Short-term air pollution exposures and responses in Los Angeles area schoolchildren.

We studied 269 school children from three Southern California communities of contrasting air quality in two successive school years, to investigate short-term effects of ambient ozone (O3), nitrogen dioxide (NO2), or particulate matter (PM) on respiratory health. We measured lung function and symptoms twice daily for one week each in fall, winter and spring; and concurrently assessed time-activity patterns and personal exposures. Average daily personal exposures correlated with pollutant concentrations at central sites (r = 0.61 for O3, 0.63 for NO2, 0.48 for PM). Questionnaire-reported outdoor activity increased slightly in communities/seasons with higher pollution. Lung function differences between communities were explainable by age differences. Morning forced vital capacity (FVC) decreased significantly with increase in PM or NO2 measured over the preceding 24 hours. Morning-to-afternoon change of forced expired volume in one second (FEV1) became significantly more negative with increase in PM, NO2, or O3 on the same day. Predicted FVC or FEV1 loss on highest- vs lowest-pollution days was < 2%. Daily symptoms showed no association with current or prior 24-hour pollution, but increased with decreasing temperature. Parents' questionnaire responses suggested excess asthma and allergy in children from one polluted community while children in the other polluted community reported more symptoms, relative to the cleaner community. We conclude that Los Angeles area children may experience slight lung function changes in association with day-to-day air quality changes, reasonably similar to responses seen by others in less polluted areas. Although short-term pollution effects appear small, they should be assessed in longitudinal lung function studies when possible, to allow maximally accurate measurement of longer-term function changes.

Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.

Effects of prolonged, repeated exposure to ozone, sulfuric acid, and their combination in healthy and asthmatic volunteers.

To evaluate effects of "acid summer haze" on individuals who exercise extensively outdoors, we exposed 45 adult volunteers (15 normal or atopic, 30 asthmatic) in a chamber to a mixture of 0.12 ppm ozone (O3) and approximately 100 micrograms/m3 of respirable sulfuric acid aerosol (H2SO4). On separate occasions we exposed the same subjects to O3 alone, to H2SO4 alone, and to clean air. In exposures involving H2SO4, excess acid was generated to consume ammonia released by the subjects, and the aerosol therefore contained ammonium salts in addition to H2SO4. Subjects were exposed to each atmosphere on two successive days, for 6.5 h/d, with six 50-min exercise periods at ventilation rates averaging 29 L/min. Exposures were conducted during four successive weeks, in random order. Lung function and symptoms were measured before exposure and hourly during exposure. Bronchial reactivity to inhaled methacholine was measured just after the end of each exposure. Exposure to H2SO4 alone caused no significant changes in lung function, symptoms, or bronchial reactivity relative to clean air. Exposure to O3 alone or O3 + H2SO4 caused a progressive, statistically significant (p < 0.05) decline in forced expiratory function, smaller on the second day than the first, as previously found by others for O3 exposure. Bronchial reactivity increased significantly after exposure to O3 with or without H2SO4. Changes in mean lung function and bronchial reactivity with O3 + H2SO4 exposure were modestly larger than changes with O3 exposure, but the differences were nonsignificant or marginally significant. A minority of individual asthmatic and nonasthmatic subjects showed substantially greater declines in function with exposure to O3 + H2SO4 relative to O3 alone. Repeat exposure studies of these subjects again showed an excess response to O3 + H2SO4 on the average, but there was no significant correlation between the excess responses of individual subjects in the original and repeat studies. We conclude that for typical healthy or asthmatic adults heavily exposed to acid summer haze, O3 is more important than H2SO4 as a cause of short-term respiratory irritant effects.

Time-activity patterns and diurnal variation of respiratory status in a panel of asthmatics: implications for short-term air pollution effects.

To understand the short-term health risks to people from air pollution exposure, we investigated time-activity patterns and temporal variation of the respiratory status in 49 asthmatic Los Angeles area residents 18-50 years old. During the summer (May-September) and winter (November-March), subjects measured their lung function two to four times daily at home for one week periods, and every hour recorded their symptoms, medication, and activity hourly in diaries. Almost all subjects recorded heart rates (HR), which were converted to ventilation rate (VR) estimates using individual laboratory exercise data. Most subjects' lung function and symptoms varied diurnally, and were worst in early morning. For subjects with clinically mild asthma, diurnal forced expired volume in 1 sec (FEV1) changes averaged 7%, versus 12% in those with moderate symptoms, and 18% in severely asthmatic subjects. Lung function was similar in summer and winter, but symptoms and medication use decreased in winter. In the aggregate, subjects reported spending 75% of waking hours indoors at self-rated slow activity and 11% in vehicles. HR records usually corroborated reports of medium or fast activity. Mean estimated VR at slow, medium, and fast activity was 19, 37, and 61 L/min for men, and 16, 24, and 32 L/min for women. Outdoor fast activity, representing the greatest vulnerability to outdoor pollution, occupied approximately 0.2% of waking hours (2 min/day on average); outdoor medium activity occupied about 2% of waking hours (19 min/day on average). Estimated cumulative ventilation was higher than that of previous healthy panels because of asthmatics' higher VR at slow activity. If these activity patterns are typical, asthmatics may be especially vulnerable to pollutants with effects dependent on cumulative inhaled dose. Effects dependent on high inhaled dose rates over a short period, e.g., sulfur dioxide effects, would be unlikely, except perhaps for uncommonly active individuals in uncommonly polluted areas.

Active and passive ozone samplers based on a reaction with a binary reagent.

Ozone is one of the most toxic common air pollutants (judging from short-term animal and human exposure studies at realistic concentrations) and one of the most difficult and expensive pollutants to control. Because of ozone's high chemical reactivity, its concentrations may vary greatly over short distances, and fixed-site air quality monitors may not accurately estimate exposures of human populations. Epidemiologic research on ozone's long-term health effects has been inconclusive, partly because of the lack of reliable personal exposure information. The objective of this project was to develop a practical personal ozone exposure monitoring technique, and to document its precision and accuracy in actual use by representatives of freely ranging, ozone-exposed populations. The project site, Los Angeles, is the nation's metropolitan area with the highest level of ozone pollution and, thus, probably the most important locale for personal exposure assessment. Our overall strategy was (1) to select the most promising laboratory technique for ozone detection from published literature and private communications; (2) to design and test personal monitors using this technique; and (3) when feasible, to evaluate concurrently alternative methodologies developed by others. As indicated below, parts 1 and 2 of our strategy yielded a limited success with respect to short-term active sampling, i.e., measuring personal ozone exposure levels during one to two hours with a monitor incorporating a battery-powered air pump of the type used in industrial hygiene investigations. The same approach was not successful in passive sampling, i.e., measuring exposure levels during multihour or multiday periods with a light-weight, diffusion-controlled "badge" sampler having no moving parts. Passive badge samplers could be calibrated reasonably well in laboratory exposures to ozone in otherwise pure air, but they greatly overestimated ozone levels in outdoor ambient air. Part 3 of our strategy yielded more promising information on an alternative passive badge design. After testing and rejecting two other possibilities, we chose a binary organic reagents, 3-methyl-2-benzothiazolinone acetone azine with 2-phenylphenol, as the most promising chemical detector of ozone. Filter papers impregnated with the binary reagent develop a characteristic intense pink color when exposed to ozone. The inventors, J.E. Lambert and associates of Kansas State University, had intended only to develop a rough qualitative ozone monitor (Lambert et al. 1989). However, our initial laboratory testing (in exposure chambers containing ozone in otherwise very clean air, away from humans), revealed fairly accurate quantitative response.(ABSTRACT TRUNCATED AT 400 WORDS)

Exposures of older adults with chronic respiratory illness to nitrogen dioxide. A combined laboratory and field study.

We combined field and laboratory experimentation to evaluate the effects of nitrogen dioxide in a panel of Los Angeles area residents with chronic respiratory illness, 15 men and 11 women aged 47 to 69. All had heavy smoking history, chronic symptoms, and low FEV1; some also had low FVC. During the fall-winter high-NO2 season, they monitored themselves for 2-wk periods using spirometers in the home, passive NO2 sampling badges, and diaries to record time and activity patterns and clinical status. In the middle of each self-monitoring week they were exposed in a chamber, once to clean air and once to 0.3 ppm NO2. Chamber exposures were double blind, lasted 4 h, and included four 7-min exercise sessions with average ventilation rates near 25 L/min. Symptom reports and hourly forced expiratory function tests showed no statistically significant differences between clean air and NO2 chamber exposures, although peak flow showed a approximately 3% loss with NO2 relative to clean air during the first 2 h of exposure only (p = 0.056). No significant overall differences were found between field self-measurements and measurements of lung function in the chamber or between field measurements in clean air and NO2 exposure weeks. Field data showed that group average lung function and symptom levels were worse in the morning than later in the day (p < 0.005) but otherwise were stable over 2 wk. Even though most subjects smoked and stayed indoors 80 to 90% of the time, personal NO2 exposures correlated significantly with outdoor NO2 concentrations as reported by local monitoring stations.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity patterns in elementary and high school students exposed to oxidant pollution.

We investigated activity patterns of 17 elementary school students aged 10-12, and 19 high school students aged 13-17, in suburban Los Angeles during the oxidant pollution season. Individuals' relationships between ventilation rate (VR) and heart rate (HR) were "calibrated" in supervised outdoor walking/jogging. Log VR was consistently proportional to HR; although "calibrations" were limited by a restricted range of exercise, and possibly by artifact due to mouthpiece breathing, which may cause overestimation of VR at rest. Each subject then recorded activities in diaries, and recorded HR once per minute by wearing Heart Watches, over 3 days (Saturday-Monday). For each activity the subject estimated a breathing rate--slow (like slow walking), medium (like fast walking), or fast (like running). VR ranges for each breathing rate and activity type were estimated from HR recordings. High-school students' diaries showed their aggregate distribution of waking hours as 68% slow inside, 8% slow outside, 10% medium inside, 9% medium outside, 1.5% fast inside, 1.5% fast outside. Elementary students' distribution was 47% slow inside, 15% slow outside, 20% medium inside, 12% medium outside, 2.5% fast inside, 3.5% fast outside. Sleep occupied 38% of high-school students' and 40% of elementary students' time; HR were generally lower in sleep than in slow waking activity. High school students' mean VR estimates were 13 L/min for slow breathing, 18 for medium, and 23 for fast; elementary students' were 14 slow, 18 medium, and 19 fast. VR distributions were approximately lognormal. Maximum estimated VR were approximately 70 L/min in elementary and approximately 100 L/min in high school students. Compared to adults studied similarly, students reported more medium or fast breathing, and had equal or higher VR estimates during slow and medium breathing despite their smaller size. These results suggest that, relative to body size, young people inhale larger doses of outdoor air pollutants than adults.

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)

Activity patterns in a panel of outdoor workers exposed to oxidant pollution.

We investigated summer activity patterns in a panel of volunteers drawn from a population segment with potentially high exposure to ambient oxidant pollution. The subjects were 15 men and 5 women aged 19-50, all of whom worked outdoors in the Los Angeles area at least 10 hr per week. The general approach was to (i) calibrate the relationship between ventilation rate (VR) and heart rate (HR) for each subject in controlled exercise; (ii) have subjects monitor their own normal activities with diaries and electronic HR recorders; (iii) estimate VR from HR recordings; and (iv) relate VR with diary descriptions of activities. Calibration data were fit to the equation log (VR) = (intercept) + (slope x HR), intercept and slope being determined separately for each individual to provide a specific equation to predict her/his VR from measured HR. Individuals' correlation coefficients relating log (VR) with HR ranged from 0.83 to 0.95. Subjects monitored themselves for three 24-hr periods during one week, including their most active work day and their most active non-work day. They wore Heart Watch(R) athletic training instruments which recorded HR once per minute; and recorded each change in their activity, location, or breathing rate in diaries. Breathing rates were classified as sleep, slow (like slow or normal walking), medium (like fast walking), or fast (like running). Diaries showed that sleep occupied about 33% of subject's time, slow activity 59%, medium 7%, and fast 1%. Fast activity was reported only at leisure, never at work. For the group, arithmetic means and standard deviations of predicted VR were 7 +/- 3 L/min for sleep, 12 +/- 7 for slow activity, 14 +/- 8 for medium, and 44 +/- 36 for fast. For the group and for most individuals, distributions of predicted VR within a given activity level (breathing rate) were approximately lognormal, with many values in a narrow range below the arithmetic mean and fewer values in a broader range above it. In the most active individuals, predicted VR exceeded 100 L/min for a total of 5 to 30 min during the three days. These data should prove useful in estimating outdoor workers' inhaled doses of ambient pollutants at existing or projected levels of air quality. Activity diary records are of significant value in pollutant dose estimation, but concurrent heart rate recording improves the estimates substantially.

Effects of carbon monoxide on myocardial ischemia.

The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

Respiratory responses of young asthmatic volunteers in controlled exposures to sulfuric acid aerosol.

Thirty-two asthmatic volunteers 8 to 16 yr of age, recruited through local schools and private physicians, were exposed in a chamber to clean air (control condition) and to sulfuric acid aerosol at a "low" concentration (46 +/- 11 micrograms/m3; mean +/- SD) and at a "high" concentration (127 +/- 21 micrograms/m3). Acid aerosols had mass median aerodynamic diameters near 0.5 microns with geometric standard deviations near 1.9. Temperature was 21 degrees C, and relative humidity was near 50%. Subjects were exposed with unencumbered oronasal breathing for 30 min at rest plus 10 min at moderate exercise (ventilation rate approximately 20 L/min/m2 of body surface). A subgroup (21 subjects) were exposed similarly to clean air and to "high" acid (134 +/- 20 micrograms/m3) with 100% oral breathing. Increased symptoms and bronchoconstriction were found after exercise under all exposure conditions. For the group, symptom and lung function responses were not statistically different during control and during acid exposures with unencumbered breathing or with oral breathing. By contrast, other investigators have reported statistically significant lung function disturbances in groups of young asthmatics exposed similarly with oral breathing. A minority of our subjects showed possibly meaningful excess bronchoconstriction with "high" acid exposure relative to control with both routes of breathing. This could be the result of chance, or it could suggest the existence of an acid-sensitive subpopulation of young asthmatics.

Responses to sulfur dioxide and exercise by medication-dependent asthmatics: effect of varying medication levels.

Twenty-one volunteers with moderate to severe asthma were exposed to sulfur dioxide (SO2) at concentrations of 0 (control), 0.3, and 0.6 ppm in each of three medication states: (1) low (much of their usual asthma medication withheld), (2) normal (each subject on his own usual medication schedule), and (3) high (usual medication supplemented by inhaled metaproterenol before exposure). Theophylline, the medication usually taken by subjects, was often supplemented by beta-adrenergics. Exposures were for 10 min and were accompanied by continuous heavy exercise (ventilation approximately 50 l/min). Lung function and symptoms were measured before and after exposure. With normal medication, symptomatic bronchoconstriction occurred with exercise and was exacerbated by 0.6 ppm SO2, as reported for mildly unmedicated asthmatics studied previously. Both baseline and post-exposure lung function were noticeably worse in the low-medication state. High medication improved baseline lung function and prevented most bronchoconstrictive effects of SO2/exercise. High medication also increased heart rate and apparently induced tremor or nervousness in some individuals.

Experimental exposures of young asthmatic volunteers to 0.3 ppm nitrogen dioxide and to ambient air pollution.

Asthmatic volunteers aged 8 to 16 (N = 34) were exposed on separate occasions to clean air (control), to 0.30 ppm nitrogen dioxide (NO2) in otherwise clean air, and to polluted Los Angeles area ambient air on summer mornings when NO2 pollution was expected. Exposures lasted 3 hr, with alternating 10-min periods of exercise and rest. In ambient pollution exposures, 3-hr average NO2 concentrations ranged from 0.01 to 0.26 ppm, with a mean of 0.09 ppm. Ambient exposures did not significantly affect lung function, symptoms, or bronchial reactivity to cold air, relative to the control condition. Responses to 0.3 ppm NO2 exposures were equivocal. Asthma symptoms were more severe during 1-week periods before 0.3 ppm exposures, and lung function was decreased immediately before 0.3 ppm exposures, compared to other conditions. Lung function declined slightly during the first hour at 0.3 ppm, but improved over the remaining 2 hr. Compared to other conditions, symptoms were not increased during 0.3 ppm exposures, but were increased during 1-week periods afterward. These observations may reflect untoward effects of 0.3 ppm NO2, or may reflect chance increases in asthma severity prior to 0.3 ppm exposures.

Acute effects of carbon monoxide exposure on individuals with coronary artery disease.

The purpose of this study was to determine, using more objective evidence than that reported in previous studies, whether or not exposures to carbon monoxide that produce approximately 2% or 4% blood carboxyhemoglobin levels cause an exacerbation of myocardial ischemia during a progressive exercise test. The objective measurements were based on the development of electrocardiographic evidence of ischemia. In addition, time to onset of angina pectoris was studied. Male subjects, ages 35 to 75, with stable exertional angina pectoris and positive exercise treadmill tests with reproducible ischemic ST-segment changes in their electrocardiograms, were studied. In addition, each subject fulfilled at least one of the following criteria of coronary artery disease: angiographic evidence of at least a 70% occlusion of one or more major coronary artery; prior documented myocardial infarction; or a positive exercise thallium test. Each subject was evaluated on four separate occasions, a qualifying visit and three blinded test visits, which involved exposure (in random order) to air without added carbon monoxide and to air that contained carbon monoxide concentrations calculated to produce approximately 2.2% or 4.4% carboxyhemoglobin, measured by gas chromatography, at the end of the exposure period. These immediate postexposure target levels were set 10% higher than the desired postexercise carboxyhemoglobin levels of 2.0% and 4.0% because exercise while breathing room air results in loss of carbon monoxide. The actual one-minute postexercise levels reached were 2.0% +/- 0.1% (mean +/- standard error of the mean) and 3.9% +/- 0.1%. On each test day, the subject performed a symptom-limited exercise test on a treadmill, was exposed for approximately one hour to air or to one of two levels of carbon monoxide in air, and then performed a second exercise test. Time to the onset of ischemic ST-segment changes and time to the onset of angina were determined for each exercise test. The percent difference for these endpoints on the pre- and postexposure exercise tests was determined, and then the results on the 2%-COHb-target day and the results on the 4%-COHb-target day were compared to those on the control day. Data from the 63 subjects who completed the three test visits and met all protocol criteria were analyzed. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) (trimmed mean) decreases in the time to development of ischemic ST-segment changes after the 2%- and 4%-COHb-target exposures, respectively, compared to the control day.(ABSTRACT TRUNCATED AT 400 WORDS)

Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease.

Patients with atherosclerotic cardiovascular disease may be adversely affected by the presence of carboxyhemoglobin, even at low concentrations. We investigated the effects of carbon monoxide exposure on myocardial ischemia during exercise in 63 men with documented coronary artery disease. On each test day, subjects performed two symptom-limited incremental exercise tests on a treadmill; the tests were separated by a recovery period and 50 to 70 minutes of exposure to either room air or air containing one of two concentrations of carbon monoxide (117 +/- 4.4 ppm or 253 +/- 6.1 ppm). The order of exposure was assigned randomly. On each occasion, neither the subjects nor the study personnel knew whether the subjects had been exposed to room air or to one of the concentrations of carbon monoxide. Exposure to room air resulted in a mean carboxyhemoglobin level of 0.6 percent, exposure to the lower level of carbon monoxide resulted in a carboxyhemoglobin level of 2.0 percent, and exposure to the higher level of carbon monoxide resulted in a level of 3.9 percent. An effect of carbon monoxide on myocardial ischemia was demonstrated objectively by electrocardiographic changes during exercise. We observed a decrease of 5.1 percent (90 percent confidence interval, 1.5 to 8.7 percent; P = 0.02) and a decrease of 12.1 percent (90 percent confidence interval, 9.0 to 15.3 percent; P less than or equal to 0.0001) in the length of time to a threshold ischemic ST-segment change (ST end point) after carbon monoxide exposures that produced carboxyhemoglobin levels of 2.0 percent and 3.9 percent, respectively. The length of time to the onset of angina decreased by 4.2 percent (90 percent confidence interval, 0.7 to 7.9 percent; P = 0.054) at the 2.0 percent carboxyhemoglobin level and by 7.1 percent (90 percent confidence interval, 3.1 to 10.9 percent; P = 0.004) at the 3.9 percent carboxyhemoglobin level. Significant dose-response relations were found in both the change in the length of time to the ST end point (P less than or equal to 0.0001) and the change in the length of time to the onset of angina (P = 0.02). We conclude that low levels of carboxyhemoglobin exacerbate myocardial ischemia during graded exercise in subjects with coronary artery disease.

Effect of droplet size on respiratory responses to inhaled sulfuric acid in normal and asthmatic volunteers.

We exposed groups of healthy and asthmatic volunteers to sulfuric acid aerosols with volume median droplet diameters of approximately 20, 10, and 1 microns, at nominal concentrations of 2,000 micrograms/m3, and exposed them similarly to aerosols of purified water as a control. Exposures lasted 1 h each, and included three 10-min periods of exercise (ventilation rate typically 40 to 45 L/min). Exposures occurred in randomized order 7 days apart. Temperature was 10 degrees C, relative humidity was approximately 100% in 20- and 10-microns (fog) exposures, and approximately 75 to 80% in 1-micron aerosol exposures. Healthy subjects showed no statistically significant changes in lung function or in bronchial reactivity to methacholine attributable to acid exposures. They showed significant increases in lower and upper respiratory irritant symptoms when exposed to 20- or 10-microns acid fog, but not when exposed to 1-micron acid aerosol. Asthmatics showed significant excess decreases in forced expiratory performance, increases in airway resistance, and increases in irritant symptoms during acid exposures, relative to control conditions. Lung function changes in asthmatics tended to increase with time during exposure; they did not vary significantly with acid droplet size. Symptoms in asthmatics were slightly worse with 10- or 20-microns fog as compared with 1-micron aerosol. In a few instances, symptoms and lung function decrements necessitated stopping exercise or terminating the exposure early. Thus, asthma is a risk factor for unfavorable physiologic response to sulfuric acid at occupational exposure concentrations. Large droplet size (i.e., fog) tends to exacerbate short-term symptomatic response, but we have not been able to demonstrate a consistent effect of droplet size on physiologic response.

Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers.

Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m3. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m3. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

Repeated laboratory ozone exposures of volunteer Los Angeles residents: an apparent seasonal variation in response.

This study was intended to help explain individual differences in susceptibility to irritant effects of ozone (O3), by determining whether prior ambient O3 exposures and/or recent acute respiratory illness modified response to laboratory O3 exposures. Response was measured in terms of lung function changes and irritant symptoms. Initially, 59 adult volunteer Los Angeles area residents underwent screening exposures in spring, before the season of frequent high ambient O3 levels. Unusually responsive and nonresponsive individuals (N = 12 and 13 respectively) underwent followup exposures in autumn (late in the high-O3 season) and in winter (low-O3 season). All exposures were to 0.18 ppm O3 for 2 hr with intermittent heavy exercise at 31 degrees C and 35% relative humidity. Nonresponders tended to remain nonresponsive throughout. In fall, responders had lost much of their reactivity, as if they had "adapted" to summer ambient O3 exposures. They did not regain reactivity by winter. Clinical laboratory findings suggestive of acute respiratory illness did not appear to correlate with O3 response. Eight responders and 9 nonresponders underwent another followup exposure in spring, about 1 yr after screening. By that time most responders had regained their reactivity; individual function changes were significantly correlated with changes 1 yr earlier. These results suggest that response to O3 is a persistent individual characteristic, but can be modified by repeated ambient exposures.

Effect of metaproterenol sulfate on mild asthmatics' response to sulfur dioxide exposure and exercise.

Twenty asthmatic volunteers, most with mild disease, underwent dose-response studies with sulfur dioxide (SO2) under three pretreatment conditions: (1) drug (metaproterenol sulfate in aerosolized saline solution), (2) placebo (aerosolized saline only), and (3) no pretreatment. Sulfur dioxide exposure concentrations were 0.0, 0.3, and 0.6 ppm. Experimental conditions were presented in random order at 1-wk intervals. Exposures lasted 10 min with heavy continuous exercise. Lung function was measured at baseline, after pretreatment (immediately pre-exposure), immediately post-exposure, and during a 2-hr follow-up. Subjects could elect to take bronchodilators during follow-up. Symptoms were monitored before, during, and for 1 wk after exposure. With no pretreatment, subjects exhibited typical exercise-induced bronchospasm at 0.0 ppm, slightly increased responses at 0.3 ppm, and more marked increases at 0.6 ppm. Seven subjects took bronchodilator after 0.6-ppm exposures, compared to 2 at lower concentrations. Within 30 min post-exposure, most subjects' symptoms and lung function had returned to near pre-exposure levels. A similar sequence was observed when subjects received placebo. Drug pretreatment improved lung function relative to baseline, prevented bronchoconstrictive responses at 0.0 and 0.3 ppm, and greatly mitigated responses at 0.6 ppm. Thus, typical bronchodilator usage by asthmatics is likely to reduce their response to ambient SO2 pollution.

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 micron, geometric standard deviation 2.5) in a chamber at 21 degrees and 50% relative humidity. Measured sulfuric acid concentrations averaged 0, 380, 1060, and 1520 micrograms/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 less than .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 degrees, median particle diameter approximately 10 micron) 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.