William S. Linn

Respiratory symptoms and peak expiratory flow in children with asthma in relation to volatile organic compounds in exhaled breath and ambient air

Indoor volatile organic compounds (VOCs) have been associated with asthma, but there is little epidemiologic work on ambient exposures, and no data on relationships between respiratory health and exhaled breath VOCs, which is a biomarker of VOC exposure. We recruited 26 Hispanic children with mild asthma in a Los Angeles community with high VOC levels near major freeways and trucking routes. Two dropped out, three had invalid peak expiratory flow (PEF) or breath VOC data, leaving 21. Children filled out symptom diaries and performed PEF maneuvers daily, November 1999–January 2000. We aimed to collect breath VOC samples on asthma episode and baseline symptom-free days, but six subjects only gave samples on symptom-free days. We analyzed 106 breath samples by GC–MS. Eight VOCs were quantifiable in >75% of breath samples (benzene, methylene chloride, styrene, tetrachloroethylene, toluene, m,p-xylene, o-xylene, and p-dichlorobenzene). Generalized estimating equation and mixed linear regression models for VOC exposure–response relationships controlled for temperature and respiratory infections. We found marginally positive associations between bothersome or more severe asthma symptoms and same day breath concentrations of benzene [odds ratio (OR) 2.03, 95% confidence interval (CI) 0.80, 5.11] but not other breath VOCs. Ambient petroleum-related VOCs measured on the same person-days as breath VOCs showed notably stronger associations with symptoms, including toluene, m,p-xylene, o-xylene, and benzene (OR 5.93, 95% CI 1.64, 21.4). On breath sample days, symptoms were also associated with 1-h ambient NO2, OR 8.13 (1.52, 43.4), and SO2, OR 2.36 (1.16, 4.81). Consistent inverse relationships were found between evening PEF and the same ambient VOCs, NO2, and SO2. There were no associations with O3. Given the high traffic density of the region, stronger associations for ambient than for breath VOCs suggest that ambient VOC measurements were better markers for daily exposure to combustion-related compounds thought to be causally related to acute asthma. Alternatively, the low sample size of symptom responses (15–21 responses per 108 breath samples) may have led to the nonsignificant results for breath VOCs.

Experimental Studies on Human Health Effects of Air Pollutants: I. Design Considerations

Because of the possible threat to public health posed by photochemical air pollution, a need exists for experimental studies of short-term respiratory effects of air pollutant exposure in humans. Such studies require rigorous control and comprehensive documentation of the experimental air environment and exposure conditions to ensure that results are both reliable and relevant to public health questions. In addition to biochemical, behavioral, and clinical evaluations, comprehensive pulmonary testing is required to assure that effects at different levels of the respiratory tract are detected. An experimental design based on these principles is described. Studies using this design have shown a wide range of sensitivity to the pollutant ozone and important adverse health effects in sensitive individuals under exposure conditions similar to those experienced during ambient pollution episodes.

Comparative respiratory effects of ozone and ambient oxidant pollution exposure during heavy exercise.

Fifty volunteer bicyclists were exposed to purified air containing ozone (O/sub 3/) at controlled concentrations of 0, 0.08, 0.16, 0.24, and 0.32 ppm, and to oxidant polluted ambient air (mean O/sub 3/ concentration 0.15 ppm, mean total particulate concentration 295 ..mu..g/m/sup 3/) in suburban Los Angeles. Exposures (in random order, 14 days apart) involved one hour of heavy continuous exercise (mean minute volume 57 L) plus brief warm up and cool down periods. Significant forced expiratory function decrements and symptom increases occurred in ambient air exposures. In controlled O/sub 3/ exposures, responses were significant at 0.16 ppm and higher; their severity increased with increasing O/sub 3/ concentration. Effects were only partially reversed after one hours rest in purified air. Ambient exposures produced about the same response as O/sub 3/ alone at the same concentration. Thus coexisting pollutants do not appear to enhance the irritancy of O/sub 3/ in typical moderate ambient oxidant pollution episodes. However, O/sub 3/ itself can produce respiratory irritation at concentrations slightly above the health based federal ambient air quality standard of 0.12 ppm O/sub 3/, at high ventilation rates required during heavy exercise.

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.

The effect of ambient air pollution on exhaled nitric oxide in the Children's Health Study

We assessed the effect of daily variations in ambient air pollutants on exhaled nitric oxide fraction (FeNO) using data from a cohort of school children with large differences in air pollutant exposures from the Childrens Health Study. Based on a cohort of 2,240 school children from 13 Southern Californian communities, cumulative lagged average regression models were fitted to determine the association between FeNO and ambient air pollution levels from central site monitors with lags of up to 30 days prior to FeNO testing. Daily 24-h cumulative lagged averages of particles with a 50% cut-off aerodynamic diameter of 2.5 µm (PM2.5; over 1–8 days) and particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10; over 1–7 days), as well as 10:00–18:00 h cumulative lagged average of O3 (over 1–23 days) were significantly associated with 17.42% (p<0.01), 9.25% (p<0.05) and 14.25% (p<0.01) higher FeNO levels over the interquartile range of 7.5 μg·m−3, 12.97 μg·m−3 and 15.42 ppb, respectively. The effects of PM2.5, PM10 and O3 were higher in the warm season. The particulate matter effects were robust to adjustments for effects of O3 and temperature and did not vary by asthma or allergy status. In summary, short-term increases in PM2.5, PM10 and O3 were associated with airway inflammation independent of asthma and allergy status, with PM10 effects significantly higher in the warm season.

Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants

Background Previous studies have reported adverse effects of either regional or near-roadway air pollution (NRAP) on lung function. However, there has been little study of the joint effects of these exposures. Objectives To assess the joint effects of NRAP and regional pollutants on childhood lung function in the Childrens Health Study. Methods Lung function was measured on 1811 children from eight Southern Californian communities. NRAP exposure was assessed based on (1) residential distance to the nearest freeway or major road and (2) estimated near-roadway contributions to residential nitrogen dioxide (NO2), nitric oxide (NO) and total nitrogen oxides (NOx). Exposure to regional ozone (O3), NO2, particulate matter with aerodynamic diameter <10 µm (PM10) and 2.5 µm (PM2.5) was measured continuously at community monitors. Results An increase in near-roadway NOx of 17.9 ppb (2 SD) was associated with deficits of 1.6% in forced vital capacity (FVC) (p=0.005) and 1.1% in forced expiratory volume in 1 s (FEV1) (p=0.048). Effects were observed in all communities and were similar for NO2 and NO. Residential proximity to a freeway was associated with a reduction in FVC. Lung function deficits of 2–3% were associated with regional PM10 and PM2.5 (FVC and FEV1) and with O3 (FEV1), but not NO2 across the range of exposure between communities. Associations with regional pollution and NRAP were independent in models adjusted for each. The effects of NRAP were not modified by regional pollutant concentrations. Conclusions The results indicate that NRAP and regional air pollution have independent adverse effects on childhood lung function.