Clinical Trial: Clinical Evidence of pH Dependent ß2 Adrenergic Transport Mechanisms in the Airway

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Clinical Evidence of pH Dependent ß2 Adrenergic Transport Mechanisms in the Airway

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 Summary: 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.
Sponsor: University of Miami

Current Primary Outcome: Changes in Airway Blood Flow After 180μg Albuterol by Inhalation (ΔQaw) vs Baseline [ Time Frame: 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.


Original Primary Outcome: Airway Blood Flow (Qaw) [ Time Frame: 15 minutes after albuterol inhalation ]

Qaw will be measured with an non invasive soluble gas uptake method.


Current Secondary Outcome: Exhaled Breath Condensate (EBC) pH Variation [ Time Frame: 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.



Original Secondary Outcome: Exhaled Breath Condensate (EBC) pH Variation [ Time Frame: immediately after the respiratory maneuver ]

EBC samples will be collected by directing the subject's exhaled breath into a pre-cooled (-10C) tube for 10 min and pH will be measured immediately after collection.


Information By: University of Miami

Dates:
Date Received: October 6, 2010
Date Started: January 2010
Date Completion:
Last Updated: April 27, 2016
Last Verified: November 2014