Transient Decrease of Exhaled Nitric Oxide after Acute Exposure to Passive Smoke in Healthy Subjects

Nitric oxide (NO) is produced and detected in the exhalate from the respiratory tract where it plays important regulatory functions. Exhaled nitric oxide (eNO) concentrations are reduced in active cigarette smokers between cigarettes and in nonsmoking subjects during short-term exposure to environmental tobacco smoke. In this study, the authors evaluated eNO before and after an acute exposure to environmental tobacco smoke in healthy, nonsmoking subjects (n = 12). Baseline eNO levels were measured by chemiluminescence at baseline (1 hr before exposure), shortly after the end of exposure, and 10 and 30 min after the end of exposure. Mean room air NO concentration increased from 3 ppb to 4 ppm (range, 560 ppb-8.5 ppm) during the exposure period. Carboxyhemoglobin levels were assessed before and after the exposure with spectrophotometry. All subjects had decreased eNO with exposure to environmental tobacco smoke (mean ± standard error of the mean: 16.65 ± 1.35 ppb to 13.86 ± 1.33 ppb; p < .001). These concentrations remained significantly decreased at 10 min and recovered within 30 min. No modifications in airway resistance or increase in carboxyhemoglobin levels were observed. Exposure to environmental tobacco smoke transiently–but consistently–decreased eNO concentration in healthy, nonsmoking subjects, suggesting that second-hand smoke can directly affect NO in the airway environment.     

Airway responses to 2.0 ppm nitrogen dioxide in normal subjects

Nitrogen dioxide (NO2) is a common indoor air pollutant. To characterize the acute respiratory responses to this gas, 18 nonsmoking normal subjects (mean age +/- standard deviation [SD] = 25 +/- 4 yr) were exposed to filtered air or 2 ppm NO2 gas for 1 hr in a 30-m3 environmental chamber on different days, typically 1 wk apart, in a double-blind randomized fashion. Lung function tests included forced vital capacity, forced expiratory volume in one second, partial expiratory flow at 40% of vital capacity (Vp40), functional residual capacity, and specific airway conductance, and were measured before and after exposure. Airway reactivity to methacholine inhalation was determined within 45 min of each exposure. The dose of methacholine in mg/ml to cause a 40% decrease in specific airway conductance (PD40) was measured. Airway reactivity to methacholine aerosol increased significantly after NO2, which is shown by a decrease in the concentration of methacholine; PD40 (AIR) = 101 +/- 44, PD40 (NO2) = 81 +/- 45 mg/ml, p = .003. No significant changes were noted in the lung function tests after NO2 exposure. These findings indicate that normal nonsmokers exposed to 2.0 ppm NO2 for 1 hr develop an increase in airway reactivity to methacholine aerosol, which is not associated with changes in lung volumes, flow rates, or respiratory symptoms.     

Possible association between passive smoking and lower exhaled nitric oxide in asthmatic children

In adults, both active and passive smoking reduce levels of exhaled nitric oxide (eNO); however, to date, passive exposure to environmental tobacco smoke (ETS) has not been shown to affect eNO in children. The authors recruited 174 asthmatic children (96 male, 78 female) and 79 nonasthmatic controls (46 male, 33 female) from a group of children aged 5 to 14 yr who attended a children's hospital for an outpatient visit or elective surgery. Each subject's exposure to ETS was ascertained by questionnaire, and their eNO levels were measured. Asthmatic children had higher eNO levels (ppb) than nonasthmatic children (p = 0.04), and asthmatic children exposed to ETS had significantly lower eNO levels than unexposed children (p = 0.005). Exposure to ETS did not alter eNO levels in nonasthmatic children (p = 0.4). Results of the study suggest that ETS exposure is associated with lower eNO levels among childhood asthmatics. Consequently, ETS exposure may need to be considered when physicians interpret eNO levels in asthmatic children. Further study of the effects of ETS on eNO levels is recommended.     

Effects of 0.60 PPM nitrogen dioxide on circulating and bronchoalveolar lavage lymphocyte phenotypes in healthy subjects

Nitrogen dioxide (NO2) is a common oxidant air pollutant. Animal studies have suggested that NO2 exposure causes a decrease in the numbers of some splenic lymphocyte subtypes and impairs lymphocyte-dependent immune responses. To investigate whether ambient levels of NO2 alter circulating and bronchoalveolar lavage fluid (BALF) human lymphocytes, we studied five healthy nonsmoking adult volunteers. In each subject, blood and bronchoalveolar lavage fluid was obtained and then, more than 2 weeks later, volunteers were exposured to 0.60 ppm NO2 for 2 hr with intermittent light to moderate exercise on 4 separate days within a 6-day period. We measured standard tests of pulmonary function (airway resistance, thoracic gas volume, maximal expiratory flow) and had the subjects rate the severity of respiratory symptoms before and after each NO2 exposure. Circulating and BALF lymphocytes were labeled with fluorochrome-conjugated monoclonal antibodies to human lymphocyte antigens and a flow cytometer was used to count lymphocyte subtypes. Neither any single day's exposure nor all four exposures caused a change in symptoms or in the results of tests of pulmonary function. The total number of circulating lymphocytes obtained after NO2 exposure was slightly greater than at baseline (1792 +/- 544 vs 1598 +/- 549 cells/mm3 at baseline; P = not significant) but the proportions of lymphocyte subtypes did not differ. In the BALF obtained after NO2 exposure and in the baseline state, the total number of lymphocytes and the percentages of T cells (CD 3), B cells (CD 20), T cytotoxic-suppressor cells (CD 8), T helper-inducer cells (CD 4), and large granular lymphocytes (CD 57) also did not differ after NO2 exposure. A slightly but significantly greater proportion of natural killer cells (CD 16) was found in the BALF obtained after NO2 exposure (7.2 +/- 3.1 vs 4.2 +/- 2.4% of total lymphocytes). We conclude that repeated exposures of healthy nonsmoking adults to 0.60 ppm NO2 are not associated with clinically significant symptoms, changes in airway caliber, or alterations in circulating and BALF lymphocyte subtypes. We suggest that brief, daily exposures to NO2 at levels higher than those achieved in urban atmosphere are unlikely to provoke acute respiratory impairment in healthy, nonsmoking adults.     

Possible Association between Passive Smoking and Lower Exhaled Nitric Oxide in Asthmatic Children

In adults, both active and passive smoking reduce levels of exhaled nitric oxide (eNO); however, to date, passive exposure to environmental tobacco smoke (ETS) has not been shown to affect eNO in children. The authors recruited 174 asthmatic children (96 male, 78 female) and 79 nonasthmatic controls (46 male, 33 female) from a group of children aged 5 to 14 yr who attended a children's hospital for an outpatient visit or elective surgery. Each subject's exposure to ETS was ascertained by questionnaire, and their eNO levels were measured. Asthmatic children had higher eNO levels (ppb) than nonasthmatic children (p = 0.04), and asthmatic children exposed to ETS had significantly lower eNO levels than unexposed children (p = 0.005). Exposure to ETS did not alter eNO levels in nonasthmatic children (p = 0.4). Results of the study suggest that ETS exposure is associated with lower eNO levels among childhood asthmatics. Consequently, ETS exposure may need to be considered when physicians interpret eNO levels in asthmatic children. Further study of the effects of ETS on eNO levels is recommended.     

Nasal inhalation challenge studies with sidestream tobacco smoke.

Environmental tobacco smoke (ETS) exposure is associated with rhinitis symptoms (i.e., runny nose and congestion) in some people. In an effort to better understand these symptoms, we recruited 18 historically ETS-sensitive subjects from the community and exposed them for 15 min to clean air and for 15 min to sidestream tobacco smoke (STS, 45 ppm carbon monoxide). Symptoms were recorded (0 = absent, 5 = severe), and posterior rhinomanometry was performed. There were significant changes in rhinitis symptoms (1.3 +/- 0.4 pre- versus 6.1 +/- 0.5 post-STS, p less than .05); nasal airway resistance (2.86 +/- 0.2 pre- versus 4.49 +/- 0.6 post-STS, p less than .05), and maximum inspiratory flow (2.74 +/- 0.3 pre- versus 2.14 +/- 0.3 post-STS, p less than .05). A spectrum of individual responsiveness to ETS was observed, and nasal resistance increased from 0% to 265%. Increased nasal resistance occurred primarily at the upstream or flow-limiting segment of the nasal airway.     

Fire fighters' exposure to carbon monoxide during Australian bushfires

Fatal entrapments of Australian bushfire fighters have led to suggestions that carbon monoxide (CO) poisoning could have contributed to these accidents by impairing the fire fighters' judgement. Carboxyhemoglobin saturation (COHb%) levels were assessed from alveolar CO levels in 24 fire fighters working with handtools and in 12 accompanying scientific observers, before and after fire fighting (duration 37-187 min) on 15 experimental bushfires. Carboxyhemoglobin levels increased on average by 0.7% per hour in the fire fighters and by 0.3% per hour in the observers. Nonsmoking fire fighters had lower COHb% after fires than the smokers had before fires. Estimates of environmental CO concentrations (including cigarette smoke) during the fires averaged 31 parts per million (ppm) for the smokers, 17 ppm for the nonsmoking crew members, and 11 ppm for the observers, none of whom smoked. The highest estimates of environmental CO arising solely from bushfire smoke were 40 to 50 ppm. Smokers were exposed to as much CO from their cigarettes as from bushfire smoke. Carboxyhemoglobin levels at the end of 8-hr fire fighting shifts, predicted from these levels of environmental CO, averaged about 5% (maximum 11%) in smokers and about 3% (maximum 7%) in nonsmokers. Acute levels of COHb% of this degree are not considered to have significant effects on health or performance. These results indicate that bushfire fighters are generally unlikely to experience hazardous levels of CO exposure.     

Exhaled NO level and number of eosinophils in nasal lavage as markers of pollen-induced upper and lower airway inflammation in children sensitive to grass pollen

OBJECTIVES: This study investigates the upper and lower inflammatory response induced by natural exposure to grass pollen in atopic and non-atopic children. METHODS: After children's atopic profile had been assessed, their nasal lavage fluid (NAL) and exhaled air was sampled once before and once during the pollen season. Level of nitric oxide (NO) was determined in exhaled air, and the following mediators were measured in NAL: ECP, IL-6, IL-8, albumin, uric acid, and urea. The number of eosinophils in NAL was determined after Giemsa staining. During the experiment ozone and pollen levels were measured continuously. RESULTS: During the pollen season the level of grass pollen was 95 pollen grains per cubic metre. At baseline, 8.0% and 5.4% of total cells in NAL of children sensitive to, respectively, house dust mite (HDM) and pollen + HDM were eosinophils, whereas virtually no eosinophils were observed in NAL of non-atopic children. In contrast to the non-atopic and HDM groups, in children sensitive only to grass pollen, grass pollen induced a threefold increase in the percentage of NAL eosinophils and a 2.5-fold increase in the NAL level of ECP ( P<0.05). In all groups, the NAL levels of albumin, uric acid, urea, IL-6 and IL-8 were not significantly increased by pollen exposure. At baseline, children sensitive to HDM showed significantly higher exhaled nitric oxide (eNO) values than non-atopic subjects and children sensitive only to pollen (79 to 141% increase). During pollen exposure eNO of children sensitive only to pollen increased from 35.8 to 64.5 ppb ( P<0.05), whereas no increase in eNO was observed in the other children. CONCLUSION: Pollen-sensitive children show a season-dependent upper and lower airway inflammatory response, resembling the continuous inflammation in HDM-sensitive children.     

A study of respiratory effects from exposure to 2 ppm formaldehyde in healthy subjects

Formaldehyde (FA) is a common indoor air pollutant with irritative properties. It has been suggested that FA may produce physiologic alterations of the respiratory system. To study such responses, 15 nonsmoking, healthy subjects were exposed in a double blind, random manner to 0 and 2 ppm FA for 40 min in an environmental chamber. In addition, the same exposures were repeated on a separate day with the subjects performing moderate exercise (450 kpm/min) for 10 min. Exposures were carried out under controlled environmental conditions (temperature = 23 degrees C, relative humidity = 50%). Pulmonary function was measured before, during, and after exposures using partial and maximal flow-volume curves and airway resistance. Symptom diaries were given to the subjects; upper and lower airway symptoms were recorded for up to 24 hr following exposures. No significant bronchoconstriction was noted in this group. In 3 subjects, sequential measurements of peak flow over a 24-hr period following FA exposure failed to reveal any delayed airway response. On a separate day, 6 healthy subjects failed to demonstrate changes from their baseline responsiveness to methacholine after exposure to 2 ppm FA. Respiratory symptoms were, in general, confined to the upper airways and were mild to moderate in severity. We conclude that short exposures to 2 ppm FA do not result in acute or subacute changes in lung function among healthy individuals either at rest or with exercise. Subjective complaints following such exposures are confined to irritative phenomena of the upper airways.     

Passive smoking at work

Summary Air pollution due to tobacco smoke and its effects on employees were investigated in 44 workrooms. For this purpose, the concentrations of CO, NO, NO₂, nicotine, and particulate matter were determined, and 472 employees were interviewed about annoyance and irritations.The mean values of the concentrations of the components due to tobacco smoke are: CO = 1.1 ppm, NO = 32 ppb, NO₂ = 24 ppb, nicotine = 0.9 g/m³, particulate matter = 133 g/m³. One third of the measured CO values exceeds a critical threshold of 2 ppm CO due to tobacco smoke.One quarter of the persons reports eye irritations at work. One third of the employees qualifies the air with regard to smoke at the workplace as bad. Forty percent of the interviewed persons are disturbed by smoke. The majority of the employees is in favor of a separation into smoking and nonsmoking rooms. This seems to be the most appropriate preventive measure for the protection of nonsmokers at work.Supported by the Swiss National Science Foundation, grant no. 3.912-0.78     

Measurement of offline exhaled nitric oxide in a study of community exposure to air pollution

As part of a large panel study in Seattle, Washington, we measured levels of exhaled nitric oxide (eNO) in children's homes and fixed-site particulate matter with aerodynamic diameters of 2.5 micro m or less (PM(2.5)) outside and inside the homes as well as personal PM(2.5) during winter and spring sessions of 2000-2001. Nineteen subjects 6-13 years of age participated; 9 of the 19 were on inhaled corticosteroid (ICS) therapy. Exhaled breath measurements were collected offline into a Mylar balloon for up to 10 consecutive days. Mean eNO values were 19.1 (SD +/- 11.4) ppb in winter sessions and 12.5 +/- 6.6 ppb in spring sessions. Fixed-site PM(2.5) mean concentrations were 10.1 +/- 5.7 microg/m(3) outside homes and 13.3 +/- 1.4 inside homes; the personal PM(2.5) mean was 13.4 +/- 3.2 microg/m(3). We used a linear mixed-effects model with random intercept and an interaction term for medications to test for within-subject-within-session associations between eNO and various PM(2.5) values. We found a 10 microg/m(3) increase in PM(2.5) from the outdoor, indoor, personal, and central-site measurements that was associated with increases in eNO in all subjects at lag day zero. The effect was 4.3 ppb [95% confidence interval (CI), 1.4-7.29] with the outdoor monitor, 4.2 ppb (95% CI, 1.02-7.4) for the indoor monitor, 4.5 ppb (95% CI, 1.02-7.9) with the personal monitor, and 3.8 ppb (95% CI, 1.2-6.4) for the central monitors. The interaction term for medication category (ICS users vs. nonusers) was significant in all analyses. These findings suggest that eNO can be used as an assessment tool in epidemiologic studies of health effects of air pollution.     

Air pollution is associated with increased level of exhaled nitric oxide in nonsmoking healthy subjects.

The authors sought to determine which air pollutant is responsible for the increase in exhaled nitric oxide observed in healthy subjects. Exhaled nitric oxide was measured in 16 nonsmoking healthy subjects on 14 workdays, during which there were varying air-pollution levels. Contamination of samples by ambient nitric oxide was excluded. The baseline value of exhaled nitric oxide, determined at times when outdoor air pollution was low, ranged from 7 to 43 ppb (mean = 28+/-5 ppb). The daily value of exhaled nitric oxide (range = 5-60 ppb) was associated positively with ambient carbon monoxide (r = .85) and nitric oxide (r = .81). Exposure during the morning hours to high levels of outdoor pollution was associated with increased exhaled nitric oxide (i.e., 50% above baseline), which persisted for up to 5 h (i.e., 32% above baseline). These results indicated that exhaled nitric oxide levels represent a useful biomonitor of individual exposure to air pollutants.     

Is smoker/nonsmoker segregation effective in reducing passive inhalation among nonsmokers?

Using expired carbon monoxide (CO) and a test of coordination as measures of tobacco smoke exposure in a natural environmental setting where smokers and nonsmokers were segregated, results indicate that by comparison to a control group, subjects seated in adjacent smoking/ nonsmoking environments were not only exposed to similar ambient levels of CO, but also show similar physical and physiological reactions to their exposure in the form of coordination test scores, expired CO, and blood carboxyhemoglobin. While the results may not be generalized to other tobacco smoke constituents or other environmental settings, they raise questions about the health benefits of smoker segregation which future research must address.     

Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy

This study investigated the association between biomarkers of fetal exposure to cigarette smoke at the end of pregnancy, cotinine in cord serum and in maternal and newborn urine samples, and quantitative measurement of smoking intake and exposure evaluated by maternal self-reported questionnaire. Study subjects were 429 mothers and their newborns from a hospital in Barcelona, Spain. A questionnaire including smoking habits was completed in the third trimester of pregnancy and on the day of delivery. Cotinine concentration in cord serum was associated with daily exposure to nicotine in nonsmokers and with daily nicotine intake in smokers. The geometric mean of cotinine concentration in cord serum statistically discriminated between newborns from nonexposed and exposed nonsmoking mothers, and between these two classes and smokers, and furthermore was able to differentiate levels of exposure to tobacco smoke and levels of intake stratified in tertiles. Urinary cotinine levels in newborns from nonsmoking mothers exposed to more than 4 mg nicotine daily were statistically different from levels in two other categories of exposure. Cotinine concentration in urine from newborns and from mothers did not differentiate between exposure and nonexposure to environmental tobacco smoke (ETS) in nonsmoking mothers. Cord serum cotinine appeared to be the most adequate biomarker of fetal exposure to smoking at the end of pregnancy, distinguishing not only active smoking from passive smoking, but also exposure to ETS from nonexposure.     

Cotinine, thioether, and glucuronide excretion among active and passive bidi smokers in India

The authors examined biomarkers for environmental tobacco smoke exposure (ETS) from bidis (Indian cigarettes) among male smokers, their nonsmoking female family members (passive smokers), and an unexposed control group (N = 66). The 3 parameters used to determine the magnitude of exposure were cotinine (a tobacco-specific alkaloid indicating nicotine exposure) and thioethers and glucuronides (indicators of electrophilic burden). Urinary excretion of cotinine was significantly higher among active smokers (4.30 +/- 1.18), compared with passive smokers (wives = 1.76 +/- 0.50; daughters = 0.50 +/- 0.26). Similar trends were noted for thioethers and glucuronides. The authors found that cotinine and glucuronide levels were correlated significantly with exposure to ETS among both active and passive bidi smokers.     

Sidestream tobacco smoke exposure acutely alters human nasal mucociliary clearance.

Nasal mucociliary clearance (NMC) is a biomarker of nasal mucosal function. Tobacco smokers have been shown to have abnormal NMC, but the acute effect of environmental tobacco smoke (ETS) on nonsmokers is unknown. This study evaluated acute tobacco smoke-induced alterations in NMC in 12 healthy adults. Subjects were studied on 2 days, separated by at least 1 week. Subjects underwent a 60-min controlled exposure at rest to air or sidestream tobacco smoke (SS) (15 ppm CO) in a controlled environmental chamber. One hour after the exposure, 99mTc-sulfur colloid was aerosolized throughout the nasal passage and counts were measured with a scintillation detector. Six out of 12 subjects showed more rapid clearance after smoke exposure than after air exposure, and 3/12 had rapid clearance on both days. However, substantial decreases in clearance occurred in 3/12 subjects, all of whom had a history of ETS rhinitis. In two subjects, more than 90% of the tracer remained 1 hr after tracer administration (2 hr after smoke exposure). Understanding the basis for biologic variability in the acute effect of tobacco smoke on NMC may advance our understanding of pathogenesis of chronic effects of ETS.     

Exhaled nitric oxide in children with asthma and short-term PM2.5 exposure in Seattle

The objective of this study was to evaluate associations between short-term (hourly) exposures to particulate matter with aerodynamic diameters < 2.5 microm (PM2.5) and the fractional concentration of nitric oxide in exhaled breath (FE(NO) in children with asthma participating in an intensive panel study in Seattle, Washington. The exposure data were collected with tapered element oscillation microbalance (TEOM) PM2.5 monitors operated by the local air agency at three sites in the Seattle area. FE(NO) is a marker of airway inflammation and is elevated in individuals with asthma. Previously, we reported that offline measurements of FE(NO) are associated with 24-hr average PM2.5 in a panel of 19 children with asthma in Seattle. In the present study using the same children, we used a polynomial distributed lag model to assess the association between hourly lags in PM2.5 exposure and FE(NO) levels. Our model controlled for age, ambient NO levels, temperature, relative humidity, and modification by use of inhaled corticosteroids. We found that FE(NO) was associated with hourly averages of PM2.5 up to 10-12 hr after exposure. The sum of the coefficients for the lag times associated with PM2.5 in the distributed lag model was 7.0 ppm FE(NO). The single-lag-model FE(NO) effect was 6.9 [95% confidence interval (CI), 3.4 to 10.6 ppb] for a 1-hr lag, 6.3 (95% CI, 2.6 to 9.9 ppb ) for a 4-hr lag, and 0.5 (95% CI, -1.1 to 2.1 ppb) for an 8-hr lag. These data provide new information concerning the lag structure between PM2.5 exposure and a respiratory health outcome in children with asthma.     

Tolerance to sulfur dioxide-induced bronchoconstriction in subjects with asthma

A study to determine whether the bronchoconstriction induced by low concentration of sulfur dioxide in subjects with asthma decreases with repeated exposure was undertaken. Eight subjects with asthma performed 3 min of voluntary eucapnic hyperpnea with 0.5 ppm of SO2 in humidified filtered air three times at 30-min intervals and we measured specific airway resistance (SRaw) before and after each period of hyperpnea. Specific airway resistance increased significantly more after the first exposure to SO2 [(from 7.6 +/- 1.7 to 15.5 +/- 2.0 L x cm H2O/liter/sec (mean +/- SEM)] than after the second (from 8.1 +/- 1.3 to 10.8 +/- 1.6) or third (from 7.6 +/- 1.6 to 10.1 +/- 1.9) exposures (P less than 0.025). When seven subjects repeated hyperpnea with SO2 24 hr and 7 days later, SRaw increased as much as it had after the first exposure (from 8.2 +/- 2.5 to 15.5 +/- 4.5 at 24 hr and from 6.6 +/- 1.4 to 15.4 +/- 2.1 at 7 days). In four subjects repeated exposure to SO2 caused short-term inhibition of the bronchomotor response to SO2 but did not inhibit the bronchomotor response to histamine aerosol. It was concluded that repeated exposures to a low concentration of SO2 over a short period (on 1 day) can induce tolerance to the bronchomotor effects of SO2 in subjects with asthma. Tolerance to the bronchomotor effects of SO2 is not caused by decreased responsiveness of airway smooth muscle or a generalized decrease in the responsiveness of vagal reflex pathways since the bronchomotor response to histamine is preserved.     

Pulmonary effects of indoor- and outdoor-generated particles in children with asthma

Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (E) to PM2.5 (PM with aerodynamic diameter < or = 2.5 microm) into its indoor-generated (Eig) and ambient-generated (Eag) components for 19 children with asthma. We then compared Eig and Eag to changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, Eag was marginally associated with increases in eNO [5.6 ppb per 10-microg/m3 increase in PM2.5; 95% confidence interval (CI), -0.6 to 11.9; p = 0.08]. Eig was not associated with eNO (-0.19 ppb change per 10 microg/m3). Our predictive model allowed us to estimate Eag and Eig for all 19 children. For those combined estimates, only Eag was significantly associated with an increase in eNO (Eag: 5.0 ppb per 10-microg/m3 increase in PM2.5; 95% CI, 0.3 to 9.7; p = 0.04; Eig: 3.3 ppb per 10-microg/m3 increase in PM2.5; 95% CI, -1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM2.5 exposure is consistently associated with increases in eNO and the indoor-generated component is less strongly associated with eNO.     

Nitrogen dioxide exposure in vivo and human alveolar macrophage inactivation of influenza virus in vitro

Epidemiologic studies have reported an increased incidence of respiratory infections and illness in association with elevated indoor levels of nitrogen dioxide (NO2). Animal exposure studies have found that brief exposures to peak levels of NO2 produce greater morbidity than continuous lower level exposure. In order to examine the effect of NO2 inhalation on human alveolar macrophages, normal volunteers were exposed sequentially to air or NO2, by double-blind randomization, in an environmental chamber. Two exposure protocols with comparable concentration x time products were used: (a) continuous 0.60 ppm NO2 (n = 9), and (b) background 0.05 ppm NO2 with three 15-min peaks of 2.0 ppm (n = 15). Inhalation of NO2 caused no significant changes in pulmonary function or airway reactivity in either exposure protocol. Alveolar macrophages obtained by bronchoalveolar lavage 3 1/2 hr after exposure to continuous 0.60 ppm NO2 tended to inactivate influenza virus in vitro less effectively than cells collected after air exposure (1.96 vs 1.25 log10 plaque-forming units on Day 2 of incubation, P less than 0.07). Four of nine subjects accounted for the observed impairment in virus inactivation; cells from these four subjects demonstrated an increase in interleukin-1 (IL-1) production after NO2 vs air, whereas the five remaining subjects decreased IL-1 production after NO2. In contrast, intermittent peak exposure did not alter the rate of viral inactivation or IL-1 production. This methodology has the potential to identify pollutant effects on mechanisms of respiratory defense in humans.