Karen R. Anderson

Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles.

Twelve mildly asthmatic and four healthy adults were exposed to filtered air (FA) and concentrated ambient coarse particles (CCP) supplied to a whole-body exposure chamber via a coarse particle concentrator with 15 parallel virtual impactors. Exposures were conducted in a Los Angeles suburb with high levels of motor-vehicle pollution and lasted 2 h with intermittent exercise. Mean CCP concentration was 157 μ g/m 3 (range: 56–218 μ g/m3) measured by continuous monitoring with a tapered-element oscillating microbalance (TEOM). On average, 80% of mass was coarse (2.5–10 μ m aerodynamic diameter) and the rest < 2.5 μ m. Relative to FA, CCP exposure did not significantly alter respiratory symptoms, spirometry, arterial oxygen saturation, or airway inflammation according to exhaled nitric oxide and total and differential cell counts of induced sputum. After CCP exposure, Holter electrocardiograms showed small (p <. 05) increases in heart rate and decreases in heart-rate variability, which were larger in healthy than in asthmatic subjects. Cardiac ectopy did not increase. In conclusion, acute exposure to elevated concentrations of ambient coarse particles elicited no obvious pulmonary effects but appeared to alter the autonomic nervous system of the heart in adult volunteers.

Controlled exposures of volunteers to respirable carbon and sulfuric acid aerosols

Respirable carbon or fly ash particles are suspected to increase the respiratory toxicity of coexisting acidic air pollutants, by concentrating acid on their surfaces and so delivering it efficiently to the lower respiratory tract. To investigate this issue, we exposed 15 healthy and 15 asthmatic volunteers in a controlled-environment chamber (21 degrees C, 50 percent relative humidity) to four test atmospheres: (i) clean air; (ii) 0.5-microns H2SO4 aerosol at approximately 100 micrograms/m3, generated from water solution; (iii) 0.5-microns carbon aerosol at approximately 250 micrograms/m3, generated from highly pure carbon black with specific surface area comparable to ambient pollution particles; and (iv) carbon as in (iii) plus approximately 100 micrograms/m3 of ultrafine H2SO4 aerosol generated from fuming sulfuric acid. Electron microscopy showed that nearly all acid in (iv) became attached to carbon particle surfaces, and that most particles remained in the sub-micron size range. Exposures were performed double-blind, 1 week apart. They lasted 1 hr each, with alternate 10-min periods of heavy exercise (ventilation approximately 50 L/min) and rest. Subjects gargled citrus juice before exposure to suppress airway ammonia. Lung function and symptoms were measured pre-exposure, after initial exercise, and at end-exposure. Bronchial reactivity to methacholine was measured after exposure. Statistical analyses tested for effects of H2SO4 or carbon, separate or interactive, on health measures. Group data showed no more than small equivocal effects of any exposure on any health measure.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposures of Healthy and Asthmatic Volunteers to Concentrated Ambient Ultrafine Particles in Los Angeles

Adult volunteers (17 healthy, 14 asthmatic) were exposed in a controlled environmental chamber to concentrated ultrafine particles (UFP) collected in a Los Angeles suburb with substantial motor vehicle pollution. Exposures lasted 2 h with intermittent exercise. Inhaled particle counts (mean 145,000/cm3, range 39,000–312,000) were typically 7–8 times higher than ambient levels. Mass concentrations (mean 100 μg/m3, range 13–277) were not highly correlated with counts. Volunteers were evaluated for lung function, symptoms, exhaled nitric oxide (eNO), Holter electrocardiography, and inflammatory markers in peripheral blood and induced sputum. Relative to control (filtered air) studies, UFP exposures were associated with a 0.5% mean fall in arterial O2 saturation estimated by pulse oximetry (p < .01), a 2% mean fall in forced expired volume in 1 sec (FEV1) the morning after exposure (p < .05), and a transient slight decrease in low-frequency (sympathetic) power in Holter recordings during quiet rest (p < .05). Healthy and asthmatic subjects were not significantly different across most endpoints. Thus, this initial experimental study of human volunteers exposed to concentrated Los Angeles area ambient UFP showed some acute deleterious cardiopulmonary responses, which, although generally small and equivocal as in previous studies of larger sized concentrated ambient particles, might help to explain reported adverse health effects associated with urban particulate pollution.

Effects of 0.2 ppm nitrogen dioxide on pulmonary function and response to bronchoprovocation in asthmatics

To study the respiratory effects of nitrogen dioxide (NO2) at ambient concentrations, we exposed 31 asthmatic volunteers to purified air (control) and to 0.2 ppm NO2 for 2-h periods with light intermittent exercise. Bronchial reactivity (loss of forced expiratory performance in response to graded doses of methacholine chloride aerosol) was determined postexposure, using a newly developed apparatus that allowed accurate quantitation of methacholine dose. Forced expiratory performance, total respiratory resistance, and symptoms were also recorded immediately pre- and postexposure (prior to methacholine challenges). No significant direct effect of NO2 exposure on forced expiratory function or total respiratory resistance was observed. Symptoms showed a small significant (p less than 0.05) excess in purified air relative to NO2 exposures. Individual responses to methacholine varied greatly. About two-thirds of the subjects showed greater response after NO2 than after purified air, but the mean excess response was small. Mean changes attained significance in some but not all applicable statistical tests. Thus we cannot conclude unequivocally that NO2 exposure increased bronchial reactivity in this group, although there was some tendency in that direction.

Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution

The elderly and individuals who have chronic obstructive pulmonary disease (COPD) may be sensitive to particulate matter (PM) air pollution. We evaluated short-term health responses of 13 elderly volunteers with COPD and 6 age-matched healthy adults to controlled exposures of ambient PM pollution in suburban Los Angeles. Using a Harvard particle concentrator and a whole-body chamber, we exposed each person on separate occasions to approximately 200 μg/m3 concentrated ambient particles (CAP) less than 2.5 μm in diameter and to filtered air (FA). Each exposure lasted 2 h with intermittent mild exercise. We found no significant effects of CAP on symptoms, spirometry, or induced sputum. A significant negative effect of CAP on arterial oxygenation (measured by pulse oximetry) immediately postexposure was more pronounced in healthy subjects. Peripheral blood basophils increased after CAP in healthy but not in COPD subjects. In both groups, red cell counts increased slightly 1 day after exposure to FA but not to CAP. Preexposure ectopic heartbeats were infrequent in healthy subjects, but increased modestly during/after CAP exposure relative to FA. Ectopic beats were more frequent in COPD subjects, but decreased modestly during/after CAP relative to FA. Heart-rate variability over multihour intervals was lower after CAP than after FA in healthy elderly subjects but not in COPD subjects. Thus, in this initial small-scale study of older volunteers experimentally exposed to ambient PM, some acute cardiopulmonary responses were consistent with effects reported from epidemiologic studies. Unexpectedly, individuals with COPD appeared less susceptible than healthy elderly individuals. Further investigation of older adults is warranted to understand the pathophysiology and public health significance of these findings.

Respiratory Responses to Exposures With Fine Particulates and Nitrogen Dioxide in the Elderly With and Without COPD

Elderly people, with and without chronic obstructive pulmonary disease (COPD), may be susceptible to particulate matter (PM) air pollution. However, the respiratory impacts of inhaled PM combined with copollutant(s) in controlled exposure studies are unclear and warrant investigation since exposures to PM–gas mixtures constitute realistic scenarios. Thus, we exposed 6 healthy subjects and 18 volunteers with COPD (mean age 71 yr) on separate days to (a) filtered air (FA); (b) 0.4 ppm NO2; (c) concentrated ambient particles (CAP), predominantly in the fine (PM2.5) size range, at concentrations near 200 μg/m3; and (d) CAP and NO2 together. Each 2-h exposure included exercise for 15 min every half hour. Most respiratory responses, including symptoms, spirometry, and total and differential counts of induced sputum cells, showed no statistically significant responses attributable to separate or combined effects of CAP and NO2. However, maximal mid-expiratory flow and arterial O2 saturation (measured by pulse oximetry) showed small but statistically significant decrements associated with CAP, greater in healthy than COPD subjects. CAP exposure was also associated with decreased percentages of columnar epithelial cells in sputum. The results suggest that the respiratory effect of the PM–NO2 mixture may be primarily PM driven since coexposure to NO2 did not significantly enhance the responses. In conclusion, older adults exposed to urban fine particles may experience acute small-airways dysfunction with impaired gas exchange. Healthy subjects appear more susceptible, suggesting that the respiratory effect may be related to efficient penetration and deposition of inhaled toxic particles in distal small airways. More clinical investigation of the elderly population is warranted.

Respiratory dose-response study of normal and asthmatic volunteers exposed to sulfuric acid aerosol in the sub-micrometer size range.

Twenty-one healthy and 21 asthmatic volunteers were exposed to respirable sulfuric acid aerosol (mass median particle diameter approximately 0.9 pm, geometric standard deviation 2.5) in a chamber at 21° and 50% relative humidity. Measured sulfuric acid concentrations averaged 0, 380, 1060, and 1520 μg/m3 (in the occupational range, higher than concentrations observed in ambient air pollution). Exposures to different concentrations occurred in randomized order 1 week apart. They lasted 1 hr and included three 10-min periods of heavy exercise. Healthy volunteers showed no statistically significant changes in pulmonary function. airway reactivity to inhaled methacholine, or overall reporting of irritant symptoms which could be attributed to acid exposure. They did show a slight statistically significant (P <. 01) increase in cough with increasing acid concentration. At the two highest acid concentrations, asthmatics showed significant increases in irritant symptoms and decrements in pulmonary function, without significant changes in airway reactivity. Their function decrements appeared to increase with time during exposure. Previous studies in fog (10°, median particle diameter approximately 10 urn) with similar concentrations of sulfuric acid showed more symptoms but less pulmonary function change, perhaps reflecting different sites of particle deposition in airways and/or different degrees of neutralization by airway ammonia. This and earlier evidence predicts little, if any, acute irritant response in short-term (1 hr or less) exposures to sulfuric acid at concentrations found in ambient air pollution.

Dose-response study of asthmatic volunteers exposed to nitrogen dioxide during intermittent exercise

Twenty-one mildly asthmatic volunteers were exposed to 0, 0.3, 1.0, and 3.0 ppm nitrogen dioxide (NO2) in purified background air in an environmental control chamber. Exposures were separated by 1-wk periods and occurred in random order. Each lasted 1 hr and included three 10-min bouts of moderately heavy exercise (mean ventilation rate 41 L/min). Exposure temperature was near 22 degrees C and relative humidity near 50%. Specific airway resistance and maximal forced expiratory performance were measured preexposure, after the initial exercise, and near the end of exposure. Bronchial reactivity was assessed immediately following exposure, by normocapnic hyperventilation with subfreezing air. Symptoms were recorded on questionnaires before, during, and for 1-wk after each exposure. Exercise induced significant bronchoconstriction regardless of NO2 level. No statistically significant untoward response to NO2 was observed at any exposure concentration. This negative finding agrees with our previous results, but contrasts with findings elsewhere of respiratory dysfunction after exposure to 0.3 ppm. The discrepancy is presently unexplained, but it may relate to different severity of asthma in different subject groups.

Short-term respiratory effects of sulfuric acid in fog: a laboratory study of healthy and asthmatic volunteers.

To explore short-term respiratory health risks from acid-polluted fog, 22 normal and 22 asthmatic adult volunteers were exposed in an environmental control chamber to light fogs (∼0.1 g/m3 liquid water content, 10 μm median droplet diameter, 10°C) containing nominally 0, 500, 1000, and 2000 μg/m3 of sulfuric acid. Fog was produced by atomizing dilute acid solution Into purified air humidified to near 100 percent by steam injection. Exposures were administered in random order at 1-week intervals, lasted 1 h, and Included three 10-min periods of moderately heavy exercise. Responses were measured in terms of forced expiratory function, airway resistance, Irritant symptoms, and bronchial reactivity to methacholine aerosol. Sulfuric acid per se showed no more than a slight effect on pulmonary function, even at the highest concentration. Asthmatics experienced bronchoconstrlction, attributable to exercise, under all exposure conditions. Despite the lack of substantial function changes, modest statistically sign...

Respiratory responses of exercising asthmatic volunteers exposed to sulfuric acid aerosol

Young asthmatic adult volunteers (N = 27) were exposed in an environmental chamber to sulfuric acid aerosol at concentrations near 0, 122, 242, and 410 μg/m3, in purified background air at 22° C and 50 percent relative humidity. The polydisperse aerosol had a mass median aerodynamic diameter near 0.6 μm. Exposures occurred in random order at one-week intervals. Each lasted 1 h, during which subjects exercised (mean ventilation 42 L/min) and rested during alternate 10-min periods. Specific airway resistance and forced expiratory function were measured pre-exposure, after the initial exercise, and at end-exposure. Bronchial reactivity was determined by challenge with cold air immediately post-exposure. Symptoms were monitored during exposure for one week afterward. Exercise-induced bronchospasm was observed under all conditions. Physiologic and symptom changes possibly attributable to sulfuric acid exposure were small and not statistically significant. Our largely negative results contrast with positive fin...