BACKGROUND: Exposure to air pollution is known to affect both short and long-term outcomes of the cardiopulmonary system; however, findings on short-term outcomes have been inconsistent and often from isolated and long-term rather than coexisting and short-term exposures, and among susceptible/unhealthy rather than healthy populations. AIMS: We aimed to investigate separately the annual, daily and daily space-time-activity-weighted effect of ambient air pollution, as well as confounding or modification by other environmental (including noise) or space-time-activity (including total daily physical activity) exposures, on cardiopulmonary outcomes in healthy adults. METHODS: Participants (N=57: 54% female) had indicators of cardiopulmonary outcomes [blood pressure (BP), pulse (HR) and heart rate variability (HRV SDNN), and lung function (spirometry FEV(1), FVC, SUM)] measured on four different mornings (at least five days apart) in a clinical setting between 2011 and 2014. Spatiotemporal ESCAPE-LUR models were used to estimate daily and annual air pollution exposures (including PM(10), PM(Coarse), but not Ozone derived from closest station) at participant residential and occupational addresses. Participants\' time-activity diaries indicated time spent at either address to allow daily space-time-activity-weighted estimates, and capture total daily physical activity (total-PA as metabolic-equivalents-of-task, METs), in the three days preceding health measurements. Multivariate-adjusted linear mixed-effects models (using either annual or daily estimates) were adjusted for possible environmental confounders or mediators including levels of ambient noise and greenness. Causal mediation analysis was also performed separately considering these factors as well as total-PA. All presented models are controlled by age, height, sex and season. RESULTS: An increase in 5mug/m(3) of daily space-time-activity-weighted PM(Coarse) exposure was statistically significantly associated with a 4.1% reduction in total heart rate variability (SDNN; p=0.01), and remained robust after adjusting for suspected confounders [except for occupational-address noise (beta=-2.7, p=0.20)]. An increase in 10ppb of annual mean Ozone concentration at the residential address was statistically significantly associated with an increase in diastolic BP of 6.4mmHg (p<0.01), which lost statistical significance when substituted with daily space-time-activity-weighted estimates. As for pulmonary function, an increase in 10mug/m(3) of annual mean PM(10) concentration at the residential address was significantly associated with a 0.3% reduction in FVC (p<0.01) and a 0.5% reduction in SUM (p<0.04), for which again significance was lost when substituted for daily space-time-activity-weighted estimates These associations with pulmonary function remained robust after adjusting for suspected confounders, including annual Ozone, as well as total-PA and bioaerosol (pollen and fungal spore) levels (but not residential-neighborhood greenness beta=-0.22, p=0.09; beta=-0.34, p=0.15, respectively). Multilevel mediation analysis indicated that the proportion mediated as a direct effect on cardiopulmonary outcomes by suspected confounders (including total-PA, residential-neighborhood greenness, and occupational-address noise level) from primary exposures (including PM(10), PM(Coarse), and O(3)) was not statistically significant. CONCLUSION: Our findings suggest that increased daily space-time-activity-weighted PM(Coarse) exposure levels significantly adversely affect cardiac autonomic modulation (as reduced total HRV) among healthy adults. Additionally, increased annual levels at the residential address of Ozone and PM(10) significantly increase diastolic blood pressure and reduce lung function, respectively, among healthy adults. These associations typically remained robust when adjusting for suspected confounders. Occupational-address noise and residential-neighborhood greenness levels, however, were seen as mediators of cardiovascular and pulmonary outcomes, respectively. Total daily physical activity was not seen as a mediator of any of the studied outcomes, which supports the promotion of active mobility within cities.