Kenneth B. Gross

Pulmonary responses of asthmatic and normal subjects to different temperature and humidity conditions in an environmental chamber

Determining the possible adverse health effects of air pollutants can be complicated by differences in the environmental conditions of temperature and humidity. To evaluate the potentially confounding effects of differences in temperature and humidity, we exposed 8 normal male subjects and 8 male subjects with asthma to the extremes in temperature and humidity that could be maintained in an environmental chamber. We performed serial pulmonary function tests for these subjects before and during 6 hr exposure periods on 5 separate occasions: cold, dry (10°C, 10% relative humidity); cold, humid (10°C, 50% relative humidity); normal ambient (22°C, 40% relative humidity); hot, dry (37°C, 15% relative humidity); and hot, humid (37°C, 60% relative humidity). The exposure period included a 12 min exercise on a cycle ergometer. We found no significant change in spirometry, airways resistance, or diffusing capacity for either group of subjects at rest alone over the 6 hr period of exposure for any exposure condition. However, there were changes in spirometry and airways resistance as a result of the 12 min period of exercise. The subjects with asthma had significant decreases in forced expiratory volume in 1 sec (FEV1) (20–21%) and increases in specific airways resistance when exercising in conditions of cold and dry, cold and humid, and hot and dry. The normal subjects had an average increase in FEV1 of approximately 6% when exercising in the hot and humid conditions. We found significant correlations for the changes in FEV1 with the water content of the exposure conditions for both groups of subjects. We also found that the work performance (expressed as the external work performed divided by the oxygen consumed) was decreased for the subjects in both groups at the conditions of the higher temperature (37°C) compared with the lower temperature (10°C). These results confirm that controlling for the conditions of temperature and humidity is essential in chamber studies, field studies, or epidemiologic evaluations determining the adverse effect of an air pollutant.

Mechanism of induction of asthmatic attacks initiated by the inhalation of particles generated by airbag system deployment

OBJECTIVE We have previously demonstrated that inhalation of the dust produced by dual frontal airbag deployment can result in significant bronchospasm in approximately 40% of mild to moderate asthmatics. This study was performed to determine the cause of the asthmatic response. DESIGN Controlled laboratory study. MATERIALS AND METHODS Asthmatics who were previously tested for their response to airbag effluents were exposed for twenty minutes to either 1) airbag effluents from airbag systems in which the airbag was insulated from the hot deployment module; 2) non-sulfur containing airbag effluents; 3) sodium chloride aerosol; or 4) sodium carbonate-bicarbonate aerosol (pH 10). Pre-exposure, post-exposure, and 2 hour post exposure pulmonary spirometry and mechanics were measured. Subjects filled out symptoms questionnaires before exposure, 2, 4, 8, 12, and 19 minutes into the exposure, immediately post-exposure, and 2 hours post-exposure. MEASUREMENTS AND MAIN RESULTS Prevention of the pyrolysis of the passenger-side bag as it rested on the hot module after deployment did not diminish the asthmatic response. Removal of sulfur-containing oxidants from the airbag pyrotechnic chemistry, which may have led to sulfite production, similarly did not alleviate the asthmatic response to the airbag effluents. Lastly, when asthmatics were exposed to sodium chloride and sodium carbonate-bicarbonate aerosols at approximately the same concentration (approximately 220 mg/m3) as the airbag aerosol concentration that occurred in the in-car tests, they had responses similar to those produced by the airbag exposures. CONCLUSIONS We conclude that the amount of soluble particulate contained in the aerosol discharged into the passenger compartment by dual frontal airbag deployment is largely the cause of the observed evoked asthmatic attacks. The alkaline pH of the airbag and carbonate aerosols may have added an additional degree of provocation.

Increased 5-lipoxygenase metabolism in the lungs of human subjects exposed to ozone

The environmental pollutant ozone, at sufficiently high levels, is known to induce pulmonary inflammation with resultant airway obstruction in normal subjects. Eicosanoids comprise one group of mediators released from alveolar macrophages which are involved in the pathogenesis of inflammatory lung diseases. We compared the effects of 2-h exposures to 0.4 ppm ozone and filtered air on pulmonary function and eicosanoid levels in bronchoalveolar lavage fluid in 11 normal healthy volunteers. Subjects were exposed to a 6-fold increase in minute ventilation using an adjusted work load on a cycle ergometer. All subjects complained of cough and dyspnea, and demonstrated increased airway obstruction, and increased specific airway resistance following ozone exposure as compared to air exposure. Bronchoalveolar lavage cell count demonstrated a 9-fold increase in the number of neutrophils with a lesser reduction in the number of alveolar macrophages following ozone exposure. Notably, bronchoalveolar lavage fluid leukotriene (LT) C4 (8-fold) and to a lesser extent LTB4 (1.5-fold) levels were higher following ozone exposure compared to air control, with no change in prostaglandins. In a subset of four subjects, alveolar macrophage arachidonic acid metabolism was studied in vitro following separate in vivo exposures to both ozone and air. Alveolar macrophages obtained following ozone exposure released more 5-lipoxygenase (1.5-fold) metabolites, with no change in cyclooxygenase metabolites, than did cells obtained following air exposure. These observations document activation of the 5-lipoxygenase pathway in the lung following ozone exposure, and suggest that alveolar macrophages may participate in the generation of LT, whose actions promote airway inflammation and obstruction.

Functional and pathologic consequences of a 52-week exposure to 0.5 PPM ozone followed by a clean air recovery period

Male Fischer 344 rats were exposed to 0.5 ppm ozone for 20 hr/day, 7 days/week, for 52 weeks after which they were allowed to recover in clean filtered air for 12 weeks. Pulmonary function testing, which included measurements of lung volumes, expiratory air flows, and DLco, was performed before the initiation of exposure, after 26 and 52 weeks of exposure, and after the 12 week recovery. Control animals were tested at the same times but exposed only to clean filtered air. Another group, periodically sacrificed for histopathologic evaluation, was similarly exposed to ozone but allowed to recover in clean air for 24 weeks. The 52 weeks of ozone exposure produced small but statistically significant changes in several of the functional measurements when compared to clean air controls (FRC + 7.0%; RV + 11.2%; DLco - 7.3%). These measurements returned to control levels with 3 months of recovery. All other parameters showed no significantly different values between the 2 groups throughout the exposure and recovery periods. After both 6 and 12 months of ozone exposure, microscopic evaluation revealed a slight inflammatory response in the alveolar duct walls and septa of the immediately adjacent alveoli. This response included the accumulation of mononuclear cells and fibroblasts, thickening of alveolar septa, and a slight increase in macrophage population. With 6 months of recovery, the inflammation had all but disappeared. There remained only a slight dilation and thickening of an occasional alveolar duct and its adjacent alveoli. We conclude that the functional changes seen in the lungs in response to the ozone insult were the result of the observed inflammation in the distal areas of the lung, and the lesions produced were reversible to the extent that they could not be detected functionally after recovery.

Pulmonary functional and morphological changes induced by a 4-week exposure to 0.7 PPM ozone followed by a 9-week recovery period

Male Fischer-344 rats (control, C = 12; experimental, E = 11) were subjected to pulmonary-function testing procedures. The experimental group was then exposed to 0.7 ppm ozone for 28 d, 20 h/d, and both groups were tested at the termination of the exposure and after 4 and 9 wk of recovery in clean filtered air. Another group of animals (C = 6, E = 12) was similarly treated, but at each test point one-third were sacrificed for microscopic evaluation. When percent changes from preexposure values were compared to controls at each time point, the ozone exposure produced obstructive changes in the lung, including significant decreases (p less than 0.05) in forced expiratory flows (MEF25 40.3%, MEF10 70.7%), lung volumes (IC 22.5%, FVC 21.8%), and DLCO (20.7%); and a significant increase in functional residual capacity (FRC 61.1%). The total lung capacity (IC + FRC) was not significantly changed by the ozone. Microscopic examination revealed characteristic lesions in the region of terminal bronchioles and central acinar alveoli marked by peribronchiolar edema, bronchiolization of alveolar duct epithelium, and type II cell proliferation in involved alveoli with increased numbers of macrophages and a few leucocytes. Clearly discernable was a focal interalveolar-alveolar duct reaction made up of fibroblasts, a few inflammatory cells, and conspicuous mast cells, all embedded in a loose metachromatic matrix. After 4 wk of recovery, all measurements of lung volume and DLCO had returned to the values of the control group; however, even after 9 wk some of the measurements of lung flow (MEF25, MEF10) remained significantly although less depressed (27.9 and 40.1%, respectively). Histologically, after 4 wk recovery, there remained only a slight unevenly disturbed inflammatory reaction. In these foci there was often a residual, narrower, more condensed band of eosinophilic material, presumably collagen, that sometimes contained interspersed mast cells. After 9 wk, this collagen accumulation within the thickened wall of the alveolar duct could occasionally still be noted. These data suggest that the florid response seen at the end of exposure was related to the obstructive changes measured and that, with recovery, the residual central acinar-alveolar duct thickening may be responsible for the persistently diminished air flows.

Feasibility Study of Using Brine for Carbon Dioxide Capture and Storage from Fixed Sources

Abstract A laboratory-scale reactor was developed to evaluate the capture of carbon dioxide (CO2) from a gas into a liquid as an approach to control greenhouse gases emitted from fixed sources. CO2 at 5–50% concentrations was passed through a gas-exchange membrane and transferred into liquid media—tap water or simulated brine. When using water, capture efficiencies exceeded 50% and could be enhanced by adding base (e.g., sodium hydroxide) or the combination of base and carbonic anhydrase, a catalyst that speeds the conversion of CO2 to carbonic acid. The transferred CO2 formed ions, such as bicarbonate or carbonate, depending on the amount of base present. Adding precipitating cations, like Ca++, produced insoluble carbonate salts. Simulated brine proved nearly as efficient as water in absorbing CO2, with less than a 6% reduction in CO2 transferred. The CO2 either dissolved into the brine or formed a mixture of gas and ions. If the chemistry was favorable, carbonate precipitate spontaneously formed. Energy expenditure of pumping brine up and down from subterranean depths was modeled. We conclude that using brine in a gas-exchange membrane system for capturing CO2 from a gas stream to liquid is technically feasible and can be accomplished at a reasonable expenditure of energy.

Breath monitoring of inhalation and dermal methanol exposure

Abstract A fundamental assumption of monitoring breath for a toxicant is that the concentration of the toxicant in breath is proportional to the concentration in blood. The present study was designed, in part, to assess the conditions under which measurement of methanol in breath would be useful for estimating the blood concentration of methanol following inhalation or dermal exposures to methanol. Paid volunteer subjects underwent controlled inhalation exposure to methanol vapor at various concentrations for 8 hours, or dermal exposures (without inhalation exposure) to methanol for varying periods of time. Blood and end-expiratory air were analyzed for methanol from samples obtained prior to exposures, and at various times during and after exposures. The results demonstrate that blood and breath concentrations of methanol are disproportional for varying periods of time during and following cessation of methanol exposure, depending on the route of exposure (dermal versus inhalation). In settings where the...

Surface-tension measurements of pulmonary lavage from ozone-exposed rats

Ozone, an important component of photochemical air pollution, has been shown to cause morphological and functional changes in the lung after acute, high-level exposure in controlled animal studies. Previous exposures of rats to 0.8 ppm ozone for 18 h showed trends toward decreased lung volumes, as well as modifications in phospholipid composition of lung lavage fluid. These results suggested that exposure to ozone may have diminished the ability of surfactant to reduce surface tension. The purpose of this pilot study was to determine if changes in the surface tension of lavaged pulmonary surfactant occur with ozone exposure. The lavage fluid from rats exposed to ozone at 0.8 ppm for 18 h had a 360% increase in protein and a 30% increase in lipid phosphorus content. Lung lavage samples from ozone-exposed rats were more potent in reducing surface tension as measured on a Wilhelmy plate balance. This difference was evident whether determined with half the total lavage or with equivalent microgram amounts of lipid phosphorus. It is concluded that at this dose and duration of ozone exposure, contrary to our hypothesis, surface-tension-lowering ability of surfactant increases and therefore does not appear to be a contributory factor in the previously observed changes in pulmonary function.

Ozone-Induced Lung Function Changes in Normal and Asthmatic Subjects and the Effect of Indomethacin

Abstract We performed a two-part study to determine 1) the effect of 0.4 ppm of ozone on subjects with already increased airways responsiveness (asthmatics), and 2) whether indomethacin could alter the pulmonary effects of ozone in normal subjects. After 2 hours of ozone exposure, both the normal and asthmatic subjects had significant, reversible falls in lung function (FE1, FVC, FEV1%, IC) with greater decreases in FWV1-and FEV1% for the asthmatics. Both groups also had increases in airways responsiveness to methacholine after the ozone exposure but the asthmatics had increases in responsiveness after exercise in air alone. The results of the second part of the study showed that pretreatment with indomethacin partially prevented the ozone-induced changes in lung function for normal subjects. Indomethacin did not prevent the ozone-induced increase in airways responsiveness.

The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function

The primary purpose of this research was to determine the effect of ozone inhalation on pulmonary vascular endothelium. Male Fischer-344 rats were exposed to 0.5 or 0.7 ppm ozone, 20 hr/day for 7 days. Lungs were excised and perfused with Krebs medium containing [14C]serotonin or [14C]hippurylhistidylleucine (HHL). When compared to controls, the animals exposed to the lower ozone concentration showed no statistically significant changes in serotonin removal. In contrast, the higher ozone concentration resulted in a 32% decrease (p less than 0.0001) in serotonin removal, but had no effect on HHL. Rats similarly exposed to 0.7 ppm ozone but allowed to recover for 14 days in clean air showed no decrease in serotonin removal compared to their controls. Animals exposed sequentially to 0.5 ppm ozone for 7 days and then to 0.7 ppm for 7 days showed no alteration in serotonin metabolism, suggesting the development of tolerance initiated by the lower dose. After 7 days exposure to 0.7 ppm ozone, lung ventilatory function measurements revealed small though significant decreases in several parameters. Electron microscopic evaluation of lung capillary endothelium from animals exposed to the 0.7 ppm ozone showed no changes. Positive control animals exposed to greater than 95% oxygen, 20 hr/day for 2 days showed a 23% decrease in serotonin removal (p less than 0.03) and a 12% decrease in HHL removal (p less than 0.017). These studies indicate that inhalation of ozone can induce functional alterations in the lung endothelium, and that this effect occurs at a dosage of ozone that produces minimal ventilatory changes and no observable endothelial ultrastructural changes.