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Air pollutants enhance rhinoconjunctivitis symptoms in pollen-allergic individuals.

BACKGROUND: Little is know about the relation of airborne pollen allergens to nasal and ocular symptoms in combination with air pollutants. OBJECTIVE: The hypothesis was that air pollutants exacerbate allergic symptoms of the nose and eyes during the pollen season. In addition, the use of allergen measurements instead of pollen counts should be tested. METHODS: Fifteen pollen-allergic, nonsmoking subjects with weak reactivity of the airways recorded rhinoconjunctival symptoms and medication every morning and evening throughout the pollen season. Symptoms were compared with air pollutants (nitrogen oxide [NOx], particulate matter smaller than 10 microm, and ozone) and birch and grass pollen counts or, alternatively, to airborne birch and grass allergens determined using ELISA-techniques. A multiple linear regression model was used which controlled for autocorrelation of the residuals of the time series (Cochrane-Orcutt approach). This model was applied to each subject individually, followed by calculations of summary scores for the group. RESULTS: Air pollution levels were moderate, often meeting air quality standards. Effect estimates (increase of score with 10-fold increase of concentration) were NOx = 1.06, P < 0.01; ozone = 1.59, P < 0.01; and pollen = 0.48, P < 0.001. Using allergen concentrations instead of pollen counts resulted in similar effect estimates. Using particulate matter smaller than 10 microm instead of NOx gave comparable but less consistent results. CONCLUSIONS: Symptoms were related to moderate levels of pollutants, suggesting that rhinoconjunctival tissue is very sensitive to irritant stimuli during an ongoing allergic inflammation, and that susceptibility toward allergens might be increased in areas with increased levels of air pollutants. Allergen measurements seem equally usable as pollen counts to investigate rhinoconjunctivitis.

Adult↗

Spatial variability of fine particle mass, components, and source contributions during the regional air pollution study in St. Louis.

Community time-series epidemiology typically uses either 24-hour integrated particulate matter (PM) concentrations averaged across several monitors in a city or data obtained at a central monitoring site to relate PM concentrations to human health effects. If the day-to-day variations in 24-hour integrated concentrations differ substantially across an urban area (i.e., daily measurements at monitors at different locations are not highly correlated), then there is a significant potential for exposure misclassification in community time-series epidemiology. If the annual average concentration differs across an urban area, then there is a potential for exposure misclassification in epidemiologic studies that use annual averages (or multi-year averages) as an index of exposure across different cities. The spatial variability in PM2.5 (particulate matter < or = 2.5 microm in aerodynamic diameter), its elemental components, and the contributions from each source category at 10 monitoring sites in St. Louis, Missouri were characterized using the ambient PM2.5 compositional data set of the Regional Air Pollution Study (RAPS) based on the Regional Air Monitoring System (RAMS) conducted between 1975 and 1977. Positive matrix factorization (PMF) was applied to each ambient PM2.5 compositional data set to estimate the contributions from the source categories. The spatial distributions of components and source contributions to PM2.5 at the 10 sites were characterized using Pearson correlation coefficients and coefficients of divergence. Sulfur and PM2.5 are highly correlated elements between all of the site pairs Although the secondary sulfate is the most highly correlated and shows the smallest spatial variability, there is a factor of 1.7 difference in secondary sulfate contributions between the highest and lowest site on average. Motor vehicles represent the next most highly correlated source component. However, there is a factor of 3.6 difference in motor vehicle contributions between the highest and lowest sites. The contributions from point source categories are much more variable. For example, the contributions from incinerators show a difference of a factor of 12.5 between the sites with the lowest and highest contributions. This study demonstrates that the spatial distributions of elemental components of PM2.5 and contributions from source categories can be highly heterogeneous within a given airshed and thus, there is the potential for exposure misclassification when a limited number of ambient PM monitors are used to represent population-average ambient exposures.

Air Pollutants↗

Association of ambient air quality with children's lung function in urban and rural Iran.

During the summer of 1994, a cross-sectional epidemiological study, in which the pulmonary function of children in Tehran was compared with pulmonary function in children in a rural town in Iran, was conducted. Four hundred children aged 5-11 y were studied. Daytime ambient nitrogen dioxide, sulfur dioxide, and particulate matter were measured with portable devices, which were placed in the children's neighborhoods on the days of study. Levels of these ambient substances were markedly higher in urban Tehran than in rural areas. Children's parents were questioned about home environmental exposures (including heating source and environmental tobacco smoke) and the children's respiratory symptoms. Pulmonary function was assessed, both by spirometry and peak expiratory flow meter. Forced expiratory volume in 1 s and forced vital capacity-as a percentage of predicted for age, sex and height-were significantly lower in urban children than in rural children. Both measurements evidenced significant reverse correlations with levels of sulfur dioxide, nitrogen dioxide, and particulate matter. Differences in spirometric lung function were not explained by nutritional status, as assessed by height and weight for age, or by home environmental exposures. Reported airway symptoms (i.e., cough, phlegm, and wheeze) were higher among rural children, whereas reported physician diagnosis of bronchitis and asthma were higher among urban children. The association between higher pollutant concentrations and reduced pulmonary function in this urban-rural comparison suggests that there is an effect of urban air pollution on short-term lung function and/or lung growth and development during the preadolescent years.

Air Pollutants↗

Minisatellite DNA mutation rate in dandelions increases with leaf-tissue concentrations of Cr, Fe, Mn, and Ni.

We have examined whether mutation rates at minisatellite DNA loci in dandelions (Taraxacum officinale Weber, sensu lato: Asteraceae) increase with increasing exposure to metal pollution. From 16 sites (Colorado to Pennsylvania, USA) covering a range of airborne particulate-matter exposures, soil metal concentrations, and leaf-tissue metal concentrations, we grew an average of 7.9 offspring from each of 10 parent plants, and we analyzed the parent-offspring transmission of 82,715 minisatellite DNA markers to 1,258 offspring for rates of mutation. The mean number of markers examined per individual (using six minisatellite probes) was 65.8. Detection of mutations is facilitated by agamospermous reproduction (clonal seed production) in dandelions. Across sites, the average single-event, parent-offspring marker transmission mutation rate was 0.0067, ranging from 0.002 to 0.015 (a 7.5-fold difference). No significant correlation was detected between site single-event mutation rates and either airborne particulate-matter or soil concentrations for any of the metals. However, across sites, mutation rates were significantly (p < 0.05) and positively correlated to increasing leaf-tissue concentrations of Cr, Fe, Mn, and Ni (Cd, Cu, Pb, and Zn exhibited no correlation). Multiple-regression analyses suggest that a model including three metals--in order of importance: Cr (p = 0.002), Fe (p = 0.02), and Ni (p = 0.005); overall, p = 0.001--may improve the ability to predict mutation rate relative to leaf metal concentrations in dandelions. Mutations at minisatellite DNA loci in sexually apomictic organisms may thus provide convenient biomarkers by which to assess the mutagen stressor risk in environments.

DNA Damage↗

Air pollution and daily mortality in Shanghai: a time-series study.

In this study, the authors assessed the relationship between air pollution and daily mortality from June 2000 to December 2001 in Shanghai, the largest city in China. They used the generalized additive model to allow for the highly flexible long-term and seasonable trends, and for nonlinear weather variables. In the single-pollutant models, the authors found significant associations between concentrations of air pollutants (particulate matter less than 10 microm in aerodynamic diameter [PM10], sulfur dioxide [SO2], and nitrogen dioxide [NO2]) and daily mortality. An increase of 10 microg/m3 in PM10, SO2, and NO2 corresponded to a respective increase in relative risk of mortality from all causes of 1.003 (95% confidence interval [CI] = 1.001, 1.005), 1.014 (95% CI = 1.008, 1.020), and 1.015 (95% CI = 1.008, 1.022). In the multiple-pollutant models, the association between SO2 and daily mortality was not affected by the inclusion of other pollutants; for PM10 and NO2, however, the inclusion of other pollutants possibly weakened the effects between these 2 pollutants and mortality. This finding suggests that gaseous pollutants may be more important than particulate matter as indicators of health in Shanghai. The authors' analyses provided evidence that the current amounts of air pollution in Shanghai continue to adversely affect population health, and strengthen the rationale for limiting the quantities of pollutants in outdoor air.

Age Distribution↗

Response of human alveolar macrophages to ultrafine, fine, and coarse urban air pollution particles.

In the lower airways, macrophages are important regulators of inflammation and indispensable in their antimicrobial activities. Thus, air pollution particles, which modulate airway macrophage host defenses may, in susceptible individuals, increase severity of inflammatory and infectious disease. In the present study, size fractionated, ultrafine (UF), fine (PM0.1-2.5), and coarse (PM2.5-10) particulate matter (PM) were collected from 2 urban sites in the Netherlands, and were compared for effects on human alveolar macrophages (AM). Inflammatory cytokine production, phagocytosis, and expression of phagocyte receptor CD11b were assessed in particle-exposed AM. Interleukin (IL)-6 levels induced by PM2.5-10 (20411 pg/mL) were > 10-fold higher than induced by PM0.1-2.5 (1781 pg/mL). Levels induced by PM0.1-2.5 were 2- to 3-fold higher than induced by UF (770 pg/mL) when cells were exposed to the same particle mass. Cytokine induction by the PM was inhibited by antibody to CD14 and required the presence of serum for optimal stimulation, implying that bacterial products or endotoxin were stimulatory moieties in both coarse and fine particulate matter. Phagocytosis of opsonized yeast was inhibited by coarse more than by fine PM, as was yeast-induced oxidative burst. Coarse particles decreased CD11b expression more than fine PM. The UF did not affect these functions. Taken together, these results suggest that PM recognition by human AM involves receptors evolved to recognize microbial cell structures, and that microbial products preferentially found in the coarse particle fraction of PM may be involved in inflammatory events and decreased pulmonary defenses associated with exposure to pollution particles.

Adolescent↗

Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid.

OBJECTIVE: Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid. STUDY DESIGN: Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid. All meconium-stained fluid was centrifuged, and the volume percentage of particulate matter (i.e., meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin levels were measured. Statistical analysis included Student t test and rank sum statistics where appropriate. Normal and Spearman correlation coefficients were also used. RESULTS: There were no significant differences in mean umbilical artery pH (7.26 +/- 0.06 vs 7.25 +/- 0.10), lactate levels (32.8 +/- 10 mg/dl vs 30.4 +/- 14.2 mg/dl), and hypoxanthine levels (13.4 +/- 6.7 mumol/L vs 14.0 +/- 6.0 mumol/L) in newborns with meconium (n = 28) compared with controls (n = 28). Erythropoietin levels were significantly greater in newborns with meconium (median 39.5 mIU/ml vs 26.8 mIU/ml, p = 0.039). There was no correlation between the amount of particulate matter and any marker of asphyxia. CONCLUSIONS: There was no correlation between markers of acute asphyxia (i.e., umbilical artery blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels were significantly elevated in newborns with meconium-stained amniotic fluid. This latter marker may better correlate with chronic asphyxia.

Acute Disease↗

Evaluation of human exposure to ambient PM10 in the metropolitan area of Mexico City using a GIS-based methodology.

The main goal of this study was to evaluate the magnitude of outdoor exposure to fine particulate matter (PM10) potentially experienced by the population of metropolitan Mexico City. With the use of a geographic information system (GIS), spatially resolved PM10 distributions were generated and linked to the local population. The PM10 concentration exceeded the 24-hr air quality standard of 150 microg/m3 on 16% of the days, and the annual air quality standard of 50 microg/m3 was exceeded by almost twice its value in some places. The basic methodology described in this paper integrates spatial demographic and air quality databases, allowing the evaluation of various air pollution reduction scenarios. Achieving the annual air quality standard would represent a reduction in the annual arithmetic average concentration of 14 microg/m3 for the typical inhabitant. Human exposure to particulate matter (PM) has been associated with mortality and morbidity in Mexico City; reducing the concentration levels of this pollutant would represent a reduction in mortality and morbidity and the associated cost of such impacts. This methodology is critical to assessing the potential benefits of the current initiative to improve air quality implemented by the Environmental Metropolitan Commission of Mexico City.

Air Pollutants↗

Genotoxicity of benzo[a]pyrene, 2-nitrofluorene and airborne particulates in the DNA-repair host-mediated assay.

The genotoxic activity of benzo[a]pyrene (BAP), 2-nitrofluorene (NF) and airborne particulate matter was evaluated in the DNA-repair host-mediated assay after intraperitoneal or intratracheal administration. Dimethylnitrosamine (DMNA), used as a positive control, showed a genotoxic effect after both intraperitoneal and intratracheal administration, the strongest effect being found in liver, followed by lungs and kidneys, whereas a weak effect was observed in the spleen. In general no difference in genotoxicity was found between the 2 administration routes used. For BAP, although clearly positive in vitro, a moderate dose-dependent effect was found only in the liver after intraperitoneal administration. NF, which was positive in vitro both with and without a metabolizing system, produced no genotoxic effect in any of the organs tested after intraperitoneal administration. Extracts of airborne particulate matter which were genotoxic in vitro failed to cause a genotoxic effect in vivo by either route of administration. Possible explanations for the differences between the data obtained in vitro and in vivo are discussed.

Administration, Oral↗

Steel dust in the New York City subway system as a source of manganese, chromium, and iron exposures for transit workers.

The United States Clean Air Act Amendments of 1990 reflected increasing concern about potential effects of low-level airborne metal exposure on a wide array of illnesses. Here we summarize results demonstrating that the New York City (NYC) subway system provides an important microenvironment for metal exposures for NYC commuters and subway workers and also describe an ongoing pilot study of NYC transit workers' exposure to steel dust. Results from the TEACH (Toxic Exposure Assessment, a Columbia and Harvard) study in 1999 of 41 high-school students strongly suggest that elevated levels of iron, manganese, and chromium in personal air samples were due to exposure to steel dust in the NYC subway. Airborne concentrations of these three metals associated with fine particulate matter were observed to be more than 100 times greater in the subway environment than in home indoor or outdoor settings in NYC. While there are currently no known health effects at the airborne levels observed in the subway system, the primary aim of the ongoing pilot study is to ascertain whether the levels of these metals in the subway air affect concentrations of these metals or related metabolites in the blood or urine of exposed transit workers, who due to their job activities could plausibly have appreciably higher exposures than typical commuters. The study design involves recruitment of 40 transit workers representing a large range in expected exposures to steel dust, the collection of personal air samples of fine particulate matter, and the collection of blood and urine samples from each monitored transit worker.

Air Pollutants↗

Factors influencing mass concentration and chemical composition of fine aerosols during a PM high pollution episode.

Results obtained during a winter field campaign for the fine fractions of particulate matter are presented. A high pollution episode together with an analysis of the main factors, which influence accumulation of pollutants is described. The measurement campaigns were carried out simultaneously at two sites in Northern Italy, Milan and Erba, during the winter of 2000. The daily variability in the mass concentration values and PM2.5/PM10 ratios appeared to be strongly dependent upon meteorological and atmospheric stability conditions and, in particular, wind regimes. During the intensive field campaign a high-pollution episode occurred that led to TSP and fine fraction concentrations well above the attention and alarm thresholds, reaching values of up to 200-250 microg m(-3). The elemental concentrations were determined by ED-XRF analysis. The elemental composition of the particulate matter indicated that crustal matter oxides (soil dust) were the main component in particles with aerodynamic diameter d(ae) > 10 microm. They were an important part also in particles with 2.5 < d(ae) < 10 microm, but strongly decreased in particles with d(ae) < 2.5 microm. In the finer fraction sulphates nitrogen and carbon compounds played a major role. The temporal patterns of mass and elemental concentrations, as well as the main components of PM were very similar at the two sites. The high-pollution episode was recorded at many locations in the Po plain, highlighting the role of meteorology and thermodynamic atmospheric conditions on pollution build-up on a large area.

Aerosols↗

Low levels of air pollution induce changes of lung function in a panel of schoolchildren.

In search of sensitive screening parameters for assessing acute effects of ambient air pollutants in young schoolchildren, the impact of 8-h average air pollution before lung function testing was investigated by oscillatory measurements of resistance and spirometry with flow-volume loops. At a central elementary school in Linz, the capital of Upper Austria, 163 children aged 7-10 yrs underwent repeated examinations at the same time of day during 1 school year, yielding a total of 11-12 lung function tests per child. Associations to mass concentrations of particulate matter and nitrogen dioxide (NO(2)) measured continuously at a nearby monitoring station were tested, applying the Generalised Estimating Equations model. Reductions per 10 microg.m(-3) (both for particles and for NO(2)) were in the magnitude of 1% for most lung function parameters. The most sensitive indicator for acute effects of combustion-related pollutants was a change in maximal expiratory flow in small airways. NO(2) at concentrations below current standards reduced (in the multipollutant model) the forced expiratory volume in one second by 1.01%, maximal instantaneous forced flow when 50% of the forced vital capacity remains to be exhaled (MEF(50%)) by 1.99% and MEF(25%) by 1.96%. Peripheral resistance increased by 1.03% per 10 microg.m(-3) of particulate matter with a 50% cut-off aerodynamic diameter of 2.5 mum (PM(2.5)). Resistance is less influenced by the child's cooperation and should be utilised more often in environmental epidemiology when screening for early signs of small airway dysfunction from urban air pollution, but cannot replace the measurement of MEF(50%) and MEF(25%). In the basic model, the reduction of these parameters per 10 microg.m(-3) was highest for NO(2), followed by PM(1), PM(2.5) and PM(10), while exposure to coarse dust (PM(10)-PM(2.5)) did not change end-expiratory flow significantly. All acute effects of urban air pollution found on the lung function of healthy pupils were evident at levels below current European limit values for nitrogen dioxide. Thus, planned reduction of nitrogen dioxide emission (Euro 5; vehicles that comply with the emission limits as defined in Directive 99/96/EC) of 20% in 2010 would seem to be insufficient.

Air Pollution↗

Ozone and short-term mortality in 95 US urban communities, 1987-2000.

CONTEXT: Ozone has been associated with various adverse health effects, including increased rates of hospital admissions and exacerbation of respiratory illnesses. Although numerous time-series studies have estimated associations between day-to-day variation in ozone levels and mortality counts, results have been inconclusive. OBJECTIVE: To investigate whether short-term (daily and weekly) exposure to ambient ozone is associated with mortality in the United States. DESIGN AND SETTING: Using analytical methods and databases developed for the National Morbidity, Mortality, and Air Pollution Study, we estimated a national average relative rate of mortality associated with short-term exposure to ambient ozone for 95 large US urban communities from 1987-2000. We used distributed-lag models for estimating community-specific relative rates of mortality adjusted for time-varying confounders (particulate matter, weather, seasonality, and long-term trends) and hierarchical models for combining relative rates across communities to estimate a national average relative rate, taking into account spatial heterogeneity. MAIN OUTCOME MEASURE: Daily counts of total non-injury-related mortality and cardiovascular and respiratory mortality in 95 large US communities during a 14-year period. RESULTS: A 10-ppb increase in the previous week's ozone was associated with a 0.52% increase in daily mortality (95% posterior interval [PI], 0.27%-0.77%) and a 0.64% increase in cardiovascular and respiratory mortality (95% PI, 0.31%-0.98%). Effect estimates for aggregate ozone during the previous week were larger than for models considering only a single day's exposure. Results were robust to adjustment for particulate matter, weather, seasonality, and long-term trends. CONCLUSIONS: These results indicate a statistically significant association between short-term changes in ozone and mortality on average for 95 large US urban communities, which include about 40% of the total US population. The findings indicate that this widespread pollutant adversely affects public health.

Air Pollution↗

Respiratory effects of seasonal exposures to ozone and particles.

Whereas human respiratory effects of brief ozone exposures are well documented, much less is known about the human health effects of mid- to long-term exposures. The authors' objective in this study was to determine whether lung function or respiratory symptom changes would occur over the course of a summer season among healthy young adults working outdoors in the presence of ozone. The authors studied 72 sophomore cadets from the U.S. Military Academy at West Point, New York, 21 of whom attended special summer training in Fort Dix, New Jersey, an area characterized by elevated ozone levels; the remaining cadets attended training in areas with moderate ozone levels (i.e., Fort Benning, Georgia; Fort Leonard Wood, Missouri; and Fort Sill, Oklahoma). The authors hypothesized that adverse respiratory outcomes, if any, would be more pronounced in the group exposed to higher ozone levels. Spirometry was performed and respiratory symptoms were assessed-both before and after the summer-in a clinic at West Point. Time spent outdoors during summer training averaged 11 hr/d. Both mean and peak ozone levels were higher at Fort Dix than at the three remaining sites. Regional levels of sulfur dioxide and particulate matter less than 10 microm in aerodynamic diameter were relatively low during the study. However, all cadets reported frequent exposure to dust, exhaust, and smoke in the course of their training. Averaged across all subjects, there was a statistically significant drop in forced expiratory volume in 1 sec of 44 ml (p = .035) over the summer. There were also significant increases in reports of cough, chest tightness, and sore throat at the follow-up clinic visit. A larger mean forced expiratory volume in 1 sec decline was observed at Fort Dix, where ozone exposures were the highest. The results of this study demonstrated a seasonal decline in respiratory function among healthy young adults working outdoors in the presence of ozone and particulate matter.

Adult↗

Pulmonary expression of preproET-1 and preproET-3 mRNAs is altered reciprocally in rats after inhalation of air pollutants.

Perturbation of vascular homeostasis is an important mechanism related to the acute health effects of inhaled pollutants. Inhalation of urban particulate matter and ozone by rats has been shown to result in increased synthesis of the potent vasoactive peptide endothelin (ET)-1 in the lungs, with spillover into the circulation. In the present work, we have analyzed the interrelationships between responses of the three major endothelin isoforms, ET-1[1-21], ET-2[1-21], and ET-3[1-21], to inhaled pollutants at the peptide and gene expression levels. Fisher-344 rats were exposed for 4 hrs by nose-only route to clean air, urban particles EHC-93 (0, 50 mg/m3), ozone (0, 0.8 ppm), or ozone and particles together. Circulating levels of both the ET-1 [1-21] and ET-3[1-21] peptides were increased immediately after exposure to particulate matter or ozone. While expression of preproET-1 mRNA in the lungs increased, expression of preproET-3 mRNA decreased immediately after exposure. PreproET-2 mRNA was not detected in the lungs, and exposure to either pollutant did not affect plasma ET-2 levels. Co-exposure to ozone and particles, while altering lung preproET-1 and preproET-3 mRNA levels in a fashion similar to ozone alone, did not cause changes in the circulating levels of the two corresponding peptides. Thus, de novo synthesis of ET-3 in the lungs is not responsible for the increase of circulating plasma ET-3 after inhalation of pollutants, which implies regulation of preproET-3 at a remote site and, hence, systemic impacts of the pollutants. Upregulation of preproET-1 coupled with down-regulation of preproET-3 in the lungs of animals exposed to air pollutants implies a mismatch of local ET-1/ET(A) receptor-mediated vasoconstriction and ET-3/ET(B) receptor-mediated vasodilation.

Administration, Inhalation↗

Effect of short-term exposure to gaseous pollution on asthma hospitalisation in children: a bi-directional case-crossover analysis.

STUDY OBJECTIVE: Assess associations between short-term exposure to gaseous pollutants and asthma hospitalisation among boys and girls 6 to12 years of age. DESIGN: A bi-directional case-crossover analysis was used. Conditional logistic regression models were fitted to the data for boys and girls separately. Exposures averaged over periods ranging from one to seven days were used to assess the effects of gaseous pollutants on asthma hospitalisation. Estimated relative risks for asthma hospitalisation were calculated for an incremental exposure corresponding to the interquartile range in pollutant levels, adjusted for daily weather conditions and concomitant exposure to particulate matter. SETTING: Toronto, Ontario, Canada. PARTICIPANTS: A total of 7319 asthma hospitalisations for children 6 to 12 years of age (4629 for boys and 2690 for girls) in Toronto between 1981 and 1993. MAIN RESULTS: A significant acute effect of carbon monoxide on asthma hospitalisation was found in boys, and sulphur dioxide showed significant effects of prolonged exposure in girls. Nitrogen dioxide was positively associated with asthma admissions in both sexes. The lag time for certain gaseous pollutant effects seemed to be shorter in boys (around two to three days for carbon monoxide and nitrogen dioxide), as compared with girls (about six to seven days for sulphur dioxide and nitrogen dioxide). The effects of gaseous pollutants on asthma hospitalisation remained after adjustment of particulate matter. The data showed no association between ozone and asthma hospitalisation in children. CONCLUSIONS: The study showed positive relations between gaseous pollutants (carbon monoxide, sulphur dioxide, and nitrogen dioxide) at comparatively low levels and asthma hospitalisation in children, using bi-directional case-crossover analyses. Though, the effects of certain specific gaseous pollutants were found to vary in boys and girls.

Air Pollutants↗

An overview of the effects of tobacco ingredients on smoke chemistry and toxicity.

This paper presents an overview of a series of studies designed to assess the influence of 482 tobacco ingredients on cigarette smoke chemistry and toxicity. The studies are: pyrolysis of the ingredients; influence of the ingredients on smoke constituents believed by regulatory authorities to be relevant to smoking-related diseases ("Hoffmann analytes"); influence of the ingredients on in vitro genotoxicity and cytotoxicity of smoke partiulate matter; and influence of the ingredients on the inhalation toxicity of smoke. The present paper brings the salient features of these studies together. A pyrolysis technique has been developed which, as far as practicably possible, mimics the combustion conditions inside a burning cigarette. The results from 291 single-substance ingredients indicate that almost a third would transfer out of the cigarette burning zone at least 99% intact (i.e. less than 1% pyrolysis), and almost two thirds would transfer at least 95% intact. Of the ingredients that underwent some degree of pyrolysis, a few "Hoffmann analytes" were detected amongst the pyrolysis products of 19 ingredients. Taking into account maximum use levels, their maximum pyrolysis levels were generally small and often insignificant compared to the levels typically present in smoke. Possible exceptions were acetaldehyde and benzene from the pyrolysis of malic acid. However, subsequent smoke chemistry studies indicated that the maximum levels predicted from pyrolysis of this involatile substance were overestimated, suggesting that malic acid does not undergo complete pyrolysis in the burning cigarette and/or generates acetaldehyde and benzene at similar rates to that of tobacco on a per weight basis. When added to tobacco, many of the ingredient mixtures produced no significant effect on the levels of many of the "Hoffmann analytes" in smoke, while some produced increases or decreases relative to the relevant control cigarettes. The study has concentrated on the increases. Many of the differences were found to be not significant when the long-term variability of the analytical methodology was taken into account. However, even taking this into account, the smoke formaldehyde levels in two of the test cigarettes were significantly increased relative to their controls, by up to 26 microg (73%). These increases are likely to be due to the pyrolysis of sugars, cellulose and other polysaccharide materials. The activity of smoke particulate matter from cigarettes containing tobacco ingredients has been determined with three in vitro bioassays, two for genotoxicity and one for cytotoxicity. These were the Ames test, the mammalian cell micronucleus assay, and the neutral red uptake cytotoxicity assay. Within the sensitivity and specificity of these bioassays, the specific activity of the cigarette smoke particulate matter was not changed by the addition of ingredients to the cigarette. Three 90-day sub-chronic inhalation studies have been undertaken and histopathological and histomorphometric assessments made within the respiratory tracts of animals exposed to smoke from cigarettes containing the various ingredient mixtures and their control cigarettes. The response due to tobacco smoke exposure was not distinguishable between the test and control cigarettes, indicating that the presence of the ingredients had made no discernable differences to the type and severity of the treatment-related changes.

Administration, Inhalation↗

Recovery of cyclic antidepressants with gastric lavage.

The role of lavage fluid volume in recovery of cyclic antidepressant with gastric lavage was determined in 13 patients treated for moderate to severe cyclic antidepressant intoxication. An orogastric tube was placed, gastric contents aspirated, and gastric lavage performed with 60 to 180 mL aliquots of tap water or 0.9% NaCl for irrigation. A volume of 12.8 +/- 4.4 liters of lavage fluid was instilled, and 97.6 +/- 6.9% of this volume was recovered. The recovered aspirate and lavage fluid were inspected for the presence of particulate matter and saved in 4 to 5 liter collections. Determination of cyclic antidepressant and metabolite concentrations was performed using gas chromatography-mass spectrometry, and the amount of cyclic antidepressant recovered was calculated. The mean total amount recovered was 110 mg and ranged from 2.4 mg to 342 mg. Of the total amount recovered, 88% +/- 13% was recovered in the first 4 to 5 liters of lavage fluid. An estimate of the dose ingested was available in 7 patients, with 8.7% (0.4% to 21.7%) of the estimated dose recovered by lavage. There were no cases of significant drug recovery in clear lavage fluid. We conclude that if gastric lavage is undertaken in cyclic antidepressant intoxications, it should utilize 5 liters initially and then continue only if particulate matter is seen.

Adolescent↗