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ABSTRACT |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Bronchial hyperresponsiveness (BHR) and peak expiratory flow (PEF) variability are associated expressions of airway lability, yet probably reflect different underlying pathophysiologic mechanisms. We investigated whether both measures can be used interchangeably to identify subjects who are
susceptible to ambient air pollution. Data on BHR (
20% fall in FEV1), PEF variability (ampl%mean
PEF > 5% on any day during an 8-d period with low air pollution levels) and diary data on upper and
lower respiratory symptoms, cough, and phlegm were collected in 189 subjects (48-73 yr). The acute effects (lag0) of particulate matter with a diameter less than 10 µm (PM10), black smoke, SO2 and
NO2 on the prevalence of symptoms were estimated with logistic regression. In subjects with airway lability, both when expressed as PEF variability (69%) and BHR (28%), the prevalence of symptoms
increased significantly with increasing levels of air pollution, especially in those with the greater PEF
variability (n = 55, 29%). We found no such consistent positive associations in adults without airway
lability. PEF variability, and to a smaller extent BHR, can be used to identify adults who are susceptible to air pollution. Though odds ratios were rather low (ranging from 1.13 to 1.41), the impact on
public health can be substantial because it applies to large populations.
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The presence of bronchial hyperresponsiveness (BHR) is associated with increased peak expiratory flow (PEF) variability in patients with respiratory disease (1) as well as in the general population (4). Evidence is accumulating that both variables are not interchangeable measures of bronchial lability, and that they probably reflect different underlying pathophysiologic mechanisms (1, 6). One reason for this assumption is the observation that BHR and PEF variability are differently associated with allergy markers. High total serum IgE is known to be associated with BHR (7, 8), and subjects with specific sensitization to various aero-allergens are more likely to have BHR (6, 9, 10). However, in a random population of adults these allergic markers were not associated with PEF variability at all (6). Nevertheless, increased PEF variability and BHR are in other respects quite comparable, e.g., they are both clearly related to the presence of respiratory symptoms (5, 6, 9, 11).
Several studies have shown consistent positive associations between an increase in air pollution levels and an increase in acute respiratory symptoms in subjects with chronic respiratory symptoms or asthma (19). We hypothesized that subjects with airway lability, identified by the presence of BHR or increased PEF variability, are especially susceptible to the acute effects of air pollution. In order to verify this hypothesis, we investigated acute effects of ambient air pollution on the prevalence of respiratory symptoms in adults with and without airway lability. Because both PEF variability and BHR were measured in each subject of the population, this enabled us to investigate whether both measures of airway lability can be used interchangeably to identify subjects who are susceptible to ambient air pollution.
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METHODS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Population Sample
Data were collected as a part of a panel study on acute effects of air
pollution on respiratory health among panels of adults with and without chronic respiratory symptoms in urban and rural areas. The study
was performed during the winter of 1993-1994 in an urban (Amsterdam) as well as a rural area (Meppel) in The Netherlands, using the
protocol of the Pollution Effects on Asthmatic Children in Europe
(PEACE) study (24). Target panel size for both symptomatic and
asymptomatic panels was 75 subjects, for both the rural and urban areas. Names and addresses of eligible adults were obtained by taking a
random sample from the municipal registration. Subjects were approached with a screening questionnaire on respiratory symptoms and
invited to participate in the current panel study. A total of 288 adults
(48-73 yr) were selected on the basis of their answers to the screening
questionnaire, such that approximately 50% had chronic respiratory
symptoms (wheeze, cough, phlegm, dyspnea grade 3, asthma attacks, or use of asthma medication) and 50% had no symptoms both
at the urban and the rural site. All 288 adults who were included into
the panel study were medically characterized.
Lung Function and Methacholine Responsiveness
Spirometry and methacholine challenge were performed according to
the European Respiratory Health Survey protocol (25). The FEV1
was recorded from at least two and up to five technically satisfactory
maneuvers, with the highest FEV1 being used in the analyses. Measurements were performed with a dry seal Morgan Spiroflow Ds12
(P. K. Morgan, Ltd., UK). Participants had refrained from the use of
short-acting 
2-agonist or anticholinergic inhaler for at least 4 h and
the use of oral 2-agonist, anticholinergic, or antimuscarinic medication for at least 8 h before methacholine provocation. Participants
with an FEV1% predicted of less than 70%, or who were taking medication for any heart disease or epilepsy, or a -blocker for any reason
were excluded from methacholine provocation testing. Adults refrained from smoking for at least 1 h.
Methacholine was administered in increasing concentrations by a Mefar MB3 dosimeter, with a maximum dose of 2.0 mg of methacholine. The provocation was stopped if there was a fall of 10% or more in FEV1 following inhalation of diluent (relative to the baseline FEV1), or a fall of 20% or greater in FEV1 (relative to the postdiluent FEV1) following inhalation of any cumulative dose of methacholine (methacholinecum). Subjects with a fall in FEV1 of 20% or greater were considered to have BHR. Within subjects with BHR, those with a 20% or greater fall in FEV1 at 1.0 mg or less of methacholinecum were considered to be the most responsive ones, i.e., to have the greater airway lability.
Peak Expiratory Flow Variability
Participants received a mini-Wright peak flowmeter (Clement Clarke International, Ltd., London, UK) and were instructed to perform three PEF measurements every morning on rising (morning PEF), and again in the evening at bedtime (evening PEF), for a period of 3 mo. The highest morning PEF and the highest evening PEF of the day were used in the analyses. Subjects had to have PEF data for at least 60% of the days in this period, to avoid large changes in the compositions of the reporting group of subjects on separate days. Subjects who did not meet this criterion or who reported exactly the same PEF value for more than a week (which is suggestive of cheating) were excluded from the analyses. Subjects on bronchodilator therapy had to measure PEF values before bronchodilator use.
In order to determine a subject's basal variability in PEF, we identified an 8-d period with consistently low levels of air pollution, with especially low levels of particulate matter with a diameter less than 10 µm (PM10) and black smoke (BS), in both the urban and rural areas. A subject's PEF variability was calculated over this 8-d period. Subjects had to have reliable PEF measurements for a minimum of 4 d over this 8-d period. PEF variability was expressed as the diurnal PEF variation (highest PEF-lowest PEF/mean; i.e., the amplitude % mean PEF) (26). After calculation of the daily amplitude % mean (ampl%mean) PEF, we determined the number of days with an ampl%mean PEF of more than 5%. This resulted in two groups: a group that consisted of subjects who had an ampl%mean PEF of 5% or less every day in the 8-d period, and a group with an ampl%mean PEF greater than 5% on at least 1 d. Within the latter group those with an ampl%mean PEF greater than 5% for more than 33% of the days were considered to have the greater PEF variability, i.e., to have the greater airway lability.
Exposure to Air Pollutants
PM10, BS, sulphur dioxide (SO2), and nitrogen dioxide (NO2) were measured daily starting at 3:00 P.M. until 3:00 P.M. the next day, as described previously (27). The rural area lacked major traffic emissions and large industrial sources. Air samplers in both the rural area (Meppel) and the urban area (Amsterdam) were sited away from local air pollution sources. In Amsterdam the sampler was situated at least 100 m from major streets. Samplers were fixed at a level of 1.5 m. Black smoke, however, was measured at a level of 3.0 m. The methods used to measure the concentrations of PM10, BS, SO2 and NO2 have been described elsewhere (24).
Acute Health Effects: Upper and Lower Respiratory Symptoms, Cough, and Phlegm
Subjects received a diary in which they recorded daily the presence of upper and lower respiratory symptoms, cough, and phlegm for a total duration of 3 mo (24). Subjects had to have diary data for at least 60% of the days in this period, to avoid large changes in the compositions of the reporting group of subjects on separate days. Subjects who did not meet this criterion were excluded from the analyses. Upper respiratory symptoms (URS) constituted of sore throat and runny or stuffed nose. Lower respiratory symptoms (LRS) constituted of wheeze, attacks of wheezing with shortness of breath, and shortness of breath. The prevalence of URS at a certain day was defined as the number of subjects who reported URS that day divided by the number of subjects who provided diary data for that given day. The prevalences of LRS, cough, and phlegm were determined the same way. Daily data on URS, LRS, cough, and phlegm were collected in a total of 288 adults.
Data Analyses
Complete data on BHR and PEF variability were collected in 189 of the 288 adults that completed the diary. Subjects with incomplete data were not different from those with complete data with regard to the sex ratio but were significantly older (62 yr [SD = 6] versus 60 yr [SD = 6] in the included group).
The acute effects of PM10, BS, SO2, and NO2 (lag0) on the prevalence of URS, LRS, cough, and phlegm were estimated with logistic regression, with additional modeling of autocorrelation of the residuals and adjusted for daily minimum temperature, linear, quadratic, and cubic time trend, and weekend/holidays. The logistic regressions were performed for the urban and rural area separately, which resulted in two prevalence estimates for each respiratory symptom and pollutant. The two estimates were weighted with the inverse of the square of the standard error (1/SE2) of these estimates. Odds ratios (OR) were expressed for the actual measured ranges of the air pollutants (between the 1st and 99th percentile of the distributions), as observed during the period of investigation; this was 100 µg/m3 for PM10 and 40 µg/m3 for BS, SO2, and NO2. ORs were considered to be significant if the 95% confidence intervals (95% CI) did not include the value 1. SPSS/PC+ version 5.01 and SAS version 6.12 for Windows were used to perform the analyses.
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RESULTS |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Population Characteristics
The characteristics of the 189 subjects who were included in the study are presented in Table 1. Fifty-two adults (28%) had BHR. Within these hyperresponsive subjects, 36 had BHR at 1.0 mg or less methacholinecum. An ampl%mean PEF greater than 5% for at least 1 d during the 8-d period was present in 129 adults (69%). Within this group, 55 had an ampl%mean PEF greater than 5% for more than 33% of the days that constituted this 8-d period. Of the total population, 40 adults (21%) had both BHR at 2.0 mg or less methacholinecum and an ampl%mean PEF greater than 5% for at least 1 d, 48 (25%) had neither BHR nor an ampl%mean PEF greater than 5%, 12 (6%) had BHR but no ampl%mean PEF greater than 5%, and 89 (47%) had an ampl%mean PEF greater than 5% for at least 1 d, but no BHR.
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The percentages of subjects with airway lability (ampl%mean PEF greater than 5%, any day), and the subgroup with the greater airway lability (ampl%mean PEF greater than 5% more than 33% of the days) in the symptomatic and asymptomatic panel were similar (approximately two-thirds and one-third of both groups, respectively).
Air Pollution
The air pollution concentrations in both the urban and rural areas during the complete winter period are shown in Table 2 and Figure 1. The median values of PM10, BS, SO2 and NO2 were somewhat higher in the urban compared with the rural area. The median and maximum concentrations of air pollution during the 8-d period over which the basal ampl%mean PEF was calculated are considerably lower than the median and maximum values over the complete winter.
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Acute Health Effects: Prevalences of URS, LRS, Cough, and Phlegm
The ORs for the prevalences of URS, LRS, cough, and phlegm with levels of PM10, BS, SO2, and NO2 (lag0) in adults are shown in Tables 3 and 4. In subjects with BHR, the prevalence of URS, LRS, and phlegm significantly increased for each 40 µg/m3 rise in NO2 (OR = 1.30, OR = 1.31, and OR = 1.22, respectively) (Table 3). Subjects with BHR at 1.0 mg or less methacholinecum (the more responsive subgroup) had an increased prevalence of URS and LRS for each 40 µg/m3 increase of NO2 that day (OR = 1.32 and OR = 1.40, respectively). Subjects with BHR at 2.0 mg or less or 1.0 mg or less methacholinecum had an increased prevalence of cough for each 100 µg/m3 rise in PM10 that same day (OR = 1.23 and OR = 1.41, respectively). We found no consistent positive associations between the prevalence of respiratory symptoms and increases in levels of air pollution in adults without BHR.
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cum 2.0 AND
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In subjects with an ampl%mean PEF greater than 5% for at least 1 d, the prevalence of phlegm was significantly increased with increasing levels of air pollution, especially in those subjects with an ampl%mean PEF greater than 5% for more than 33% of the days during the 8-d period. ORs were 1.14 for each 100 µg/m3 rise in PM10, 1.29 for each 40 µg/m3 rise in BS, 1.36 for each 40 µg/m3 rise in SO2, and 1.17 for each 40 µg/m3 rise in NO2 (all p < 0.05) (Table 4). In the same subjects with an ampl%mean PEF greater than 5% for more than 33% of the days, the prevalence of URS was significantly increased with each 40 µg/m3 rise in NO2 (OR = 1.15), and the prevalence of cough was significantly increased with each 40 µg/m3 rise in BS and NO2 (OR = 1.29 and OR = 1.19, respectively). We found no consistent positive associations between the prevalence of respiratory symptoms and increases in levels of air pollution in adults with an ampl%mean PEF of 5% or less (Table 4). We did find, however, some significant negative associations between the prevalence of respiratory symptoms and increases in levels of air pollution in adults with an ampl%mean PEF of 5% or less. We have no explanation for this unexpected finding other than that this might be due to chance.
All results presented in this section reflect the immediate effects of an increase in levels of air pollution on the prevalence of URS, LRS, cough, and phlegm that same day (lag0). We found no consistent positive association whatsoever between lag1, lag2, and 5-d mean (i.e., of lag0, lag1, lag2, lag3, lag4) increase in levels of air pollution and the prevalence of URS, LRS, cough, or phlegm. Thus, the effects of air pollution only occurred immediately (lag0), and not with a lag of 1, 2, or more days.
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DISCUSSION |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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Adults with airway lability, both when expressed as PEF variability and BHR, had significantly increased prevalences of respiratory symptoms with increasing levels of air pollution. This was especially the case in subjects with PEF variability, specifically those subjects with an ampl%mean PEF greater than 5% for more than 33% of the days as measured during an 8-d period with low levels of air pollution. We found no consistent positive associations between the prevalence of respiratory symptoms and increases in levels of air pollution in adults without airway lability. In adults, PEF variability, and to a smaller extent BHR, can be used to identify subjects who are susceptible to ambient air pollution. PEF variability and BHR cannot be used interchangeably to identify subjects who are susceptible to ambient air pollution.
In the current study, we identified subjects susceptible to air pollution from those less susceptible on basis of their PEF variability, as determined over a period with low levels of air pollution. It is well known that PEF values show a 24-h rhythm, with minimum PEF values usually at night or early morning at rising and with maximum values at the end of the afternoon (28, 29). This circadian PEF rhythm is enhanced in subjects with unstable asthma, and therefore can be easily detected in this specific group of patients. Normal subjects also have a circadian rhythm in PEF. However, their PEF amplitude is usually relatively low, and therefore may not always be detected (30). The detection of such low amplitude rhythms might be even more problematic when relatively crude methods of PEF monitoring are used. Our twice daily measurement of the PEF on the mini-Wright can be considered to be such a crude method of monitoring, resulting in a potential drawback of our study. Notwithstanding this, we show that twice daily measurements of PEF on the mini-Wright served our study goals properly. We were able to separate subjects without any relevant PEF amplitude (26) from those with a measurable, minimally relevant PEF amplitude. In subjects with an ampl%mean PEF greater than 5%, specifically those who had this amplitude more than 33% of the days during an 8-d period, we did find increased prevalences of respiratory symptoms in association with increased levels of air pollution, as visualized in Figure 2. In adults without any relevant amplitude in PEF (ampl%mean PEF of 5% or less), we did not find any increase in the prevalences of respiratory symptoms in association with increased levels of air pollution (Figure 3).
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In normal, healthy subjects debris and pathogens are cleared from the bronchial tree by production of mucus, which is carried upward by ciliary action and then swallowed. Small particles such as PM10 may have a direct, irritating effect on the bronchial tract. Deposition of these particles may cause the airway epithelium to respond with increased secretion of mucus and stimulate irritant receptors, which results in coughing up phlegm (31). Not to our surprise, cough and phlegm seemed to be major modes of response to air pollution in the adults we investigated in our study. In subjects with PEF variability, the prevalence of cough increased by 20% and the prevalence of phlegm increased by 14 to 36% (OR = 1.14 to OR = 1.36). These increased risks appear to be low but are in the same range of effect as those of passive smoking. For instance, Schwartz and Zeger (32) estimated that having a smoking roommate increased the risk of phlegm by 41% (OR = 1.41).
The increased risks of cough, URS, and LRS for our adult subjects with airway lability are minimally of the same magnitude as those reported in other studies on the acute health effects of air pollution in children. Dockery and Pope (33) reported a combined weighted estimate of 3% increase in LRS, 0.7% increase in URS, and 1.2% increase in cough with each 10 µg/m3 in PM10 in children. These increased risks in children are in the same moderate range as those we present in adults with airway lability. At first glance ORs appear to be rather low and might suggest to be of little relevance. The increased risks usually refer to large groups of the population, and therefore their impact on public health can be substantial.
Relatively few panel studies have been performed on the negative health effect of air pollution in normal adults. The majority of studies on air pollution have been performed in children, who are supposed to be more susceptible to air pollution than adults. Moreover, studying children has the advantage that potentially confounding factors such as active smoking are less important than in adults. Most of the panel studies on adults focused on adults with respiratory impairment such as asthma or chronic obstructive pulmonary disease. Pope and coworkers (34) found no significant associations between PM10 and reported symptoms. This lack of association was probably due to the fact that there was a significant increased use of asthma medication during elevated PM10 levels, resulting in proper management of the respiratory symptoms.
We studied the effect of a number of single air pollutants on respiratory health. This approach does not take into account that air pollution is in fact a mixture of a number of air pollutants that may confound and modify each others' effect on respiratory health. However, this strategy is considered to be appropriate and effective for hazard identification of susceptible groups and public health purposes (35). Therefore, investigating the respiratory health effect of single air pollutants seemed appropriate; it indeed identified susceptible subgroups of adults.
The levels of the single air pollutants in the urban and rural areas were comparable, with the exception of NO2, which was higher in the urban area. Despite the differences in levels of NO2, the negative health effect of NO2 was found in both areas and was not limited to the urban site.
In adults, PEF variability, and to a smaller extent BHR, can be used to identify adults who are susceptible to ambient air pollution. However, when one has to choose between the two measurements of airway lability, we would recommend the use of PEF variability. There are a number of reasons for our recommendation, the major one being the fact that the use of PEF variability appears to identify the susceptible adults more effectively than assessment of BHR. We hypothesize that this is because PEF variability reflects the actual lability of the airways better than one single measurement of BHR. If BHR is measured only once, it gives a "certain time point" indication of the ongoing and past process of inflammation in the airways. This is supported by findings in clinical studies. Kerstjens and coworkers (2) showed that patients with moderately severe obstructive airway disease had a decrease in PEF variability with inhaled steroids within 3 mo, without further decrease after this period. BHR, however, decreased within the first 3 mo of treatment, but continued to decrease during the following 15 mo, suggesting a continued reduction of (structural changes due to) airway inflammation. Finally, we prefer PEF variability over BHR testing because it has high safety and low costs (14, 26) and subjects are more willing to participate in a PEF variability study than in a study with BHR testing (5).
We conclude that adults with airway lability have increased prevalences of respiratory symptoms with increasing levels of ambient air pollution. It seems worthwhile to determine the PEF variability to identify these susceptible subjects with airway lability. PEF variability and BHR cannot be used interchangeably in studies on the acute effects of ambient air pollution.
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Footnotes |
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Correspondence and requests for reprints should be addressed to Professor D. S. Postma, Department of Pulmonology, University Hospital Groningen, Hanzeplein 1 NL-9313 GZ Groningen, The Netherlands. E-mail: d.s.postma{at}int.azg.nl
(Received in original form April 10, 1998 and in revised form July 27, 1998).
The PEACE study was funded by the EU ENVIRONMENT Programme Contract EV5V-CT92-0220 (seven centers) and two additional EU PECO contracts to allow participation of five centers in central and eastern Europe. The center in The Netherlands was funded by a grant of the Ministry of Housing and Environment (VROM), The Netherlands and The Netherlands Asthma Foundation.Acknowledgments: The authors thank R. Cardynaals, M.D., S. Kusmic, and N. Boluyt, M.D., for performing the medical characterization.
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References |
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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