Air pollution: the pathobiologic issues

In defining the adverse effects of ambient levels of ozone on the human lung, research has tended to emphasize direct cause and effect responses. However, disease is generally multicausative and the lung has relatively few ways to respond to injury. Moreover, all adult lungs have some disease. Thus, pathogenesis is more appropriately addressed by asking "What role does the agent in question play in the causation, promotion, facilitation, and/or exacerbation of disease that is present?" Our recent studies of the lungs of 107 ostensibly healthy youths between 14 and 25 years of age (violent death cases in Los Angeles County) add suggestive evidence to epidemiologic and experimental data indicating that air pollution is adversely affecting the human lung. We found 80% of the youths with some degree of presumably subclinical Centriacinar Region disease and, in 27%, the Centriacinar Region disease was severe and extensive. Centriacinar Region disease has been linked to infectious organisms, cigarette smoke, ozone, mineral dusts, and other noxious agents. Recently, a mild form of Centriacinar Region disease has been produced in primates exposed to a level of ozone (0.15 ppm) that is frequently exceeded in Los Angeles. Since there is suggestive evidence that air pollution in Los Angeles increases the rate of decline of lung function, we suspect that there has also been an increase in the rate of structural decline, manifest in part by accentuated Centriacinar Region disease. The health significance of Centriacinar Region disease is just beginning to be appreciated. At the very least, reserve depletion reflected in the Centriacinar Region disease implies some reduction in lung performance and some increase in susceptibility to disease in general. At worst, the unexpected severity of the Centriacinar Region disease may be a bellwether for an impending rise in clinically manifested lung disease for the general population. An urgent research need is the monitoring of health through inventories of the functional and structural units of the human lung, with special emphasis on subpopulations of cell societies of the lung. The feasibility of applying image analysis for large volume objective quantitations has been demonstrated and should be implemented. Multicity studies, in cooperation with Offices of the Medical Examiner-Coroner and autopsy services in general, can help meet the critical need for increased sensitivity in the monitoring of the public health in a changing environment.