Pulmonary and Critical Care Medicine

Gaseous and Particulate Air Pollution

Each day the average person breathes about 15,000 liters, or approximately 35 pounds, of air. Gaseous and particulate contaminants in that air gain access to the body with each breath, and may have both short and long-term effects on human health. Our ongoing studies examine the effects of particle exposure on lung function, airway inflammation, and cardiovascular function.  Utilizing both environmental chamber and mouthpiece exposure systems, subjects are exposed to environmentally relevant concentrations of pollutants,with or without exercise.  Respiratory and systemic effects are determined using measures of lung function, examination for markers of inflammation in exhaled air, characterization of bloodleukocyte and platelet responses using 3-color flow cytometry, assessment of vascular function, and detailed cardiovascular monitoring.

Ultrafine particles (UFP, <100 nm diameter) may be particularly important with regard to cardiovascular effects because of their potential for evading clearance mechanisms and entering the lung interstitium and vascular space. Our studies explore the hypothesis that inhalation of ultrafine particles alters endothelial function in healthy and susceptible people.  Endothelial dysfunction is critically linked to the pathogenesis of atherosclerotic vascular disease. Drs. Frampton and Utell direct human clinical studies of pulmonary, cardiac, and vascular responses to inhaled particles and gases.  This work is part of the U.S. Environmental Protection Agency-funded research center at the University of Rochester, focusing on ultrafine particle air pollution, and is also funded by the National Institutes of Health and other sources.We have demonstrated in healthy nonsmokers that inhalation of low concentrations of UFP causes changes in leukocyte expression of adhesion molecules (1) (Figure 1), and reductions in the pulmonary diffusing capacity (2) (Figure 2), that are consistent with altered pulmonary vascular function.

Does UFP exposure alter systemic vascular function?  Healthy subjects inhaled 50 µg/m3 carbon UFP or air, and systemic vascular function was assessed using venous occlusion plethysmography and reactive hyperemia of the forearm (RH) (3).  RH increased after air exposure in response to the exercise during exposure, and this increase was blunted by inhalation of UFP (Figure 3).  Impaired RH correlates with impaired endothelial function in the coronary circulation, and RH is reduced in people with risk factors for atherosclerotic vascular disease.  In these same subjects, blood nitrate levels were reduced after UFP exposure (Figure 4), consistent with reduced bioavailability of nitric oxide (NO), the most important vasodilator.  Thus our findings provide support for the hypothesis that UFP alters vascular function in both the pulmonary and systemic circulations, and one of the mechanisms may involve depletion of NO.

Data from these human clinical studies of exposure to air pollutants help to elucidate the mechanisms responsible for pollutant health effects, and assist in establishing rational air quality standards.

Figure 1. Gaseous and Particulate Air Pollution Figure 2. Gaseous and Particulate Air Pollution Figure 3. Gaseous and Particulate Air Pollution Figure 4. Gaseous and Particulate Air Pollution

 References

  1. Frampton MW, Stewart JC, Oberdörster G, Morrow PE, Chalupa D, Pietropaoli AP, Frasier LM, Speers DM, Cox C, Huang L-S, et al. Inhalation of carbon ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Environ Health Perspect 2006;114:51-58.
  2. Pietropaoli AP, Frampton MW, Hyde RW, Morrow PE, Oberdörster G, Cox C, Speers DM, Frasier LM, Chalupa DC, Huang L-S, et al. Pulmonary function, diffusing capacity and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Inhal Toxicol 2004;16 (Suppl. 1):59-72.
  3. Shah AP, Pietropaoli AP, Frasier LM, Speers DM, Chalupa DC, Delehanty JM, Huang L-S, Utell MJ, Frampton MW. Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy human subjects. Environ Health Perspect 2008;116:375-380.

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