Charles E. Spier

Effects of Exposure to 4 PPM Nitrogen Dioxide in Healthy and Asthmatic Volunteers

Healthy and asthmatic volunteer subjects (N = 25 and N = 23, respectively) were exposed twice each to purified air (control) and to 4 ppm nitrogen dioxide (NO2) in a controlled-environment chamber. Exposures lasted 75 min, and included 15 min each of light exercise (ventilation rate near 25 L/min) and heavy exercise (near 50 L/min). Compared to control, NO2 exposure produced no statistically significant untoward effects on airway resistance, symptoms, heart rate, skin conductance, or self-reported emotional state in normal or asthmatic subjects. Exercise was associated with significantly (P less than .001) increased airway resistance in both subject groups, although the increase in normals was small. In both groups, systolic blood pressure showed small but significant (P less than .01) decreases with NO2 exposure, compared to control. This effect, if real, may relate to formation of a vasodilating nitrite or nitrate from inhaled NO2. The lack of respiratory response contrasts with previous findings elsewhere; at present, this inconsistency is unexplained.

Experimental Studies on Human Health Effects of Air Pollutants. IV. Short-Term Physiological and Clinical Effects of Nitrogen Dioxide Exposure

Adult male volunteers were exposed to nitrogen dioxide (NO2) at 1.0 ppm in purified air under conditions simulating ambient photochemical smog exposures (2-hr exposure with intermittent light exercise at 31 degrees C and 35% relative humidity). Sham exposures to purified air alone served as controls. Exposure effects were assessed by pulmonary physiological tests and by a standardized clinical evaluation. No statistically physiological changes attributable to NO2 exposure were found except for a marginal loss in forced vital capacity after exposure on two successive days (1.5% mean decrease, P less than .05). Reported respiratory and other symptoms were slightly increased with exposure as compared to control, but the change was not significant. Short-term toxicity of NO2 at peak ambient concentrations appears to be substantially less than that of ozone in healthy people, but adverse NO2 effects in diseased people or in long-term exposures cannot be ruled out at present.

Respiratory effects of 0.75 ppm sulfur dioxide in exercising asthmatics: Influence of upper-respiratory defenses

To determine the influence of mouthpiece breathing on respiratory responses to sulfur dioxide (SO2), 23 young adult asthmatic volunteers were exposed in a chamber to 0.75 ppm SO2 during heavy exercise, once with breathing unencumbered and once while they wore noseclips and mouthpieces. These conditions (more severe than in typical ambient exposures) were deliberately chosen to produce significant physiological and clinical responses. Similar exposures to clean air served as controls. Exposure studies were separated by 1-week intervals and order was randomized. The protocol consisted of 10 min on a bicycle ergometer (mean load 650 kg-m/min, mean ventilation 40 liter/min), preceded and followed by response testing (body plethysmography, symptom questionnaires, and forced expiratory function tests; the last were performed only postexposure). During clean-air exposures, specific airway resistance (SRaw) and symptoms increased significantly, but no meaningful differences between mouthpiece breathing and unencumbered breathing were observed. Exposures to SO2 under these relatively severe conditions produced greater increases in SRaw than clean-air exposures regardless of the mode of breathing, but the excess increase was significantly greater with mouthpiece than with unencumbered breathing. Symptom changes and postexposure forced expiratory function showed qualitatively the same pattern of decrements with SO2 ad did SRaw, but the excess responses attributable to mouthpiece breathing did not attain statistical significance. Mouthpiece breathing can compromise upper-respiratory defenses against SO2 to the extent that responses are greater than with more natural breathing. The mode of breathing should be taken in account when applying laboratory human exposure data to air-quality risk assessment.

A Dose-Response Study of Healthy, Heavily Exercising Men Exposed To Ozone At Concentrations Near the Ambient Air Quality Standard

Twenty-four healthy, well-conditioned young adult male volun teers, free of asthma or clinical respiratory allergies, were exposed to purified air containing ozone (03) at 0.16, 0.14, 0.12, 0.10, 0.08, and 0.00 part per million (ppm). Exposures were separated by 2- week intervals, occurred in random order, and lasted 2 hours each. Temperature was 32 ± 1° C and relative humidity was 38 ± 3%, simulating Los Angeles area smog conditions. Subjects exercised 15 minutes of each half hour, attaining ventilation rates averaging 68 L/min (∼35 L/min per m2 body surface area). Lung function was measured pre-exposure and after 1 hr and 2 hr of exposure. Airway responsiveness to a cold-air challenge was measured immediately following the 2-hr exposure. Symptoms were recorded before, dur ing, and for one-week periods following exposures. For the group as a whole, no meaningful untoward effects were found except for a mild typical respiratory irritant response after 2 hr exposure to 0.16 ppm 03. Two individual subjects showed possible responses at 0.14 ppm, and one of them also at 0.12 ppm. In comparison to some previous investigations, this study showed generally less response to 03. The comparative lack of response may relate to the favorable clinical status of the subjects, the pattern of exercise dur ing exposure, or some other factor not yet identified.

Short-Term Respiratory Effects of Photochemical Oxidant Exposure in Exercising Children

To assess the short-term respiratory effects of photochemical oxidant pollution in children, 66 volunteers—33 boys and 33 girls aged 8 to 11—were exposed in a movable laboratory to polluted Los Angeles area ambient air and to purified air as a control. Exposures lasted one hour, during which subjects exercised continuously at roughly 50 percent of maximal oxygen consumption. Forced expiratory function and symptoms were evaluated prior to and at the end of exposure. The mean ozone concentration in ambient exposures was 0.113 ppm, reflecting an unusually mild pollution season. As a group, the subjects showed no statistically significant untoward responses to ambient air in comparison to purified air, and no significant differences in response between sexes. Nevertheless, regression analyses of individual data indicated a significant (p < 0.05) trend toward forced expiratory dysfunction with increasing ambient ozone concentrations. When the regression analyses were expanded to include older children and adul...

Response to ozone in volunteers with chronic obstructive pulmonary disease.

Twenty-eight volunteers with chronic obstructive pulmonary disease were exposed to 0.0, 0.18, and 0.25 ppm ozone in purified air for 1-hr periods with light intermittent exercise, with exposure conditions presented in random order at 1-month intervals. No statistically significant changes attributable to ozone were found in forced expiratory performance or percent oxyhemoglobin (measured near the beginning and end of each exposure). No ozone-related changes in clinical status were found by interviews that included the time for 1 wk before to 1 wk after each exposure, except that a moderate increase in lower respiratory symptoms was reported by nonsmokers in 0.18 ppm exposures only. Thus, a slight decrement in hemoglobin saturation with ozone exposure (reported in two previous studies of chronic obstructive pulmonary disease subjects) may not be a common occurrence under typical ambient exposure conditions.

Effect of high concentrations of oxygen on reparative regeneration of damaged alveolar epithelium in mice

Abstract The main purpose of the present study was to determine if high concentrations of oxygen (O 2 ) would inhibit cell division in alveoli undergoing reparative regeneration following injury by ozone (O 3 ). Mice were exposed to 2.5 ppm O 3 for 6 hr to injure the alveolar epithelium. Groups of animals were then allowed to recover in 20% O 2 with and without food, 40, 61, 80, and 95% O 2 with food. At daily intervals, the mice were injected with tritiated thymidine to label cells preparing to divide, and sacrificed 1 hr later. Lung tissue was prepared for light microscopic autoradiography and the proportion of labeled cells were determined. In mice exposed to O 3 , type 1 epithelium is injured and type 2 cells proliferate in order to repair the damage. Mice allowed to recover in 20% O 2 with and without food, and in 40% O 2 , had a maximum proliferation of type 2 cells (about eight times control) on the second day of recovery. By the fourth day repair seemed to be complete and labeling indexes had returned to normal. In mice allowed to recover in 61, 80, and 95% O 2 , type 2 cell proliferation was less than control on the second day and did not increase during 4 days of recovery. It was concluded that concentrations of O 2 at 61% and higher inhibit reparative cell division in O 3 -damaged alveoli of mice.

Controlled Exposure of Volunteers with Chronic Obstructive Pulmonary Disease to Nitrogen Dioxide

Twenty-two volunteers with chronic obstructive pulmonary disease were exposed to nitrogen dioxide at 0.0, 0.5, 1.0, and 2.0 ppm in a controlled environment chamber. Exposure lasted 1 hr and included two 15-min exercise periods, during which the mean ventilation rate was roughly 16 L/min. Pulmonary mechanical function was evaluated pre-exposure, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry pre-exposure and during the second exposure period. Symptoms were recorded during exposures and for 1-wk periods afterward. No statistically significant changes in symptom reporting could be attributed to nitrogen dioxide exposure at any concentration, compared to the 0.0 ppm control condition. Measures of pulmonary mechanics showed either no significant changes, or small and equivocal changes. Arterial oxygen saturation showed marginal improvement with exercise, regardless of nitrogen dioxide concentration.

Respiratory effects of mixed nitrogen dioxide and sulfur dioxide in human volunteers under simulated ambient exposure conditions

Abstract Normal and asthmatic volunteers (N = 24 and 19, respectively) were exposed to mixed nitrogen dioxide (NO2) and sulfur dioxide (SO2) in purified background air in an environmental chamber under conditions simulating an ambient pollution episode. The NO2 concentration was 0.5 ppm; the SO2 concentration was 0.5 ppm for normals and 0.3 ppm for asthmatics. Exposures lasted 2 hr and included intermittent exercise and heat stress. Control studies consisted of similar exposures to purified air alone. The mixed pollutant gases may have reacted chemically in the exposure chamber, but no appreciable amounts of sulfate or nitrate aerosol were detected there. Group mean lung function changes during exposure generally were not significantly different from control for normals or for asthmatics. Symptoms reported by the normal group showed a small significant overall increase during pollutant exposure and later the same day relative to the corresponding control periods; the asthmatics showed a small significant increase later in the day but not during exposure. The increased symptom reporting showed little consistency from subject to subject: there were small increases for most individual symptom categories evaluated, none of them statistically significant. The results are not sufficient to establish whether this slight and nonspecific clinical response should be attributed to the pollutant mixture or to some other aspect of the exposure protocol.

Human respiratory responses to an aerosol containing zinc ammonium sulfate

Abstract Twenty-one normal volunteers and 19 volunteers with asthma were exposed in an environmental control chamber to a polydisperse aerosol of zinc ammonium sulfate (ZnSO 4 ·(NH 4 ) 2 SO 4 )—a model of ambient metallic sulfate aerosols derived from trace metals in fossil fuels—at a nominal concentration of 20 μg/m 3 . As a model of the background ambient particulate burden, polydisperse sodium chloride aerosol at a nominal concentration of 300 μg/m 3 was added to the chamber atmosphere during control as well as exposure studies. Exposure temperature was 20°C and relative humidity was 85%, simulating weather conditions typical of fall/winter ambient pollution episodes. Exposure and control studies were performed on separate days, separated by about 3 weeks, in random order under double-blind conditions. Exposure periods lasted 2 hr and included intermittent light exercise. Lung function and symptoms were evaluated before and at the end of the exposure or control period. Symptom reports showed no significant variation attributable to zinc ammonium sulfate exposure. Group mean lung function measures showed a few significant changes possibly attributable to the sulfate exposure, but these were small and inconsistent. It was concluded that zinc ammonium sulfate produced minimal or no short-term respiratory effects observable under the conditions of the experiment.