ABSTRACT
Determinants of PM Toxicity ........................................................................................... 104
5.5 Particle-Induced Toxicity: Lessons from Cigarette Smoke and Fiber Research ............ 105
5.6 Evidence of Particle-Induced Oxidative Stress from Animal Studies............................. 106
5.7 Concentrated Ambient and Diesel Exhaust Particle Exposure in Human Subjects ........ 107
5.8 Modeling the Interaction of Ambient PM with RTLF Antioxidants............................... 109
5.9 Particle-Induced Oxidation Reactions at the Air-Lung Interface as a Predictor
of Observed Health Effects ............................................................................................... 109
5.10 Conclusions ....................................................................................................................... 110
Acknowledgments ........................................................................................................................ 110
References .................................................................................................................................... 110
During the last decade, concerns have increased within both political and scientific communities
over the impact of airborne particulate matter (PM) on public health. This concern has arisen
primarily based on the findings of American epidemiological studies demonstrating an association
between the mass concentration of PM (particularly particles with an aerodynamic diameter of less
than 10 mm) in the air we breathe, and rates of respiratory and cardiac mortality and morbidity
(Dockery et al. 1993; Pope et al. 1995; Samet et al. 2000). These associations have subsequently
proven to be robust in numerous epidemiological studies worldwide (Brunekreef and Holgate
2002), with stronger associations usually associated with PM with an aerodynamic diameter of
!2.5 mm. Moreover, the estimated decrease in life span associated with long-term residence in
areas with high ambient PM is estimated to be between 1 and 2 years, which is large compared with
other environmental risk factors. Whilst the data demonstrating PM-induced health effects is
irrefutable, major questions remain concerning the mechanisms by which these compositionally
heterogeneous species elicit their toxic actions. It has been argued that as exposure to a broad
spectrum of particle types (vehicle emissions, cigarette and wood smoke PM, mineral dusts etc)
elicits similar acute responses in humans, namely neutrophilic inflammation (Burns 1991; Salvi
et al. 1999; Ghio 2000), reduced inspiratory capacity (Salvi et al. 1999; Stenfors et al. 2004) and
heightened bronchial reactivity (Sherman et al. 1989; Menon et al. 1992; Nordenhall et al. 2000),
they may act through a common mechanism. Currently numerous groups are investigating the
hypothesis that these common mechanisms may relate to the capacity of these particles to cause
damaging oxidation reactions in the lung, as well as systemically. In this review we will consider
this hypothesis in detail, with specific emphasis on initial interactions between inhaled PM and
components of the thin liquid layer that overlies the respiratory epithelium, the respiratory tract
lining fluid (RTLF). This compartment represents the first physical interface with which PM
interacts, upon deposition in the airways. A clear understanding of the initial reactions between
PM constituents and components of the RTLF is thus critical in understanding any
observed toxicity.
