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Project Status: complete

Title: Clinical pilot study to develop sensitive markers for detecting the health effects of acidic atmospheres

Principal Investigator / Author(s): Roger, L. Jack

Contractor: TRC Environmental Corporation

Contract Number: A933-112

Research Program Area: Health & Exposure

Topic Areas: Acid Deposition


Nitric acid (HNO3) is a common component of air pollution possibly associated with the epidemiological observations that acid atmospheres may cause or aggravate pulmonary disease. Because studies of classical pulmonary mechanics have generally not shown effects of acid atmospheres except at high acid concentrations, other endpoints, such as pulmonary clearance and pulmonary immune effects need to be examined. In this reported research we studied human pulmonary immune responses to inhaled nitric acid as represented by two types of sensitive and biologically meaningful markers of immunological effects --inflammation and macrophage function.

We exposed nine healthy non-smoking volunteers once to HNO3 vapor (200 mg/m3, 0.08 ppm), and once to filtered air in random order with natural (unencumbered) breathing, for two hours with 100 minutes of moderate exercise (ventilation rate of 39 liters/minute). Pulmonary function (spirometry and airway resistance) were measured as were subjective symptoms of response. Bronchoalveolar lavage (BAL) was performed 18 hours after exposure and the fluid was analyzed for indicators of airway injury and inflammation. The alveolar macrophages (AM) were tested for phagocytosis of Candida albicans and for susceptibility to infection with respiratory syncytial virus (RSV).

The exposure to HNO3 did not change pulmonary function (spirometry and airway resistance) nor measures of symptoms. Compared to BAL from air-exposed subjects, there were no significant increases in protein, LDH, fibronectin, PGE2, C3a, alpha-1-antitrypsin, or in polymorphonuclear phagocytes (PMN), in the BAL from HNO3-exposed subjects. This indicates that HNO3 did not cause permeability changes, cell damage, or inflammation in the lung. In contrast, there was a significant increase in the phagocytic activity of AM. Phagocytosis of both unopsonized and serum-opsonized Candida albicans was increased by 85% (unopsonized) versus 24% (opsonized). Furthermore, AM from HNO3-exposed subjects showed increased resistance to infection with RSV and released 70% less RSV than AM from air-exposed subjects. Superoxide production by AM was reduced in subjects after HNO3 exposure compared to that after air exposure.

The results of this study indicate that HNO3 at 0.08 ppm does not cause acute injury in the lung nor responses suggestive of inflammation. Likewise, it is clear that in vivo exposure to HNO3 did not result in an "immunological" activation of the alveolar macrophages, although they were activated to some extent as evidenced by increased phagocytosis and response to RSV infection. Further investigations into the generality of these observations both with HNO3 and other acid air pollutants deserve attention.


For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753

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