Ambient air pollution, lung function, and airway responsiveness in asthmatic children.

BACKGROUND: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking. OBJECTIVE: We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. METHODS: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders. RESULTS: Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20. CONCLUSIONS: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

Adopting Clean Fuels and Technologies on School Buses. Pollution and Health Impacts in Children.

RATIONALE: More than 25 million American children breathe polluted air on diesel school buses. Emission reduction policies exist, but the health impacts to individual children have not been evaluated. METHODS: Using a natural experiment, we characterized the exposures and health of 275 school bus riders before, during, and after the adoption of clean technologies and fuels between 2005 and 2009. Air pollution was measured during 597 trips on 188 school buses. Repeated measures of exhaled nitric oxide (FeNO), lung function (FEV1, FVC), and absenteeism were also collected monthly (1,768 visits). Mixed-effects models longitudinally related the adoption of diesel oxidation catalysts (DOCs), closed crankcase ventilation systems (CCVs), ultralow-sulfur diesel (ULSD), or biodiesel with exposures and health. MEASUREMENTS AND MAIN RESULTS: Fine and ultrafine particle concentrations were 10-50% lower on buses using ULSD, DOCs, and/or CCVs. ULSD adoption was also associated with reduced FeNO (-16% [95% confidence interval (CI), -21 to -10%]), greater changes in FVC and FEV1 (0.02 [95% CI, 0.003 to 0.05] and 0.01 [95% CI, -0.006 to 0.03] L/yr, respectively), and lower absenteeism (-8% [95% CI, -16.0 to -0.7%]), with stronger associations among patients with asthma. DOCs, and to a lesser extent CCVs, also were associated with improved FeNO, FVC growth, and absenteeism, but these findings were primarily restricted to patients with persistent asthma and were often sensitive to control for ULSD. No health benefits were noted for biodiesel. Extrapolating to the U.S. population, changed fuel/technologies likely reduced absenteeism by more than 14 million/yr. CONCLUSIONS: National and local diesel policies appear to have reduced children's exposures and improved health.

Novel NMDA receptor-specific desensitization/inactivation produced by ingestion of the neurotoxins, ß-N-methylamino-L-alanine (BMAA) or ß-N-oxalylamino-L-alanine (BOAA/ß-ODAP).

The environmental neurotoxins BMAA (ß-N-methylamino-L-alanine) and BOAA (ß-N-oxalylamino-L-alanine) are implicated as possible causative agents for the neurodegenerative diseases, amyotrophic lateral sclerosis/ParkinsonismDementia complex (ALS/PDC) and neurolathyrism, respectively. Both are structural analogs of the neurotransmitter, glutamate, and bind postsynaptic glutamate receptors. In this study, the effect of ingestion of these toxins on the response of a singly-innervated, identified, glutamatergic postsynaptic cell in a living, undissected Drosophila is observed by intracellular recording. Previously we have reported that ingested BMAA behaves as an NMDA agonist that produces an abnormal NMDA response in the postsynaptic cell. It is shown here that BOAA also behaves as an NMDA agonist, and produces an effect very similar to that of BMAA on the postsynaptic response. In response to a single stimulus, the amplitude of the NMDA component is decreased, while the time to peak and duration of the NMDA component are greatly increased. No discernable effect on the AMPA component of the response was observed. Furthermore, both BMAA and BOAA cause an NMDAR-specific desensitization in response to repetitive stimulation at the physiological frequency for the postsynaptic cell (5 Hz). The possibility that this phenomenon may represent a response to excessive Ca(2+) entry through NMDAR channels is discussed. This desensitization phenomenon, as well as the abnormal NMDAR gating characteristics induced by BMAA, appears to be rescued during higher frequency stimulation (e.g. 10, 20 Hz).

The physiological effect of ingested ß-N-methylamino-L-alanine on a glutamatergic synapse in an in vivo preparation.

The neurotoxin, BMAA (ß-N-methylamino-L-alanine), may be a risk factor for amyotrophic lateral sclerosis (ALS), Parkinson's (PD) and Alzheimer's (AD) disease. In vivo experiments have demonstrated that BMAA can cause a number of motor dysfunctions if ingested or injected, and in vitro experiments show that this toxin binds to glutamate receptors with deleterious results. Also, BMAA exists in the human food chain worldwide, and has been detected in the brains of ALS and AD patients. This paper offers the first demonstration by intracellular recording of the effect of ingested BMAA on the postsynaptic response of an identified glutamatergic cell in a living, undissected organism (Drosophila melanogaster), and correlates these observations with the specific motor dysfunctions that result from ingestion. The results suggest that BMAA acts as a glutamate agonist, causing NMDA receptor channels to remain open for prolonged periods of time, thereby damaging the cell by excitotoxicity. The effect on the postsynaptic response became apparent days before the function of the postsynaptic cell (wing beat) became affected. Severely depolarized cells were able to fully recover with the removal of BMAA from the food source, suggesting that blocking BMAA binding in the brain might be a good treatment strategy.

Ambient carbon monoxide and fine particulate matter in relation to preeclampsia and preterm delivery in western Washington State.

BACKGROUND: Preterm delivery and preeclampsia are common adverse pregnancy outcomes that have been inconsistently associated with ambient air pollutant exposures. OBJECTIVES: We aimed to prospectively examine relations between exposures to ambient carbon monoxide (CO) and fine particulate matter [≤ 2.5 µm in aerodynamic diameter (PM2.5)] and risks of preeclampsia and preterm delivery. METHODS: We used data from 3,509 western Washington women who delivered infants between 1996 and 2006. We predicted ambient CO and PM2.5 exposures using regression models based on regional air pollutant monitoring data. Models contained predictor terms for year, month, weather, and land use characteristics. We evaluated several exposure windows, including prepregnancy, early pregnancy, the first two trimesters, the last month, and the last 3 months of pregnancy. Outcomes were identified using abstracted maternal medical record data. Covariate information was obtained from maternal interviews. RESULTS: Predicted periconceptional CO exposure was significantly associated with preeclampsia after adjustment for maternal characteristics and season of conception [adjusted odds ratio (OR) per 0.1 ppm=1.07; 95% confidence interval (CI), 1.02-1.13]. However, further adjustment for year of conception essentially nullified the association (adjusted OR=0.98; 95% CI, 0.91-1.06). Associations between PM2.5 and preeclampsia were nonsignificant and weaker than associations estimated for CO, and neither air pollutant was strongly associated with preterm delivery. Patterns were similar across all exposure windows. CONCLUSIONS: Because both CO concentrations and preeclampsia incidence declined during the study period, secular changes in another preeclampsia risk factor may explain the association observed here. We saw little evidence of other associations with preeclampsia or preterm delivery in this setting.

Associations between asthma emergency visits and particulate matter sources, including diesel emissions from stationary generators in Tacoma, Washington.

The objective of this research was to evaluate the effect of particulate matter air pollution, including emissions from diesel generators, on visits to emergency departments for asthma. Daily asthma case data from participating hospitals in the greater Tacoma, Washington area were obtained. Daily asthma emergency room visit data were available from six Tacoma hospitals from January 3, 1998 to May 30, 2002. Only emergency visits where the primary discharge diagnosis was asthma were included in the analysis. Air pollution, daily temperature and relative humidity data were obtained from the Puget Sound Clean Air Agency. An association between daily PM2.5 and emergency department (ED) visits for asthma at lag days 2 and 3 was observed. The relative risk for lag day 2 was 1.04 (95% confidence interval[CI]: 1.01, 1.07) and for lag day 3 was 1.03 (1.0, 1.06). A significant association between ED visits for asthma and increased use of diesel generators was not detected. The use of low-sulfur diesel oil may have mitigated potential adverse health effects. These data indicate that air pollution in a medium-sized coastal city may be sufficient to have a public health impact on asthma.

Relation of whole blood carboxyhemoglobin concentration to ambient carbon monoxide exposure estimated using regression.

Exposure to carbon monoxide (CO) and other ambient air pollutants is associated with adverse pregnancy outcomes. While there are several methods of estimating CO exposure, few have been evaluated against exposure biomarkers. The authors examined the relation between estimated CO exposure and blood carboxyhemoglobin concentration in 708 pregnant western Washington State women (1996-2004). Carboxyhemoglobin was measured in whole blood drawn around 13 weeks' gestation. CO exposure during the month of blood draw was estimated using a regression model containing predictor terms for year, month, street and population densities, and distance to the nearest major road. Year and month were the strongest predictors. Carboxyhemoglobin level was correlated with estimated CO exposure (rho = 0.22, 95% confidence interval (CI): 0.15, 0.29). After adjustment for covariates, each 10% increase in estimated exposure was associated with a 1.12% increase in median carboxyhemoglobin level (95% CI: 0.54, 1.69). This association remained after exclusion of 286 women who reported smoking or being exposed to secondhand smoke (rho = 0.24). In this subgroup, the median carboxyhemoglobin concentration increased 1.29% (95% CI: 0.67, 1.91) for each 10% increase in CO exposure. Monthly estimated CO exposure was moderately correlated with an exposure biomarker. These results support the validity of this regression model for estimating ambient CO exposures in this population and geographic setting.

A prospective study of maternal carboxyhaemoglobin and pre-eclampsia risk.

We aimed to measure the relationship between early-pregnancy maternal carboxyhaemoglobin and subsequent pre-eclampsia risk. A nested case-control analysis was conducted using data from a western Washington State cohort study (1996-2004). We measured maternal whole blood carboxyhaemoglobin in 128 women who developed pre-eclampsia and 419 normotensive controls (mean gestational age at blood draw, 14.8 weeks). After adjustment for confounders, high (>/=1%) vs. low (<0.7%) carboxyhaemoglobin odds ratios [OR] and 95% confidence intervals [CI] were 4.09 [1.30, 12.9] in multiparous women, 0.53 [0.23, 1.26] in primiparae and 1.11 [0.55, 2.25] in the overall study population (parity interaction P = 0.01). The influence of parity on the association was unexpected. The association between high carboxyhaemoglobin and pre-eclampsia risk in multiparae implicates hypoxia at the fetal-maternal interface as a pathogenic mechanism. These results also suggest that the aetiology of the disease may differ according to parity.

Infant exposure to fine particulate matter and traffic and risk of hospitalization for RSV bronchiolitis in a region with lower ambient air pollution.

Few studies investigate the impact of air pollution on the leading cause of infant morbidity, acute bronchiolitis. We investigated the influence of PM(2.5) and other metrics of traffic-derived air pollution exposure using a matched case-control dataset derived from 1997 to 2003 birth and infant hospitalization records from the Puget Sound Region, Washington State. Mean daily PM(2.5) exposure for 7, 30, 60 and lifetime days before case bronchiolitis hospitalization date were derived from community monitors. A regional land use regression model of NO(2) was applied to characterize subject's exposure in the month prior to case hospitalization and lifetime average before hospitalization. Subject's residential proximity within 150 m of highways, major roadways, and truck routes was also assigned. We evaluated 2604 (83%) cases and 23,354 (85%) controls with information allowing adjustment for mother's education, mother's smoking during pregnancy, and infant race/ethnicity. Effect estimates derived from conditional logistic regression revealed very modest increased risk and were not statistically significant for any of the exposure metrics in fully adjusted models. Overall, risk estimates were stronger when restricted to bronchiolitis cases attributed to respiratory syncytial virus (RSV) versus unspecified and for longer exposure windows. The adjusted odds ratio (OR(adj)) and 95% confidence interval per 10 mcg/m(3) increase in lifetime PM(2.5) was 1.14, 0.88-1.46 for RSV bronchiolitis hospitalization. This risk was also elevated for infants who resided within 150 m of a highway (OR(adj) 1.17, 0.95-1.44). This study supports a developing hypothesis that there may be a modest increased risk of bronchiolitis attributable to chronic traffic-derived particulate matter exposure particularly for infants born just before or during peak RSV season. Future studies are needed that can investigate threshold effects and capture larger variability in spatial contrasts among populations of infants.

Relationship between visits to emergency departments for asthma and ozone exposure in greater Seattle, Washington.

BACKGROUND: Air pollution is known to affect asthma symptoms in controlled and epidemiologic studies. OBJECTIVE: To determine whether ozone exposure in Seattle is associated with increased use of hospital emergency departments. METHODS: Hospital data on daily asthma cases for all ages were obtained for 1998 through 2002. Ozone and fine particulate matter (< or = 2.5 microm in diameter) (PM2.5) data were obtained from local air agencies. Poisson regression models were used to assess the association between asthma visits to emergency departments and air pollutants. Maximum daily 1- and 8-hour average ozone concentrations and the daily PM2.5 concentration were used. RESULTS: We observed associations between both ozone metrics and emergency department visits in children. For the maximum daily 1- and 8-hour average ozone concentrations, the relative risks (RRs) were 1.08 (95% confidence interval [CI], 1.00-1.18) and 1.11 (95% CI, 1.02-1.21), respectively, at 3 days' lag. Weaker but significant associations were also observed for adults. For the maximum daily 1-hour average ozone concentration, the RR was 1.06 (95% CI, 1.01-1.11) at 4 days' lag, and for the maximum daily 8-hour average ozone concentration, the RR was 1.06 (95% CI, 1.01-1.12) at 2 days' lag and 1.08 (95% CI, 1.02-1.14) at 4 days' lag. CONCLUSION: Ozone exposure exacerbates asthma in people in the Seattle area, especially in children.

Changes in lung function and airway inflammation among asthmatic children residing in a woodsmoke-impacted urban area.

Fine particulate matter (PM(2.5)) is associated with respiratory effects, and asthmatic children are especially sensitive. Preliminary evidence suggests that combustion-derived particles play an important role. Our objective was to evaluate effect estimates from different PM(2.5) exposure metrics in relation to airway inflammation and lung function among children residing in woodsmoke-impacted areas of Seattle. Nineteen children (ages 6-13 yr) with asthma were monitored during the heating season. We measured 24-h outdoor and personal concentrations of PM(2.5) and light-absorbing carbon (LAC). Levoglucosan (LG), a marker of woodsmoke, was also measured outdoors. We partitioned PM(2.5) exposure into its ambient-generated (E(ag)) and nonambient (E(na)) components. These exposure metrics were evaluated in relation to daily changes in exhaled nitric oxide (FE(NO)), a marker of airway inflammation, and four lung function measures: midexpiratory flow (MEF), peak expiratory flow (PEF), forced expiratory volume in the first second (FEV(1)), and forced vital capacity (FVC). E(ag), but not E(na), was correlated with combustion markers. Significant associations with respiratory health were seen only among participants not using inhaled corticosteroids. Increases in FE(NO) were associated with personal PM(2.5), personal LAC, and E(ag) but not with ambient PM(2.5) or its combustion markers. In contrast, MEF and PEF decrements were associated with ambient PM(2.5), its combustion markers, and E(ag), but not with personal PM(2.5) or personal LAC. FEV(1) was associated only with ambient LG. Our results suggest that lung function may be especially sensitive to the combustion-generated component of ambient PM(2.5), whereas airway inflammation may be more closely related to some other constituent of the ambient PM(2.5) mixture.

A community study of the effect of particulate matter on blood measures of inflammation and thrombosis in an elderly population.

BACKGROUND: The mechanism behind the triggering effect of fine particulate matter (PM) air pollution on cardiovascular events remains elusive. We postulated that elevated levels of PM would be associated with increased blood levels of inflammatory and thrombotic markers in elderly individuals. We also hypothesized that elevated PM would increase levels of cytokines in individuals with heart disease. METHODS: We measured these blood markers in 47 elderly individuals with (23) and without (16 COPD and 8 healthy) cardiovascular disease (CVD) on 2 or 3 mornings over a 5 or 10-day period between February 2000 and March 2002. Blood measures were paired with residence level outdoor PM measured by nephelometry. Analyses determined the within-individual effect of 24-hour averaged outdoor PM on blood measures. RESULTS: Analyses found no statistically significant effect of a same day 10 ug/m3 increase in fine PM on log transformed levels of CRP 1.21 fold-rise [95% CI: 0.86, 1.70], fibrinogen 1.02 fold-rise [95% CI: 0.98, 1.06], or D-dimer 1.02 fold-rise [95% CI: 0.88, 1.17] in individuals with CVD. One-day lagged analyses in the CVD subgroup found similar null results. These same models found no change in these blood markers at the same-day or 1-day lag in the group without CVD. In 21 individuals with CVD, a 10 mug/m3 increase in same-day PM was associated with a 1.3 fold-rise [95% CI: 1.1, 1.7] in the level of monocyte chemoattractant protein-1. CONCLUSION: We did not find consistent effects of low ambient levels of PM on blood measures of inflammation or thrombosis in elderly individuals.

Woodsmoke health effects: a review.

The sentiment that woodsmoke, being a natural substance, must be benign to humans is still sometimes heard. It is now well established, however, that wood-burning stoves and fireplaces as well as wildland and agricultural fires emit significant quantities of known health-damaging pollutants, including several carcinogenic compounds. Two of the principal gaseous pollutants in woodsmoke, CO and NOx, add to the atmospheric levels of these regulated gases emitted by other combustion sources. Health impacts of exposures to these gases and some of the other woodsmoke constituents (e.g., benzene) are well characterized in thousands of publications. As these gases are indistinguishable no matter where they come from, there is no urgent need to examine their particular health implications in woodsmoke. With this as the backdrop, this review approaches the issue of why woodsmoke may be a special case requiring separate health evaluation through two questions. The first question we address is whether woodsmoke should be regulated and/or managed separately, even though some of its separate constituents are already regulated in many jurisdictions. The second question we address is whether woodsmoke particles pose different levels of risk than other ambient particles of similar size. To address these two key questions, we examine several topics: the chemical and physical nature of woodsmoke; the exposures and epidemiology of smoke from wildland fires and agricultural burning, and related controlled human laboratory exposures to biomass smoke; the epidemiology of outdoor and indoor woodsmoke exposures from residential woodburning in developed countries; and the toxicology of woodsmoke, based on animal exposures and laboratory tests. In addition, a short summary of the exposures and health effects of biomass smoke in developing countries is provided as an additional line of evidence. In the concluding section, we return to the two key issues above to summarize (1) what is currently known about the health effects of inhaled woodsmoke at exposure levels experienced in developed countries, and (2) whether there exists sufficient reason to believe that woodsmoke particles are sufficiently different to warrant separate treatment from other regulated particles. In addition, we provide recommendations for additional woodsmoke research.

Influence of exposure error and effect modification by socioeconomic status on the association of acute cardiovascular mortality with particulate matter in Phoenix.

Using ZIP code-level mortality data, the association of cardiovascular mortality with PM(2.5) and PM(10-2.5), measured at a central monitoring site, was determined for three populations at different distances from the monitoring site but with similar numbers of deaths and therefore similar statistical power. The % risk and statistical significance for the association of mortality with PM(2.5) fell off with distance from the monitor, as would be expected if exposure error increased with distance. However, the % risk for PM(10-2.5) increased in going from the population in Central Phoenix, where the monitoring site was located, to a population in a Middle Ring around Phoenix and fell off in an Outer Ring population. The % risks for the Outer Ring were low for each of the six lag days (0-5) and for the 6-day moving average. The lag structures for PM(2.5) and PM(10-2.5) also differed for the Central Phoenix and Middle Ring populations. These differences led us to examine the socioeconomic status (SES) of the populations. On the basis of education and income, the population in Central Phoenix had a lower SES than the Middle Ring. Thus, the differences between Central Phoenix and the Middle Ring may be due to effect modification by SES and differences in exposure error. However, the effect modification by SES may be different for thoracic coarse particulate matter (PM) than for fine PM. This study provides new information on the association of PM(10-2.5) with cardiovascular mortality. In the Middle Ring, the % risk per 10 microg/m3 increase in PM(10-2.5) concentration (lower and upper 95% confidence levels) for lag day 1 was 3.4 (1.0, 5.8) and for the 6-day distributed-lag was 3.8 (0.3, 7.5). The differences in lag structure for PM(2.5) and PM(10-2.5) provide evidence that the two particle size classes have health effects that are different and independent. This study also helps explain the high % risks for PM(2.5) found for Central Phoenix, 6.6 (1.1, 12.5) for lag day 1, and 11.5 (2.8, 20.9) for the 6-day moving average. The smaller area may have a lower exposure error, and the lower SES population may be more susceptible to fine PM as compared to the larger areas and more heterogeneous populations used in many studies.

Effect of particulate air pollution on lung function in adult and pediatric subjects in a Seattle panel study.

STUDY OBJECTIVE: To determine whether increased exposure to particulate matter air pollution (PM), measured with personal, residential, or central site monitoring, was associated with pulmonary function decrements in either adults with COPD or children with asthma. PARTICIPANTS: We studied 57 adults with or without COPD and 17 children aged 6 to 13 years with physician-diagnosed asthma in Seattle during a 3-year panel study. STUDY DESIGN AND MEASUREMENTS: Indoor and outdoor PM measurements were made at subjects' homes. The subjects wore personal exposure monitors for 10 consecutive 24-h periods, and PM was also measured at a central outdoor location. We assessed the within-subject effect of particulate exposure on FEV(1) and peak expiratory flow (PEF) in adults, and maximal midexpiratory flow (MMEF), PEF, FEV(1), and symptoms in children. RESULTS: FEV(1) decrements were associated with 1-day lagged central site PM

Ambient air pollution and asthma exacerbations in children: an eight-city analysis.

The authors investigated the relation between ambient concentrations of five of the Environmental Protection Agency's criteria pollutants and asthma exacerbations (daily symptoms and use of rescue inhalers) among 990 children in eight North American cities during the 22-month prerandomization phase (November 1993-September 1995) of the Childhood Asthma Management Program. Short-term effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mum in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were examined in both one-pollutant and two-pollutant models, using lags of up to 2 days. Lags in carbon monoxide and nitrogen dioxide were positively associated with both measures of asthma exacerbation, and the 3-day moving sum of sulfur dioxide levels was marginally related to asthma symptoms. PM10 and ozone were unrelated to exacerbations. The strongest effects tended to be seen with 2-day lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per-billion change in nitrogen dioxide were associated with symptom odds ratios of 1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15), respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01, 1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the observed carbon monoxide and nitrogen dioxide associations can probably be attributed to mobile-source emissions, though more research is required.

Effects of select PM-associated metals on alveolar macrophage phosphorylated ERK1 and -2 and iNOS expression during ongoing alteration in iron homeostasis.

It was hypothesized that relative mass relationships among select constituent metals and iron (Fe3+) govern the pulmonary immunotoxic potential of any PM(2.5) sample, as these determine the extent to which Fe3+ binding by transferrin is affected (resulting in altered alveolar macrophage [AM] Fe status and subsequent antibacterial function). Iron response protein (IRP) binding activity is a useful indirect measurement of changes in Fe status, as reductions in cell Fe levels lead to increases in IRP binding. However, AM IRP activity can be affected by an increased presence of nitric oxide generated by inducible nitric oxide synthase (iNOS). This study sought to determine if any changes in AM IRP activity induced by PM(2.5) constituents V, Mn, or Al were independent from effects of the metals on cell NO formation. NR8383 rat AM were exposed to Fe3+ alone or combined with V, Mn, or Al at metal:Fe ratios representative of those in PM(2.5) collected in New York City, Los Angeles, and Seattle during fall 2001. Cells were then assessed for changes in IRP activity and iNOS expression. Phosphorylated extracellular signal-regulated kinase (ERK) 1 and 2 levels were also measured since activated ERKs are involved in signaling pathways that lead to increased iNOS expression. The results indicate that V and Al, and to a lesser extent Mn, altered IRP activity, though the effects were not consistently concentration dependent. Furthermore, while V and Mn treatments did not induce iNOS expression, Al did. These results confirmed our hypothesis that certain metals associated with PM(2.5) might alter the pulmonary immunocompetence of exposed hosts by affecting the Fe status of AM, a major class of deep lung defense cells.

PM source apportionment and health effects. 3. Investigation of inter-method variations in associations between estimated source contributions of PM2.5 and daily mortality in Phoenix, AZ.

As part of an EPA-sponsored workshop to investigate the use of source apportionment in health effects analyses, the associations between the participant's estimated source contributions of PM(2.5) for Phoenix, AZ for the period from 1995-1997 and cardiovascular and total nonaccidental mortality were analyzed using Poisson generalized linear models (GLM). The base model controlled for extreme temperatures, relative humidity, day of week, and time trends using natural spline smoothers. The same mortality model was applied to all of the apportionment results to provide a consistent comparison across source components and investigators/methods. Of the apportioned anthropogenic PM(2.5) source categories, secondary sulfate, traffic, and copper smelter-derived particles were most consistently associated with cardiovascular mortality. The sources with the largest cardiovascular mortality effect size were secondary sulfate (median estimate=16.0% per 5th-to-95th percentile increment at lag 0 day among eight investigators/methods) and traffic (median estimate=13.2% per 5th-to-95th percentile increment at lag 1 day among nine investigators/methods). For total mortality, the associations were weaker. Sea salt was also found to be associated with both total and cardiovascular mortality, but at 5 days lag. Fine particle soil and biomass burning factors were not associated with increased risks. Variations in the maximum effect lag varied by source category suggesting that past analyses considering only single lags of PM(2.5) may have underestimated health impact contributions at different lags. Further research is needed on the possibility that different PM(2.5) source components may have different effect lag structure. There was considerable consistency in the health effects results across source apportionments in their effect estimates and their lag structures. Variations in results across investigators/methods were small compared to the variations across source categories. These results indicate reproducibility of source apportionment results across investigative groups and support applicability of these methods to effects studies. However, future research will also need to investigate a number of other important issues including accuracy of results.

Associations between health effects and particulate matter and black carbon in subjects with respiratory disease.

We measured fractional exhaled nitric oxide (FE(NO)), spirometry, blood pressure, oxygen saturation of the blood (SaO2), and pulse rate in 16 older subjects with asthma or chronic obstructive pulmonary disease (COPD) in Seattle, Washington. Data were collected daily for 12 days. We simultaneously collected PM10 and PM2.5 (particulate matter < or = 10 microm or < or = 2.5 microm, respectively) filter samples at a central outdoor site, as well as outside and inside the subjects' homes. Personal PM10 filter samples were also collected. All filters were analyzed for mass and light absorbance. We analyzed within-subject associations between health outcomes and air pollution metrics using a linear mixed-effects model with random intercept, controlling for age, ambient relative humidity, and ambient temperature. For the 7 subjects with asthma, a 10 microg/m3 increase in 24-hr average outdoor PM10 and PM2.5 was associated with a 5.9 [95% confidence interval (CI), 2.9-8.9] and 4.2 ppb (95% CI, 1.3-7.1) increase in FE(NO), respectively. A 1 microg/m3 increase in outdoor, indoor, and personal black carbon (BC) was associated with increases in FE(NO) of 2.3 ppb (95% CI, 1.1-3.6), 4.0 ppb (95% CI, 2.0-5.9), and 1.2 ppb (95% CI, 0.2-2.2), respectively. No significant association was found between PM or BC measures and changes in spirometry, blood pressure, pulse rate, or SaO2 in these subjects. Results from this study indicate that FE(NO) may be a more sensitive marker of PM exposure than traditional health outcomes and that particle-associated BC is useful for examining associations between primary combustion constituents of PM and health outcomes.

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.