Airborne Ultrafine and Fine Particulate Matter: A Cause for Endothelial Dysfunction in Man?

The purpose of this study is to examine biological pathways of altered blood vessel function resulting from breathing airborne particulate. Blood artery function in healthy men will be measured after particulate exposure either on placebo or on an asthma medication that stops production of an inflammatory biological agent. Lung and blood profiles will be obtained before and after exposure to exhaust fumes. We believe that the inflammatory agent produced by the lungs from breathing these particles causes abnormal artery function.

Study Overview

• Status: Completed
• Conditions: Airway Inflammation
• Intervention / Treatment: Other: placebo; Drug: Montelukast

Detailed Description

Hourly ice resurfacing by gas and propane fueled machines creates high levels of ultrafine and fine particulate matter (PM1) in indoor ice rinks. PM1 exposure may disrupt the normal nitric oxide (NO)/endothelin (ET)-1 vasodilation system and promote atherosclerosis, and/or increase the risk of an acute cardiac event. Our specific aims are 1) to determine whether impaired endothelial-mediated vasodilation and forearm muscle tissue reoxygenation rate and blood volume change (to reactive hyperemia following artery occlusion) is associated with combustion-derived PM1 exposure, and 2) To characterize a PM1 induced mechanism of endothelial dysfunction which occurs via a leukotriene (LT)-associated, airway generated tumor necrosis factor-alpha (TNF-a) mediated pathway. Healthy low PM1 exposed males will be evaluated for endothelial dysfunction before and after artery occlusion using high resolution ultrasound and near-infrared spectroscopy (NIRS), before and after moderate exercise in blinded high and low [PM1]. Endothelial dysfunction among chronically PM¬1 exposed ice rink athletes will be determined to evaluate the feasibility of using this population as a model in future studies. TNF-a, IL-8, LTB4, LTC4, LTD4, LTE4, ET-1, NO, and differential cell counts will be measured in sputum and serum. [PM1] will be monitored and exposure levels will be typical of indoor ice rinks. LT involvement will be assessed in vivo by double-blind pharmacological manipulation during PM1 exposure during light exercise. Results will demonstrate whether endothelial-mediated vasodilation and muscle hemodynamics are influenced by PM1 exposure, and will elucidate an LT initiated TNF-a mediated pathway in ET-1 upregulation. Our results should provide information for understanding the effects of PM1 exposure on the atherosclerotic process and cardiovascular risk, and give insight to novel treatment and diagnostic modalities.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Scranton, Pennsylvania, United States, 18509
      • Marywood University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects
• between 18 and 30 years of age
• participant in endurance sport

Exclusion Criteria:

• history of blood clotting
• history of coagulation problems
• History of spontaneous pneumothorax

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Subject will exercise in high levels of ultrafine and fine particulate air pollution 1 hour after ingesting a placebo.	Other: placebo; Placebo; Other Names: Sugar Pill
Placebo Comparator: 2; Subject will exercise in low levels of ultrafine and fine particulate air pollution 1 hour after ingesting a placebo.	Other: placebo; Placebo; Other Names: Sugar Pill
Experimental: 3; Subject will exercise in high levels of ultrafine and fine particulate air pollution 1 hour after ingesting Montelukast 10 mg orally.	Drug: Montelukast; 10 mg ingested orally 1 hour prior to exercise testing; Other Names: Singulair
Experimental: 4; Subject will exercise in low levels of ultrafine and fine particulate air pollution 1 hour after ingesting Montelukast 10 mg orally.	Drug: Montelukast; 10 mg ingested orally 1 hour prior to exercise testing; Other Names: Singulair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Exposure to airborne ultrafine and fine particulate matter causes vascular dysfunction.	February 2009

Secondary Outcome Measures

Outcome Measure	Time Frame
Montelukast protects against pollution induced vascular dysfunction.	February 2009

Collaborators and Investigators

• Sponsor: Marywood University
• Investigators: Principal Investigator: Kenneth W Rundell, PhD, Marywood University

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: December 22, 2008
• First Submitted That Met QC Criteria: December 23, 2008
• First Posted (Estimate): December 24, 2008

Study Record Updates

• Last Update Posted (Estimate): May 21, 2009
• Last Update Submitted That Met QC Criteria: May 20, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: asthma; leukotriene; montelukast; vascular endothelial dysfunction; particulate air pollution; nitric oxide(NO)endothelin (ET) system
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: MU2007-005