A Comparison of Studies on the Effects of Controlled Exposure to Fine, Coarse and Ultrafine Ambient Particulate Matter from a Single Location

Abstract

Particle size has been implicated by epidemiological and toxicological studies as an important determinant of the toxicity of ambient particulate matter (PM). In an effort to characterize the cardiovascular, hematological and pulmonary effects of different PM size fractions in humans, we have conducted controlled human exposures of normal volunteers to ultrafine-, fine- and coarse- fraction PM concentrated from ambient air in Chapel Hill, North Carolina. Healthy non-smoking male and female subjects between the ages of 18 and 35 participated in these studies. Exposures were undertaken with the use of particle concentrators fitted with size-selective outlets. These devices are capable of generating concentration factors between 10- and 20-fold over ambient levels. Cardiovascular endpoints measured include heart rate variability and T-wave alternans, as well as pulmonary function parameters. Subjects underwent bronchoscopy and bronchoalveolar lavage 18 hrs following exposure to PM or to clean air. Lavage fluids and blood samples were assayed for a battery of markers of hematological, cytotoxic and inflammatory injury. The design of these studies permits direct comparison of the effects of concentrated ambient PM as a function of particle size. The data to be presented reveal modest size fraction-dependent effects of concentrated PM exposure on cardiovascular, pulmonary and hematological parameters in normal adult human subjects. These findings have relevant implications for the design of future chamber studies and the role of particle size fraction in the adverse health effects of PM exposure in humans.

Particulate Matter Air Pollution and Cardiovascular Disease

“…In many of these single-episode short-term exposures, no overt changes in plasma cytokine levels were observed after CAP [381][382][383] or diesel exhaust. 345,384 -386 Similarly, CRP levels have not consistently been found to increase in the time frame and context of most of these studies.…”

“…Serum amyloid A and the ratio of factor VIII to von Willebrand factor, an indicator of an increased risk of venous thromboembolism, were increased at 4 hours after exposure. 395 Samet et al 383 reported an association between various coagulation markers and exposure to ultrafine, fine, and thoracic coarse CAP among healthy young adults. Although exposure to coarse CAP did not result in significant changes in hemostatic variables, the overall trend suggested a prothrombotic effect.…”

Human inhalation exposure to iron oxide particles

“…The authors are not aware of any published human inhalation studies using iron oxide nanoparticles. However, several controlled human inhalation studies have exposed volunteers to other ultrafine particles [57][58][59][60][61][62][63][64][65][66]. In addition, many human inhalation studies have been conducted using Technegas or 99m Tc labeled ultrafine carbon particles; however, this literature is beyond the scope of this review.…”

Impact of air pollution on lung inflammation and the role of Toll-like receptors

“…26 Healthy human subjects exposed to concentrated ambient particles developed pulmonary inflammation characterized by increased presence of inflammatory cells and alterations in IL-8 expression in the lung lavage fluid. 27,28 Similarly, human subjects exposed to diesel particulates, a major component of ambient PM, developed neutrophilic airway inflammation and increased IL-8 expression and had altered levels of oxidative stress markers myeloperoxidase and reduced glutathione and urate. 29 Allen and colleagues measured an association between ambient PM exposure and significant alterations in inflammatory (exhaled NO) and lung-function measurements in children.…”