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1.  Effects of Ambient Ozone Exposure on Mail Carriers’ Peak Expiratory Flow Rates 
Environmental Health Perspectives  2005;113(6):735-738.
The extent to which occupational exposure to ozone in ambient air can affect lung function remains unclear. We conducted a panel study in 43 mail carriers by measuring their peak expiratory flow rates (PEFRs) twice daily for 6 weeks in 2001. The daily exposure of each mail carrier to O3, particulate matter < 10 μm in aerodynamic diameter (PM10), and nitrogen dioxide was estimated by one air monitoring station in the center of the mail carrier’s delivery area. Hourly concentrations of air pollutants during their exposure periods were 6–96 ppb for O3, 11–249 μg/m3 for PM10, and 14–92 ppb for NO2. Linear mixed-effects models were used to estimate the association between air pollution exposures and PEFR after adjusting for subject’s sex, age, and disease status and for temperature and humidity. We found that night PEFR and the deviation in night PEFR were significantly decreased in association with 8-hr O3 exposures with a lag 0–2 days and by daily maximum O3 exposures with a lag of 0–1 day in our multipollutant models. By contrast, neither PM10 nor NO2 was associated with a PEFR reduction. Daily 8-hr mean concentrations of O3 had greater reduction effects on PEFR than did daily maximum concentrations. For a 10-ppb increase in the 8-hr average O3 concentration, the night PEFR was decreased by 0.54% for a 0-day lag, 0.69% for a 1-day lag, and 0.52% for a 2-day lag. We found that an acute lung function reduction occurs in mail carriers exposed to O3 concentrations below current ambient air quality standards and occupational exposure limits.
PMCID: PMC1257599  PMID: 15929897
deviation; lung function; mail carrier; ozone exposure; peak expiratory flow rate
2.  Respiratory effects of air pollution in chronic obstructive pulmonary disease: a three month prospective study 
Thorax  1997;52(12):1040-1044.
BACKGROUND: A study was undertaken to investigate the relationship between air pollution levels and respiratory symptoms and peak expiratory flow rate (PEFR) in subjects with chronic obstructive pulmonary disease (COPD) living in Christchurch, New Zealand. METHODS: Forty subjects aged over 55 years with COPD completed twice daily diaries for three months during the winter of 1994. Subjects recorded respiratory symptoms, PEFR, outdoor activity, visits to doctor or hospital, and medication use. All were resident within a 5 km radius of the regional council's air pollution monitoring site. Daily and hourly mean pollutant levels (particulates (PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and carbon monoxide (CO)) were measured at the monitoring site. RESULTS: Pollution levels were generally low relative to those recorded in previous years. The New Zealand Ministry for the Environment guidelines for PM10 were exceeded on five occasions, and for CO six times. No association was found between PEFR and any of the pollution variables. A rise in the PM10 concentration equivalent to the interquartile range was associated with an increase in night time chest symptoms (relative risk 1.38, 95% CI 1.07 to 1.78). A rise in NO2 concentrations equivalent to the interquartile range was associated with increased reliever inhaler use (relative risk 1.42, 95% CI 1.13 to 1.79) and for 24 hour lag analysis with increased nebuliser use (relative risk 2.81, 95% CI 1.81 to 4.39). There was no increase in the relative risk of other symptoms in relation to pollution levels. CONCLUSIONS: These effects, demonstrated in a small susceptible group of subjects with COPD, indicate that adverse outcomes can be measured in response to pollution levels that are within current guidelines. 

PMCID: PMC1758472  PMID: 9516896
3.  Effects of ozone and other pollutants on the pulmonary function of adult hikers. 
This study evaluated the acute effects of ambient ozone (O3), fine particulate matter (PM2.5), and strong aerosol acidity on the pulmonary function of exercising adults. During the summers of 1991 and 1992, volunteers (18-64 years of age) were solicited from hikers on Mt. Washington, New Hampshire. Volunteer nonsmokers with complete covariates (n = 530) had pulmonary function measured before and after their hikes. We calculated each hiker's posthike percentage change in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), the ratio of these two (FEV1/FVC), forced expiratory flow between 25 and 75% of FVC(FEF25-75%), and peak expiratory flow rate (PEFR). Average O3 exposures ranged from 21 to 74 ppb. After adjustment for age,sex, smoking status (former versus never), history of asthma or wheeze, hours hiked, ambient temperature, and other covariates, there was a 2.6% decline in FEV1 [95% confidence interval (CI), 0.4-4.7; p = 0.02] and a 2.2% decline in FVC (CI, 0.8-3.5; p =0.003) for each 50 ppb increment in mean O3. There were consistent associations of decrements in both FVC (0.4% decline; CI,0.2-0.6, p = 0.001) and PEFR (0.8% decline; CI, 0.01-1.6; p = 0.05) with PM2.5 and of decrements in PEFR (0.4% decline; CI, 0.1-0.7; p = 0.02) with strong aerosol acidity across the interquartile range of these exposures. Hikers with asthma or a history of wheeze (n = 40) had fourfold greater responsiveness to ozone than others. With prolonged outdoor exercise, low-level exposures to O3, PM2.5, and strong aerosol acidity were associated with significant effects on pulmonary function among adults. Hikers with a history of asthma or wheeze had significantly greater air pollution-related changes in pulmonary function.
PMCID: PMC1533017  PMID: 9435151
4.  Time trends in respiratory symptoms in childhood over a 24 year period. 
Archives of Disease in Childhood  1993;68(6):729-734.
Two cross sectional surveys, 24 years apart, using the same respiratory questionnaire, were carried out to examine changes in prevalence rates of cough, phlegm, and wheeze and to relate changes in wheeze to objective peak expiratory flow rates (PEFRs). The surveys were done in towns in southern and northern England and South Wales in schoolchildren aged 6.0-7.5 years; n = 1655 in 1966 and n = 2323 in 1990. Parents reported on winter cough and winter phlegm (early morning or day/night) and wheeze; PEFRs were also measured. The proportion of children reported as wheezing on most days or nights increased from 3.9% to 6.1% (95% confidence interval (CI) for increase -0.2 to 4.6), with a smaller increase in the prevalence of those who had ever wheezed. The proportion of children with day or night time cough increased from 21.1% to 33.3% (95% CI for increase 3.8 to 20.6) and the proportion with day or night time phlegm increased from 5.8% to 10.0% (95% CI for increase 0.4 to 8.0). Smaller increases in the prevalence of persistent cough (from 9.0% to 12.4%) and persistent phlegm (from 2.4% to 3.5%) were also observed, while morning cough and morning phlegm showed little change. The increases in cough and phlegm were apparent in subjects with and without a history of wheeze. Both absolute and proportional changes in symptom prevalence were generally greater in the north than in the south. Similar social class trends were seen in each survey. The mean difference in PEFR between subjects with and without wheeze was smaller in 1990 than in 1966, but this result could be influenced by a greater proportion of subjects receiving antiasthmatic treatment in the 1990 survey. These apparent increases in the prevalence of persistent wheeze, day and night time cough and phlegm, occurring over a period during which outdoor air pollution levels have decreased substantially, deserve further investigation.
PMCID: PMC1029362  PMID: 8333760
5.  Cardiorespiratory Biomarker Responses in Healthy Young Adults to Drastic Air Quality Changes Surrounding the 2008 Beijing Olympics 
Associations between air pollution and cardiorespiratory mortality and morbidity have been well established, but data to support biologic mechanisms underlying these associations are limited. We designed this study to examine several prominently hypothesized mechanisms by assessing Beijing residents’ biologic responses, at the biomarker level, to drastic changes in air quality brought about by unprecedented air pollution control measures implemented during the 2008 Beijing Olympics.
To test the hypothesis that changes in air pollution levels are associated with changes in biomarker levels reflecting inflammation, hemostasis, oxidative stress, and autonomic tone, we recruited and retained 125 nonsmoking adults (19 to 33 years old) free of cardiorespiratory and other chronic diseases. Using the combination of a quasi-experimental design and a panel-study approach, we measured biomarkers of autonomic dysfunction (heart rate [HR*] and heart rate variability [HRV]), of systemic inflammation and oxidative stress (plasma C-reactive protein [CRP], fibrinogen, blood cell counts and differentials, and urinary 8-hydroxy-2′-deoxyguanosine [8-OHdG]), of pulmonary inflammation and oxidative stress (fractional exhaled nitric oxide [FeNO], exhaled breath condensate [EBC] pH, EBC nitrate, EBC nitrite, EBC nitrite+nitrate [sum of the concentrations of nitrite and nitrate], and EBC 8-isoprostane), of hemostasis (platelet activation [plasma sCD62P and sCD40L], platelet aggregation, and von Willebrand factor [vWF]), and of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). These biomarkers were measured on each subject twice before, twice during, and twice after the Beijing Olympics. For each subject, repeated measurements were separated by at least one week to avoid potential residual effects from a prior measurement. We measured a large suite of air pollutants (PM2.5 [particulate matter ≤ 2.5 μm in aerodynamic diameter] and constituents, sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and ozone [O3]) throughout the study at a central Beijing site near the residences and workplaces of the subjects on a daily basis. Total particle number (TPN) was also measured at a separate site. We used a time-series analysis to assess changes in pollutant concentration by period (pre-, during-, and post-Olympics periods). We used mixed-effects models to assess changes in biomarker levels by period and to estimate changes associated with increases in pollutant concentrations, controlling for ambient temperature, relative humidity (RH), sex, and the day of the week of the biomarker measurements. We conducted sensitivity analyses to assess the impact of potential temporal confounding and exposure misclassification.
We observed reductions in mean concentrations for all measured pollutants except O3 from the pre-Olympics period to the during-Olympics period. On average, elemental carbon (EC) changed by −36%, TPN by −22%, SO2 by −60%, CO by −48%, and NO2 by −43% (P < 0.05 for all these pollutants). Reductions were observed in mean concentrations of PM2.5 (by −27%), sulfate (SO42−) (by −13%), and organic carbon (OC) (by −23%); however, these values were not statistically significant. Both 24-hour averages and 1-hour maximums of O3 increased (by 20% and 17%, respectively) from the pre-Olympics to the during-Olympics period. In the post-Olympics period after the pollution control measures were relaxed, mean concentrations of most pollutants (with the exception of SO42− and O3) increased to levels similar to or higher than pre-Olympics levels.
Concomitantly and consistent with the hypothesis, we observed, from the pre-Olympics to the during-Olympics period, statistically significant (P ≤ 0.05) or marginally significant (0.05 < P < 0.1) decreases in HR (−1 bpm or −1.7% [95% CI, −3.4 to −0.1]), SBP (−1.6 mmHg or − 1.8% [95% CI, −3.9 to 0.4]), 8-OHdG (−58.3% [95% CI, −72.5 to −36.7]), FeNO (−60.3% [95% CI, −66.0 to −53.6]), EBC nitrite (−30.0% [95% CI, −39.3 to −19.3]), EBC nitrate (−21.5% [95% CI, −35.5 to −4.5]), EBC nitrite+nitrate (−17.6% [95% CI, −28.4 to −5.1]), EBC hydrogen ions (−46% [calculated from EBC pH], or +3.5% in EBC pH [95% CI, 2.2 to 4.9]), sCD62P (−34% [95% CI, −38.4 to −29.2]), sCD40L (−5.7% [95% CI, −10.5 to −0.7]), and vWF (−13.1% [95% CI, −18.6 to −7.5]). Moreover, the percentages of above-detection values out of all observations were significantly lower for plasma CRP and EBC 8-isoprostane in the during-Olympics period compared with the pre-Olympics period. In the post-Olympics period, the levels of the following biomarkers reversed (increased, either with or without statistical significance) from those in the during-Olympics period: SBP (10.7% [95% CI, 2.8 to 18.6]), fibrinogen (4.3% [95% CI, −1.7 to 10.2), neutrophil count (4.7% [95% CI, −7.7 to 17.0]), 8-OHdG (315% [95% CI, 62.0 to 962]), FeNO (130% [95% CI, 62.5 to 225]), EBC nitrite (159% [95% CI, 71.8 to 292]), EBC nitrate (161% [95% CI, 48.0 to 362]), EBC nitrite+nitrate (124% [95% CI, 50.9 to 233]), EBC hydrogen ions (146% [calculated from EBC pH] or −4.8% in EBC pH [95% CI, −9.4 to −0.2]), sCD62P (33.7% [95% CI, 17.7 to 51.8]), and sCD40L (9.1% [95% CI, −3.7 to 23.5]).
Furthermore, these biomarkers also showed statistically significant associations with multiple pollutants across different lags after adjusting for meteorologic parameters. The associations were in the directions hypothesized and were consistent with the findings from the comparisons between periods, providing further evidence that the period effects were due to changes in air quality, independent of season and meteorologic conditions or other potential confounders. Contrary to our hypothesis, however, we observed increases in platelet aggregation, red blood cells (RBCs) and white blood cells (WBCs) associated with the during-Olympics period, as well as significant negative associations of these biomarkers with pollutant concentrations. We did not observe significant changes in any of the HRV indices and DBP by period. However, we observed associations between a few HRV indices and pollutant concentrations.
Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of pulmonary and systemic inflammation, oxidative stress, and hemostasis and in measures of cardiovascular physiology (HR and SBP) in healthy, young adults. These changes support the prominently hypothesized mechanistic pathways underlying the cardiorespiratory effects of air pollution.
PMCID: PMC4086245  PMID: 23646463
6.  Using community level strategies to reduce asthma attacks triggered by outdoor air pollution: a case crossover analysis 
Environmental Health  2014;13:58.
Evidence indicates that asthma attacks can be triggered by exposure to ambient air pollutants, however, detailed pollution information is missing from asthma action plans. Asthma is commonly associated with four criteria pollutants with standards derived by the United States Environmental Protection Agency. Since multiple pollutants trigger attacks and risks depend upon city-specific mixtures of pollutants, there is lack of specific guidance to reduce exposure. Until multi-pollutant statistical modeling fully addresses this gap, some guidance on pollutant attack risk is required. This study examines the risks from exposure to the asthma-related pollutants in a large metropolitan city and defines the city-specific association between attacks and pollutant mixtures. Our goal is that city-specific pollution risks be incorporated into individual asthma action plans as additional guidance to prevent attacks.
Case-crossover analysis and conditional logistic regression were used to measure the association between ozone, fine particulate matter, nitrogen dioxide, sulfur dioxide and carbon monoxide pollution and 11,754 emergency medical service ambulance treated asthma attacks in Houston, Texas from 2004-2011. Both single and multi-pollutant models are presented.
In Houston, ozone and nitrogen dioxide are important triggers (RR = 1.05; 95% CI: 1.00, 1.09), (RR = 1.10; 95% CI: 1.05, 1.15) with 20 and 8 ppb increase in ozone and nitrogen dioxide, respectively, in a multi-pollutant model. Both pollutants are simultaneously high at certain times of the year. The risk attributed to these pollutants differs when they are considered together, especially as concentrations increase. Cumulative exposure for ozone (0-2 day lag) is of concern, whereas for nitrogen dioxide the concern is with single day exposure. Persons at highest risk are aged 46-66, African Americans, and males.
Accounting for cumulative and concomitant outdoor pollutant exposure is important to effectively attribute risk for triggering of an asthma attack, especially as concentrations increase. Improved asthma action plans for Houston individuals should warn of these pollutants, their trends, correlation and cumulative effects. Our Houston based study identifies nitrogen dioxide levels and the three-day exposure to ozone to be of concern whereas current single pollutant based national standards do not.
PMCID: PMC4108967  PMID: 25012280
Asthma; Air pollution; Risk; Ozone; Nitrogen dioxide; Action plans
7.  The effects of ambient ozone on lung function in children: a reanalysis of six summer camp studies. 
Environmental Health Perspectives  1996;104(2):170-174.
Studies of children attending summer camps often have observed relationships between daily outdoor ozone (O3) concentrations and decreased lung function that are qualitatively similar to results seen in human chamber studies. The former studies, focusing on the pulmonary effects of O3 and associated pollutants on children under natural conditions of exposure, are potentially of great importance to understanding the public health impact of ambient O3. However, a thorough assessment of the results of these studies has been hampered by differences in the analysis and reporting of data across the various studies. We obtained data sets from six summer camp studies carried out by three separate investigative groups, including two New Jersey studies performed by New York University, two studies in Ontario carried out by Health and Welfare Canada, and two studies in southern California. The data consisted of sequential, daily measurements of forced expiratory volume in 1 sec (FEV1), peak expiratory flow rate (PEFR), and 1-hr O3 concentration in the hour preceding lung function measurements for each child. We analyzed the relationships between lung function and O3 using linear regression models that fit subject-specific intercepts and a single, pooled O3 slope. These models were fit for each of the six studies separately and for all studies combined. All of the study-specific slopes of FEV1 on O3 were negative (i.e., increased O3 associated with decreased FEV1); five of six were statistically significant. Analysis of the combined six-study data set yielded a slope of -0.50 ml FEV1/ppb O3 (p<0.0001). Addition of time-trend variables to the combined-data analysis diminished, but did not eliminate, the FEV1-O3 relationship. Study-specific slopes for PEFR on O3 were more variable. Combined over studies, no significant relationship was observed between PEFR and O3. However, this negative finding appeared to be partially confounded by time trends in PEFR. The results of this reanalysis provide strong evidence that children exposed to O3 under natural conditions experience decreases in FEV1 of the kind demonstrated in laboratory studies, and raise concern that other acute respiratory effects observed in those studies (e.g., pulmonary inflammation) may also occur in young people exposed to ambient O3.
PMCID: PMC1469279  PMID: 8820584
8.  Acute effects of summer air pollution on respiratory function in primary school children in southern England. 
Thorax  1996;51(11):1109-1114.
BACKGROUND: There is growing concern about health effects of air pollution in the UK. Studies in the USA have reported adverse effects on lung function among children but no comparable studies have been published in the UK. This study investigates the relationship between daily changes in ambient air pollution and short term variations in lung function in a panel of school children. METHODS: One hundred and fifty four children aged 7-11 attending a primary school adjacent to a major motorway in Surrey, south-east England, were studied. Bellows spirometry was performed daily on 31 schooldays between 6 June and 21 July 1994. Levels of ozone, nitrogen dioxide, and particulates of less than 10 microns in diameter (PM10) were measured continuously at the school and the pollen count was measured six miles away. Relationships between daily changes in forced expiratory volume in 0.75 seconds (FEV0.75), forced vital capacity (FVC), the FEV0.75/FVC ratio and pollutants were analysed using separate autoregressive models for each child. A weighted average of the resulting slopes was then calculated. RESULTS: There was a significant inverse relationship between daily mean PM10 levels lagged one day and FVC, with a reduction in lung function of 1% (95% CI 0.3% to 2%) across the whole range of PM10 levels (20-150 micrograms/m3). The effect on FEV0.75 was similar (-0.5%) but was not significant when weighted by 1/SE2 (95% CI -1.2% to 0.2%). There was no effect of PM10 levels on the FEV0.75/FVC ratio. No significant association was seen between FEV0.75, FVC, or the FEV0.75/FVC ratio and either ozone or nitrogen dioxide levels. There was no evidence that wheezy children were more affected than healthy children. Pollen levels on the previous day had no effect on lung function and did not change the air pollution results. CONCLUSIONS: There is a very small, but statistically significant, adverse effect of airborne respirable particulate matter, measured as PM10, on lung function in this study group. There is no evidence for an inverse association of lung function with levels of ozone or NO2 measured on the previous day.
PMCID: PMC1090522  PMID: 8958894
9.  The effect of outdoor fungal spore concentrations on daily asthma severity. 
Environmental Health Perspectives  1997;105(6):622-635.
The relationship between day-to-day changes in asthma severity and combined exposures to community air pollutants and aeroallergens remains to be clearly defined. We examined the effects of outdoor air pollutants, fungi, and pollen on asthma. Twenty-two asthmatics ages 9-46 years were followed for 8 weeks (9 May-3 July 1994) in a semirural Southern California community around the air inversion base elevation (1,200 ft). Daily diary responses included asthma symptom severity (6 levels), morning and evening peak expiratory flow rates (PEFR), and as-needed beta-agonist inhaler use. Exposures included 24-hr outdoor concentrations of fungi, pollen, and particulate matter with a diameter < 10 microns (PM10; maximum = 51 micrograms/m3) and 12-hour day-time personal ozone (O3) measurements (90th percentile = 38 ppb). Random effects longitudinal regression models controlled for autocorrelation and weather. Higher temperatures were strongly protective, probably due to air conditioning use and diminished indoor allergens during hot, dry periods. Controlling for weather, total fungal spore concentrations were associated with all outcomes: per minimum to 90th percentile increase of nearly 4,000 spores/m3, asthma symptom scores increased 0.36 (95% CI, 0.16-0.56), inhaler use increased 0.33 puffs (95% CI, -0.02-0.69), and evening PEFR decreased 12.1 l/min (95% CI, -1.8-22.3). These associations were greatly enhanced by examining certain fungal types (e.g., Alternaria, basidiospores, and hyphal fragments) and stratifying on 16 asthmatics allergic to tested deuteromycete fungi. There were no significant associations to low levels of pollen or O3, but inhaler use was associated with PM10 (0.15 inhaler puffs/10 micrograms/m3; p < 0.02). These findings suggest that exposure to fungal spores can adversely effect the daily respiratory status of some asthmatics.
PMCID: PMC1470068  PMID: 9288497
10.  Association of air pollution with daily GP consultations for asthma and other lower respiratory conditions in London 
Thorax  1999;54(7):597-605.
BACKGROUND—Very few published studies have looked at the effects of air pollution on health in the primary care setting. As part of a large study to examine the association between air pollution and a number of health outcomes, the relationship between daily GP consultations for asthma and other lower respiratory diseases (LRD) and air pollution in London was investigated.
METHODS—Time-series analysis of daily numbers of GP consultations controlling for time trends, seasonal factors, day of week cycles, influenza, weather, pollen levels, and serial correlation was performed. Consultation data were available from between 268 718 and 295 740 registered patients from 45-47 London practices contributing to the General Practice Research Database during 1992-4.
RESULTS—Positive associations, weakly significant and consistent across lags, were observed between asthma consultations and nitrogen dioxide (NO2) and carbon monoxide (CO) in children and particulate matter of less than 10 µm in diameter (PM10) in adults, and between other LRD consultations and sulphur dioxide (SO2) in children. A consistently negative association with ozone in children was observed in both disease categories. The effect estimates of most pollutants were much larger when analysed separately by season, particularly in the children: percentage change in asthma consultations during the warm season (April-September) for a 10-90th percentile increase in 24 hour NO2 lagged by one day = 13.2% (95% CI 5.6to 21.3), with CO = 11.4% (95% CI 3.3 to 20.0), and with SO2 =9.0% (95% CI 2.2 to 16.2). In adults the only association consistent over different lag periods was with PM10 = 9.2% (3.7 to 15.1). The associations of pollution and consultations for LRD were increased mainly in the winter months: percentage change in consultations by children in winter with NO2 = 7.2% (95% CI 2.8 to 11.6), CO= 6.2% (95% CI 2.3 to 10.2), and SO2 = 5.8% (95% CI 1.6 to 10.2).
CONCLUSIONS—There are associations between air pollution and daily consultations for asthma and other lower respiratory disease in London. The most significant associations were observed in children and the most important pollutants were NO2, CO, and SO2. In adults the only consistent association was with PM10.

PMCID: PMC1745519  PMID: 10377204
11.  Season, Sex, Age, and Education as Modifiers of the Effects of Outdoor Air Pollution on Daily Mortality in Shanghai, China: The Public Health and Air Pollution in Asia (PAPA) Study 
Environmental Health Perspectives  2008;116(9):1183-1188.
Various factors can modify the health effects of outdoor air pollution. Prior findings about modifiers are inconsistent, and most of these studies were conducted in developed countries.
We conducted a time-series analysis to examine the modifying effect of season, sex, age, and education on the association between outdoor air pollutants [particulate matter < 10 μm in aerodynamic diameter (PM10), sulfur dioxide, nitrogen dioxide, and ozone] and daily mortality in Shanghai, China, using 4 years of daily data (2001–2004).
Using a natural spline model to analyze the data, we examined effects of air pollution for the warm season (April–September) and cool season (October–March) separately. For total mortality, we examined the association stratified by sex and age. Stratified analysis by educational attainment was conducted for total, cardiovascular, and respiratory mortality.
Outdoor air pollution was associated with mortality from all causes and from cardiorespiratory diseases in Shanghai. An increase of 10 μg/m3 in a 2-day average concentration of PM10, SO2, NO2, and O3 corresponds to increases in all-cause mortality of 0.25% [95% confidence interval (CI), 0.14–0.37), 0.95% (95% CI, 0.62–1.28), 0.97% (95% CI, 0.66–1.27), and 0.31% (95% CI, 0.04–0.58), respectively. The effects of air pollutants were more evident in the cool season than in the warm season, and females and the elderly were more vulnerable to outdoor air pollution. Effects of air pollution were generally greater in residents with low educational attainment (illiterate or primary school) compared with those with high educational attainment (middle school or above).
Season, sex, age, and education may modify the health effects of outdoor air pollution in Shanghai. These findings provide new information about the effects of modifiers on the relationship between daily mortality and air pollution in developing countries and may have implications for local environmental and social policies.
PMCID: PMC2535620  PMID: 18795161
air pollution; modifiers; mortality; time-series studies
12.  Temporal association between hospital admissions for asthma in Birmingham and ambient levels of sulphur dioxide and smoke. 
Thorax  1994;49(2):133-140.
BACKGROUND--A study was performed to determine whether daily and weekly variations in the levels of smoke and sulphur dioxide (SO2) in Birmingham are related to hospital admissions for asthma and acute respiratory diseases. METHODS--Daily numbers of hospital admissions for asthma (ICD code 493) and acute respiratory conditions (ICD 466, 480-486, 490-496) for residents of Birmingham between 1988 and 1990 were obtained from West Midlands RHA Körner inpatient data. Average daily levels of sulphur dioxide and smoke were obtained from Birmingham City Council for the same period, together with daily meteorological summaries from the Department of Geography, University of Birmingham. With the exception of one day, all air pollution measurements remained within current EC guide levels. Data were divided into seasons and the relation between hospital admissions and pollutant levels were explored by stepwise least squares regression models. Meteorological variables (temperature, pressure, humidity) were entered into the model if they showed significant association with hospital admissions during the season in question. Analysis was undertaken for daily (same day and lagged by two days) and weekly pollutant levels. Admissions were lagged behind pollution levels to allow for delayed effects of pollutants. RESULTS--The mean daily level of smoke was 12.7 micrograms/m3 and of SO2 was 39.1 micrograms/m3, with maxima of 188.3 micrograms/m3 and 126.3 micrograms/m3, respectively. Significant associations were found between hospital admissions for respiratory disease lagged by two days, and smoke and SO2 levels during winter. Associations between admissions for asthma and smoke and SO2 levels were significant at the 5% level. These were independent of temperature, pressure, and humidity. Stepwise regression including both pollutants showed that smoke, but not SO2, was a significant independent predictor of hospital admissions for both asthma and all respiratory conditions. During winter a rise of 100 micrograms/m3 smoke might result in five (95% CI 0.6 to 9) more asthma admissions and 21.5 (95% CI 10 to 33) more acute respiratory admissions each day in Birmingham. A 100 micrograms/m3 rise in SO2 might result in four (0 to 7) more asthma admissions and 15.5 (6 to 25) more respiratory admissions each day. Independent associations were also found between weekly mean smoke and SO2 levels and all respiratory admissions during autumn and winter. During summer, daily mean smoke and SO2 levels were significantly associated with non-lagged daily admissions for all respiratory diseases (p < 0.02). There was no association between air pollution and hospital admissions during spring. CONCLUSIONS--Daily variations in smoke and SO2 levels are significantly associated with hospital admissions for asthma and respiratory disease during winter in Birmingham at levels of air pollutants within the EC guide levels. This association was independent of potential confounding effects of weather (temperature, pressure, humidity) and suggests that current levels of air pollution can still produce significant health effects.
PMCID: PMC474324  PMID: 8128402
13.  Associations between ambient ozone, hydrocarbons, and childhood wheezy episodes: a prospective observational study in south east London 
OBJECTIVES—To explore the hypothesis that hydrocarbon species and other air pollutants which accumulate at low and high concentrations of ozone are more directly associated with childhood wheezy episodes than ozone.
METHODS—Prospective observational study over 1 year set in the Lewisham district of south east London. The daily attendance rate of children with acute wheeze at the accident and emergency department of Lewisham Hospital was related to local measurements of ozone, hydrocarbon species, nitrogen dioxide (NO2), sulphur dioxide (SO2) and small particulate matter with diameter <10µm (PM10).
RESULTS—An inverse relation was found between the air pollutants and ozone. After seasonal and meteorological adjustment a non-linear U shaped trend was found between incidence of wheeze and ozone. The trend was significant in children <2 years of age but not in older children. In the younger age group, after adjustment for season, temperature, wind speed, and respiratory infection, the incidence relative to that at the mean daily ozone concentration of 32.7 µg/m3, was estimated to increase by 65% (95% confidence interval (95% CI) 22% to 122%) at an ozone concentration of 5 µg/m3 (1.5 SDs below the mean) and by 63% (95%CI −6% to 184%) at 80 µg/m3 (2.5 SDs above the mean). For several hydrocarbons there were significant positive linear relations found, again in children <2 years of age but not older children. For benzene, the incidence increased by 8% (95% CI 2 to 13%) per SD (SD 2.8 µg/m3) increase in benzene concentration. A same day association between incidence and ozone was found to be the most significant but for other pollutants a lag of 2 days gave the most significant associations. No significant association was found for the non-hydrocarbon pollutants including SO2, NO2, and PM10.
CONCLUSIONS—A U shaped relation was found between ozone and the incidence of wheezy episodes in young children. Certain hydrocarbon pollutants accumulate in the atmosphere when ozone concentrations are low, and are associated with childhood wheezy episodes. However, the U shaped association of ozone on incidence cannot be explained by these other pollutants. The finding supports an earlier finding that incidences of wheeze are at a minimum when ozone concentrations are 30-40 µg/m3.

Keywords: air pollution; ozone; hydrocarbons; childhood wheezing
PMCID: PMC1739904  PMID: 10711275
14.  Air Pollution and the Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of Atherosclerosis (MESA) 
PLoS Medicine  2010;7(11):e1000372.
Sara Adar and colleagues show that residing in locations with higher air pollution concentrations and experiencing daily increases in air pollution are associated with narrower retinal arteriolar diameters in older individuals, thus providing a link between air pollution and cardiovascular disease.
Long- and short-term exposures to air pollution, especially fine particulate matter (PM2.5), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature.
Methods and Findings
Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000–2002). Long-term outdoor concentrations of PM2.5 were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM2.5. These relationships were observed in a joint exposure model with −0.8 µm (95% confidence interval [CI] −1.1 to −0.5) and −0.4 µm (95% CI −0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m3) and short-term (9 µg/m3) PM2.5 levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a −0.7 µm decrease (95% CI −1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM2.5 concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM2.5.
Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease.
Please see later in the article for the Editors' Summary
Editors' Summary
Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a common cause of illness and death among adults in developed countries. In the United States, for example, the leading cause of death is coronary heart disease, a CVD in which narrowing of the heart's arteries by atherosclerotic plaques (fatty deposits that build up with age) slows the blood supply to the heart and may eventually cause a heart attack (myocardial infarction). Other types of CVD include stroke (in which atherosclerotic plaques interrupt the brain's blood supply) and peripheral arterial disease (in which the blood supply to the limbs is blocked). Smoking, high blood pressure, high blood levels of cholesterol (a type of fat), having diabetes, being overweight, and being physically inactive all increase a person's risk of developing CVD. Treatments for CVD include lifestyle changes and taking drugs that lower blood pressure or blood cholesterol levels.
Why Was This Study Done?
Another risk factor for CVD is exposure to long-term and/or short-term air pollution. Fine particle pollution or PM2.5 is particularly strongly associated with an increased risk of CVD. PM2.5—particulate matter 2.5 µm in diameter or 1/30th the diameter of a human hair—is mainly produced by motor vehicles, power plants, and other combustion sources. Why PM2.5 increases CVD risk is not clear but one possibility is that it alters the body's microvasculature (fine blood vessels known as capillaries, arterioles, and venules), thereby impairing the blood flow through the heart and brain. In this study, the researchers use noninvasive digital retinal photography to investigate whether there is an association between air pollution and changes in the human microvasculature. The retina—a light-sensitive layer at the back of the eye that converts images into electrical messages and sends them to the brain—has a dense microvasculature. Retinal photography is used to check the retinal microvasculature for signs of potentially blinding eye diseases such as diabetic retinopathy. Previous studies have found that narrower than normal retinal arterioles and wider than normal retinal venules are associated with CVD.
What Did the Researchers Do and Find?
The researchers used digital retinal photography to measure the diameters of retinal blood vessels in the participants of the Multi-Ethnic Study of Atherosclerosis (MESA). This study is investigating CVD progression in people aged 45–84 years of various ethnic backgrounds who had no CVD symptoms when they enrolled in the study in 2000–2002. The researchers modeled the long-term outdoor concentration of PM2.5 at each participant's house for the 2-year period preceding the retinal examination (which was done between 2002 and 2003) using data on PM2.5 levels collected by regulatory monitoring stations as well as study-specific air samples collected outside of the homes and in the communities of study participants. Outdoor PM2.5 measurements taken the day before the examination provided short-term PM2.5 levels. Among the 4,607 MESA participants who had complete data, retinal arteriolar diameters were narrowed among those who lived in regions with increased long- and short-term PM2.5 levels. Specifically, an increase in long-term PM2.5 concentrations of 3 µg/m3 was associated with a 0.8 µm decrease in arteriolar diameter, a reduction equivalent to that seen for a 7-year increase in age in this group of people. Living near a major road, another indicator of long-term exposure to PM2.5 pollution, was also associated with narrowed arterioles. Finally, increased retinal venular diameters were weakly associated with long-term high PM2.5 concentrations.
What Do These Findings Mean?
These findings indicate that living in areas with long-term air pollution or being exposed to short-term air pollution is associated with narrowing of the retinal arterioles in older individuals. They also show that widening of retinal venules is associated with long-term (but not short-term) PM2.5 pollution. Together, these findings support the hypothesis that long- and short-term air pollution increases CVD risk through effects on the microvasculature. However, they do not prove that PM2.5 is the constituent of air pollution that drives microvascular changes—these findings could reflect the toxicity of another pollutant or the pollution mixture as a whole. Importantly, these findings show that microvascular changes can occur at the PM2.5 levels that commonly occur in developed countries, which are well below those seen in developing countries. Worryingly, they also suggest that the deleterious cardiovascular effects of air pollution could occur at levels below existing regulatory standards.
Additional Information
Please access these Web sites via the online version of this summary at 10.1371/journal.pmed.1000372.
The American Heart Association provides information for patients and caregivers on all aspects of cardiovascular disease (in several languages), including information on air pollution, heart disease, and stroke
The US Centers for Disease Control and Prevention has information on heart disease and on stroke
Information is available from the British Heart Foundation on cardiovascular disease
The UK National Health Service Choices website provides information for patients and caregivers about cardiovascular disease
MedlinePlus provides links to other sources of information on heart disease and on vascular disease (in English and Spanish)
The AIRNow site provides information about US air quality and about air pollution and health
The Air Quality Archive has up-to-date information about air pollution in the UK and information about the health effects of air pollution
The US Environmental Protection Agency has information on PM2.5
The following Web sites contain information available on the MESA and MESA Air studies
PMCID: PMC2994677  PMID: 21152417
15.  Asthmatic Symptoms among Pupils in Relation to Winter Indoor and Outdoor Air Pollution in Schools in Taiyuan, China 
There are few studies on associations between children’s respiratory heath and air pollution in schools in China. The industrial development and increased traffic may affect the indoor exposure to air pollutants in school environment. Moreover, there is a need to study respiratory effects of environmental tobacco smoke (ETS) and emissions from new building materials in homes in China.
We studied the associations between pupils’ asthmatic symptoms and indoor and outdoor air pollution in schools, as well as selected home exposures, in a coal-burning city in north China.
A questionnaire survey was administered to pupils (11–15 years of age) in 10 schools in urban Taiyuan, collecting data on respiratory health and selected home environmental factors. Indoor and outdoor school air pollutants and climate factors were measured in winter.
A total of 1,993 pupils (90.2%) participated; 1.8% had cumulative asthma, 8.4% wheezing, 29.8% had daytime attacks of breathlessness. The indoor average concentrations of sulfur dioxide, nitrogen dioxide, ozone, and formaldehyde by class were 264.8, 39.4, 10.1, and 2.3 μg/m3, respectively. Outdoor levels were two to three times higher. Controlling for possible confounders, either wheeze or daytime or nocturnal attacks of breathlessness were positively associated with SO2, NO2, or formaldehyde. In addition, ETS and new furniture at home were risk factors for wheeze, daytime breathlessness, and respiratory infections.
Indoor chemical air pollutants of mainly outdoor origin could be risk factors for pupils’ respiratory symptoms at school, and home exposure to ETS and chemical emissions from new furniture could affect pupils’ respiratory health.
PMCID: PMC2199281  PMID: 18197305
air pollution; asthma; China; formaldehyde; indoor; nitrogen dioxide; ozone; outdoor; school; sulfur dioxide
16.  Air pollution, pollens, and daily admissions for asthma in London 1987-92 
Thorax  1998;53(10):842-848.
BACKGROUND—A study was undertaken to investigate the relationship between daily hospital admissions for asthma and air pollution in London in 1987-92 and the possible confounding and modifying effects of airborne pollen.
METHODS—For all ages together and the age groups 0-14, 15-64 and 65+ years, Poisson regression was used to estimate the relative risk of daily asthma admissions associated with changes in ozone, sulphur dioxide, nitrogen dioxide and particles (black smoke), controlling for time trends, seasonal factors, calendar effects, influenza epidemics, temperature, humidity, and autocorrelation. Independent effects of individual pollutants and interactions with aeroallergens were explored using two pollutant models and models including pollen counts (grass, oak and birch).
RESULTS—In all-year analyses ozone was significantly associated with admissions in the 15-64 age group (10 ppb eight hour ozone, 3.93% increase), nitrogen dioxide in the 0-14 and 65+ age groups (10ppb 24 hour nitrogen dioxide, 1.25% and 2.96%, respectively), sulphur dioxide in the 0-14 age group (10 µg/m3 24 hour sulphur dioxide, 1.64%), and black smoke in the 65+ age group (10 µg/m3 black smoke, 5.60%). Significant seasonal differences were observed for ozone in the 0-14 and 15-64 age groups, and in the 0-14 age group there were negative associations with ozone in the cool season. In general, cumulative lags of up to three days tended to show stronger and more significant effects than single day lags. In two-pollutant models these associations were most robust for ozone and least for nitrogen dioxide. There was no evidence that the associations with air pollutants were due to confounding by any of the pollens, and little evidence of an interaction between pollens and pollution except for synergism of sulphur dioxide and grass pollen in children (p<0.01).
CONCLUSIONS—Ozone, sulphur dioxide, nitrogen dioxide, and particles were all found to have significant associations with daily hospital admissions for asthma, but there was a lack of consistency across the age groups in the specific pollutant. These associations were not explained by confounding by airborne pollens nor was there convincing evidence that the effects of air pollutants and airborne pollens interact in causing hospital admissions for asthma.

PMCID: PMC1745078  PMID: 10193370
17.  Ozone and Daily Mortality in Shanghai, China 
Environmental Health Perspectives  2006;114(8):1227-1232.
Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O3 on death risk. Given the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China’s large cities, it is worthwhile to investigate the acute effect of O3 on mortality outcomes in the country.
We conducted a time-series study to investigate the relation between O3 and daily mortality in Shanghai using 4 years of daily data (2001–2004).
We used the generalized additive model with penalized splines to analyze mortality, O3 pollution, and covariate data in warm and cold seasons. We considered daily counts of all-cause mortality and several cause-specific subcategories (respiratory and cardiovascular). We also examined these associations among several subpopulations based on age and sex.
O3 was significantly associated with total and cardiovascular mortality in the cold season but not in the warm season. In the whole-year analysis, an increase of 10 μg/m3 of 2-day average (lag01) O3 corresponds to 0.45% [95% confidence interval (CI), 0.16–0.73%], 0.53% (95% CI, 0.10–0.96%), and 0.35% (95% CI, −0.40 to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory mortality, respectively. In the cold season, the estimates increased to 1.38% (95% CI, 0.68–2.07%), 1.53% (95% CI, 0.54–2.52%), and 0.95% (95% CI, −0.71 to 2.60%), respectively. In the warm season, we did not observe significant associations for both total and cause-specific mortality. The results were generally insensitive to model specifications such as lag structure of O3 concentrations and degree of freedom for time trend. Multipollutant models indicate that the effect of O3 was not confounded by particulate matter ≤ 10 μm in diameter (PM10) or by sulfur dioxide; however, after adding nitrogen dioxide into the model, the association of O3 with total and cardiovascular mortality became statistically insignificant.
O3 pollution has stronger health effects in the cold than in the warm season in Shanghai. Our analyses also strengthen the rationale for further limiting levels of O3 pollution in outdoor air in the city.
PMCID: PMC1552011  PMID: 16882530
air pollution; mortality; ozone; time-series studies
18.  Temporal relationship between air pollutants and hospital admissions for chronic obstructive pulmonary disease in Hong Kong 
Thorax  2007;62(9):780-785.
To assess any relationship between the levels of ambient air pollutants and hospital admissions for chronic obstructive pulmonary disease (COPD) in Hong Kong.
A retrospective ecological study was undertaken. Data of daily emergency hospital admissions to 15 major hospitals in Hong Kong for COPD and indices of air pollutants (sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), particulates with an aerodynamic diameter of <10 μm (PM10) and 2.5 μm (PM2.5)) and meteorological variables from January 2000 to December 2004 were obtained from several government departments. Analysis was performed using generalised additive models with Poisson distribution, adjusted for the effects of time trend, season, other cyclical factors, temperature and humidity. Autocorrelation and overdispersion were corrected.
Significant associations were found between hospital admissions for COPD with all five air pollutants. Relative risks for admission for every 10 μg/m3 increase in SO2, NO2, O3, PM10 and PM2.5 were 1.007, 1.026, 1.034, 1.024 and 1.031, respectively, at a lag day ranging from lag 0 to cumulative lag 0–5. In a multipollutant model, O3, SO2 and PM2.5 were significantly associated with increased admissions for COPD. SO2, NO2 and O3 had a greater effect on COPD admissions in the cold season (December to March) than during the warm season.
Ambient concentrations of air pollutants have an adverse effect on hospital admissions for COPD in Hong Kong, especially during the winter season. This might be due to indoor exposure to outdoor pollution through open windows as central heating is not required in the mild winter. Measures to improve air quality are urgently needed.
PMCID: PMC2117326  PMID: 17311838
19.  Evaluating Multipollutant Exposure and Urban Air Quality: Pollutant Interrelationships, Neighborhood Variability, and Nitrogen Dioxide as a Proxy Pollutant 
Background: Although urban air pollution is a complex mix containing multiple constituents, studies of the health effects of long-term exposure often focus on a single pollutant as a proxy for the entire mixture. A better understanding of the component pollutant concentrations and interrelationships would be useful in epidemiological studies that exploit spatial differences in exposure by clarifying the extent to which measures of individual pollutants, particularly nitrogen dioxide (NO2), represent spatial patterns in the multipollutant mixture.
Objectives: We examined air pollutant concentrations and interrelationships at the intraurban scale to obtain insight into the nature of the urban mixture of air pollutants.
Methods: Mobile measurements of 23 air pollutants were taken systematically at high resolution in Montreal, Quebec, Canada, over 34 days in the winter, summer, and autumn of 2009.
Results: We observed variability in pollution levels and in the statistical correlations between different pollutants according to season and neighborhood. Nitrogen oxide species (nitric oxide, NO2, nitrogen oxides, and total oxidized nitrogen species) had the highest overall spatial correlations with the suite of pollutants measured. Ultrafine particles and hydrocarbon-like organic aerosol concentration, a derived measure used as a specific indicator of traffic particles, also had very high correlations.
Conclusions: Our findings indicate that the multipollutant mix varies considerably throughout the city, both in time and in space, and thus, no single pollutant would be a perfect proxy measure for the entire mix under all circumstances. However, based on overall average spatial correlations with the suite of pollutants measured, nitrogen oxide species appeared to be the best available indicators of spatial variation in exposure to the outdoor urban air pollutant mixture.
Citation: Levy I, Mihele C, Lu G, Narayan J, Brook JR. 2014. Evaluating multipollutant exposure and urban air quality: pollutant interrelationships, neighborhood variability, and nitrogen dioxide as a proxy pollutant. Environ Health Perspect 122:65–72;
PMCID: PMC3888565  PMID: 24225648
20.  Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use. 
Environmental Health Perspectives  2002;110(10):A607-A617.
Maxima of hourly data from outdoor monitors may capture adverse effects of outdoor particulate matter (PM) exposures in asthmatic children better than do 24-hr PM averages, which form the basis of current regulations in the United States. Also, asthmatic children on anti-inflammatory medications may be protected against the proinflammatory effects of air pollutants and aeroallergens. We examined strengths of pollutant associations with asthma symptoms between subgroups of asthmatic children who were on versus not on regularly scheduled anti-inflammatory medications, and tested associations for different particle averaging times. This is a daily panel study of 22 asthmatic children (9-19 years of age) followed March through April 1996 (1,248 person-days). They lived in nonsmoking households in a semirural area of Southern California within the air inversion mixing zone (range, 1,200-2,100 feet) with transported air pollution from urban areas of Southern California. The dependent variable derived from diary ordinal scores is episodes of asthma symptoms that interfered with daily activities. Minimum to 90th-percentile levels of exposures at the outdoor monitoring site were 12-63 microg/m(3) for 1-hr PM < 10 microm in aerodynamic diameter (PM(10)); 8-46 microg/m(3) for 8-hr PM(10); 7-32 microg/m(3) for 24-hr PM(10); 45-88 ppb for 1-hr O(3); 6-26 ppb for 8-hr NO(2); 70-4,714 particles/m(3) for 12-hr daytime fungi; and 12-744 particles/m(3) for 24-hr pollen. Data were analyzed with generalized estimating equations controlling for autocorrelation. There was no confounding by weather, day of week, or linear time trend. Associations were notably stronger in 12 asthmatic children who were not taking anti-inflammatory medications versus 10 subjects who were. Odds ratios (95% confidence intervals) for asthma episodes in relation to lag 0 minimum to 90th-percentile pollutant changes were, respectively, 1-hr maximum PM(10), 1.92 (1.22-3.02) versus 0.96 (0.25-3.69); 8-hr maximum PM(10), 1.68 (0.91-3.09) versus 0.75 (0.18-3.04); 24-hr average PM(10), 1.35 (0.82-2.22) versus 0.80 (0.24-2.69); 1-hr maximum O(3), 1.28 (0.75-2.17) versus 0.76 (0.24-2.44); 8-hr maximum NO(2), 1.91 (1.07-3.39) versus 1.08 (0.30-3.93); 12-hr fungi, 1.89 (1.24-2.89) versus 0.90 (0.35-2.30); 24-hr pollen, 1.90 (0.99-3.67) versus 0.85 (0.18-3.91). Pollutant associations were stronger during respiratory infections in subjects not on anti-inflammatory medications. Although lag 0 1-hr maximum PM(10) showed the strongest association, the most robust associations were for lag 0 and 3-day moving averages (lags 0-2) of 8-hr maximum and 24-hr mean PM(10) in sensitivity analyses testing for thresholds. Most pollutant effects were largely driven by concentrations in the upper quintile. The divergence of exposure-response relationships by anti-inflammatory medication use is consistent with experimental data on inflammatory mechanisms of airborne pollutants and allergens.
PMCID: PMC1241047  PMID: 12361942
21.  Air pollution and emergency room visits for asthma in Santa Clara County, California. 
Environmental Health Perspectives  1997;105(2):216-222.
During the winters of 1986-1987 through 1991-1992, rainfall throughout much of Northern California was subnormal, resulting in intermittent accumulation of air pollution, much of which was attributable to residential wood combustion (RWC). This investigation examined whether there was a relationship between ambient air pollution in Santa Clara County, California and emergency room visits for asthma during the winters of 1988-1989 through 1991-1992. Emergency room (ER) records from three acute-care hospitals were abstracted to compile daily visits for asthma and a control diagnosis (gastroenteritis) for 3-month periods during each winter. Air monitoring data included daily coefficient of haze (COH) and every-other-day particulate matter with aerodynamic diameter equal to or less than 10 microns (PM10, 24-hr average), as well as hourly nitrogen dioxide and ozone concentrations. Daily COH measurements were used to predict values for missing days of PM10 to develop a complete PM10 time series. Daily data were also obtained for temperature, precipitation, and relative humidity. In time-series analyses using Poisson regression, consistent relationships were found between ER visits for asthma and PM10. Same-day nitrogen dioxide concentrations were also associated with asthma ER visits, while ozone was not. Because there was a significant interaction between PM10 and minimum temperature in this data set, estimates of relative risks (RRs) for PM10-associated asthma ER visits were temperature-dependent. A 60 micrograms/m3 change in PM10 (2-day lag) corresponded to RRs of 1.43 (95% CI = 1.18-1.69) at 20 degrees F, representing the low end of the temperature distribution, 1.27 (95% CI = 1.13-1.42) at 30 degrees F, and 1.11 (95% CI = 1.03-1.19) at 41 degrees F, the mean of the observed minimum temperature. ER visits for gastroenteritis were not significantly associated with any pollutant variable. Several sensitivity analyses, including the use of robust regressions and of nonparametric methods for fitting time trends and temperature effects in the data, supported these findings. These results demonstrate an association between ambient wintertime PM10 and exacerbations of asthma in an area where one of the principal sources of PM10 is RWC.
PMCID: PMC1469790  PMID: 9105797
22.  Modification by antioxidant supplementation of changes in human lung function associated with air pollutant exposure: A systematic review 
BMC Public Health  2011;11:532.
Outdoor air pollution, given its demonstrated negative effects on the respiratory system, is a growing public health concern worldwide, particularly in urban cities. Human exposure to pollutants such as ozone, nitrogen oxides, combustion-related particulate matter and oxides of sulfur is responsible for significant cardiopulmonary morbidity and mortality in both adults and children. Several antioxidants have shown an ability to partially attenuate the negative physiological and functional impacts of air pollutants. This study systematically presents current data on the potential benefits of antioxidant supplementation on lung function outcomes associated with air pollutant exposures in intact humans.
Electronic databases (MEDLINE, EMBASE, BIOSIS Previews, Web of Sciences, Environmental Sciences & Pollution Management and TOXNET) were systematically searched for all studies published up to April 2009. Search terms relating to the concepts of respiratory tract diseases, respiratory function tests, air pollution, and antioxidants were used. Data was systematically abstracted from original articles that satisfied selection criteria for inclusion. For inclusion, the studies needed to have evaluated human subjects, given supplemental antioxidants, under conditions of known levels of air pollutants with measured lung function before and after antioxidant administration and/or air pollution exposure. Selected studies were summarized and conclusions presented.
Eight studies investigated the role of antioxidant supplementation on measured lung function outcomes after subject exposure to air pollutants under controlled conditions; 5 of these studies concluded that pollutant-induced airway hyper-responsiveness and diminution in lung function measurements were attenuated by antioxidant supplementation. The remaining five studies took place under ambient (uncontrolled) exposures and unanimously concluded that antioxidant supplementations attenuate the negative effects of urban air pollution on lung function.
The data evaluating modification of changes in lung function associated with air pollutant exposure by antioxidant supplementation, in intact humans, is limited. Of 13 studies dedicated to this concern, ten demonstrated an attenuation of pollution-associated decrements. There is growing evidence for the benefit of anti-oxidant supplementation in moderating the effects of air pollution on lung function, but more research on human participants is needed to inform this topic.
PMCID: PMC3158771  PMID: 21729301
23.  The use of alternative pollutant metrics in time-series studies of ambient air pollution and respiratory emergency department visits 
Various temporal metrics of daily pollution levels have been used to examine relationships between air pollutants and acute health outcomes. However, daily metrics of the same pollutant have rarely been systematically compared within a study. In this analysis, we describe the variability of effect estimates attributable to the use of different temporal metrics of daily pollution levels.
We obtained hourly measurements of ambient particulate matter (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3) from air monitoring networks in 20-county Atlanta for the time period 1993–2004. For each pollutant we created: 1) a daily 1-hour maximum; 2) a 24-hour average; 3) a commute average; 4) a day-time average; 5) a night-time average; and a daily 8-hour maximum (only for O3). Using Poisson generalized linear models, we examined associations between daily counts of respiratory emergency department visits and the previous day’s pollutant metrics.
Variability was greatest across O3 metrics, with the 8-hour maximum, 1-hour maximum, and day-time metrics yielding strong positive associations and the night-time O3 metric yielding a negative association (likely reflecting confounding by air pollutants oxidized by O3). With the exception of the day-time metric, all of the CO and NO2 metrics were positively associated with respiratory emergency department visits.
Differences in observed associations with respiratory emergency room visits among temporal metrics of the same pollutant were influenced by the diurnal patterns of the pollutant, spatial representativeness of the metrics, and correlation between each metric and copollutant concentrations. Overall, the use of metrics based on the US National Ambient Air Quality Standards (e.g., the use of a daily 8-hour maximum O3 as opposed to a 24-hour average metric) was supported by this analysis. Comparative analysis of temporal metrics also provided insight into underlying relationships between specific air pollutants and respiratory health.
PMCID: PMC3743225  PMID: 19756042
air pollution; respiratory disease; emergency department visits; exposure assessment; criteria pollutants; time-series
24.  Air Pollution, Aeroallergens, and Emergency Room Visits for Acute Respiratory Diseases and Gastroenteric Disorders among Young Children in Six Italian Cities 
Environmental Health Perspectives  2009;117(11):1780-1785.
Past studies reported evidence of associations between air pollution and respiratory symptoms and morbidity for children. Few studies examined associations between air pollution and emergency room (ER) visits for wheezing, and even fewer for gastroenteric illness. We conducted a multicity analysis of the relationship between air pollution and ER visits for wheezing and gastroenteric disorder in children 0–2 years of age.
We obtained ER visit records for wheezing and gastroenteric disorder from six Italian cities. A city-specific case–crossover analysis was applied to estimate effects of particulate matter (PM), nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide, adjusting for immediate and delayed effects of temperature. Lagged effects of air pollutants up to 6 prior days were examined. The city-specific results were combined using a random-effect meta-analysis.
CO and SO2 were most strongly associated with wheezing, with a 2.7% increase [95% confidence interval (CI), 0.5–4.9] for a 1.04-μg/m3 increase in 7-day average CO and a 3.4% (95% CI, 1.5–5.3) increase for an 8.0-μg/m3 increase in SO2. Positive associations were also found for PM with aerodynamic diameter ≤ 10 μg and NO2. We found a significant association between the 3-day moving average CO and gastroenteric disorders [3.8% increase (95% CI, 1.0–6.8)]. When data were stratified by season, the associations were stronger in summer for wheezing and in winter for gastroenteric disorders.
Air pollution is associated with triggering of wheezing and gastroenteric disorders in children 0–2 years of age; more work is needed to understand the mechanisms to help prevent wheezing in children.
PMCID: PMC2801171  PMID: 20049132
air pollution; asthma in children; epidemiology of asthma; children’s health
25.  Acute Effects of Air Pollution on Pulmonary Function, Airway Inflammation, and Oxidative Stress in Asthmatic Children 
Environmental Health Perspectives  2008;117(4):668-674.
Air pollution is associated with respiratory symptoms, lung function decrements, and hospitalizations. However, there is little information about the influence of air pollution on lung injury.
In this study we investigated acute effects of air pollution on pulmonary function and airway oxidative stress and inflammation in asthmatic children.
We studied 182 children with asthma, 9–14 years of age, for 4 weeks. Daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) were monitored from two stations. Once a week we measured spirometry and fractional exhaled nitric oxide (FeNO), and determined thiobarbituric acid reactive substances (TBARS) and 8-isoprostane—two oxidative stress markers—and interleukin-6 (IL-6) in breath condensate. We tested associations using mixed-effects regression models, adjusting for confounding variables.
Interquartile-range increases in 3-day average SO2 (5.4 ppb), NO2 (6.8 ppb), and PM2.5 (5.4 μg/m3) were associated with decreases in forced expiratory flow between 25% and 75% of forced vital capacity, with changes being −3.1% [95% confidence interval (CI), −5.8 to −0.3], −2.8% (95% CI, −4.8 to −0.8), and −3.0% (95% CI, −4.7 to −1.2), respectively. SO2, NO2, and PM2.5 were associated with increases in TBARS, with changes being 36.2% (95% CI, 15.7 to 57.2), 21.8% (95% CI, 8.2 to 36.0), and 24.8% (95% CI, 10.8 to 39.4), respectively. Risk estimates appear to be larger in children not taking corticosteroids than in children taking corticosteroids. O3 (5.3 ppb) was not associated with health end points. FeNO, 8-isoprostane, and IL-6 were not associated with air pollutants.
Air pollution may increase airway oxidative stress and decrease small airway function of asthmatic children. Inhaled corticosteroids may reduce oxidative stress and improve airway function.
PMCID: PMC2679614  PMID: 19440509
air pollution; asthma; children; exhaled breath condensate; inflammation; oxidative stress; pulmonary function

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