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Pulmonary function responses of older men and women to NO2
ENVIRONMENTAL RESEARCH 44, 206-212 (1987)
Pulmonary Function Responses of Older Men and Women to NO2 D. M. DRECHSLER-PARKS, 1 J. F. BEDI, AND S. M. HORVATH 2 Institute of Environmental Stress, University of California, Santa Barbara, California 93106 Received December, 1986 The pulmonary function of eight men and eight women (51 to 76 years of age), all nonsmokers, was measured before and after 2-hr exposures to filtered air (FA) and 0.60 ppm nitrogen dioxide (NO2). The subjects alternated 20-rain periods of rest and 20-rain periods of cycle ergometer exercise at a work load predetermined to elicit a ventilatory minute volume (VE) of approximately 25 liter/min. Functional residual capacity was determined pre- and postexposure. Forced vital capacity was determined preexposure and 5 min after each exercise period. Vu was measured during the last 2 min of each exercise period, and heart rate was monitored throughout each exposure. The pulmonary function data were evaluated as the percentage change from pre- to postexposure to partially remove the effect of differences between men and women in absolute lung volume. There were no statistically significant (P > 0.05) differences between the responses of men and women to FA or NO2 exposure. There were no significant (P > 0.05) changes in any variable consequent to FA or NO2 exposure. Our older subjects had responses to NO 2 exposure similar to those of young adults, suggesting that, at least for healthy people, exposure to 0.60 ppm NO2 has little effect. © 1987AcademicPress, Inc.
INTRODUCTION The U.S. Environmental Protection Agency set the current nitrogen dioxide (NO2) standard at 0.05 ppm for 24 hr. The acute exposure studies which were evaluated in the NO2 criteria document (U.S. EPA, 1982), on which the current standard was based, presented data primarily on young men. At the time the NO2 criteria document was prepared, there was insufficient information available on the responses of most other subpopulations to include them in the standard regulating process. Several epidemiological studies (Shy et al., 1970; Kagawa et al., 1976; Speizer et al. 1980) have been reported suggesting a relationship between ambient NO2 exposure and respiratory dysfunction, but clear-cut evidence of changes in pulmonary function at concentrations of NO2 below 1 ppm has been lacking (Horvath, 1980). The findings of these epidemiological studies present some difficulties for evaluation because of uncertainties in assessing the contributions of other environmental factors, such as particulates, other ambient pollutants, air temperature, and relative humidity, to the observed responses. Present peak ambient concentrations of NOz are less than 1 ppm. Studies of the pulmonary function responses of young men (18 to 30 years of age) to acute (2-4 t Dr. Drechsler-Parks was a recipient of a postdoctoral fellowship from the Health Effects Institute. 2 To whom correspondence and reprint requests should be addressed. 206 0013-9351/87 $3.00 Copyright© 1987by AcademicPress, Inc. All rightsof reproductionin any formreserved.
207
O L D E R A D U L T S ' R E S P O N S E TO NO2 TABLE 1 CHARACTERIZATION OF SUBJECTS Age (year)
Height (cm)
Weight (kg)
BSA (m2)
FVC (liter)
% Pred. FVC
FEV1.0 (liter)
% Pred. FEV1.0
X SD Range
61.2 6.2 51-69
177.9 6.7 171.4-190.4
78.5 5.1 70.7-83.8
1.96 0.08 1.87-2.13
4.97 0.53 4.41-6.17
107 5 99-117
3.81 0.570 3.13-4.96
117 11 106-138
Women X SD Range
64.5 6.3 56-76
163.1 4.8 155.7-170.5
60.8 9.8 45.6-77.8
1.64 0.15 1.42-1.90
3.11 0.49 2.59-3.78
104 13 84-123
2.43 0.41 2.00-2.92
112 17 86-137
Men
hr) exposure to less than 1 ppm N O 2 have found no significant effects (e.g., Folinsbee et al., 1978; Kerr et al., 1979; Kulle, 1982). However, several recent studies of the responses of adult asthmatics and patients with chronic obstructive pulmonary disease (who were generally older adults) to acute exposure to ambient concentrations of N O 2 have suggested that at least some of these patients may be more responsive to N O 2 than healthy persons (Bauer et al., 1984, 1986), opening the possibility that other subpopulations may also be at risk of adverse responses upon exposure to ambient concentrations of NO2. Other studies (Hazucha et al., 1983; Kleinman et al., 1983) have found no increased responsiveness to NO 2 in asthmatics. The paucity of data available on the responses of older adults to air pollutants in, general, along with the observation that some patients with chronic obstructive pulmonary disease (COPD) may be sensitive to ambient concentrations of NO2, raises concern as to whether the observed responses were due to the age of the COPD patients or to their health status. A study of the pulmonary function responses of a group of healthy older men and women to an acute N O 2 challenge would provide information useful for evaluating the responsiveness to N O 2 of healthy older individuals.
METHODS Sixteen healthy nonsmokers (eight men and eight women), between 51 and 76 years of age, volunteered to participate in this pilot study (Table 1). 3 Each potential subject was screened by medical history, resting 12-lead electrocardiogram, a battery of clinical pulmonary function tests, and a submaximal bicycle exercise test. The subjects participated in two 2-hr experiments, which were given in random order and were separated by at least 1 week: (1) filtered air (FA), and (2) 0.60 ppm NO2. The exposures were carried out in a 1.75 x 1.75 x 2.24-m double-walled acrylic chamber. Inlet air was chemically and mechanically filtered prior to entering the chamber and was exhausted to the roof. The chamber air turnover time 3 T h e nature and purpose of the study and the risks involved were explained verbally and given on a written form to each subject prior to his or her voluntary c o n s e n t to participate. T h e protocol and procedures for this study have been approved by the C o m m i t t e e on Activities Involving H u m a n Subjects, of the University of California, Santa Barbara.
208
DRECHSLER-PARK BEDI, S , AND HORVATH
was approximately 2.5 min. The mean (+_ SD) dry bulb temperatures, relative humidities, Wet Bulb Globe Temperatures (WBGT = 0.7 Twet bulb + 0.3 Tdry bulb or globe), and N O 2 concentrations were 23.6 + 1.1°C, 53 _-_ 22%, 19.0 +_ 2.3°C, and 0.0 ppm NOz for the FA exposure, and 23.8 + 1.2°C, 54 _+ 21%, 18.9 +_ 2.2°C, and 0.603 + 0.014 ppm NO 2 for the N O 2 exposure. The subjects alternated 20-rain periods of rest (n = 3) and 20-rain periods of exercise (n = 3) on a cycle ergometer (Monark) at a work load sufficient to induce a ventilatory minute volume (VE) of approximately 25 liter/min (BTPS). The appropriate work load for each subject was determined in a practice session prior to the first experiment, and confirmed during each exercise period to ensure achievement of the target ventilation. Functional residual capacity (FRC) was determined prior to and immediately after each exposure by a helium dilution method on a 13.5-liter Benedict-Roth type spirometer (W. E. Collins, Braintree, MA). Three forced vital capacity (FVC) maneuvers, performed with the subject standing, were recorded before exposure began and 5 rain after each exercise period on a rolling seal spirometer (Model 822, Ohio Medical, San Leandro, CA) which was interfaced to a microprocessor (Spirotech 300, Spirotech, Inc., Atlanta, GA) which analyzed, corrected to BTPS, and printed out the results of each test. The following were calculated from the FVC recordings: forced expiratory volume in 1 and 3 sec (FEV1.0, FEV3.0), forced expiratory flow rate between 25 and 75% of vital capacity (FEF25-75%), and forced expiratory flow rate at 25% of vital capacity (FEF25%). Nitrogen dioxide (1% NOz in nitrogen) was introduced to the chamber through Teflon tubing via the chamber air intake duct. The chamber NO z concentration was continuously monitored by a chemiluminescent N O 2 analyzer (Thermo-Electron, Model 14B/E, Hopkinton, MA) which was periodically calibrated by the California Air Resources Board (El Monte, CA). Following each exposure the subjects completed a written questionnaire on which they were asked to indicate whether or not they experienced each of a list of symptoms commonly associated with exercise and/or oxidant pollutant exposure. Symptoms were not rated for severity. Data were analyzed by a three-factor analysis of variance (one grouping factor - - s e x ; two repeated measures factors--time period and exposure condition). Significant factors (P < 0.01) were further analyzed by the Tukey multiple comparison procedure to determine significant factor interactions. The data were analyzed as the percentage change from pre- to postexposure to reduce effects of differences between men and women in absolute lung size. The symptom data were analyzed by the Cochran Q test (Siegel, 1956). RESULTS
There was no significant (P > 0.05) difference between the responses of men and women when compared on a percentage change basis. Neither FA nor 0.603ppm NOz exposure induced significant effects on any pulmonary function (Table 2). The absolute volume changes, on an individual basis (Table 3), ranged from
209
OLDER ADULTS' RESPONSE TO NO 2 TABLE 2 MEAN PERCENTAGE CHANGES IN PULMONARY FUNCTIONS FROM PRE- TO POSTEXPOSURE
FA NOz
Mean SE Mean SE
FVC (liter)
FEV-1 (liter)
FEV-3 (liter)
FEF25-75% (liter/sec)
FEF25% (liter/sec)
+1.5 1.2 +1.8 1.0
+1.4 1.6 0.0 1.1
+1.1 1.0 +2.0 0.9
+2.3 3.7 +2.0 3.4
+5.9 5.8 +1.0 4.3
- 0 . 1 8 to + 0.33 liter for FVC, from - 0 . 2 0 to +0.17 liter for FEVL0, and from - 0.45 to + 0.39 liter for FEF25-75%. Table 4 presents the total number of subjects and the number of men and women reporting each of a list of symptoms commonly associated with exercise and oxidant pollutant exposure. The Cochran Q test found no significant (P > 0.05) difference in the symptom responses to the FA and NO 2 exposures. Table 4 also compares the symptom responses of the subjects in the present study with a group of young men and women we studied under the same protocol as that for the present study. DISCUSSION Studies of the effects of acute exposures to less than 1 ppm NOz on healthy young men have suggested that only minimal responses occur. We were unable to find published data on the responses of healthy older men and women to acute N O 2 exposure. The minimal data available (Folinsbee et al., 1985; Schlenker and Jaeger, 1980) on the effect of aging on pulmonary function responses to ozone (O3), or to 03 + sulfur dioxide (SO2) suggest that healthy older adults may be less responsive than young adults, although the implications of the 03 and 03 + SO2 data for N O 2 exposure are unknown. Compared to 03 and SO2, NOz is relatively water insoluble, enabling it to penetrate to more peripheral airways than either 03 or SOz. Bauer et al. (1986) examined the responses of eight patients (47-63 years of age) with COPD to exposure to 0.30 ppm NO z for 4 hr, which included three 7-min periods of cycle ergometer exercise. There were no changes in any measure of pulmonary function following air exposure. Exposure to NO2, however, induced mild airway impairment as evidenced by small but consistent decrements in FVC and FEV1.0 after 4 hr of NO 2 exposure, contrary to our finding of no changes in FVC and FEV1.0. Since Bauer et al. (1986) studied only COPD patients, it is unclear whether the observed responses were due to the age of the subjects or to their COPD status. Another possible reason why our results are different from those of Bauer et al, (1986) is the different exposure protocols employed. Bauer et al. exposed their COPD patients to N O 2 for 4 hr, compared to our 2-hr exposures, although our NO2 concentration (0.603 ppm) was twice that of Bauer et al. The older subjects (Table 4) reported fewer symptoms (31) compared to young subjects (42) we had studied with the same protocol. The only major difference in
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TABLE 4 NUMBEROF SUBJECTSREPORTINGSYMPTOMSFOLLOWINGNO2 EXPOSUREPRESENTSTUDYON OLDER MEN ANDWOMENCOMPAREDTO ANDYOUNGMEN AND WOMEN Older
Young
Symptom
Men
Women
Total
Men
Women
Total
Unusual odor Nausea Cough Sputum Substernal soreness Muscle soreness Sore throat Shortness of breath Nasal discharge/stuffiness Wheezing Tightness in chest Dizziness Fatigue Eye irritation Headache Other Total
1 1 2 2 1 1 2 0 2 0 1 1 3 1 1 0 19
0 1 1 0 0 2 1 0 1 0 0 1 3 0 1 1 12
1 2 3 2 1 3 3 0 3 0 1 2 6 1 2 1 31
3 1 0 1 0 0 1 1 1 1 0 1 3 0 0 1 14
4 0 3 3 2 1 2 0 3 0 2 1 5 1 1 0 28
7 1 3 4 2 1 3 1 4 1 2 2 8 1 1 1 42
Note. n = 8 subjects/age-sex group. r e p o r t i n g f r e q u e n c y b e t w e e n the t w o age g r o u p s in r e p o r t i n g f r e q u e n c y was for the s y m p t o m " u n u s u a l o d o r , " with m o r e y o u n g s u b j e c t s (7) n o t i c i n g the o d o r o f N O 2 t h a n o l d e r s u b j e c t s (1). T h e o t h e r r e p o r t e d s y m p t o m s w e r e a m i x o f r e s p i r a t o r y a n d e x e r c i s e - r e l a t e d c o m p l a i n t s with n o p a t t e r n w h i c h c o u l d b e a t t r i b u t e d to NO 2 exposure. O v e r a l l , o u r r e s u l t s suggest that e x p o s u r e of healthy, o l d e r m e n a n d w o m e n to 0.60 p p m N O 2 has n o statistically significant effects o n p u l m o n a r y f u n c t i o n , alt h o u g h the p a u c i t y of s i m i l a r d a t a o n o t h e r h e a l t h y o l d e r i n d i v i d u a l s l e a v e s o u r c o n c l u s i o n s as to the r e s p o n s i v e n e s s o f h e a l t h y o l d e r m e n a n d w o m e n to N O 2 to b e c o n f i r m e d . F u r t h e r i n v e s t i g a t i o n into the r e s p o n s e s o f o l d e r m e n a n d w o m e n to N O 2 is w a r r a n t e d , as well as f u r t h e r i n v e s t i g a t i o n into the r e s p o n s e s o b s e r v e d b y B a u e r et al. (1986) in p a t i e n t s with C O P D .
ACKNOWLEDGMENTS Research described in this article was supported in part by the Health Effects Institute (HEI), an organization that supports the conduct of independent research and is jointly funded by the U.S. Environmental Protection Agency (EPA) and automotive manufacturers, and the California Air Resources Board (CARB). Although the work described in this article has been funded in part by the EPA under Assistance Agreement X808859 with HEI, the contents do not necessarily reflect the views and policies of that agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors gratefully acknowledge the valuable technical assistance of Karl Friedl, Ron Jackson, Nancy Hamme, and Ginny Smith, and the secretarial assistance of Diana Bedi, and the patient and enthusiastic cooperation of our subjects which made this work possible.
212
DRECHSLER-PARKS, BEDI, AND HORVATH
REFERENCES Bauer, M. A., Utell, M. J., Morrow, P. E., Speers, D. M., and Gibb, E R. (1984). 0.30 ppm nitrogen dioxide inhalation potentiates bronchospasm in asthmatics. Amer. Rev. Respir. Dis. 129, A151. Bauer, M. A., Utell, M. J., Smeglin, A. M., Speers, D. M., Gibb, E R., and Morrow, E E. (1986). Effects of low-level nitrogen dioxide on lung function in exercising subjects with chronic obstructive pulmonary disease (COPD). Amer. Rev. Respir. Dis. 133, A215. Drechsler-Parks, D. M., Bedi, J. E, and Horvath, S. M. (1987). Pulmonary function responses of older men and women to ozone exposure. Exp. Gerontol. 22, 91-101. Folinsbee, L. J., Bedi, J. E, and Horvath S. M. (1985). Pulmonary response to threshold levels of sulfur dioxide (1 ppm) and ozone (0.3 ppm). J. Appl. Physiol. 58, 1783-1787. Folinsbee, L. J., Horvath, S. M., Bedi, J. E, and Delehunt, J. C. (1978). Effect of 0.62 ppm N O 2 o n cardiopulmonary function in young male nonsmokers. Environ. Res. 15, 199-205. Gliner, J. A., Horvath, S. M., and Folinsbee, L. J. (1983). Preexposure to low ozone concentrations does not diminish the pulmonary function response on exposure to higher ozone concentrations. Amer. Rev. Respir. Dis. 127, 51-55. Hazucha, M. J., Ginsberg J. E, McDonnell, W. E Haak, E. D., Jr., Pimmel, R. L., Salaam, S. A., House, D. E., and Bromberg, E A. (1983). Effects of 0.1 ppm nitrogen dioxide on airways of normal and asthmatic subjects. J. Appl. Physiol. 54, 730-739. Horvath, S. M. (1980). Nitrogen dioxide, pulmonary function, and respiratory disease. Bull. N.Y. Acad. Med. 56, 835-846. Horvath, S. M., Gliner, J. A., and Folinsbee, L. J. (1981). Adaptation to ozone: Duration of effect. Amer. Rev. Respir. Dis. 123,496-499. Kagawa, J., Toyama, T., and Nakaza, M. (1976). Pulmonary function test in children exposed to air pollution. In "Clinical Implications of Air Pollution Research" (A. J. Finkel, Jr. and W. C. Duel, Eds.), pp. 305-320. Publishing Sciences Group, Acton, MA. Kerr, H. D., Kulle, T. J., McIlhany, M. L., and Swidersky, E (1979). Effect of nitrogen dioxide on pulmonary function in human subjects: An environmental chamber study. Environ. Res. 19, 392-404. Kleinman, M. T., Bailey, R. M., Linn, W. S., Anderson, K. R., Whynot, J. D., Shamoo, D. A., and Hackney, J. D. (1983). Effects of 0.2 ppm nitrogen dioxide on pulmonary function and response to bronchoprovocation in asthmatics. J. Toxicol. Environ. Health 12, 815-826. Kulle, T. J. (1982). Effects of nitrogen dioxide on pulmonary function in normal healthy humans and subjects with asthma and chronic bronchitis. In "Air Pollution by Nitrogen Oxides" (T. Schneider and L. Grant, Eds.), pp. 477-486. Elsevier Scientific, Amsterdam. Schlenker, E., and Jaegar, M. (1980). Airways response of young and elderly subjects to 0.5 ppm SO2 and 0.5 ppm 03. Physiologist 23, 77 (abstract). Shy, C. M., Creason, J. E, Pearlman, M. E., McClain, K., Benson, E, and Young, M. (1970). The Chattanooga school children study: Effects of community exposure to nitrogen dioxide. In Pulmonary Function. J. Air Pollut. Control Assoc. 20, 539-545. Siegel, S. (1956). "Nonparametric Statistics for the Behavioral Sciences." Pp. 161-166. McGrawHill, New York. Speizer, E E., Ferris, B., Jr., Bishop, Y. M. M., and Spengler, J. (1980). Respiratory disease rates and pulmonary function in children associated with N O 2 exposure. Amer. Rev. Respir. Dis. 121, 3-10. U.S. Environmental Protection Agency (1982). "Air Quality Criteria for Oxides of Nitrogen." Environmental Criteria and Assessment Office, Research Triangle Park, NC.
Pulmonary Function Responses of Older Men and Women to NO2 D. M. DRECHSLER-PARKS, 1 J. F. BEDI, AND S. M. HORVATH 2 Institute of Environmental Stress, University of California, Santa Barbara, California 93106 Received December, 1986 The pulmonary function of eight men and eight women (51 to 76 years of age), all nonsmokers, was measured before and after 2-hr exposures to filtered air (FA) and 0.60 ppm nitrogen dioxide (NO2). The subjects alternated 20-rain periods of rest and 20-rain periods of cycle ergometer exercise at a work load predetermined to elicit a ventilatory minute volume (VE) of approximately 25 liter/min. Functional residual capacity was determined pre- and postexposure. Forced vital capacity was determined preexposure and 5 min after each exercise period. Vu was measured during the last 2 min of each exercise period, and heart rate was monitored throughout each exposure. The pulmonary function data were evaluated as the percentage change from pre- to postexposure to partially remove the effect of differences between men and women in absolute lung volume. There were no statistically significant (P > 0.05) differences between the responses of men and women to FA or NO2 exposure. There were no significant (P > 0.05) changes in any variable consequent to FA or NO2 exposure. Our older subjects had responses to NO 2 exposure similar to those of young adults, suggesting that, at least for healthy people, exposure to 0.60 ppm NO2 has little effect. © 1987AcademicPress, Inc.
INTRODUCTION The U.S. Environmental Protection Agency set the current nitrogen dioxide (NO2) standard at 0.05 ppm for 24 hr. The acute exposure studies which were evaluated in the NO2 criteria document (U.S. EPA, 1982), on which the current standard was based, presented data primarily on young men. At the time the NO2 criteria document was prepared, there was insufficient information available on the responses of most other subpopulations to include them in the standard regulating process. Several epidemiological studies (Shy et al., 1970; Kagawa et al., 1976; Speizer et al. 1980) have been reported suggesting a relationship between ambient NO2 exposure and respiratory dysfunction, but clear-cut evidence of changes in pulmonary function at concentrations of NO2 below 1 ppm has been lacking (Horvath, 1980). The findings of these epidemiological studies present some difficulties for evaluation because of uncertainties in assessing the contributions of other environmental factors, such as particulates, other ambient pollutants, air temperature, and relative humidity, to the observed responses. Present peak ambient concentrations of NOz are less than 1 ppm. Studies of the pulmonary function responses of young men (18 to 30 years of age) to acute (2-4 t Dr. Drechsler-Parks was a recipient of a postdoctoral fellowship from the Health Effects Institute. 2 To whom correspondence and reprint requests should be addressed. 206 0013-9351/87 $3.00 Copyright© 1987by AcademicPress, Inc. All rightsof reproductionin any formreserved.
207
O L D E R A D U L T S ' R E S P O N S E TO NO2 TABLE 1 CHARACTERIZATION OF SUBJECTS Age (year)
Height (cm)
Weight (kg)
BSA (m2)
FVC (liter)
% Pred. FVC
FEV1.0 (liter)
% Pred. FEV1.0
X SD Range
61.2 6.2 51-69
177.9 6.7 171.4-190.4
78.5 5.1 70.7-83.8
1.96 0.08 1.87-2.13
4.97 0.53 4.41-6.17
107 5 99-117
3.81 0.570 3.13-4.96
117 11 106-138
Women X SD Range
64.5 6.3 56-76
163.1 4.8 155.7-170.5
60.8 9.8 45.6-77.8
1.64 0.15 1.42-1.90
3.11 0.49 2.59-3.78
104 13 84-123
2.43 0.41 2.00-2.92
112 17 86-137
Men
hr) exposure to less than 1 ppm N O 2 have found no significant effects (e.g., Folinsbee et al., 1978; Kerr et al., 1979; Kulle, 1982). However, several recent studies of the responses of adult asthmatics and patients with chronic obstructive pulmonary disease (who were generally older adults) to acute exposure to ambient concentrations of N O 2 have suggested that at least some of these patients may be more responsive to N O 2 than healthy persons (Bauer et al., 1984, 1986), opening the possibility that other subpopulations may also be at risk of adverse responses upon exposure to ambient concentrations of NO2. Other studies (Hazucha et al., 1983; Kleinman et al., 1983) have found no increased responsiveness to NO 2 in asthmatics. The paucity of data available on the responses of older adults to air pollutants in, general, along with the observation that some patients with chronic obstructive pulmonary disease (COPD) may be sensitive to ambient concentrations of NO2, raises concern as to whether the observed responses were due to the age of the COPD patients or to their health status. A study of the pulmonary function responses of a group of healthy older men and women to an acute N O 2 challenge would provide information useful for evaluating the responsiveness to N O 2 of healthy older individuals.
METHODS Sixteen healthy nonsmokers (eight men and eight women), between 51 and 76 years of age, volunteered to participate in this pilot study (Table 1). 3 Each potential subject was screened by medical history, resting 12-lead electrocardiogram, a battery of clinical pulmonary function tests, and a submaximal bicycle exercise test. The subjects participated in two 2-hr experiments, which were given in random order and were separated by at least 1 week: (1) filtered air (FA), and (2) 0.60 ppm NO2. The exposures were carried out in a 1.75 x 1.75 x 2.24-m double-walled acrylic chamber. Inlet air was chemically and mechanically filtered prior to entering the chamber and was exhausted to the roof. The chamber air turnover time 3 T h e nature and purpose of the study and the risks involved were explained verbally and given on a written form to each subject prior to his or her voluntary c o n s e n t to participate. T h e protocol and procedures for this study have been approved by the C o m m i t t e e on Activities Involving H u m a n Subjects, of the University of California, Santa Barbara.
208
DRECHSLER-PARK BEDI, S , AND HORVATH
was approximately 2.5 min. The mean (+_ SD) dry bulb temperatures, relative humidities, Wet Bulb Globe Temperatures (WBGT = 0.7 Twet bulb + 0.3 Tdry bulb or globe), and N O 2 concentrations were 23.6 + 1.1°C, 53 _-_ 22%, 19.0 +_ 2.3°C, and 0.0 ppm NOz for the FA exposure, and 23.8 + 1.2°C, 54 _+ 21%, 18.9 +_ 2.2°C, and 0.603 + 0.014 ppm NO 2 for the N O 2 exposure. The subjects alternated 20-rain periods of rest (n = 3) and 20-rain periods of exercise (n = 3) on a cycle ergometer (Monark) at a work load sufficient to induce a ventilatory minute volume (VE) of approximately 25 liter/min (BTPS). The appropriate work load for each subject was determined in a practice session prior to the first experiment, and confirmed during each exercise period to ensure achievement of the target ventilation. Functional residual capacity (FRC) was determined prior to and immediately after each exposure by a helium dilution method on a 13.5-liter Benedict-Roth type spirometer (W. E. Collins, Braintree, MA). Three forced vital capacity (FVC) maneuvers, performed with the subject standing, were recorded before exposure began and 5 rain after each exercise period on a rolling seal spirometer (Model 822, Ohio Medical, San Leandro, CA) which was interfaced to a microprocessor (Spirotech 300, Spirotech, Inc., Atlanta, GA) which analyzed, corrected to BTPS, and printed out the results of each test. The following were calculated from the FVC recordings: forced expiratory volume in 1 and 3 sec (FEV1.0, FEV3.0), forced expiratory flow rate between 25 and 75% of vital capacity (FEF25-75%), and forced expiratory flow rate at 25% of vital capacity (FEF25%). Nitrogen dioxide (1% NOz in nitrogen) was introduced to the chamber through Teflon tubing via the chamber air intake duct. The chamber NO z concentration was continuously monitored by a chemiluminescent N O 2 analyzer (Thermo-Electron, Model 14B/E, Hopkinton, MA) which was periodically calibrated by the California Air Resources Board (El Monte, CA). Following each exposure the subjects completed a written questionnaire on which they were asked to indicate whether or not they experienced each of a list of symptoms commonly associated with exercise and/or oxidant pollutant exposure. Symptoms were not rated for severity. Data were analyzed by a three-factor analysis of variance (one grouping factor - - s e x ; two repeated measures factors--time period and exposure condition). Significant factors (P < 0.01) were further analyzed by the Tukey multiple comparison procedure to determine significant factor interactions. The data were analyzed as the percentage change from pre- to postexposure to reduce effects of differences between men and women in absolute lung size. The symptom data were analyzed by the Cochran Q test (Siegel, 1956). RESULTS
There was no significant (P > 0.05) difference between the responses of men and women when compared on a percentage change basis. Neither FA nor 0.603ppm NOz exposure induced significant effects on any pulmonary function (Table 2). The absolute volume changes, on an individual basis (Table 3), ranged from
209
OLDER ADULTS' RESPONSE TO NO 2 TABLE 2 MEAN PERCENTAGE CHANGES IN PULMONARY FUNCTIONS FROM PRE- TO POSTEXPOSURE
FA NOz
Mean SE Mean SE
FVC (liter)
FEV-1 (liter)
FEV-3 (liter)
FEF25-75% (liter/sec)
FEF25% (liter/sec)
+1.5 1.2 +1.8 1.0
+1.4 1.6 0.0 1.1
+1.1 1.0 +2.0 0.9
+2.3 3.7 +2.0 3.4
+5.9 5.8 +1.0 4.3
- 0 . 1 8 to + 0.33 liter for FVC, from - 0 . 2 0 to +0.17 liter for FEVL0, and from - 0.45 to + 0.39 liter for FEF25-75%. Table 4 presents the total number of subjects and the number of men and women reporting each of a list of symptoms commonly associated with exercise and oxidant pollutant exposure. The Cochran Q test found no significant (P > 0.05) difference in the symptom responses to the FA and NO 2 exposures. Table 4 also compares the symptom responses of the subjects in the present study with a group of young men and women we studied under the same protocol as that for the present study. DISCUSSION Studies of the effects of acute exposures to less than 1 ppm NOz on healthy young men have suggested that only minimal responses occur. We were unable to find published data on the responses of healthy older men and women to acute N O 2 exposure. The minimal data available (Folinsbee et al., 1985; Schlenker and Jaeger, 1980) on the effect of aging on pulmonary function responses to ozone (O3), or to 03 + sulfur dioxide (SO2) suggest that healthy older adults may be less responsive than young adults, although the implications of the 03 and 03 + SO2 data for N O 2 exposure are unknown. Compared to 03 and SO2, NOz is relatively water insoluble, enabling it to penetrate to more peripheral airways than either 03 or SOz. Bauer et al. (1986) examined the responses of eight patients (47-63 years of age) with COPD to exposure to 0.30 ppm NO z for 4 hr, which included three 7-min periods of cycle ergometer exercise. There were no changes in any measure of pulmonary function following air exposure. Exposure to NO2, however, induced mild airway impairment as evidenced by small but consistent decrements in FVC and FEV1.0 after 4 hr of NO 2 exposure, contrary to our finding of no changes in FVC and FEV1.0. Since Bauer et al. (1986) studied only COPD patients, it is unclear whether the observed responses were due to the age of the subjects or to their COPD status. Another possible reason why our results are different from those of Bauer et al, (1986) is the different exposure protocols employed. Bauer et al. exposed their COPD patients to N O 2 for 4 hr, compared to our 2-hr exposures, although our NO2 concentration (0.603 ppm) was twice that of Bauer et al. The older subjects (Table 4) reported fewer symptoms (31) compared to young subjects (42) we had studied with the same protocol. The only major difference in
210
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TABLE 4 NUMBEROF SUBJECTSREPORTINGSYMPTOMSFOLLOWINGNO2 EXPOSUREPRESENTSTUDYON OLDER MEN ANDWOMENCOMPAREDTO ANDYOUNGMEN AND WOMEN Older
Young
Symptom
Men
Women
Total
Men
Women
Total
Unusual odor Nausea Cough Sputum Substernal soreness Muscle soreness Sore throat Shortness of breath Nasal discharge/stuffiness Wheezing Tightness in chest Dizziness Fatigue Eye irritation Headache Other Total
1 1 2 2 1 1 2 0 2 0 1 1 3 1 1 0 19
0 1 1 0 0 2 1 0 1 0 0 1 3 0 1 1 12
1 2 3 2 1 3 3 0 3 0 1 2 6 1 2 1 31
3 1 0 1 0 0 1 1 1 1 0 1 3 0 0 1 14
4 0 3 3 2 1 2 0 3 0 2 1 5 1 1 0 28
7 1 3 4 2 1 3 1 4 1 2 2 8 1 1 1 42
Note. n = 8 subjects/age-sex group. r e p o r t i n g f r e q u e n c y b e t w e e n the t w o age g r o u p s in r e p o r t i n g f r e q u e n c y was for the s y m p t o m " u n u s u a l o d o r , " with m o r e y o u n g s u b j e c t s (7) n o t i c i n g the o d o r o f N O 2 t h a n o l d e r s u b j e c t s (1). T h e o t h e r r e p o r t e d s y m p t o m s w e r e a m i x o f r e s p i r a t o r y a n d e x e r c i s e - r e l a t e d c o m p l a i n t s with n o p a t t e r n w h i c h c o u l d b e a t t r i b u t e d to NO 2 exposure. O v e r a l l , o u r r e s u l t s suggest that e x p o s u r e of healthy, o l d e r m e n a n d w o m e n to 0.60 p p m N O 2 has n o statistically significant effects o n p u l m o n a r y f u n c t i o n , alt h o u g h the p a u c i t y of s i m i l a r d a t a o n o t h e r h e a l t h y o l d e r i n d i v i d u a l s l e a v e s o u r c o n c l u s i o n s as to the r e s p o n s i v e n e s s o f h e a l t h y o l d e r m e n a n d w o m e n to N O 2 to b e c o n f i r m e d . F u r t h e r i n v e s t i g a t i o n into the r e s p o n s e s o f o l d e r m e n a n d w o m e n to N O 2 is w a r r a n t e d , as well as f u r t h e r i n v e s t i g a t i o n into the r e s p o n s e s o b s e r v e d b y B a u e r et al. (1986) in p a t i e n t s with C O P D .
ACKNOWLEDGMENTS Research described in this article was supported in part by the Health Effects Institute (HEI), an organization that supports the conduct of independent research and is jointly funded by the U.S. Environmental Protection Agency (EPA) and automotive manufacturers, and the California Air Resources Board (CARB). Although the work described in this article has been funded in part by the EPA under Assistance Agreement X808859 with HEI, the contents do not necessarily reflect the views and policies of that agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The authors gratefully acknowledge the valuable technical assistance of Karl Friedl, Ron Jackson, Nancy Hamme, and Ginny Smith, and the secretarial assistance of Diana Bedi, and the patient and enthusiastic cooperation of our subjects which made this work possible.
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