This article was downloaded by: [New York University] On: 09 January 2015, At: 16:46 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Effects of Particulate Matter Exposure and Medication Use on Asthmatics F. Silverman Ph.D. a
a b
, H. R. Hosein
a b
, P. Corey
a b
, S. Holton
a b
& S. M. Tarlo
a b
The Gage Research Institute, University of Toronto , Toronto, Ontario, Canada
b
Departments of Medicine, Preventive Medicine and Biostatistics , University of Toronto , Toronto, Ontario, Canada Published online: 03 Aug 2010.
To cite this article: F. Silverman Ph.D. , H. R. Hosein , P. Corey , S. Holton & S. M. Tarlo (1992) Effects of Particulate Matter Exposure and Medication Use on Asthmatics, Archives of Environmental Health: An International Journal, 47:1, 51-56, DOI: 10.1080/00039896.1992.9935944 To link to this article: http://dx.doi.org/10.1080/00039896.1992.9935944
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
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Effects of Particulate Matter Exposure and Medication Use on Asthmatics
F. SILVERMAN H. R. HOSEIN P. COREY S. HOLTON S. M. TARLO The Gage Research Institute and Depathents of Medicine, Preventive Medicine and Biostatistks U n M i of Toronto Toronto, Ontario Canada
ABSTRACT. The health risk associated with low-lewl air pollution exposure is still uncertain, The association between exposure and pulmonary function was assessed with penona1 sampling. Small, portable multipollutant samplers wece used to assess personal e x p sure to rtkulate matter. Thirty-six asthmatic subjects participated in the study for up to 2 0 d i n bh summer (n = 10 d) and winter (n = 10 d); pulmonary function was assessed at the beginning and end of each sampling day, and medication use was recorded. A
within-individual longitudinal analysis of the relationship between pulmonary function and particulate matter reve;lkd an effect of season. In winter, pulmonary function i d as particulateexpowre i n m a d , which was explained by a confoundingeffect of medication use. TherPfore, in addition to exporurp, season of the year and medication use are facton that must be considered.
STUDIES conducted to determine health effects of air pollution exposure, particularly at low levels, are often inconclusive because of limitations in assessments of both exposure and response.' Until recently, estimates of exposure have relied upon measurements made at fixed outdoor sites that were usually oriented for source control purposes. It is now recognized that not only are there variations in pollutant levels horizontally and vertically, but that the indoor environment can be vastly different from the outdoor environment.'*' Thus, the actual exposures of individuals or populations may JsnwrylFebrusry1992 [Vd. 47 (No. l)]
not be represented adequately by one or more tixed outdoor sites.' Definitions of populations with respect to differences in diagnostic criteria, health status, measures of sensitivity, and objectives measures (e.g., pulmonary function) are either not clear, not uniform, or absent. We attempted to address these issues by designing a study in which the following were used: a well-defined group of asthmatic subjects, objective (pulmonary function) and subjective (symptoms) measures of response, and personal air pollution exposure measurements. 51
Downloaded by [New York University] at 16:46 09 January 2015
Methods Personal sampling for particulate matter was conducted in two groups of asthmatics while they conducted their daily activities. The subjects carried personal samplers for a 6- to 8-h period, which commenced between 8:OO and 9:OO A.M. and ended between 3:OO and 5:OO P.M. Each subject was sampled for up to 20 d (10 d in the winter or heating season and 10 d in the summer or nonheating season). On each day, pulmonary function (spirometry) was obtained in the morning when the sampler was switched on and at the end of the sampling period during late afternoon. Selection of subjects. In the first and second study, 17 subjects (Study 1) and 19 subjects (Study 2) were selected from a pool of approximately 800 asthmatics in the patient population of an Asthma Clinic at The Gage Research Institute in Toronto, Canada, a tertiary referral center for patients with asthma. The patient population is weighted with patients who have more severe asthma and who tend to have a greater frequency of symptoms5; these patients might be more sensitive to irritant pollutants than asthmatics who have infrequent symptoms. The certainty of the diagnosis of asthma in patients who attend the Asthma Clinic is established with uniform criteria that are based on history consistent with intermittent diffuse airways obstruction, physical examination, pulmonary function tests, and at least 15% reversibility of airflow limitation after inhalation of salbutamol, a bronchodilator. Patients were selected if they had a diagnosis of asthma and if they experienced wheezing at least a few times a week, as recorded during their most recent visit to the clinic and verified by a preliminary questionnaire. Primary patient care was conducted by the patients' physicians. Medications were not controlled but their use was recorded in a daily diary. Exposure. Subjects carried a portable, personal multipollutant sampler, which was used to measure exposure to sulfur dioxide, nitrogen dioxide, and to particulate matter of 2 particle size fractions. Only the particulate matter results are presented in this report. The personal sampler was worn either on a shoulder strap or on a belt around the waist, and the sampling probe was held in the vicinity of the breathing zone with lapel clips. The sampler was developed at The Gage Institute,6 and it was designed to be portable, lightweight, and quiet. The sampling system was powered by a rechargeable battery and consisted of a pump, a filter assembly with Teflon fabric of 1 p pore size that effectively collected submicronic particulate matter, and two impingers, each containing the appropriate absorbing reagents for nitrogen dioxide and sulfur dioxide, respectively, The samplers were prepared and calibrated for flow in the laboratory each day before they were taken into the field for use. At the start of the sampling period, the air flow was recorded and the timer started. The subjects were instructed on the proper care and use of the personal samplers. At the end of the sampling period,the flows and elapsed times of each sampler were recorded. The filters were dismounted from the sam52
pler case and stored flat in small, covered Petri dishes until conditioning and weighing could be completed. Calibration and quality-control procedures have been reported previou~ly.~~~~' In Study 1, the flow capability of the pump (0.9 Ilmin) and the air inlet dimensions allowed us to collect particulates up to approximately 25 p in size. In Study 2, we increased the flow rate to 1.7 I/min, which allowed use of a 10-mm nylon cyclone assembly that effectively collected particulate matter in the respirable range (i.e., < 10 p).' Medications. The subjects kept daily records of their clinical status and activities in a diary. In Study 2, use of medication for control of asthma was recorded and included number of tablets, capsules or inhalations per 24 h of oral and inhaled bronchodilators, and oral and inhaled corticosteroids. In response to the varied medication regimes taken by the study patients, a drug score was developed that used a weighted combination of dose equivalents from three classes of drugs: (1) xanthines, (2) corticosteroids, and (3) agonists. Consensus was obtained among three asthma physicians about the amount of each drug within the three drug classes -xanthines, agonists, and steroids-that would give approximately an equivalent effect. For example, if a patient who used only low-dose beclomethasone (an inhaled corticosteroid, two puffs four times a day) were to instead use only salbutarnol, an inhaled agonist, two puffs eight times a day might be required. Therefore, two equivalent units of an inhaled bronchodilator were weighted the same as one equivalent unit of inhaled steroid. These unit equivalents of the drugs used in each of the three drug classes were summed for each patient to derive the patient's asthma medication score (AMS). Empirical drug scores were also used by Burns et al.' Pulmonary function. A wedge-balloon spirometer was used at the beginning and end of each monitoring period to test the subjects' lung function. Measurements included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV,,,), and forced expiratory flow during the middle half of a maximum expiratory maneuver (FEF,5-,5,c). The tests were administered according to standard recommended procedures." Data analysis. All data were verified, coded, and keypunched. The University of Toronto computer and the SAS statistical package" were used for data management and statistical analyses. Data were included in the analysis if they met the following criteria: (a) on a given day, all of the mean pulmonary function (mean FVC, mean FEVl.o, mean FEF25-75%VC) and particulate measurements were available for an individual; and (b) each person contributed at least two sets of observations per season. Analysis of variance was used to analyze data. A further analysis involved the calculation of slopes for each subject from the line of best fit that related the daily mean (of the morning and afternoon values) of each pulmonary function variable (FVC, FEV,., FEFzs-7snvc) with the particulate exposure for the corresponding day, over all the days of monitoring. Slopes were o b tained separately for each of the pulmonary function Archives of Environmental Health
was expected because the aerodynamic diameter of particles collected was smaller; however, mean values were again the same for the two seasons. The mean AMS was similar for summer and winter. The mean pulmonary function was slightly higher in the summer. Analysis of variance of the joint effects of season, daily particulate matter concentration, and daily mean slopes of FVC, FEV,.o, and FEF2S75XVC are shown in Table 3. During Study 1, the seasonal effect approached sta-09) for only the daily mean tistical significance (p FEF2575XVC.There was, however, a significant seasonal effect (p < .04)in Study 2 for all three of the pulmonary function variables, i.e., FVC, FEV,.o, and FEFz,75,Vc. When the data were combined across the two studies (Fishers‘ Method of Combining Information”), a significant (p < .02) seasonal effect was noted for FEV,, and FEFz,!5,vF. There was a tendency for the slopes to be negative in the summer and positive in winter.
variables and for each of the two particulate fractions. If an increase in pollutant exposure for a given individual were to cause pulmonary function to decrease, the relationship between daily mean pulmonary function and daify particulate exposure would be expected to have a negative slope.
Results
-
The subjects in Studies 1 and 2 were similar with respect to age, height, and weight, and the ratio of females to males was approximately 3:l (Table 1). There were no significant differences in mean pulmonary function (p > .05) between measurements taken in summer and winter (Table 2). In Study 1, the mean particulate levels recorded by the personal sampler were the same in summer and winter. In Study 2, the mean particulate values were lower than in Study 1, which
Downloaded by [New York University] at 16:46 09 January 2015
Table 1.-Characteristics of SubSex
Study 1 (n Study 2 (n Overall (n
--
17) 19)
Age (y)
Male
Female
x f SD
Height (cm) X f SD
Weight (@ X f SD
5 4
12 15 22
5 O f 15 48 f 14 48f 14
165 f 9
65 f 11 65 f 11 65 f 11
a
30)*
im f a
167 f 9
*There were 6 subjects who participated in both studies. I
Table Z.--Seraonal
Variation in Pulmonay Function, Palthlate Exposurer, and Drug Score Study 1 & f SD)
-
-
Summer (n 17)
I
Winter (n 17)
P values.
Pulmonary function
Fvc (1)
FEV1.o (1) FEF~~J~,v,:(11s) Particulate PS,-personal (rs/m3)
3.14 f 0.99 2.18 0.84 1.65 f 1.11 108.5 f 31.0
I
Study 2 &
-
Summer (n 19)
januay/Februay 1992 [Vd. 47 (No. l)]
3.12 f 0.91 2.11 f 0.74 1.49 f 0.94 108.9 f 36.5
.% .a7 .65 .97
SD)
-
Winter (n 19)
P values
53
cations. Cold air, specifically cold dry air, is a potent trigger of bronchoconstriction in almost all asthmatics. Common advice given to asthmatics is to take an extra dose of their bronchodilator before leaving their home to go outside during the winter. It is possible that particulate levels may have been lower on cold dry days and higher on slightly warmer or more humid days when the negative airway effects of the cold were a b sent. Thus, any negative airway effects of the particulates may have been offset by the absence of the cold dry air effects, and may have been further offset by use of prophylactic bronchodilators, which might have led to a paradoxical increase in pulmonary function. Total AMS was not significantly different in the winter and summer, which probably reflects the many other triggering factors in asthma, some of which (pollen, fungal spores, exercise) are likely to be less important factors during the winter. Another possible explanation would be an increased drug intake by patients on days that exposure to higher particulate concentrations occurred, which would tend to reduce the adverse effects of exposure. However, in both summer and winter, there was no evidence within individuals of a relationship between the drug index and particulate levels (p > .8). The independent effects of season or climatic factors have been shown previously,"" as have interactive effects of season and air quality,17 but the possible
Downloaded by [New York University] at 16:46 09 January 2015
Study 2 data were analyzed, including the effect of medication and particulate exposure and season (Table 4). There was a significant positive relationship during the winter between daily drug intake and the corresponding daily mean pulmonary function, and a significant positive relationship existed between pulmonary function and daily particulate exposure. The results of analyses of variance for winter data, which, in addition to particulate exposure, drug intake, and patient identification, included an interaction term between drug intake and particulate exposure are shown in Table 5. A statistically significant positive interaction between drug intake and particulate exposure was found for daily mean pulmonary function (FVC, FEV,,o, and FEF,,7,%Vc) during the winter. This analysis also resulted in negative, but not significant, coefficients between particulate matter and pulmonary function.
Discussion The data suggest that there was a seasonal difference with respect to relationships between pulmonary function and exposure to particulate matter. In summer, there was a tendency for pulmonary function to decrease as exposure increased, i.e., an adverse effect of particulates on the lung. However, in winter, the o p have been the effect of cold air and consequent medi-
Table 3.--slopes of Daily Mean Pulmonary Function and Daily Personal Particulate Exposures, by Season
-
-
Study 1 (n 17) Slope* Summer Winter
Pulmonary function Fvc (1) FEVl.0 (1) FEF,5_75,vc
- 0.46 - 0.78 (I&
-2.03
Study 2 (n 19)
Slope
Pt value
Summer
Winter
Pt value
P* overall
.54 .26 .09
- 0.65 -1.65 -1.13
2.58 2.83 4.40
.04 .01 .03
.10 .02 .02
0.06 0.18 -0.10
*Mean slopes of the relationships between each subject's daily mean pulmonary function and daily mean personal particulate exposure multiplied by 1 OOO. tp values associated with a two-way analysis of variance of the slopes; factors are season and individual. *Fisher's method of combining information. I
I
I
I
Table 4.-Effects (Study 2)
of Particulate E x p u r e and Medication Use on Pulmonary Function
Pulmonary function
Particulate Coefficient. p t
Summer
Fvc (1) FEVl.0
(1)
FEF,5_x,%vc
(115)
-1.02 -1.10 -1.47
.13 .12 .15
AMS Coefficient
p
0.98 1.87 2.86
.51 .24 .22
Winter Particulate AMS Coefficient p Coefficient 2.37 2.35 4.35
.025 .024
.OM
8.09 9.35 6.89
p
.OOO1 .OOO1 .OO08
*Regression coefficient-l/pg . m3 and VAMS unit. tp values related to individual personal particulate exposure and AMS (asthma medication score).
54
Archives of Environmental Health
Tabk 5.-Effict of Inttmctm ' &(wcm Particulate E x p o w ~ eand Mediation Use on Pulmonary FuncuOn in Winter (Study 2) Particulate
Pulmonary function ~~~~
Coefficient*
Particulate x AM%
AMS pt
Coefficient
p
Coefficient
P
3.16 5.69 0.71
.17 .01 .84
0.10
.01 .05 .03
~~~
PJC (1) FEVl.0 (1) FEF2!5-75%VC
(Ik)
-1.21 -0.31 -0.15
.a .85 .95
0.08 0.13
-
Downloaded by [New York University] at 16:46 09 January 2015
*Regression coefficient--I/# maand I/AMS unit. tp values related to individual personal particulate exposure, AMS, and interaction of particulate and AMS. $Interaction of particulate and AMS.
posite occurred: pulmonary function increased as exposure increased, a tendency that appeared to be stronger in Study 2. A possible explanation for the paradoxical increase in pulmonary function as particulate exposure increased during the winter months might mitigating influence of drug intake on pulmonary function response has not been documented. Consistent and statistically significant positive relationships were found between the drug index and the three pulmonary functions, i.e., pulmonary function was better on days when higher drug intake occurred. Adding the interaction term to the regression analysis of the effects of drug index and particulates on pulmonary function resulted in relationships that were more understandable. Although not statistically significant, the relationship between particulate level and pulmonary function was, in all cases, negative. Finally, the significant positive interaction suggests that the adverse effea of particulates was diminished by an increased drug intake. The difficulty in establishing an effect of particulate matter on asthmatics' lung function has been identified in this analysis, i.e., the confounding effect of drug use masked the negative effect of particulate matter exposure in asthmatics. However, the data suggest that drug intake by patients who participated in the study ameliorated the potential negative effects of particulate exposure. The composite asthma drug score was derived from empirical weightings given to three classes of drugs: (1) steroids, (2) xanthines, and (3) & agonists. Although these medications have different actions and cannot be compared precisely, the weightings used reflect the prescribed use by the physicians who treated these patients, both for daily maintenance and for any fluctuations in asthma symptoms. Therefore, the type(s) and dosage of medications used were variable, both within and between individuals. Because the functional status of the airways, as assessed by tests of pulmonary function, are in part reflective of the total medication regime, a composite drug score-although empiricalprovides a better index of airway function than any one drug class alone. In previous studies in which the health effects of air pollution exposure were not evident or were minimal, january/Fcbruary 1992 [Vd. 47 (No. l)]
it is possible that the confounding effects of season and drug intake may have played a role. Our study showed that, in at least one group of a sensitive population, drug intake was an important factor in explaining the effects of air pollution on pulmonary response. * * * * * * * * I
We wish to acknowledge the support of the Ministry of the Environment of Ontario (through its grant program and the assistance and cooperation of its staff), Health and Welfare Canada, and the World Health OrganizationlUnited Nations Environment Program. We are grateful to the staff of The Gage Research Institute for their dedication and our volunteer subjects for their cooperation. We also appreciate the assistance of Dr. A. Leznoff and Dr. G. Davies in the mation of the asthma medication score. Requests for reprints should be sent to: F. Silverman, Ph.D., The Gage Research Institute, 223 College Street, Toronto, Ontario Canada M5T 1R4. I * * * * * * * * *
Refcrrncer 1. Bouhuys A, Beck GJ, Schoenber J. Do present levels of air pollution outdoors affect respiratory health? Nature 1978; 276 466-71. 2. Silverman F, Mintz S, Olver P, et al. Human expourre to sol, NO2,and suspended particulate matter in Toronto, Canada. Pub lished under the joint sponsorship of the United Nations Environmental Programme and the World Health O1.ganization. Geneva, Switzerland: 1982, EFP/82.38. 3. Hosein HR, Corey P. Domestic air pollution and respiratory function in a group of housewives. Can J Public Health 1987; 7 7 44-50. 4. Hosein HR, Mitchell C, Bouhuys A. Daily variation in air q u a l i . Arch Environ Health 1977; 32:1420. 5. Langlois PH. Factors associated with the severity at presentation and prognosis of asthma in clinic patients as assessed by pulmonary function. Master of science thesis. University of Toronto, Ontario Canada: Department of Community Health, School of Graduate Studies, 1984. 6. Mintz S, Hosein HR, Batten B, Silverman F. A personal sampler for three respiratory irritants. JAPCA 1982; 32:106869. 7. Silverman F, Mink S, Hosein R, Corey P. To investigate and report on the health effectsof ambient air pollution on asthmatics. 1982. Report submitted to the Health and Welfare Canada, Environmental Health Directorate, Ottawa, Canada. 8. Fletcher RA. A review of personalfportable monitors and samplers for airborne particles. JAPCA 1984; M1014. 9. Burns RBP, Brandon ML, Haddad ZH, et al. Factorial rating system for comparative efficacy of antiasthmatic medication: a
5s
exacerbation of chronic bronchitis. Atmos Environ 1970; 4 453-68. 15. Emerson P. Air pollution, atmospheric conditions and chronic obstructive airways. J Occup Med 1973; 15(8):835-38. 16. Skoogh BE, Simonsson BC, Berggren A. Climate and environment change in patients with chronic airway obstruction. Arch Environ Health 1976 1:15-20. 17. HolbergCJ, O’Roavke MK, Lebowitz MD. Multivariate analysis of ambient environmental factors and respiratory effects. Int J Epidemiol 1987; 16(3):399-410.
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multicentric study report. J Asthma 1983; 20105-13. 10. ATS Statement-Snowbird Workshop on standardization of spirometry. Am Rev Respir Dis 1979; 19831-38. 1 1 . Statkjtical Analysis System. SAS users guide. Cary, North Carolina: SAS Institute, 1979. 12. Fisher RA. The design of experiments. New York: Hafnen Press, 1971. 13. Spicer WS, Kerr DH. Effect of the environment on respiratory function in males. Arch Environ Health 1976; 21:635-42. 14. Gregory J. The influence of climate and atmospheric pollution on
56
Archives of EnvironmentalHealth
Archives of Environmental Health: An International Journal Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/vzeh20
Effects of Particulate Matter Exposure and Medication Use on Asthmatics F. Silverman Ph.D. a
a b
, H. R. Hosein
a b
, P. Corey
a b
, S. Holton
a b
& S. M. Tarlo
a b
The Gage Research Institute, University of Toronto , Toronto, Ontario, Canada
b
Departments of Medicine, Preventive Medicine and Biostatistics , University of Toronto , Toronto, Ontario, Canada Published online: 03 Aug 2010.
To cite this article: F. Silverman Ph.D. , H. R. Hosein , P. Corey , S. Holton & S. M. Tarlo (1992) Effects of Particulate Matter Exposure and Medication Use on Asthmatics, Archives of Environmental Health: An International Journal, 47:1, 51-56, DOI: 10.1080/00039896.1992.9935944 To link to this article: http://dx.doi.org/10.1080/00039896.1992.9935944
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Downloaded by [New York University] at 16:46 09 January 2015
Effects of Particulate Matter Exposure and Medication Use on Asthmatics
F. SILVERMAN H. R. HOSEIN P. COREY S. HOLTON S. M. TARLO The Gage Research Institute and Depathents of Medicine, Preventive Medicine and Biostatistks U n M i of Toronto Toronto, Ontario Canada
ABSTRACT. The health risk associated with low-lewl air pollution exposure is still uncertain, The association between exposure and pulmonary function was assessed with penona1 sampling. Small, portable multipollutant samplers wece used to assess personal e x p sure to rtkulate matter. Thirty-six asthmatic subjects participated in the study for up to 2 0 d i n bh summer (n = 10 d) and winter (n = 10 d); pulmonary function was assessed at the beginning and end of each sampling day, and medication use was recorded. A
within-individual longitudinal analysis of the relationship between pulmonary function and particulate matter reve;lkd an effect of season. In winter, pulmonary function i d as particulateexpowre i n m a d , which was explained by a confoundingeffect of medication use. TherPfore, in addition to exporurp, season of the year and medication use are facton that must be considered.
STUDIES conducted to determine health effects of air pollution exposure, particularly at low levels, are often inconclusive because of limitations in assessments of both exposure and response.' Until recently, estimates of exposure have relied upon measurements made at fixed outdoor sites that were usually oriented for source control purposes. It is now recognized that not only are there variations in pollutant levels horizontally and vertically, but that the indoor environment can be vastly different from the outdoor environment.'*' Thus, the actual exposures of individuals or populations may JsnwrylFebrusry1992 [Vd. 47 (No. l)]
not be represented adequately by one or more tixed outdoor sites.' Definitions of populations with respect to differences in diagnostic criteria, health status, measures of sensitivity, and objectives measures (e.g., pulmonary function) are either not clear, not uniform, or absent. We attempted to address these issues by designing a study in which the following were used: a well-defined group of asthmatic subjects, objective (pulmonary function) and subjective (symptoms) measures of response, and personal air pollution exposure measurements. 51
Downloaded by [New York University] at 16:46 09 January 2015
Methods Personal sampling for particulate matter was conducted in two groups of asthmatics while they conducted their daily activities. The subjects carried personal samplers for a 6- to 8-h period, which commenced between 8:OO and 9:OO A.M. and ended between 3:OO and 5:OO P.M. Each subject was sampled for up to 20 d (10 d in the winter or heating season and 10 d in the summer or nonheating season). On each day, pulmonary function (spirometry) was obtained in the morning when the sampler was switched on and at the end of the sampling period during late afternoon. Selection of subjects. In the first and second study, 17 subjects (Study 1) and 19 subjects (Study 2) were selected from a pool of approximately 800 asthmatics in the patient population of an Asthma Clinic at The Gage Research Institute in Toronto, Canada, a tertiary referral center for patients with asthma. The patient population is weighted with patients who have more severe asthma and who tend to have a greater frequency of symptoms5; these patients might be more sensitive to irritant pollutants than asthmatics who have infrequent symptoms. The certainty of the diagnosis of asthma in patients who attend the Asthma Clinic is established with uniform criteria that are based on history consistent with intermittent diffuse airways obstruction, physical examination, pulmonary function tests, and at least 15% reversibility of airflow limitation after inhalation of salbutamol, a bronchodilator. Patients were selected if they had a diagnosis of asthma and if they experienced wheezing at least a few times a week, as recorded during their most recent visit to the clinic and verified by a preliminary questionnaire. Primary patient care was conducted by the patients' physicians. Medications were not controlled but their use was recorded in a daily diary. Exposure. Subjects carried a portable, personal multipollutant sampler, which was used to measure exposure to sulfur dioxide, nitrogen dioxide, and to particulate matter of 2 particle size fractions. Only the particulate matter results are presented in this report. The personal sampler was worn either on a shoulder strap or on a belt around the waist, and the sampling probe was held in the vicinity of the breathing zone with lapel clips. The sampler was developed at The Gage Institute,6 and it was designed to be portable, lightweight, and quiet. The sampling system was powered by a rechargeable battery and consisted of a pump, a filter assembly with Teflon fabric of 1 p pore size that effectively collected submicronic particulate matter, and two impingers, each containing the appropriate absorbing reagents for nitrogen dioxide and sulfur dioxide, respectively, The samplers were prepared and calibrated for flow in the laboratory each day before they were taken into the field for use. At the start of the sampling period, the air flow was recorded and the timer started. The subjects were instructed on the proper care and use of the personal samplers. At the end of the sampling period,the flows and elapsed times of each sampler were recorded. The filters were dismounted from the sam52
pler case and stored flat in small, covered Petri dishes until conditioning and weighing could be completed. Calibration and quality-control procedures have been reported previou~ly.~~~~' In Study 1, the flow capability of the pump (0.9 Ilmin) and the air inlet dimensions allowed us to collect particulates up to approximately 25 p in size. In Study 2, we increased the flow rate to 1.7 I/min, which allowed use of a 10-mm nylon cyclone assembly that effectively collected particulate matter in the respirable range (i.e., < 10 p).' Medications. The subjects kept daily records of their clinical status and activities in a diary. In Study 2, use of medication for control of asthma was recorded and included number of tablets, capsules or inhalations per 24 h of oral and inhaled bronchodilators, and oral and inhaled corticosteroids. In response to the varied medication regimes taken by the study patients, a drug score was developed that used a weighted combination of dose equivalents from three classes of drugs: (1) xanthines, (2) corticosteroids, and (3) agonists. Consensus was obtained among three asthma physicians about the amount of each drug within the three drug classes -xanthines, agonists, and steroids-that would give approximately an equivalent effect. For example, if a patient who used only low-dose beclomethasone (an inhaled corticosteroid, two puffs four times a day) were to instead use only salbutarnol, an inhaled agonist, two puffs eight times a day might be required. Therefore, two equivalent units of an inhaled bronchodilator were weighted the same as one equivalent unit of inhaled steroid. These unit equivalents of the drugs used in each of the three drug classes were summed for each patient to derive the patient's asthma medication score (AMS). Empirical drug scores were also used by Burns et al.' Pulmonary function. A wedge-balloon spirometer was used at the beginning and end of each monitoring period to test the subjects' lung function. Measurements included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV,,,), and forced expiratory flow during the middle half of a maximum expiratory maneuver (FEF,5-,5,c). The tests were administered according to standard recommended procedures." Data analysis. All data were verified, coded, and keypunched. The University of Toronto computer and the SAS statistical package" were used for data management and statistical analyses. Data were included in the analysis if they met the following criteria: (a) on a given day, all of the mean pulmonary function (mean FVC, mean FEVl.o, mean FEF25-75%VC) and particulate measurements were available for an individual; and (b) each person contributed at least two sets of observations per season. Analysis of variance was used to analyze data. A further analysis involved the calculation of slopes for each subject from the line of best fit that related the daily mean (of the morning and afternoon values) of each pulmonary function variable (FVC, FEV,., FEFzs-7snvc) with the particulate exposure for the corresponding day, over all the days of monitoring. Slopes were o b tained separately for each of the pulmonary function Archives of Environmental Health
was expected because the aerodynamic diameter of particles collected was smaller; however, mean values were again the same for the two seasons. The mean AMS was similar for summer and winter. The mean pulmonary function was slightly higher in the summer. Analysis of variance of the joint effects of season, daily particulate matter concentration, and daily mean slopes of FVC, FEV,.o, and FEF2S75XVC are shown in Table 3. During Study 1, the seasonal effect approached sta-09) for only the daily mean tistical significance (p FEF2575XVC.There was, however, a significant seasonal effect (p < .04)in Study 2 for all three of the pulmonary function variables, i.e., FVC, FEV,.o, and FEFz,75,Vc. When the data were combined across the two studies (Fishers‘ Method of Combining Information”), a significant (p < .02) seasonal effect was noted for FEV,, and FEFz,!5,vF. There was a tendency for the slopes to be negative in the summer and positive in winter.
variables and for each of the two particulate fractions. If an increase in pollutant exposure for a given individual were to cause pulmonary function to decrease, the relationship between daily mean pulmonary function and daify particulate exposure would be expected to have a negative slope.
Results
-
The subjects in Studies 1 and 2 were similar with respect to age, height, and weight, and the ratio of females to males was approximately 3:l (Table 1). There were no significant differences in mean pulmonary function (p > .05) between measurements taken in summer and winter (Table 2). In Study 1, the mean particulate levels recorded by the personal sampler were the same in summer and winter. In Study 2, the mean particulate values were lower than in Study 1, which
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Table 1.-Characteristics of SubSex
Study 1 (n Study 2 (n Overall (n
--
17) 19)
Age (y)
Male
Female
x f SD
Height (cm) X f SD
Weight (@ X f SD
5 4
12 15 22
5 O f 15 48 f 14 48f 14
165 f 9
65 f 11 65 f 11 65 f 11
a
30)*
im f a
167 f 9
*There were 6 subjects who participated in both studies. I
Table Z.--Seraonal
Variation in Pulmonay Function, Palthlate Exposurer, and Drug Score Study 1 & f SD)
-
-
Summer (n 17)
I
Winter (n 17)
P values.
Pulmonary function
Fvc (1)
FEV1.o (1) FEF~~J~,v,:(11s) Particulate PS,-personal (rs/m3)
3.14 f 0.99 2.18 0.84 1.65 f 1.11 108.5 f 31.0
I
Study 2 &
-
Summer (n 19)
januay/Februay 1992 [Vd. 47 (No. l)]
3.12 f 0.91 2.11 f 0.74 1.49 f 0.94 108.9 f 36.5
.% .a7 .65 .97
SD)
-
Winter (n 19)
P values
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cations. Cold air, specifically cold dry air, is a potent trigger of bronchoconstriction in almost all asthmatics. Common advice given to asthmatics is to take an extra dose of their bronchodilator before leaving their home to go outside during the winter. It is possible that particulate levels may have been lower on cold dry days and higher on slightly warmer or more humid days when the negative airway effects of the cold were a b sent. Thus, any negative airway effects of the particulates may have been offset by the absence of the cold dry air effects, and may have been further offset by use of prophylactic bronchodilators, which might have led to a paradoxical increase in pulmonary function. Total AMS was not significantly different in the winter and summer, which probably reflects the many other triggering factors in asthma, some of which (pollen, fungal spores, exercise) are likely to be less important factors during the winter. Another possible explanation would be an increased drug intake by patients on days that exposure to higher particulate concentrations occurred, which would tend to reduce the adverse effects of exposure. However, in both summer and winter, there was no evidence within individuals of a relationship between the drug index and particulate levels (p > .8). The independent effects of season or climatic factors have been shown previously,"" as have interactive effects of season and air quality,17 but the possible
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Study 2 data were analyzed, including the effect of medication and particulate exposure and season (Table 4). There was a significant positive relationship during the winter between daily drug intake and the corresponding daily mean pulmonary function, and a significant positive relationship existed between pulmonary function and daily particulate exposure. The results of analyses of variance for winter data, which, in addition to particulate exposure, drug intake, and patient identification, included an interaction term between drug intake and particulate exposure are shown in Table 5. A statistically significant positive interaction between drug intake and particulate exposure was found for daily mean pulmonary function (FVC, FEV,,o, and FEF,,7,%Vc) during the winter. This analysis also resulted in negative, but not significant, coefficients between particulate matter and pulmonary function.
Discussion The data suggest that there was a seasonal difference with respect to relationships between pulmonary function and exposure to particulate matter. In summer, there was a tendency for pulmonary function to decrease as exposure increased, i.e., an adverse effect of particulates on the lung. However, in winter, the o p have been the effect of cold air and consequent medi-
Table 3.--slopes of Daily Mean Pulmonary Function and Daily Personal Particulate Exposures, by Season
-
-
Study 1 (n 17) Slope* Summer Winter
Pulmonary function Fvc (1) FEVl.0 (1) FEF,5_75,vc
- 0.46 - 0.78 (I&
-2.03
Study 2 (n 19)
Slope
Pt value
Summer
Winter
Pt value
P* overall
.54 .26 .09
- 0.65 -1.65 -1.13
2.58 2.83 4.40
.04 .01 .03
.10 .02 .02
0.06 0.18 -0.10
*Mean slopes of the relationships between each subject's daily mean pulmonary function and daily mean personal particulate exposure multiplied by 1 OOO. tp values associated with a two-way analysis of variance of the slopes; factors are season and individual. *Fisher's method of combining information. I
I
I
I
Table 4.-Effects (Study 2)
of Particulate E x p u r e and Medication Use on Pulmonary Function
Pulmonary function
Particulate Coefficient. p t
Summer
Fvc (1) FEVl.0
(1)
FEF,5_x,%vc
(115)
-1.02 -1.10 -1.47
.13 .12 .15
AMS Coefficient
p
0.98 1.87 2.86
.51 .24 .22
Winter Particulate AMS Coefficient p Coefficient 2.37 2.35 4.35
.025 .024
.OM
8.09 9.35 6.89
p
.OOO1 .OOO1 .OO08
*Regression coefficient-l/pg . m3 and VAMS unit. tp values related to individual personal particulate exposure and AMS (asthma medication score).
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Archives of Environmental Health
Tabk 5.-Effict of Inttmctm ' &(wcm Particulate E x p o w ~ eand Mediation Use on Pulmonary FuncuOn in Winter (Study 2) Particulate
Pulmonary function ~~~~
Coefficient*
Particulate x AM%
AMS pt
Coefficient
p
Coefficient
P
3.16 5.69 0.71
.17 .01 .84
0.10
.01 .05 .03
~~~
PJC (1) FEVl.0 (1) FEF2!5-75%VC
(Ik)
-1.21 -0.31 -0.15
.a .85 .95
0.08 0.13
-
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*Regression coefficient--I/# maand I/AMS unit. tp values related to individual personal particulate exposure, AMS, and interaction of particulate and AMS. $Interaction of particulate and AMS.
posite occurred: pulmonary function increased as exposure increased, a tendency that appeared to be stronger in Study 2. A possible explanation for the paradoxical increase in pulmonary function as particulate exposure increased during the winter months might mitigating influence of drug intake on pulmonary function response has not been documented. Consistent and statistically significant positive relationships were found between the drug index and the three pulmonary functions, i.e., pulmonary function was better on days when higher drug intake occurred. Adding the interaction term to the regression analysis of the effects of drug index and particulates on pulmonary function resulted in relationships that were more understandable. Although not statistically significant, the relationship between particulate level and pulmonary function was, in all cases, negative. Finally, the significant positive interaction suggests that the adverse effea of particulates was diminished by an increased drug intake. The difficulty in establishing an effect of particulate matter on asthmatics' lung function has been identified in this analysis, i.e., the confounding effect of drug use masked the negative effect of particulate matter exposure in asthmatics. However, the data suggest that drug intake by patients who participated in the study ameliorated the potential negative effects of particulate exposure. The composite asthma drug score was derived from empirical weightings given to three classes of drugs: (1) steroids, (2) xanthines, and (3) & agonists. Although these medications have different actions and cannot be compared precisely, the weightings used reflect the prescribed use by the physicians who treated these patients, both for daily maintenance and for any fluctuations in asthma symptoms. Therefore, the type(s) and dosage of medications used were variable, both within and between individuals. Because the functional status of the airways, as assessed by tests of pulmonary function, are in part reflective of the total medication regime, a composite drug score-although empiricalprovides a better index of airway function than any one drug class alone. In previous studies in which the health effects of air pollution exposure were not evident or were minimal, january/Fcbruary 1992 [Vd. 47 (No. l)]
it is possible that the confounding effects of season and drug intake may have played a role. Our study showed that, in at least one group of a sensitive population, drug intake was an important factor in explaining the effects of air pollution on pulmonary response. * * * * * * * * I
We wish to acknowledge the support of the Ministry of the Environment of Ontario (through its grant program and the assistance and cooperation of its staff), Health and Welfare Canada, and the World Health OrganizationlUnited Nations Environment Program. We are grateful to the staff of The Gage Research Institute for their dedication and our volunteer subjects for their cooperation. We also appreciate the assistance of Dr. A. Leznoff and Dr. G. Davies in the mation of the asthma medication score. Requests for reprints should be sent to: F. Silverman, Ph.D., The Gage Research Institute, 223 College Street, Toronto, Ontario Canada M5T 1R4. I * * * * * * * * *
Refcrrncer 1. Bouhuys A, Beck GJ, Schoenber J. Do present levels of air pollution outdoors affect respiratory health? Nature 1978; 276 466-71. 2. Silverman F, Mintz S, Olver P, et al. Human expourre to sol, NO2,and suspended particulate matter in Toronto, Canada. Pub lished under the joint sponsorship of the United Nations Environmental Programme and the World Health O1.ganization. Geneva, Switzerland: 1982, EFP/82.38. 3. Hosein HR, Corey P. Domestic air pollution and respiratory function in a group of housewives. Can J Public Health 1987; 7 7 44-50. 4. Hosein HR, Mitchell C, Bouhuys A. Daily variation in air q u a l i . Arch Environ Health 1977; 32:1420. 5. Langlois PH. Factors associated with the severity at presentation and prognosis of asthma in clinic patients as assessed by pulmonary function. Master of science thesis. University of Toronto, Ontario Canada: Department of Community Health, School of Graduate Studies, 1984. 6. Mintz S, Hosein HR, Batten B, Silverman F. A personal sampler for three respiratory irritants. JAPCA 1982; 32:106869. 7. Silverman F, Mink S, Hosein R, Corey P. To investigate and report on the health effectsof ambient air pollution on asthmatics. 1982. Report submitted to the Health and Welfare Canada, Environmental Health Directorate, Ottawa, Canada. 8. Fletcher RA. A review of personalfportable monitors and samplers for airborne particles. JAPCA 1984; M1014. 9. Burns RBP, Brandon ML, Haddad ZH, et al. Factorial rating system for comparative efficacy of antiasthmatic medication: a
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exacerbation of chronic bronchitis. Atmos Environ 1970; 4 453-68. 15. Emerson P. Air pollution, atmospheric conditions and chronic obstructive airways. J Occup Med 1973; 15(8):835-38. 16. Skoogh BE, Simonsson BC, Berggren A. Climate and environment change in patients with chronic airway obstruction. Arch Environ Health 1976 1:15-20. 17. HolbergCJ, O’Roavke MK, Lebowitz MD. Multivariate analysis of ambient environmental factors and respiratory effects. Int J Epidemiol 1987; 16(3):399-410.
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multicentric study report. J Asthma 1983; 20105-13. 10. ATS Statement-Snowbird Workshop on standardization of spirometry. Am Rev Respir Dis 1979; 19831-38. 1 1 . Statkjtical Analysis System. SAS users guide. Cary, North Carolina: SAS Institute, 1979. 12. Fisher RA. The design of experiments. New York: Hafnen Press, 1971. 13. Spicer WS, Kerr DH. Effect of the environment on respiratory function in males. Arch Environ Health 1976; 21:635-42. 14. Gregory J. The influence of climate and atmospheric pollution on
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