.2 changes from baseline in μl.min-1.ml-1 | Standard Error 1.8 |
| Health Controls | Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline | hypercapnic hyperventilation | 2.0 changes from baseline in μl.min-1.ml-1 | Standard Error 1.5 |
Secondary
Exhaled Breath Condensate (EBC) pH Variation
EBC samples were collected at each respiratory maneuver by directing the subject's exhaled breath into a pre-cooled (-10C) tube for 10 min. pH was measured immediately after collection.
Time frame: 10 minutes after each respiratory manouver.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Health Controls | Exhaled Breath Condensate (EBC) pH Variation | quiet breathing | 6.39 pH | Standard Error 0.14 |
| Health Controls | Exhaled Breath Condensate (EBC) pH Variation | hypocapnic hyperventilation | 6.31 pH | Standard Error 0.08 |
| Health Controls | Exhaled Breath Condensate (EBC) pH Variation | hypercapnic hyperventilation | 6.59 pH | Standard Error 0.15 |
| Health Controls | Exhaled Breath Condensate (EBC) pH Variation | eucapnic hyperventilation | 5.88 pH | Standard Error 0.14 |