Human health effects of air pollution.

Over the past three or four decades, there have been important advances in the understanding of the actions, exposure-response characteristics, and mechanisms of action of many common air pollutants. A multidisciplinary approach using epidemiology, animal toxicology, and controlled human exposure studies has contributed to the database. This review will emphasize studies of humans but will also draw on findings from the other disciplines. Air pollutants have been shown to cause responses ranging from reversible changes in respiratory symptoms and lung function, changes in airway reactivity and inflammation, structural remodeling of pulmonary airways, and impairment of pulmonary host defenses, to increased respiratory morbidity and mortality. Quantitative and qualitative understanding of the effects of a small group of air pollutants has advanced considerably, but the understanding is by no means complete, and the breadth of effects of all air pollutants is only partially understood.

Human health effects of exposure to airborne acid.

This paper summarizes and critiques a series of reports on the health effects of acid aerosol exposure, presented at the Symposium on the Health Effects of Acid Aerosols and compares these data to selected previous studies. The role of the two major defenses against acid aerosols, the conversion of acid to the ammonium salts by respiratory ammonia and buffering of acid by airway surface liquid are discussed in relation to airway acid burdens expected from typical inhalation exposures. The roles of particle size and hygroscopicity on airway deposition of aerosol are also included. The major health effects studied were the effects of acid aerosol on mucociliary clearance in healthy individuals and changes in lung function in asthmatics, an important sensitive subpopulation. The broad range of response in asthmatics suggests the need for further study.

Pulmonary response to threshold levels of sulfur dioxide (1.0 ppm) and ozone (0.3 ppm).

We exposed 22 healthy adult nonsmoking male subjects for 2 h to filtered air, 1.0 ppm sulfur dioxide (SO2), 0.3 ppm ozone (O3), or the combination of 1.0 ppm SO2 + 0.3 ppm O3. We hypothesized that exposure to near-threshold concentrations of these pollutants would allow us to observe any interaction between the two pollutants that might have been masked by the more obvious response to the higher concentrations of O3 used in previous studies. Each subject alternated 30-min treadmill exercise with 10-min rest periods for the 2 h. The average exercise ventilation measured during the last 5 min of exercise was 38 1/min (BTPS). Forced expiratory maneuvers were performed before exposure and 5 min after each of the three exercise periods. Maximum voluntary ventilation, He dilution functional residual capacity, thoracic gas volume, and airway resistance were measured before and after the exposure. After O3 exposure alone, forced expiratory measurements (FVC, FEV1.0, and FEF25-75%) were significantly decreased. The combined exposure to SO2 + O3 produced similar but smaller decreases in these measures. There were small but significant differences between the O3 and the O3 + SO2 exposure for FVC, FEV1.0, FEV2.0, FEV3.0, and FEF25-75% at the end of the 2-h exposure. We conclude that, with these pollutant concentrations, there is no additive or synergistic effect of the two pollutants on pulmonary function.

Exercise respiratory pattern in elite cyclists and sedentary subjects.

We investigated the breath-by-breath pattern of ventilatory response to bicycle exercise in seven elite male cyclists (VO2max = 71.7 ml X min-1 X kg-1) and ten sedentary males (VO2max = 47.3 ml X min-1 X kg-1) to analyze differences in breathing patterns between individuals with normal and high exercise ventilations (VE). The mean VEmax of the athletes (ATH) exceeded that of the sedentary subjects (SED) by 34.6% (183 vs 136 l X min-1) and was proportional to the difference in VCO2max between the groups (5.9 vs 4.23 l X min-1). The ATH used an average of 89% of their 15-s maximum voluntary ventilation (MVV) during maximum exercise while SED used only 71%. The ATH had slightly, but not significantly, larger vital capacity (FVC). Both groups used about half of their FVC at maximum tidal volume (VT), VT was 47% and 49% of FVC in ATH and SED, respectively. The ATH achieved the higher VEmax by achieving a greater increase in respiratory frequency (63/min vs 49/min), which was accomplished by significant decreases in both inspiratory (T1) and, more importantly, expiratory (TE) time. There was a tendency for athletes to have a somewhat more regular breathing pattern. Both 1/T1 and mean inspiratory flow (VT/T1) were highly correlated with VE, but there were no differences in these relationships between ATH and SED. Highly-conditioned athletes, therefore, respond to the increased demand for CO2 elimination by utilizing a higher respiratory frequency achieved through a reduction of both inspiratory and expiratory duration, but not by utilizing a larger tidal volume (i.e., as percent FVC) than less fit individuals.

Effects of ozone exposure on lung function in man: a review.

Ozone, an important component of photochemical smog, has a decided impact on lung function in man. In this review, the effects of zone on human lung function are discussed with particular attention to levels which are near the threshold of producing no effect. Attempts to define dose-response relationships and effects on sensitive subject populations are described. The relationship between exercise and ozone toxicity is presented in addition to the potential impact of ambient ozone exposure on athletic performance. Effects of ozone on respiratory symptoms and the interaction of ozone with other pollutants are briefly examined. Considerable attention has been directed at the phenomenon of adaptation to repeated ozone exposure and to possible mechanism of action of ozone.

Persistence of the acute effects of ozone exposure.

Reexposure to ozone 24 h after an initial exposure results in greater decreases in forced expiratory tests of lung function following the second exposure. The purpose of this study was to determine whether this hyperresponsiveness was present earlier than 24 h or persisted beyond 24 h. Four groups of subjects (n = 6,6,7,7) were exposed to 0.25 ppm ozone and then reexposed at 12, 24, 48, or 72 h, respectively. During the 1-h exposures (Ta = 20 degrees C, RH = 70%) all subjects exercised continuously at approximately 65% of their respective peak VO2; VE averaged 63 L X min-1. The decrease in FEV1.0 after the second ozone exposure was significantly larger than that after the first for subjects reexposed at 12 or 24 h; FEV1.0 dropped 12% and 19% in the 12 h group, and 20% and 35% in the 24 h group. Subjects reexposed at 48 or 72 h had FEV1.0 responses which were not significantly different from the first exposure. Delta FEV1.0 on the first and second exposures were significantly correlated (r = 0.59). Symptoms generally paralleled changes in function. We conclude that the hyperresponsiveness to ozone following exposure to 0.25 ppm ozone under the conditions of this study is apparent within 12 h and is not present at 72 h.

Ocular functions and incidence of acute mountain sickness in women at altitude.

The effects of altitude on a series of ocular functions were studied on seven expedition members, all women aged 23-53 years, during the first ascent of the 6798-m peak Brigupanth in the Indian Himalayas. The only consistent change was a decrease in convergence amplitude. The amplitude of accommodation remained stable among the younger climbers, but decreased markedly among the older ones as higher altitudes were reached. There also appeared to be a lessened vascular reactivity to the hypoxia of altitude in the older members. Stereoscopic vision was unimpaired at all altitudes tested and extra-ocular muscle balance remained unaffected in all but two members who had an increase in their baseline phorias. Two of the summit climbers developed retinal hemorrhages. There was an average weight loss of 5.4 kg during the climb, but general health was good. Symptoms of acute mountain sickness were noted infrequently, and there were only moderate changes in the menstrual cycle.

Women at altitude: cardiovascular responses to hypoxia.

Six women mountaineers, 23-43 years of age, participated in a series of physiological tests prior to and during an expedition to Bhrigupanth (6798 m) in the Indian Himalayas. During a three-phase step test at sea level, carrying 0, 4.5, and 9.0 kg backpack weights, oxygen requirements represented 49.5-54.8% VO2 max. Recovery heart rates (HR) at 5-15 s were linearly related to exercise HR. At 4250 m, 5-15 s postexercise HR's were significantly higher than those at SL but returned to SL values after 3 min of rest. At 5000 m, HR's remained higher than those at SL throughout recovery. On returning to 4250 m after 3 weeks at higher altitudes, all postexercise HR's were back to SL levels. Supine HR's, higher at altitude than at SL during the ascent, returned to SL rates on return to 4250 m. Hemoglobin and hematocrit increased from 13.7 mg% and 42.4% at SL to 16.4 mg% and 52.6% after the climb. Resting blood pressure was significantly elevated at 4250 m during ascent but returned to SL values on the descent. During the cold pressor test, systolic pressure was unaffected by altitude; diastolic pressure increased less at altitude. While HR was unchanged at SL, a significant increase in HR was observed in postclimb CPT tests, even though perceived discomfort decreased.

Response of women mountaineers to maximal exercise during hypoxia.

Eight members of the American Women's Himalayan Expedition, ranging in age from 20-49, performed maximal exercise on a treadmill under normoxic and acute hypoxic (12.58% O2) conditions. Normoxic values for VO2 max were above average for all subjects and did not decline with age. The mean decrease in VO2 max (26.7%) during hypoxia was equivalent to that reported for younger males, which suggests that age was not a factor in response to hypoxia. Maximal heart rate, respiratory exchange ratio, oxygen pulse, and walk time were lower in hypoxia while ventilatory equivalent and blood lactate were higher. VEmax BTPS, was the same under both conditions. The combination of laboratory results and field observations by the Expedition physician suggest that women are capable of performing hard work at high altitude if they are in good condition and properly acclimatized.

Human exposure to sulfur dioxide and ozone: absence of a synergistic effect.

Studies of the human health effects of exposure to a combination of ozone and sulfur dioxide have produced somewhat conflicting results; the possibility of a synergistic enhancement of toxicity when the two gases are present simultaneously remains equivocal. We evaluated the effects of 0.40 ppm sulfur dioxide, 0.40 ppm ozone, and the combination of these two under one environmental condition (25 degrees C and 45% relative humidity). Subjects alternately walked and rested during a 2-hr exposure. Subjects exposed to filtered air or to 0.40 ppm sulfur dioxide showed no significant changes in pulmonary function. When exposed to either ozone or ozone plus sulfur dioxide, significant decreases in maximum expiratory flow, forced vital capacity, and inspiratory capacity were observed. There were no significant differences in response between ozone alone and ozone plus sulfur dioxide exposures, thus, in our subjects on synergistic effects were discernible.

Respiratory response of humans exposed to low levels of ozone for 6.6 hours.

Recent evidence suggests that prolonged exposures of exercising men to 0.08 ppm ozone (O3) result in significant decrements in lung function, induction of respiratory symptoms, and increases in nonspecific airway reactivity. The purpose of this study was to confirm or refute these findings by exposing 38 healthy young men to 0.08 ppm O3 for 6.6 h. During exposure, subjects performed exercise for a total of 5 h, which required a minute ventilation of 40 l/min. Significant O3-induced decrements were observed for forced vital capacity (FVC, -0.25 l), forced expiratory volume in 1 s (FEV1.0, -0.35 l), and mean expiratory flow rate between 25% and 75% of FVC (FEF25-75, -0.57 l/s), and significant increases were observed in airway reactivity (35%), specific airway resistance (0.77 cm H2O/s), and respiratory symptoms. These results essentially confirm previous findings. A large range in individual responses was noted (e.g., percentage change in FEV1.0; 4% increase to 38% decrease). Responses also appeared to be nonlinear in time under these experimental conditions.

Does nitrogen dioxide exposure increase airways responsiveness?

A number of reports have suggested that exposure to nitrogen dioxide (NO2) may cause increased airways responsiveness (AR). Twenty studies of asthmatics and five studies of healthy subjects exposed to NO2 were used to test this hypothesis using a simple method of meta-analysis. Individual data were obtained for the above studies and the direction of change in AR was determined for each subject. Only studies with available individual data were used. Subjects from these studies whose directional change in AR could not be determined were excluded. The fraction of positive responses (i.e. increased AR) was determined for all subjects within a group and tested for significance using a sign test. Data were also grouped according to NO2 concentration and by whether the exposure included exercise. There was an overall trend among asthmatics for AR to increase (60%) but this was primarily due to increased AR seen in resting exposures (70%). Among healthy subjects AR also increased with NO2 exposure but only at concentrations above 1.0 ppm. This analysis suggests that NO2 exposure causes increased airway responsiveness in healthy and asthmatic subjects but that exercise during exposure may modify this response in asthmatics.

Time course of response to ozone exposure in healthy adult females.

Ozone exposure causes acute decrements in pulmonary function, increases airway responsiveness, and changes the breathing pattern. We examined these responses in 19 ozone-responsive (DeltaFEV(1) > 5%) young females exposed to both air and 0.35 ppm ozone. The randomized 75-min exposures included two 30-min exercise periods at V(E) approximately 40 L/min. Responses were measured before, during, and after exposure and at 18 and 42 h postexposure. FVC, FEV(1), and FIV(0.5) decreased (p <.01) immediately postexposure by 13.2%, 19.9%, and 20.8%, respectively, and the airway responsiveness was significantly increased. Raw increased (p <.05), while TGV remained essentially unchanged. At 18 h postexposure, the airways were still hyperresponsive and FEV(1) and FIV(0.5) were still 5% below the preexposure levels. There were no residual effects in any of the variables at 42 h postexposure. During exercise in ozone the tidal volume was decreased (-14%) and respiratory frequency increased (+15%). The changes in airway responsiveness were not related to changes in spirometric measurements. We found no significant differences between postair and postozone mouth occlusion pressure (Pm(0.1)) and the hypercapnic response to CO(2) rebreathing. We conclude that ozone induced typical acute changes in airway responsiveness and that ventilatory (exercise), spirometric (inspiratory and expiratory), and plethysmographic pulmonary function may show some residual effects for up to 18 h after exposure. The ozone-induced alteration in breathing pattern during exercise does not appear to be related to a change in ventilatory drive.

Combined effect of ozone and sulfuric acid on pulmonary function in man.

A potential effect of the combination of ozone and sulfuric acid mist (H2SO4) on respiratory function has been postulated for humans simultaneously exposed to these two pollutants. Nine young men were exposed to 0.25 ppm ozone (O3), 1200-1600 micrograms/m3 sulfuric acid aerosol (H2SO4), and a combination of O3 and H2SO4. During the 2-hr exposures, the subjects exercised (ventilation = 30 L/min) three times for 20 min each. Air temperature was 35 degrees C and relative humidity 83%. Pulmonary function changes after exposure to ozone alone were not expected and were not demonstrated. If a reaction between the combination of O3 and H2SO4 and pulmonary function occurred, pulmonary function responses may have been anticipated following the combination exposure, but no significant changes were seen. It was concluded that the combination of ozone and sulfuric acid aerosol at levels in excess of Threshold Limit Values (TLV) levels do not cause pulmonary dysfunction.

Effects of steady-state and variable ozone concentration profiles on pulmonary function.

Measurements of ambient ozone (O2) concentration during daylight hours have shown a spectrum of concentration profiles, from a relatively stable to a variable pattern usually reaching a peak level in the early afternoon. Several recent studies have suggested that in estimating exposure dose (O3 concentration [C] x exposure time [T] x ventilation [V]), O3 concentration needs to be weighted more heavily than either ventilation or duration of exposure in the estimates. In this study we tested the hypothesis that regardless of concentration pattern and exposure rate the same exposure dose of O3 will induce the same spirometric response. We exposed 23 healthy male volunteers (20 to 35 yr of age) for 8 h to air, 0.12 ppm O3 (steady-state), and a triangular exposure pattern (concentration increased steadily from zero to 0.24 ppm over the first 4 h and decreased back to zero by 8 h). During the first 30 min of each hour, subjects exercised for 30 min at minute ventilation (VE) approximately 40 L/min. The order of the exposures was randomized, and the exposures were separated by at least 7 days. The response patterns over the 8-h periods for spirometric variables in both O3 exposures were statistically different from air exposure changes and from each other. For FEV1 the p values were 0.017 between air and steady-state profile, 0.002 between air and triangular profile, and 0.037 between steady-state and triangular profiles. Although in the triangular pattern of exposure the maximal O3 concentration was reached at 4 h, the maximum FEV1 decrement (10.2%) was observed at 6 h of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Decrease of maximum work performance following ozone exposure.

A bicycle ergometer was used to measure maximum exercise oxygen consumption following 2 h of intermittent exercise in an environmental chamber ventilated with air (FA test) or filtered air plus 0.75 ppm ozone (PO test). Thirteen adult males performed both tests according to a random sequence. The maximum attained VO2 declined 10% (P less than 0.01), maximum attained work load was reduced by 10% (P less than 0.01), maximum ventilation decreased 16% (P less than 0.01), and maximum heart rate dropped 6% (P less than 0.05) in the PO test. At the highest common work load, heart rate and oxygen consumption were similar and ventilation was slightly higher (P less than 0.05); however, frequency of respiration increased 45% (P less than 0.01) and tidal voluem fell by 29% (P less than 0.01) following ozone exposure. During maximum exercise, the respiratory frequency was similar in both tests, but tidal volume was 21% lower (P less than 0.01) in PO experiments. Decreases in vital capacity and FEV1.0 as well as cough and chest discomfort were also noted following ozone exposure. We conclude that the reduction of maximum attained VO2 is a consequence of ventilatory limitation of maximum effort, probably related to respiratory discomfort.

Exercise responses following ozone exposure.

We have tested the response of 28 subjects to a three-stage ergometer test, with loads adjusted to 45, 60, and 75% of maximum aerobic power following ozone exposure. The subjects were exposed to one of 0.37, 0.50, or 0.75 ppm O3 for 2 h either at rest (R) or while exercising intermittently (IE) (15 min rest alternated with 15 min exercise at approximately 50 W. sufficient to increase VE by a factor of 2.5). Also, all subjects completed a mock exposure VE, respiratory frequency (fR), mixed expired PO2 and PCO2, and electrocardiogram were monitored continuously during the exercise test. Neither submaximal exercise oxygen consumption nor minute ventilation was significantly altered following any level of ozone exposure. The major response noted was an increase in respiratory frequency during exercise following ozone exposure. The increase in fR was closely correlated with the total dose of ozone (r = 0.98) and was accompanied by a decrease in tidal volume (r = 0.91) so that minute volume was unchanged. It is concluded that through its irritant properties, ozone modifies the normal ventilatory response to exercise, and that this effect is dose dependent.

Preexposure to low ozone concentrations does not diminish the pulmonary function response on exposure to higher ozone concentrations.

To determine whether persons repeatedly exposed to low ozone concentrations would demonstrate a diminished responsivity, as a result of adaptation or desensitization, when subsequently exposed to a higher ozone concentration, we performed the following study. Respiratory sensitivity (pulmonary function response) to 2 h of exposure to 0.42 or 0.50 ppm ozone (acute exposure) was determined 3 months before or 6 to 8 wk after the study. Twenty-one subjects (8 men, 13 women) were exposed for 2 h or 5 consecutive days to filtered air, 0.20, 0.20, 0.20, and 0.42 to 0.50 ppm ozone, respectively. There were no significant differences between the responses of men and women to ozone. Subjects were divided into a sensitive group (greater than 20% drop in FEV1) and a nonsensitive group (less than 10% drop in FEV1) on the basis of their responses to the acute exposure. Neither the overall group nor the nonsensitive group showed a significant response to 0.20 ppm. Sensitive subjects (n = 9) showed small but significant decreases in FEV1 on exposure to 0.20 ppm. The predominant finding was that the 3 days of preexposure to 0.20 ppm ozone had no effect on the response to 0.42 or 0.50 ppm ozone on the fourth day (when compared with the previous acute exposure to 0.42 or 0.50 ppm). We conclude that subjects repeatedly (3 times) exposed to a low (0.20 ppm) concentration of ozone do not demonstrate a pulmonary function adaptation or desensitization on a subsequent exposure to a higher (0.42 or 0.50 ppm) ozone concentration.

Effect of threshold loads on voluntary control of slow and rapid inspiratory movements.

The purpose of this study was to examine the hypothesis that voluntarily produced inspiratory movements are preplanned. Subjects performed both rapid (0.5 s) and slow (2.0 s) voluntary inspirations to a target volume of 50% of their inspiratory capacity under two conditions: 1) normally unloaded with random loading; and 2) normally loaded with random unloading. The load was a 10 cmH2O threshold load. When the load was unexpectedly applied, the subjects undershot the target volume by 397 ml (fast) and 284 ml (slow). When the load was unexpectedly removed, the subjects overshot the target volume by 303 ml (fast) and 224 ml (slow). The duration of inspiration did not change significantly. These observations are consistent with an "impulse-timing" model of preplanned voluntary movement, which incorporates reflex modification of the movement to compensate for loads which may be added or removed.

Human exposure to sulfur dioxide and ozone in a high temperature-humidity environment.

In order to examine the role of high temperature and humidity in the possible synergistic action of ozone and sulfur dioxide on human pulmonary function previously reported by some investigators and repudiated by others, we randomly exposed eight healthy young male nonsmokers to filtered air, 0.4 ppm SO2, 0.4 ppm O3, and 0.4 ppm SO2 plus 0.4 ppm O3 at 35 degrees C--85% rh for 2 hours. Subjects exercised for 15 minutes of each half hour at a workload sufficient to elicit a minute ventilation of 30 liters (BTPS). Pulmonary function tests were performed prior to, during, and following exposure. Observed alterations in pulmonary functions in the SO2 + O3 exposure reflected the changes occurring during the O3 exposure, clearly indicating that no synergistic effects related to the additional presence of SO2 were evident in this study. We considered factors suggested as causes for a potential synergism in comparing the conflicting studies on O3 and SO2, and suggest that factors other than temperature-humidity and/or sulfate aerosol production must be sought.