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

NCT01216748 | Completed Results

• 2 other identifiers: 20070583R01HL060644
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Volunteers

Keywords

airway blood flow; albuterol; acidosis; alkalosis

Outcome Measures

Primary Outcomes (1)

• 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.

  15 minutes after albuterol inhalation

Secondary Outcomes (1)

• Exhaled Breath Condensate (EBC) pH Variation

  10 minutes after each respiratory manouver.

Study Arms (1)

health life-time non smokers

EXPERIMENTAL

health lifetime non-smokers will be challenged with 4 respiratory maneuvers:quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation

Other: quiet breathing; Other: Hypocapnic Hyperventilation; Other: Hypercapnic Hyperventilation; Other: eucapnic hyperventilation

Interventions

quiet breathing OTHER

Subjects were instructed to breath normally at room air.

health life-time non smokers

Hypocapnic Hyperventilation OTHER

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.

health life-time non smokers

Hypercapnic Hyperventilation OTHER

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

health life-time non smokers

eucapnic hyperventilation OTHER

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.

health life-time non smokers

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Lifetime non-smokers
• FEV1 \> 80% predicted value and FEV1/FVC \> 0.75

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Miami: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Pulmonary Human Research Laboratory, University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Related Publications (4)

• Vaughan J, Ngamtrakulpanit L, Pajewski TN, Turner R, Nguyen TA, Smith A, Urban P, Hom S, Gaston B, Hunt J. Exhaled breath condensate pH is a robust and reproducible assay of airway acidity. Eur Respir J. 2003 Dec;22(6):889-94. doi: 10.1183/09031936.03.00038803.

  PMID: 14680074 BACKGROUND

• Paget-Brown AO, Ngamtrakulpanit L, Smith A, Bunyan D, Hom S, Nguyen A, Hunt JF. Normative data for pH of exhaled breath condensate. Chest. 2006 Feb;129(2):426-430. doi: 10.1378/chest.129.2.426.

  PMID: 16478862 BACKGROUND

• Horvath G, Schmid N, Fragoso MA, Schmid A, Conner GE, Salathe M, Wanner A. Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway. Am J Respir Cell Mol Biol. 2007 Jan;36(1):53-60. doi: 10.1165/rcmb.2006-0230OC. Epub 2006 Aug 17.

  PMID: 16917073 BACKGROUND

• Cancado JE, Mendes ES, Arana J, Horvath G, Monzon ME, Salathe M, Wanner A. Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol. BMC Pharmacol Toxicol. 2015 Apr 2;16:9. doi: 10.1186/s40360-015-0008-y.

  PMID: 25889594 DERIVED

MeSH Terms

Conditions

Acidosis; Alkalosis

Condition Hierarchy (Ancestors)

Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Matthias Salathe, MD
• Organization: University of Miami

msalathe@med.miami.edu

(305)243-2568

Study Officials

• Matthias Salathe

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 7, 2010
• Study Start: January 1, 2010
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: May 27, 2016
• Results First Posted: December 17, 2014

Record last verified: 2014-11

Locations

US (1)