Studies on the effect of community air pollution on sensitive individuals, such as those with chronic obstructive pulmonary disease (COPD) or heart disease, have produced conflicting results.1 The health endpoints in these previous studies were chosen primarily to evaluate both the cardiac and respiratory systems. Typical respiratory endpoints include measures of lung function, arterial oxygen saturation, and airway inflammation. Cardiac endpoints include blood pressure, heart rate, heart rate variability or other aspects ofthe electrocardiogram, and markers in serum, such as fibrinogen.
In a study of blood oxygen saturation using pulse oximetry, heart rate, and particulate matter (PM) exposure, Pope et al2 found that oxygen saturation decreased in association with PM in the Utah Valley. However, the association estimates were imprecise and may have been confounded by atmospheric pressure. These authors also reported that a 10-μg/m3 increase in the previous 1- to 5-day average PM10 was associated with an average pulse rate increase of 0.8 beats per minute. Examining the effects of an air pollution episode in Europe in January 1985, Peters et al3 reported an increase in pulse rate associated and an association between blood pressure and air pollution.4 Linn et al5 measured blood pressure, electrocardiogram, and oxygen saturation in a panel study of 30 subjects in Los Angeles during autumn and winter. Among these health endpoints, only daily diastolic blood pressure increases were associated with daily measures of particulate matter (0.95 mm Hg for a 10 μg/m3 increase in PM10). In a study of 21 subjects 53 to 87 years of age in Boston during the summer when PM was elevated, Gold et al6 found that heart rate was associated with 24-hour average PM2.5 concentrations.
Therefore, on the basis of the literature, there is some suggestion of associations between PM and changes in cardiac rhythm, arterial oxygen saturation, pulse rate, and blood pressure. These studies, however, were limited by their use of central monitors for PM data. To determine whether residential and personal PM exposures were associated with arterial oxygen saturation, heart rate, or blood pressure in subjects with COPD or congestive heart disease or angina, we performed a panel study in Seattle that included daily measures of these endpoints in 88 susceptible elderly subjects. We hypothesized that elevations in PM2.5 would be associated with decreases in oxygen saturation in the subjects with respiratory disease and with increases in heart rate and blood pressure in the subjects with cardiac disease.
We performed a panel study during the years 1999 to 2001 in Seattle to evaluate cardiac and respiratory effects of personal, indoor, and outdoor measures of air pollution in 88elderly subjects who were either healthy (n = 27), or who hadrespiratory disease (n = 34) or cardiac disease (n = 27). Details regarding study methods have been published previously.7
Subjects were recruited through distribution of flyers at clinics, senior centers, and retirement homes. All but one of the subjects was older than 65 years of age; 85% were between 71 and 90 years of age. Many of the subjects (55%) enrolled for more than one 10-day session. The inclusion criteria for the subjects with respiratory disease were physician-diagnosed COPD and forced expiratory volume in 1 second (FEV1) between 40% and 70% of predicted. Criteria for inclusion for cardiovascular disease subjects were a history of myocardial infarction, angina, or congestive heart failure. We excluded subjects with chronic atrial fibrillation or severe congestive heart failure. Because of the high incidence of hypertension in normal elderly subjects, subjects with hypertension were not excluded from the healthy group. All subjects were nonsmokers and lived with nonsmokers. Most of the COPD and healthy subjects lived in group homes or private residences. Most of the cardiac subjects lived in private homes or apartments.7
Personal, indoor, and outdoor monitoring for particulate matter ≤2.5 micrometers (PM2.5) and ≤10 micrometers (PM10) was conducted for all subjects. PM2.5 and PM10 gravimetric 24-hour measurements were taken inside and outside subjects’ residences using Harvard impactors.7 Each subject also wore the personal PM2.5 monitor for 24 hours each day and placed it at the bedside while sleeping. These integrated fixed-site and personal measurements were collected over 24 hours (4 PM to 4 PM) for 10 consecutive session days. There were a total of 26 exposure sessions, 13 in year 1 (October 1999 through August 2000) and 13 in year 2 (October 2000 through May 2001).
Daily health end point measurements were taken at approximately 4 PM during the 10-day session. Systolic and diastolic blood pressure were measured in the home daily at the same time of day by a technician visit to the home using an automatic digital blood pressure monitor (Omron Model HEM-705CP, Vermont Hills, IL). Blood pressure was taken when the subject was seated and resting. The same arm was used consistently for a given subject.
Oxygen saturation and heart rate were measured with a NONIN Model 8500 (Plymouth, MN) pulse oximeter by study personnel in the subjects’ home at the same time of day. Measurements were taken after 10 minutes of rest, while the subject was seated. The oximeter sensor was clipped onto the left index finger of the subject and arterial oxygen saturation measurements were taken for 3 minutes. The pulse oximeter was calibrated approximately every 2 months with a Finger Phantom Oximeter Test System set to simulate a subject with 97%, 90%, and 80% oxygen saturation conditions. Averages during the 3-minute period were used in our analysis.
Medication usage was recorded during screening. Subjects were queried about medication use each day; however, these daily records were not complete and thus could not be used in our analysis. Therefore, medication data from the screening visit were used for the medication term in our statistical model. Medications included in our analysis were bronchodilators, inhaled corticosteroids, and cardiac medications (antihypertensives, beta-blockers, calcium channel blockers, and cardiac glycosides).
We assessed associations of 24-hour daily indoor, outdoor, and personal PM exposure with daily average subject blood pressure, heart rate, and oxygen saturation. The data were analyzed using generalized estimating equations with an exchangeable working correlation matrix and robust standard errors to account for autocorrelation of the data. The linear model included terms for the within-subject, within-session (10 day monitoring period) effect; the within-subject, between-session effect; and an interaction term for medication usage. We classified each subject as taking any medications (bronchodilators, inhaled corticosteroids, or cardiac medications) or no medications at all. All but one of the COPD subjects was taking medications; we therefore omitted this one subject and did not include medication use in the COPD analysis. We also controlled for temperature, relative humidity, body mass index, and age. The last 2 variables did not affect the model. Daily temperature values were obtained from the Beacon Hill central site. In the models for oxygen saturation and blood pressure we controlled for heart rate that was measured concurrently with oximetry or blood pressure. Our primary interest in this analysis was the within-subject/within-session effect of PM (B1 in the model). Short-term associations between health endpoints and PM also were tested using 1-hour lagged outdoor nephelometer values. Outdoor nephelometer values were averaged from 7 PM to 4 AM to represent peak wood smoke concentrations. For each PM metric, we only included subjects who had at least 4 days of PM and health measurement data in the analysis. STATA 6.0 (Stata Corporation, College Station, TX) was used for the analysis.
The model was as follows:
where Xids is the PM reading for individual i on day d during session s.
X̄isis the mean PM reading for a subject during a session.
X̄iis the mean PM reading for a subject during all of their sessions.
medi is an indicator variable for medication use (constant for each subject).
We tested for heterogeneity of effects by creating a variable from 1 to 6 for health status and medication use. (There was not a “no medication” group for subjects with COPD because only one subject was in that category.) This variable was used in place of medication use in the aforementioned model. We then tested the hypothesis that the coefficients for each level of the interaction term were jointly zero. Our criterion for heterogeneity was P < 0.05.
Average values for percent predicted FEV1, oxygen saturation heart rate, and blood pressure, as well as other summary statistics for the groups, are given in Table 1. Baseline values differed substantially among the 3 groups of subjects with COPD subjects having much lower percent predicted FEV1 and lower arterial oxygen saturation than the other groups. The average age among the 3 health groups was 76 to 78 years. We had 1179 person-days of oxygen saturation and heart rate data and 1029 person-days of blood pressure data. Sixteen healthy subjects were prescribed cardiac medication; only 8 of the cardiac subjects used no medication.
PM data for each health group are given in Table 2. Personal exposures were not substantially different from outdoor concentrations, whereas indoor concentrations were lower than both personal and outdoor measurements.7 For Winter 1999 to 2000 (December to February) the interquartile ranges for outdoor PM2.5 and PM10 were 8.1 and 9.9 μg/m3, respectively; these values were 4.6 and 7.6 μg/m3, respectively, for Spring and Summer 2000. The interquartile range for outdoor PM2.5 and PM10 were 10.8 and 11.3 μg/m3, respectively, for Winter 2000 to 2001, and 4.7 and 6.6 μg/m3, respectively, for Spring and Summer 2001.
We first evaluated the association of PM exposure and health outcomes for all subjects combined. We report associations based on a 10-μg/m3 increase in each PM metric averaged over the course of 24 hours and at a 0-day lag relative to each subject’s session mean, except for nephelometer data when the PM measurements were averaged from 7 PM to 4 AM.8 We observed only very minor associations with PM metrics (Table 3).
In the second analysis, stratifying by health status and controlling for medication use, we did observe a small increase in systolic blood pressure with personal PM2.5 in cardiac subjects who were on medication (4.2 mm Hg; 95% confidence interval = 1.04–7.37). This association met our criterion for heterogeneity of effect for systolic blood pressure and personal PM2.5.
We also saw a small increase in systolic blood pressure with indoor PM2.5 and outdoor PM10 in the healthy subjects (Fig. 1) on medications. However, the effect of indoor or outdoor PM on blood pressure was not statistically heterogeneous among the different health groups.
We observed more consistent findings with heart rate. Heart rate decreased with all PM2.5 metrics except personal PM2.5 in the healthy subjects not on medication. The decreases in heart rate ranged from 1.5 to 3.4 beats per minute. COPD subjects also had a small decrease in heart rate associated with PM2.5 averaged from 7 PM to 4 AM. In contrast, cardiac subjects on medications had a small increase in heart rate with personal PM2.5 (Fig. 1). Tests of heterogeneity across the 5 subgroups (2 medication categories and 3 health groups) suggests differences in the effect of outdoor PM2.5, indoor PM2.5, outdoor PM10, and indoor PM10 and PM2.5 averaged from 7 PM to 4 AM on heart rate among the different subgroups. No heterogeneity of effect was found between heart rate and personal concentrations of PM2.5. There were no appreciable associations between oxygen saturation and any measure of air pollution in any of the subject groups.
We found associations between PM and heart rate in subjects in all health groups; however, the only consistent change was in the healthy subjects. Our test of heterogeneity suggested unequal effects of PM among the 3 health groups and by medication use. Decreased heart rate was associated with all PM metrics except personal PM2.5 in healthy subjects not on medications. Other studies of the relationship between heart rate and PM air pollution have reported increases in heart rate. Peters et al3 reported associations between increased heart rate and PM. Another recent panel study of subjects with COPD found that PM exposure was associated with increased heart rate and ectopic heartbeats.9 Although we had hypothesized that heart rate would be associated with air pollution in cardiac subjects, we found no evidence of such an association. We do not have an explanation for the difference between our study and the other studies. Animal studies have reported both increased and decreased heart rate after PM exposure. Chang et al10 reported increases in heart rate in rats with pulmonary hypertension exposed to concentrated PM and similar results have been reported with monocrotaline-treated rats, again using concentrated particle exposure.11 However, Tankersley et al12 reported a slowing of heart rate in senescent rats exposed to carbon black. Also, Campen et al13 found that diesel exposure was associated with reduced heart rate in spontaneously hypertensive rats compared with clean air exposure.
We observed small changes in systolic blood pressure in each group. We found increased blood pressure with indoor PM2.5 and outdoor PM10 in the healthy subjects on medications. Although we found no statistical heterogeneity in the effect of PM on blood pressure among the different health groupings, our blood pressure trends do agree with other published findings. The decreases that we report in systolic and diastolic blood pressure are in agreement with those of Ebelt14 and associates who saw decreases in systolic blood pressure in subjects with COPD in a panel study conducted in Vancouver, British Columbia.
Speculation exists in the literature that arterial oxygen saturation might be associated with PM exposure.2 We see no evidence that PM exposure (personal, indoor or outdoor) affects oxygen saturation. In this respect, our data agree with those of Pope et al,2 who also reported no consistent change in arterial oxygen saturation associated with PM10. Pope et al did, however, report an association between barometric pressure and arterial oxygen saturation in Utah Valley. We believe that this relationship is unlikely to be present in Seattle, a coastal city with sea level barometric pressure. Nevertheless, in a controlled exposure study with concentrated air particles in Los Angeles, Gong et al15 reported a mean 0.4% decrease in arterial oxygen saturation in 13 subjects with moderate COPD.
Although the effects observed in our study are small, we did find consistent PM-associated decreases in heart rate in elderly subjects without cardiac or respiratory disease. This raises the question of the general state of health of elderly subjects. As mentioned earlier, 17 of our healthy subjects were prescribed medication to control blood pressure. Studies showing decreases in heart rate variability associated with PM air pollution6,16–18 suggest that exposure to fine particles is related to alteration of the autonomic nervous system. Alteration in autonomic tone could be one mechanism responsible for the fluctuations in heart rate seen in our study.
COPD and cardiac subjects in this study were chosen as representative of populations susceptible to air pollution. In both cases, and especially for the COPD subjects, the demographic data indicate that these subjects had moderate to severe signs or symptoms of disease (50% predicted FEV1 values in the respiratory subjects).
The inclusion of indoor monitoring as well as personal and outdoor monitoring are strengths of this study. Our heart rate results with healthy subjects not on medications are difficult to interpret with respect to the site (indoor, outdoor, or personal) of the particles responsible for the observed effects. However, from other studies in Seattle19 we know that approximately 74% of outdoor particles infiltrate indoors. Further, Ebelt and associates14 and Koenig et al20 show that it is outdoor-generated particles that are associated with health effects such as ectopic heart beats and airway inflammation. Another strength of this study is the length of the health and exposure monitoring period (10 days). Twenty-eight subjects repeated the ten-day sessions at least once.
A limitation of our study is the small sample size. Unfortunately, panel studies are sufficiently time and labor intensive so that larger panel studies are almost prohibitive. It should also be noted, however, that our panel protocol was sufficiently demanding that some susceptible subjects chose not to enroll. Subjects were required to wear the personal monitor and air pump continuously (except when sleeping or showering, etc) and had to agree to daily technician visits. Another limitation is the relatively low concentration of PM in Seattle making demonstration of effects in our study difficult. The concentration of particles in the Gong study15 (∼200 μg/m3) was considerably higher than that in our Seattle panel study. The mean PM2.5 concentration in Seattle in the winter (when outdoor PM2.5 is highest) for years 1 and 2 were 9.2 and 12.6 μg/m3 respectively. These values for PM10 were 14.3 and 18 μg/m3, respectively. In the first year of our study when the healthy and COPD subjects were studied, PM levels in Seattle were lower than average. Lippmann21 discussed the difficulty in finding air pollution effects in developed countries with relatively clean air. On the other hand, PM concentrations in Seattle are very similar to those reported by Brauer et al9 in Vancouver, BC. They reported mean values for PM2.5 and PM10 of 11.4 and 18 μg/m3 respectively.
In conclusion, on the basis of this study, it appears that oxygen saturation of arterial blood does not have a consistent response to PM air pollution. However, the differential effects on heart rate changes among different susceptibility groups of older subjects add new information on the adverse health effects of fine particles.
We thank the subjects for their generous contribution to air pollution research. We also thank Liz Tuttle and Tim Gould for their excellent technical assistance.
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