The Air Pollution Detectives

William S. Beckett, M.D.

University of Rochester School of Medicine and Dentistry, Rochester, New York

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In a strikingly innovative study in this issue (pp. 704-708) (1), Ghio and Devlin have cleverly turned back the hands of the clock to investigate a scientifically important air pollution episode.

The story begins in the late 1980s, when C. Arden Pope III suspected that particulate air pollution in the high Utah Valley (near Salt Lake) was causing illness in his own community. Turning the powerful tools of econometrics to the tasks of epidemiology, he and his colleagues studied associations between fine particles in the outdoor air and important health effectsthings like children's school absence rates (2), asthmatics' peak flows (3), hospitalizations (4), and death rates for cardiac as well as respiratory disease (5). Their methodto focus on short-term peaks and troughs of pollutant levels and their associations with short-term patterns of illnessfound associations that had been difficult previously to detect.

Other air pollution epidemiologists began to apply these analytic methods, and ushered in a period of intense, worldwide study of the health effects of fine particles. Although one epidemiologic association does not a causal relationship make, the consistency of findings by many investigators led eventually to tightening of health regulations on particles in our air. In addition, these important epidemiologic findings have stimulated an intense effort, supported by the U.S. Environmental Protection Agency, to understand the hitherto unknown mechanisms by which tiny particles cause such significant health effects. Our current health-protective approach is to limit exposure to particles, based on the mass of particles per volume of breathing air within certain size rangeshence we now have regulations for fine particles less than 10 µm and 2.5 µm in diameter. But all kinds of particles are treated equallywind-blown dust particles are regulated the same as the smoke from burning oil and coal.

Pope's initial studies were bolstered by a chance event that has made possible the striking observations presented more than 10 yr later by Ghio and Devlin of the Environmental Protection Agency National Health and Environmental Effects Research Laboratory, far from Utah in North Carolina. Over the period of several years that Pope collected data on particles and health effects in his community, a smoke-belching steel mill in the Utah Valley poured clouds of fine particulate pollution into a bowl. This valley, inhabited by the burgeoning suburban population of Provo and Orem, Utah, was home to unusually persistent winter temperature inversionsweather episodes that trap pollutants close to ground levels for days at a time. Butand here is where chance favored sciencefor 1 yr, the furnaces of the steel mill went cold during a labor dispute. Particle levels fell dramatically, only to rebound when the steel mill roared back into operation the following year. Because this happened, entirely by coincidence, in the middle of Pope's studies, he was able to catch the improvement in peak flows in his asthmatic children, and a 1-yr dip in wintertime hospital admissionsall of which reversed when the smoke poured again into the air. Thus was added a further dimension of associations between particles and health effects this time on a year-long basis. Epidemiologic observations, it is again emphasized, cannot usually demonstrate cause-and- effect, and Pope's assertions of the evidence of particle toxicity were challenged by alternative explanationschance, bias, confoundingor perhaps, suggested a steel mill consultant, two coincidentally timed wintertime epidemics of respiratory syncytial virus, bracketing the winter of the steel mill shutdown.

One of several questions raised by the series of studies was, "Is there something particularly harmful about the steel mill combustion particles, and if so, what?"

Fast forward, now, to Chapel Hill, North Carolina, 2000. Aware of the significance of the Utah Valley events, Ghio and Devlin were investigating whetherand howfine particles in pollution might be potent enough to be responsible for the pulmonary and other effects Pope and his colleague epidemiologists described. A key question is, "What characteristics made these small particles toxic to human beingsthe size alone, the chemical composition, the presence of adsorbed metals, endotoxin or gasesor something else?" As Ghio, Devlin, and others worked on these questions, out of the past emerged some powerful evidence: samples from air pollution collecting devices that had been running, in the Utah Valley and close to the steel mill site, during the 3 yr of the steel mill's ups and downs. Here were some well-preserved remains of the particulate phase of those air pollution episodessome with particles from the year the steel mill was closed, and some with particles from the years before and after. When Ghio and Devlin instilled a soluble supernatant from each of the specimens into the bronchi of healthy subjects, the bronchoalveolar lavage the following day told a fascinating story: more inflammation from the material collected from a sampling site near to the steel mill, and during the years when the steel mill was running, compared with the year in-between. (Based on previous studies instilling this material into the lungs of rats, it seems possible that material eluted from the glass filter fibers themselves may have contributed to the baseline inflammatory response, but could not account for the enhanced response to material taken when the mill was in operation) (6). Because the steel mill produced more than 80% of the fine particulate matter sampled in the Utah Valley during its years of operation, it seems safe to conclude that the presence of more particles in the air, as well as something different about the makeup of those steel mill furnace combustion particles, is capable of inducing a significantly greater inflammatory response in the lungs of even healthy adults. Analysis of the metals content of the three samples shows higher amounts of iron, copper, zinc, lead, and nickel in the samples taken while the steel mill was operational, consistent with the metals hypothesis of fine particulate air pollution toxicity. This theory of particle toxicity emphasizes the ability of metals on fine particulates to induce toxic oxygen radical species and subsequent inflammatory response in the lung. In fact, the particles collected while the steel mill was operating had more oxygen-radical generating capacity, which was inhibited in vitro by chelating metals from the particle extracts.

The inescapable implication of this study is that, while size does matter, particle composition seems also to be extremely important in the pulmonary inflammatory response to particulate air pollution. The next mystery for the air pollution detectives is to find out, more specifically, which chemical constituents of particles correspond most directly with health effects. I understand they're already hot on the trail.

	References

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1. Ghio AJ, Devlin RB. Inflammatory lung injury after bronchial instillation of air pollution particles. Am J Respir Crit Care Med 2001; 164: 704-708 [Abstract/Free Full Text].

2. Ransom MR, Pope CA III.. Elementary school absences and PM₁₀ pollution in Utah Valley. Env Res 1992; 58: 204-219 .

3. Pope CA III,, Dockery DW, Spengler JD, Raizenne ME. Respiratory health and PM₁₀ pollution: a daily time series analysis. Am Rev Respir Dis 1991; 144: 668-674 [Medline].

4. Pope CA III.. Respiratory disease associated with community air pollution and a steel mill, Utah Valley. Am J Public Health 1989; 79: 623-628 [Abstract/Free Full Text].

5. Pope CA III,, Schwartz J, Ransom MR. Daily mortality and PM₁₀ pollution in Utah Valley. Arch Environ Health 1992; 47: 211-216 [Medline].

6. Dye JA, Lehmann JR, McGee JK, Winsett DW, Ledbetter AD, Everitt JI, Ghio AJ, Costa DL. Acute pulmonary toxicity of particulate matter (PM) filter extracts in rats: coherence with epidemiological studies in Utah Valley residents. Environ Health Perspect 2001;109(Suppl):395-403.