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 < or = 2.5 microm 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 (SO4(2-)) (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 SO4(2-) 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 < or = 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 -0.21), 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.