Use of human lung tissue for studies of structural changes associated with chronic ozone exposure: opportunities and critical issues.

Definitive information on the chronic effects of exposure to ozone (O3) in humans is not available. There is a strong concern that ozone could produce chronic lung damage in humans on the basis that exposures are ubiquitous at levels that produce transient symptoms, function deficits, and lung inflammation in humans and chronic lung damage in laboratory animals. Both prospective and national population surveys suggest an association between chronic O3 exposure and reduced lung function, and a pilot investigation of autopsied lungs of accident victims in Los Angeles reported an unexpectedly high incidence of disease in the centriacinar region, the lung region known to receive the highest dose of inhaled O3. This paper discusses the advantages and limitations of further studies of structural changes in human lung tissue in relation to chronic O3 exposure. The major advantages of such studies are that a) measurable effects may be related to realistic chronic exposures, b) the effects may be described quantitatively and compared directly to those obtained in chronic animal inhalation exposures, and c) evidence for chronic effects may be obtained much more rapidly than in prospective studies. The major limitations are the difficulties in obtaining sufficient reliable information on residential history, physical activity out-of-doors, and smoking and other confounding exposures to lung irritants from next of kin, and limited availability of adequate air quality data for determining ambient concentrations at places of residence and/or outdoor exercise. The paper also discusses approaches to minimizing these limitations in the design of specific studies.