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Knowledge about the health effects of exposure to formaldehyde associated with automotive emissions is of pivotal importance in the risk assessment of this agent. Mobile sources emit many combustion-derived pollutants, including formaldehyde, in association with respirable carbon particles. Because it is hydrophilic, most of the inhaled formaldehyde is absorbed in the upper respiratory tract. However, if the organic vapor is adsorbed on respirable particles, formaldehyde may be deposited in the deep lung with the inhaled particles and may be available to interact adversely with cells along the lung parenchyma. On the respiratory surface, the alveolar macrophage phagocytic system plays the pivotal role in defending the lung against infectious agents. Susceptibility to respiratory infections is a relevant and sensitive indicator of the adverse effects of air pollution because acute and chronic exposures to a variety of air pollutants have been shown to decrease pulmonary antibacterial defenses. The goal of this research was to investigate whether exposure to formaldehyde decreases resistance to respiratory infections through dysfunctions of the alveolar macrophage phagocytic system. The study also explored whether interactions between formaldehyde and respirable carbon black particles alter susceptibility to respiratory infections and impairment of alveolar macrophage phagocytosis by delivering adsorbed formaldehyde to the deep lung with the inhaled particles. A carbon black, Regal GR, was used in these studies as a surrogate for the carbonaceous core of Diesel particulate matter. This material was selected to represent the worst-case scenario because the carbon black was expected to adsorb formaldehyde strongly. To accomplish this goal, mice were exposed to formaldehyde and to carbon black and formaldehyde combinations; increased susceptibility to respiratory infections was quantified by alveolar macrophage-dependent intrapulmonary killing of Staphylococcus aureus after an inhalation challenge with the bacterium. The salient findings of the bactericidal studies are as follows: Fifteen parts per million (ppm)* formaldehyde impaired the intrapulmonary killing of S. aureus when exposure followed the bacterial challenge. One ppm formaldehyde impaired the intrapulmonary killing of S. aureus when exposure preceded and was continued after the bacterial challenge. Coexposures to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde, or 10 mg/m3 carbon black and 5 ppm formaldehyde after the bacterial challenge had no effect on the intrapulmonary killing of S. aureus. Preexposure for four hours per day for four days to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde had no effect on the intrapulmonary killing of S. aureus when the assay was performed one day after the cessation of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Alpha-cristobalite causes pulmonary interstitial disease in humans and experimental animals. Aerosol exposure of rats to cristobalite for 8 days results in early and sustained alveolar type II cell hyperplasia in areas of inflammation characterized by the presence of macrophages and polymorphonuclear leukocytes. Irregular interstitial fibrosis and coalescence of alveoli are apparent by day 120. The inflammatory response is characterized by increased lavage cell recoveries, principally macrophages and neutrophils. Lavage recoveries of protein, nonpolar lipid, phospholipid, and saturated phosphatidylcholine also are increased. The recovery ratio for two important surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol, is decreased at all points following exposure. Our morphologic analyses, together with results correlating lavage cell and lipid recoveries, point to the potential importance of macrophages and neutrophils in the epithelial cell response to cristobalite exposure.

Cristobalite is a crystalline silicon dioxide that elicits pulmonary inflammation and fibrosis in humans and experimental animals. Exposure of rats to aerosols of respirable cristobalite for 8 days led to a rapid influx of neutrophils and macrophages into alveolar and tissue compartments of the lung followed by a more gradual accumulation of T lymphocytes. This inflammatory response persisted throughout 52 weeks after the end of the exposure. For some variables studied there appeared to be a cyclical nature to the response. Statistical analysis of alveolar cell populations and lung tissue weight, protein, and hydroxyproline showed significant time-dependent fluctuations. Histologic analysis revealed a progressive deposition of collagen and type II cell hyperplasia centered on airways, however, there appeared to be some correlation between fluctuations in alveolar cell populations and overall tissue pathology. The observed cellular and biochemical fluctuations and the persistence of the inflammatory response may be due to the presence of silica in the lung, which serves as a source of repetitive stimulation of lung cells.

The goal of this study was to develop an early marker of lung injury that might change in response to exposure to a mobile source emission. Nitrogen dioxide (NO2)2 was chosen as an example of an atmospheric pollutant that is related to automobile emissions. Since reorganization of the connective tissue matrix of the lung occurs in response to injury, markers of connective tissue metabolism were selected as targets. Hydroxylysine became the marker of choice. It is an amino acid that is virtually exclusive to collagen, although it does occur in minimal amounts in other proteins. Furthermore, it is excreted in the urine, which makes it readily available for analysis using noninvasive techniques. Other markers evaluated as part of the study included angiotensin-converting enzyme as a marker of lung injury, desmosine as a marker of elastin degradation, and hydroxyproline as another marker of collagen metabolism. Male Fischer-344 rats were exposed in whole-body chambers to controlled concentrations of NO2 for various doses and periods of time. The concentrations of NO2 ranged from 0.5 to 30 parts per million (ppm); the rats were exposed for six hours per day for periods of two days to four weeks. Urine and bronchoalveolar lavage samples were collected and analyzed for the appropriate marker. In addition, pulmonary function studies and histologic examinations of the lungs were completed at selected time points. Urinary hydroxylysine concentration increased as a function of NO2 concentration during six-hour-per-day exposures for two days. This short-term exposure required relatively high doses to achieve significant changes in the hydroxylysine output. During one-week exposures to either 25 or 30 ppm NO2, there was an increase in urinary hydroxylysine associated with changes in lavage concentrations of angiotensin-converting enzyme and hydroxylysine. The lungs of these animals demonstrated histologic changes typical of oxidant injury. Four-week exposure protocols using 0.5 and 1 ppm NO2 were most interesting in terms of the sensitivity of the marker. There was minimal damage revealed by the histology and function studies, yet there were significant increases in the excretion of hydroxylysine. It appears that hydroxylysine can be indicative of exposure when other parameters are normal. It will require long-term follow-up of exposed rats to determine whether or not the change in marker concentration is predictive of damage. Hydroxylysine may be an excellent marker of exposure to oxidants in the human population. Controlled studies to establish base-line values are needed, followed by carefully controlled studies in individuals with connective tissue abnormalities of the lung.