Asthmatics' Responses to 6-Hr Sulfur Dioxide Exposures on Two Successive Days

Asthmatic volunteers (N = 14) aged 18 to 33 yr with documented sensitivity to sulfur dioxide (SO₂) were exposed in a chamber to 0.6 ppm SO₂ for 6-hr periods on 2 successive days. Similar exposures to purified air, 1 wk later or earlier, served as controls. Subjects exercised heavily (target ventilation rate 50 L/min) for 5 min near the beginning of exposure (early exercise) and for an additional 5 min beginning after 5-hr of exposure (late exercise). At all other times, they rested. Body plethysmographic measurements and symptom questionnaires were administered pre-exposure, after each exercise period, and hourly during rest. Bronchoconstriction and lower respiratory symptoms were observed during or immediately following exercise—to a slight extent with clean air, and to a more marked extent with SO₂. Bronchoconstriction and symptoms were modestly less severe on the second day of SO₂ exposure than on the first day, but there were no meaningful differences in response between early and late exercise periods on either day.     

Time course of exercise-induced bronchoconstriction in asthmatics exposed to sulfur dioxide

Young adult asthmatic volunteers (N = 17) were exposed to 0.75 ppm sulfur dioxide (SO₂) for 3-hr periods, exercising vigorously for the first 10 min and resting thereafter. Specific airway resistance (SR_aw) and symptoms were recorded preexposure, immediately postexercise, and after 1, 2, and 3 hr of exposure. Symptoms and SR_aw were significantly increased after exercise, relative to preexposure measurements. Group mean SR_aw and symptom increases were no longer significant at 1 hr. In a few individuals, effects may have persisted for 2 hr or more. On separate occasions, comparable exposures were conducted, and forced expiratory spirometry was performed preexposure and postexercise, in addition to the other tests. Inclusion of spirometry did not significantly affect the other results. Spirometry and SR_aw showed nearly equal significance in changes postexercise. Thus, in general, asthmatics' bronchoconstriction induced by exercise in SO₂ seems to reverse quickly with rest, even if SO₂ exposure continues. Spirometry may be useful for studying pollution-induced bronchoconstriction when SR_aw measurements are impractical.     

Human respiratory responses to an aerosol containing zinc ammonium sulfate

Twenty-one normal volunteers and 19 volunteers with asthma were exposed in an environmental control chamber to a polydisperse aerosol of zinc ammonium sulfate (ZnSO₄·(NH₄)₂SO₄)—a model of ambient metallic sulfate aerosols derived from trace metals in fossil fuels—at a nominal concentration of 20 μg/m³. As a model of the background ambient particulate burden, polydisperse sodium chloride aerosol at a nominal concentration of 300 μg/m³ was added to the chamber atmosphere during control as well as exposure studies. Exposure temperature was 20°C and relative humidity was 85%, simulating weather conditions typical of fall/winter ambient pollution episodes. Exposure and control studies were performed on separate days, separated by about 3 weeks, in random order under double-blind conditions. Exposure periods lasted 2 hr and included intermittent light exercise. Lung function and symptoms were evaluated before and at the end of the exposure or control period. Symptom reports showed no significant variation attributable to zinc ammonium sulfate exposure. Group mean lung function measures showed a few significant changes possibly attributable to the sulfate exposure, but these were small and inconsistent. It was concluded that zinc ammonium sulfate produced minimal or no short-term respiratory effects observable under the conditions of the experiment.     

A Comparison of Changes in Pulmonary Flow Resistance in Healthy Volunteers Acutely Exposed to SO2 by Mouth and by Nose

On separate occasions, healthy male volunteers were exposed either by nose or by mouth to one of two concentrations of sulphur dioxide, 15 and 28 p.p.m. Exposure to SO₂ lasted 10 minutes. Pulmonary flow resistance (R1) was measured by the oesophageal catheter method, and the lung volume was measured by a modification of the gas-compression method; when SO₂ was administered by nose, nasal flow resistance (Rn) was measured by means of a catheter placed in the posterior pharynx. The increase in R1 was greater when SO₂ was administered by mouth than when it was administered by nose. Similarly, irritative symptoms of the posterior pharynx and chest were more common during exposure by mouth. These findings suggest that the mouth is less effective than the nose as an absorptive surface for SO₂.     

Effect of sulfur dioxide on mucociliary activity and ciliary beat frequency in guinea pig trachea

Summary The effects of 30 min exposure to sulfur dioxide on mucociliary activity (MCA) and ciliary beat frequency (CBF) were studied in 31 guinea pig tracheas. MCA was measured by recording the light reflected from ciliated mucous membranes using an infrared bar code reader. CBF of single ciliated cells obtained by brushing was measured with phase-contrast microscopy. Each tracheal sample was exposed to SO₂ at concentrations ranging from 2.5 to 12.5 ppm, or to air for control purposes. MCA and CBF were measured before and immediately after gas exposure. A reduction in mean MCA of 63% (P = 0.0007) and statistically insignificant changes in CBF (P > 0.05) were recorded at concentrations of 2.5 PPM SO₂. Higher SO₂ concentrations caused a further impairment of MCA as well as a dose-dependent decrease in CBF (P = 0.002). A concentration of 12.5 PPM SO₂ induced a decrease from baseline values of approximately 80% in mean MCA and of roughly 70% in mean CBE This study demonstrates a dose-dependent SO₂-induced decrease in MCA of guinea pig tracheas. The decrease in MCA was associated with an impairment of CBF only at SO₂ concentrations higher than 5.0 ppm.     

Organic Dusts,Sulfur Dioxide,and the Respiratory Tract of Swine

Six piglets were continuously exposed to corn dust, corn dust and sulfur dioxide, or corn starch and SO₂. There were no clinical or pathological changes in the piglets exposed to corn dust alone. When combined with SO₂, both corn dust and com starch produced lesions similar to those observed earlier with SO₂ alone. Clinical changes included ocular and nasal irritation with increased salivation and central nervous system depression. Histologically, alterations in the epithelium of the turbinates and trachea included loss of cilia, disappearance of goblet cells, alteration of cell type, and metaplasia. There was a loss of cilia from epithelium of larger bronchi following exposure to corn starch and SO₂. There were no changes in the respiratory area of the lung which were attributable to exposure to dust or SO₂.     

Sulfur (S35) metabolism in rats exposed to 535O2 contained in the air with simultaneous use of the method of (S35O2) binding by ammonia

Summary Sulfur metabolism was traced in experimental investigations on rats, and the importance of the method for neutralizing sulfur dioxide with ammonia was estimated.The animals were exposed to S³⁵O₂ by means of inhalation, and radioactivity in several organs at different periods of exposure was traced.Sulfur incorporation into proteins and mucopolysaccharides, as well as elimination of isotope with urine and feces at different periods of time after exposure, were also determined. The second group of animals was exposed to the products of S³⁵O₂ neutralized by ammonia; after performing identical investigations it was found that the use of ammonia to neutralize sulfur dioxide in the air decreased the amount of sulfur which could pass into the organism through the breathing of air contaminated by SO₂. The use of S³⁵O₂ neutralized by ammonia brings about a faster elimination of sulfur from the organism.This work was supported by the Environmental Protection Agency USA, Project No. 5-533-1.     

Controlled exposures of volunteers with chronic obstructive pulmonary disease to sulfur dioxide

Twenty-four volunteers with chronic obstructive pulmonary disease (COPD) were exposed to sulfur dioxide (SO2) at 0, 0.4, and 0.8 ppm in an environmental control chamber. Exposures lasted 1 hr and included two 15-min exercise periods (mean exercise ventilation rate 18 liter/min). Pulmonary mechanical function was evaluated before exposure, after initial exercise, and at the end of exposure. Blood oxygenation was measured by ear oximetry before exposure and during the second exercise period. Symptoms were recorded throughout exposure periods and for 1 week afterward. No statistically significant changes in physiology or symptoms could be attributed to SO2 exposure. Older adults with COPD seem less reactive to a given concentration of SO2 than heavily exercising young adult asthmatics. This may be due to lower ventilation rates (i.e., lower SO2 dose rates) and/or to lower airway reactivity in the COPD group.     

Response to Ozone in Volunteers with Chronic Obstructive Pulmonary Disease

Twenty-eight volunteers with chronic obstructive pulmonary disease were exposed to 0.0, 0.18, and 0.25 ppm ozone in purified air for 1-hr periods with light intermittent exercise, with exposure conditions presented in random order at 1-month intervals. No statistically significant changes attributable to ozone were found in forced expiratory performance or percent oxyhemoglobin (measured near the beginning and end of each exposure). No ozone-related changes in clinical status were found by interviews that included the time for 1 wk before to 1 wk after each exposure, except that a moderate increase in lower respiratory symptoms was reported by nonsmokers in 0.18 ppm exposures only. Thus, a slight decrement in hemoglobin saturation with ozone exposure (reported in two previous studies of chronic obstructive pulmonary disease subjects) may not be a common occurrence under typical ambient exposure conditions.     

Response to ozone in volunteers with chronic obstructive pulmonary disease

Twenty-eight volunteers with chronic obstructive pulmonary disease were exposed to 0.0, 0.18, and 0.25 ppm ozone in purified air for 1-hr periods with light intermittent exercise, with exposure conditions presented in random order at 1-month intervals. No statistically significant changes attributable to ozone were found in forced expiratory performance or percent oxyhemoglobin (measured near the beginning and end of each exposure). No ozone-related changes in clinical status were found by interviews that included the time for 1 wk before to 1 wk after each exposure, except that a moderate increase in lower respiratory symptoms was reported by nonsmokers in 0.18 ppm exposures only. Thus, a slight decrement in hemoglobin saturation with ozone exposure (reported in two previous studies of chronic obstructive pulmonary disease subjects) may not be a common occurrence under typical ambient exposure conditions.     

Effects of SO2 plus NaCl aerosol combined with moderate exercise on pulmonary function in asthmatic adolescents

Eight adolescent subjects with a diagnosis of extrinsic asthma and exercise-induced bronchospasm were exposed for 30 min at rest followed by 10 min of moderate exercise on a treadmill to the following experimental modes: (a) filtered air, (b) 1 ppm of sulfur dioxide (SO₂) and 1 mg/m³ of sodium chloride (NaCl) droplet aerosol, or (c) 1 mg/m³ of NaCl droplet aerosol alone. All exposures were at ?75% relative humidity and 22°C. Functional measurements of total respiratory resistance (R_T), maximal flow at 50 and 75% expired vital capacity ($\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext><mtext>50</mtext>}}$ and $\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext><mtext>75</mtext>}}$), forced expiratory volume in 1 sec (FEV_1.0), and functional residual capacity (FRC) were recorded before and after exposure. Statistically significant changes were seen in R_T, $\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext><mtext>50</mtext>}}$ and $\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext><mtext>75</mtext>}}$, and FEV_1.0 following exposure to SO₂  NaCl droplet aerosol during exercise. The changes seen were greater than those seen in the same subjects during exposure at rest or in healthy adult subjects exposed to various air pollutants.     

Atmospheric Pollutants and the Pathogenesis

Influenza-infected mice exposed continuously to 20 ppm of sulfur dioxide (SO₂) for seven days after virus exposure developed more pneumonia than virus control mice. Dose-response experiments suggested that the post virus SO₂-induced increase in influenzal pneumonia began at about 7 to 10 ppm. The increase in pneumonia was not influenced by altering the virus dosage within a 5 to 100 mouse infectious dose range. A similar increase (15% to 20%) in influenzal pneumonia was observed when mice were exposed to 25 ppm of SO₂ prior to initiation of virus infection. The SO₂ exposure had no effect on the growth of influenza virus in the lungs of mice. Rather, the increase in She amount of pneumonia was associated with SO₂ concentrations which induced low-grade, inflammatory lesions in the lung.     

Experimental Studies on Human Health Effects of Air Pollutants. IV. Short-Term Physiological and Clinical Effects of Nitrogen Dioxide Exposure

Adult male volunteers were exposed to nitrogen dioxide (NO₂) at 1.0 ppm in purified air under conditions simulating ambient photochemical smog exposures (2-hr exposure with intermittent light exercise at 31°C and 35% relative humidity). Sham exposures to purified air alone served as controls. Exposure effects were assessed by pulmonary physiological tests and by a standardized clinical evaluation. No statistically significant physiological changes attributable to NO₂ exposure were found except for a marginal loss in forced vital capacity after exposure on two successive days (1.5%mean decrease p<.05). Reported respiratory and other symptoms were slightly increased with exposure as compared to control, but the change was not significant. Short-term toxicity of NO₂ at peak ambient concentrations appears to be substantially less than that of ozone in healthy people, but adverse NO₂ effects in diseased people or in long-term exposures cannot be ruled out at present.     

Potentiating effects of manganese dioxide on experimental respiratory infections

Single and multiple 3-hour-long exposures to manganese dioxide (MnO₂) aerosol in respirable particle size, altered the resistance to bacterial and viral pneumonias. Increased mortality rates and reduced survival times were observed in mice exposed daily for 3 or 4 days to MnO₂ aerosol and challenged with airborne Klebsiella pneumoniae within 1 hour of termination of the last aerosol exposure. When the interval between the exposure and challenge was extended to 5 hours, the altered resistance to infection was seen already after a single 3-hour-long exposure to MnO₂ aerosol. Mice infected with airborne influenza virus 24 or 48 hours before initiation of the MnO₂ exposures also showed increased mortality rates, reduced survival times, and increased pulmonary lesions. The effect was more pronounced in mice exposed to MnO₂ at 48 hours after the infectious challenge.     

Respiratory effects of mixed nitrogen dioxide and sulfur dioxide in human volunteers under simulated ambient exposure conditions

Normal and asthmatic volunteers (N = 24 and 19, respectively) were exposed to mixed nitrogen dioxide (NO₂) and sulfur dioxide (SO₂) in purified background air in an environmental chamber under conditions simulating an ambient pollution episode. The NO₂ concentration was 0.5 ppm; the SO₂ concentration was 0.5 ppm for normals and 0.3 ppm for asthmatics. Exposures lasted 2 hr and included intermittent exercise and heat stress. Control studies consisted of similar exposures to purified air alone. The mixed pollutant gases may have reacted chemically in the exposure chamber, but no appreciable amounts of sulfate or nitrate aerosol were detected there. Group mean lung function changes during exposure generally were not significantly different from control for normals or for asthmatics. Symptoms reported by the normal group showed a small significant overall increase during pollutant exposure and later the same day relative to the corresponding control periods; the asthmatics showed a small significant increase later in the day but not during exposure. The increased symptom reporting showed little consistency from subject to subject: there were small increases for most individual symptom categories evaluated, none of them statistically significant. The results are not sufficient to establish whether this slight and nonspecific clinical response should be attributed to the pollutant mixture or to some other aspect of the exposure protocol.     

Relationship between the airway response to inhaled sulfur dioxide,isocapnic hyperventilation,and histamine in asthmatic subjects

Summary To determine whether bronchoconstriction induced by sulfur dioxide can be predicted by the airway response to inhaled histamine, we exposed on two days 46 patients with asthma to air or 0.5 ppm SO₂. The exposure protocol consisted of 10 min of tidal breathing followed by 10 min of isocapnic hyperventilation at a rate of 301/min. Airway response was measured before (baseline) and after hyperventilation in terms of specific airway resistance, SRaw. Exposure to air increased baseline mean (SD) SRaw from 6.27 (2.12) to mean (SD) maximum post-hyperventilation SRaw of 9.10 (4.38) cmH₂O^*s (P < 0.0001). Exposure to SO₂ increased mean (SD) baseline SRaw from 6.93 (3.29) to mean (SD) maximum posthyperventilation SRaw of 18.21 (18.69) cmH₂O^*s (P < 0.0001). Mean (SD) effect of SO₂. defined as difference between maximum post-hyperventilation SRaw after SO₂ versus air was 9.11 (16.14) cmH₂O^*s. When evaluated individually, 26 and 34 of the 46 patients showed an airway response to hyperventilation of air and SO₂, respectively. Airway response to histamine was determined as the histamine concentration necessary to increase specific airway resistance by 100%, PC₁₀₀SRaw. The airway response after SO₂ and PC₁₀₀SRaw showed a weak but significant correlation (R = –0.48), whereas the responses to hyperventilation and SO₂ did not correlate. We suggest that the mechanisms by which histamine and SO₂ exert their bronchomotor effects are different and that in asthmatic patients the risk of pollutant-induced asthmatic symptoms can be poorly predicted by histamine responsiveness.Supported by a grant from the Minister für Jugend, Familie und Gesundheit, Bonn, Federal Repubic of GermanyDedicated to Johannes Piiper on the occasion of the 65th birthday     

Dose-response study of asthmatic volunteers exposed to nitrogen dioxide during intermittent exercise

Twenty-one mildly asthmatic volunteers were exposed to 0, 0.3, 1.0, and 3.0 ppm nitrogen dioxide (NO2) in purified background air in an environmental control chamber. Exposures were separated by 1-wk periods and occurred in random order. Each lasted 1 hr and included three 10-min bouts of moderately heavy exercise (mean ventilation rate 41 L/min). Exposure temperature was near 22 degrees C and relative humidity near 50%. Specific airway resistance and maximal forced expiratory performance were measured preexposure, after the initial exercise, and near the end of exposure. Bronchial reactivity was assessed immediately following exposure, by normocapnic hyperventilation with subfreezing air. Symptoms were recorded on questionnaires before, during, and for 1-wk after each exposure. Exercise induced significant bronchoconstriction regardless of NO2 level. No statistically significant untoward response to NO2 was observed at any exposure concentration. This negative finding agrees with our previous results, but contrasts with findings elsewhere of respiratory dysfunction after exposure to 0.3 ppm. The discrepancy is presently unexplained, but it may relate to different severity of asthma in different subject groups.     

The pulmonary effects of ozone and nitrogen dioxide alone and combined in healthy and asthmatic adolescent subjects

Separate exposures to 0.12 ppm ozone (O3) or 0.18 ppm nitrogen dioxide (NO2) have not demonstrated consistent changes in pulmonary function in adolescent subjects. However, in polluted urban air, O3 and NO2 occur in combination. Therefore, this project was designed to investigate the pulmonary effects of combined O3 and NO2 exposures during intermittent exercise in adolescent subjects. Twelve healthy and twelve well-characterized asthmatic adolescent subjects were exposed randomly to clean air or 0.12 ppm O3 and 0.30 ppm NO2 alone or in combination during 60 minutes of intermittent moderate exercise (32.5 1/min). The inhalation exposures were carried out while the subjects breathed on a rubber mouthpiece with nose clips in place. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance, maximal flow at 50 and 75 percent of expired vital capacity, forced expiratory volume in one second and forced vital capacity (FVC). Statistical significance of pulmonary function changes was tested by analysis of covariance for repeated measures. After exposure to 0.12 ppm O3 a significant decrease was seen in maximal flow at 50% of FVC in asthmatic subjects. After exposure to 0.30 ppm NO2 a significant decrease was seen in FVC also in the asthmatic subjects. One possible explanation for these changes is the multiple comparison effect. No significant changes in any parameters were seen in the asthmatic subjects after the combined O3-NO2 exposure or in the healthy subjects after any of the exposures.     

Effects of 0.75ppm Sulfur Dioxide on Pulmonary Function Parameters of Normal Human Subjects

Of 31 young, healthy male volunteers who participated in this study, 15 were exposed to air (control) and 16 to 0.75 ppm (2.15 mg/m³) SO₂ for 2 hr at 21°C and 60% relative humidity. At the end of the first hour, the subjects exercised for 15 min on a treadmill at 6.4 kmph, with a 10% grade. Methods employed in evaluation of pulmonary function included body plethysmography, spirometry, and multigas rebreathing test. From the battery of 15 pulmonary function parameters, only the pattern of airway resistance changes was significantly altered by SO₂ exposure, although spirometric parameters followed a similar pattern. Eight of the SO₂-exposed subjects, with one or more positive allergen skin tests, appeared to be significantly more reactive to SO₂ than skin test-negative subjects. All subjects remained asymptomatic. The small number of changes observed appeared to be reversible and do not suggest a significant health hazard to normal human subjects exposed to SO₂ under these conditions.     

Oral and Oronasal Breathing During Continuous Exercise Produce Similar Responses to Ozone Inhalation

Breathing route has a profound effect on sulfur dioxide-induced pulmonary function response in human subjects. There is comparatively little evidence of the effects of oral, nasal, and oronasal breathing on ozone (O₃)-induced responses in humans. In this study, six young adult males were exposed on five occasions to 0.40 parts per million (ppm) O₃ while exercising continuously at one of two workloads (minute ventilation, [Vdot]_E, of ～ 30 and 75 1/min). The [Vdot]_E exposure time product was similar for all protocols. Four exposures were delivered randomly with a Hans-Rudolph respiratory valve attached to a silicone facemask, with breathing route effected with and without noseclip. A 2 × 2 analysis of variance revealed no statistically significant differences (p < .05) across conditions in pulmonary function, exercise ventilatory pattern, or subjective symptoms responses. The fifth exposure, delivered via the same respiratory valve with mouthpiece, but without facemask, revealed significantly greater forced expiratory volume in 1 s (FEV_1.0) impairment than that observed for the respiratory valve, facemask with noseclip exposure (-20.4% and -15.9%, respectively). The latter suggests partial O₃ reactivity to the facemask and clean shaven facial surface of the subjects, although reduced oral scrubbing by mouthpiece-induced bypassing of the oral vestibule might account, in part, for this difference. Recent O₃ uptake evidence from another laboratory,¹⁵ however, supports our conclusion that breathing route during moderate and heavy continuous exercise does not affect acute physiologic responses to 0.40 ppm O₃.