Airborne Ultrafine and Fine Particulate Matter: A Cause for Endothelial Dysfunction in Man?
Condition: Airway Inflammation
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): placebo; Montelukast
Intervention type(s): Other; Drug
Intervention description(s): Placebo; 10 mg ingested orally 1 hour prior to exercise testing
Other intervention name(s): Sugar Pill; Singulair
Intervention MeSH terms: Montelukast
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: particulate air pollution; leukotriene; asthma; montelukast; vascular endothelial dysfunction; nitric oxide(NO)endothelin (ET) system