Ozone and the lung: a sensitive issue.

In this paper we examine scientific evidence and related uncertainties in two steps of benefit-cost analyses of ozone reduction: estimating the health improvements attributable to reductions in ozone and determining the appropriate monetary values of these improvements. Although substantial evidence exists on molecular and physiologic impacts, the evidence needed to establish concentration-response functions is somewhat limited. Furthermore, because exposure to ozone depends on factors such as air conditioning use, past epidemiologic studies may not be directly applicable in unstudied settings. To evaluate the evidence likely to contribute significantly to benefits, we focus on four health outcomes: premature mortality, chronic asthma, respiratory hospital admissions, and minor restricted activity days. We determine concentration-response functions for these health outcomes for a hypothetical case study in Houston, Texas, using probabilistic weighting reflecting our judgment of the strength of the evidence and the possibility of confounding. We make a similar presentation for valuation, where uncertainty is due primarily to the lack of willingness-to-pay data for the population affected by ozone. We estimate that the annual monetary value of health benefits from reducing ozone concentrations in Houston is approximately $10 per person per microgram per cubic meter (24-hr average) reduced (95% confidence interval, $0.70-$40). The central estimate exceeds past estimates by approximately a factor of five, driven by the inclusion of mortality. We discuss the implications of our findings for future analyses and determine areas of research that might help reduce the uncertainties in benefit estimation.

Assessing the public health benefits of reduced ozone concentrations.

The airway epithelial lining serves as an efficient barrier against penetration of exogenous particles and macromolecules. Disruption of this barrier following O3 exposure represents a state of compromised epithelial defenses leading to increased transmucosal permeability. Although the barrier disruption following an acute exposure is transient in nature, the brief period of disruption caused by O3, an oxidant air pollutant, provides an opportunity for facilitated entry of a potentially toxic particulate copollutant(s) across the airway epithelia. The subsequent deposition and retention of the copollutant(s) in the subepithelial compartment for prolonged periods adds the risk of injury due to chronic exposure following an acute episode. Toxicological studies from several laboratories have demonstrated alterations in epithelial permeability, suggestive of barrier disruption, in animals and humans exposed to O3. Inflammatory cells represent another important component of pulmonary defenses, but upon activat...

Ozone-induced lung inflammation and mucosal barrier disruption: toxicology, mechanisms, and implications.

This review presents a brief overview of the health effects and exposures of two criteria pollutants--ozone and particulate matter--and two toxic air pollutants--benzene and formaldehyde. These pollutants were selected from the six criteria pollutants and from the 189 toxic air pollutants on the basis of their prevalence in the United States, their physicochemical behavior, and the magnitude of their potential health threat. The health effects data included in this review primarily include results from epidemiologic studies; however, some findings from animal studies are also discussed when no other information is available. Health effects findings for each pollutant are related in this review to corresponding information about outdoor, indoor, and personal exposures and pollutant sources.

Criteria air pollutants and toxic air pollutants.

We previously demonstrated the importance of the surface area burden as the key dose metric in the elicitation of inflammation in rat lungs by low-solubility, low-toxicity particles (LSLTP). We have now explored the dosimetry of LSLTP in vitro using epithelial cell interleukin (IL)-8 gene expression as a surrogate for potential of particles to cause inflammation. The proximal alveolar region (PAR) of the lung has been identified as a key site for the retention of respirable particles, as it receives high deposition but has slow clearance compared to the larger airways. For these reasons, a few days after exposure to particles the residual dose is concentrated in the PAR region. Re-expressing our rat lung data as particle surface area burden per unit of PAR surface area we obtained a threshold value for onset of inflammation of 1 cm2/cm2. We carried out dose responses in vitro for onset of IL-8 gene expression with the same particles as we had used in vivo. When we expressed the in vitro dose as surface ar...

/pdf/concordance-between-in-vitro-and-in-vivo-dosimetry-in-the-4j024deood.pdf

Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles: the key role of the proximal alveolar region.

https://ftp.cdc.gov/pub/Documents/OEL/02.%20Kuempel/References/Chang_1992_Toxicol%20Appl%20Pharmacol.pdf

Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone.

Exposures to low levels of O{sub 3} cause epithelial and interstitial injury in the proximal alveolar region. The sequential development of this lesion caused by a simulated ambient pattern of O{sub 3} was studied by exposing Fisher 344 rats to 0.06ppm O{sub 3} overnight with an 8 hr daytime exposure having a slow increase to a peak of 0.25 ppm and then gradually decreasing back to 0.06 ppm. Animals were studied using EM morphometric techniques after 7, 21 and 90 days exposure as well as post 90 days exposures. The early changes in O{sub 3} exposed animals included increases of volumes in type II epithelium (60%), type I epithelium (16%), cellular interstitium (52%), non-cell interstitium (33%), and in alveolar macrophages (180%). The response showed a biphasic reaction with the early injury subsiding after 21 days of O{sub 3} exposure. The animals exposed for 90 days showed a 28% increase in relative volume of type I and a 42% increase in type II epithelia.

Ying Huang

Papers

Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone.

Lung Injury Caused by Ambient Levels of Ozone