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A strong and consistent association has been observed between adjusted mortality rates and ambient particle concentration. The strongest associations are seen for respiratory and cardiac deaths, particularly among the elderly. Particulate air pollution is also associated with asthma exacerbations, increased respiratory symptoms, decreased lung function, increased medication use, and increased hospital admissions. The U.S. Environmental Protection Agency (EPA) has recently promulgated a new national ambient air quality standard for fine particles, and yet the mechanisms for health effects at such low particle mass concentrations remain unclear. Hypotheses to identify the responsible particles have focused on particle acidity, particle content of transition metals, bioaerosols, and ultrafine particles. Because ultrafine particles are efficiently deposited in the respiratory tract and may be important in initiating airway inflammation, we have initiated clinical studies with ultrafine carbon particles in healthy subjects. These studies examine the role of ultrafines in: (1) the induction of airway inflammation; (2) expression of leukocyte and endothelial adhesion molecules in blood; (3) the alteration of blood coagulability; and (4) alteration in cardiac electrical activity. These events could lead to exacerbation of underlying cardiorespiratory disease. For example, airway inflammation may activate endothelium and circulating leukocytes, and induce a systemic acute phase response with transient hypercoagulability; this could explain the epidemiologic linkages between pollutant exposures and cardiovascular events. These approaches should be useful in identifying mechanisms for pollutant-induced respiratory and systemic effects, and in providing data for determining appropriate air quality standards.

The assessment of risk from exposure to environmental air pollutants is complex, and involves the disciplines of epidemiology, animal toxicology, and human inhalation studies. Controlled, quantitative studies of exposed humans help determine health-related effects that result from breathing the atmosphere. The major unique feature of the clinical study is the ability to select, control, and quantify pollutant exposures of subjects of known clinical status, and determine their effects under ideal experimental conditions. The choice of outcomes to be assessed in human clinical studies can be guided by both scientific and practical considerations, but the diversity of human responses and responsiveness must be considered. Subjects considered to be among the most susceptible include those with asthma, chronic obstructive lung disease, and cardiovascular disease. New experimental approaches include exposures to concentrated ambient air particles, diesel engine exhaust, combustion products from smoking machines, and experimental model particles. Future investigations of the health effects of air pollution will benefit from collaborative efforts among the disciplines of epidemiology, animal toxicology, and human clinical studies.

The focus of public health concern and research in regard to environmental lung diseases has changed across the century. Illustrative agents include radon, indoor asbestos, environmental tobacco smoke, acidic aerosols, and oxidant gases. Tremendous progress has been made in understanding and preventing environmental lung diseases. However, we remain concerned about adverse consequences of breathing polluted outdoor and indoor air. In the persistent concerns about adverse effects of polluted air on the lung, a new emphasis is pervasive; the focus has shifted from avoiding clinical disease among highly exposed individuals to protecting the population from an unacceptable burden of risk. The technique of quantitative risk assessment has become increasingly important for characterizing the safety of environmental agents. The resulting emphasis on the final risk projection and attendant uncertainties may overly emphasize gaps in our knowledge.

Controlled clinical studies represent an important tool for quantifying the effects of air pollutants. Examinations can be carried out with the aid of exposure chambers, or employing inhalation via a mask. To date, pulmonary function tests have been the major means of establishing the effects of pollutants. Studies performed to date have served to identify high-risk groups, to demonstrate dose-effect relationships, and to examine borderline values. It is probable that pulmonary function tests are not suitable for detecting the influence of some of the environmental pollutants. More recent clinical techniques, such as broncho-alveolar lavage, nasal lavage, the measurement of alveolar permeability with the aid of labelled aerosols, represent possibilities for investigating other pollutant-induced effects. We need clinical studies because, over and beyond the traditional methods of epidemiology and animal experiments, they can contribute important aspects of the estimation of the risks of environmental pollutants.

To determine predictors of mortality in immunocompromised patients with pulmonary infiltrates, we reviewed the records of all such patients admitted to two community teaching hospitals who underwent a lung biopsy over a ten-year period. We examined the consequences of advancing age, primary disease, fever, neutropenia, immunosuppressive corticosteroid therapy, previous lung radiation, roentgenographic pattern, result of lung biopsy, room air arterial oxygen pressure (Pao2), early mechanical ventilation, and the presence of a comorbid disease on eventual outcome. We identified 104 episodes in 99 patients. Sixty-seven (64%) survived and 37 died. By both discriminant analysis and logistic regression statistical methods, mechanical ventilation, the initial room air Pao2, and corticosteroid therapy were the dominant independent variables, in that order, to significantly predict mortality. No patient survived who simultaneously had a room air Pao2 less than or equal to 50 mm Hg, was on corticosteroids, and was mechanically ventilated. Eighty-three percent of survivors had either none or, at most, one of these three variables present. We conclude that hypoxia, immunosuppression by corticosteroids, and the necessity for mechanical ventilation within 72 hours of hospitalization indicate a poor prognosis in the immunocompromised patient with pulmonary infiltrates who has undergone a lung biopsy.