| Summary: | <p><b>Background:</b> Ambient air pollution (AAP) exposure was estimated as contributing to 4.9 million deaths and 147 million disability-adjusted-life-years globally in 2017. The majority of this health burden (an estimated 91%) falls upon populations in low- and middle-income countries, particularly China. However, robust epidemiological evidence examining the cardio-respiratory health effects of AAP exposure remains limited in China relative to that of
high-income countries.</p>
<p><b>Methods:</b> A systematic review and meta-analysis were first performed synthesising evidence on cardio-respiratory health impacts of AAP exposure from low-and-middle-income countries (LMICs) exclusively, pooling risk estimates by pollutant, associated lag time (in days), and health outcome (cardiovascular and respiratory morbidity or mortality). The China Kadoorie Biobank (CKB) study, a large prospective cohort study of ~0.5 million Chinese
adults (aged 30-79 years at baseline) was then utilised to examine the acute and chronic cardio-respiratory health impacts of AAP exposure. For acute cardio-respiratory impacts, both time-series and case-crossover analyses were employed, examining the percent excess risk (100 x [relative risk-1]) of first-time cardio-respiratory hospitalisations and readmissions, respectively, in the 219,020 participants located in five urban localities across years 2013-2016 (2010-2016 for Suzhou). Risk estimates of cardio-respiratory spells associated with AAP exposure were also pooled across all five urban regions collectively, by
lag structure, cardio-respiratory spell type, and pollutant. For chronic cardio-respiratory impacts, 53,002 participants located in the CKB region of Suzhou had AAP exposure assigned to their respective CKB baseline clinic locations for years (2013-2015) using localised spatiotemporal modelling. Cox proportional hazards models with time-dependent covariates were used to estimate hazard ratios (HR) of incident cardiovascular and respiratory disease associated with a 10μg increase per cubic metre in annual AAP levels.</p>
<p><b>Results:</b> Eighty-five and sixty studies were identified examining the cardio-respiratory impacts of particulate matter (PM) and gaseous AAP exposure, respectively, in LMICs; the majority performed in the East Asia and Pacific region. Risk estimates varied by pollutant, health outcome, associated lag time and outcome but more significant risk estimates were observed for mortality versus morbidity. In CKB, 94,479 cardio-respiratory hospitalisation spells occurred in urban regions during the study period, including 65,168 (69%)
readmissions. Daily AAP levels varied by region but consistent declines in sulphur dioxide (SO<sub>2</sub>) and particulate matter (PM) were observed. Acute AAP exposure was associated with increased risk of cardio-respiratory spells in CKB participants for both first-time spells and readmissions with a minimal overall difference in risk by admission type, but some apparent risk differences by region. In pooled analysis, 100 μg/m<sup>3</sup> increase in carbon monoxide (CO)
and 10 μg/m<sup>3</sup> increases in nitrogen dioxide (NO<sub>2</sub>), PM10 and PM2.5 were associated with first-time cardio-respiratory disease (percent excess risk = 5.65% [95% CI 0.84, 10.70] for CO and cardiovascular disease, 2.13% [0.75, 3.53] for NO2 and stroke, and 0.92% [0.34, 1.49] and 0.66 [0.23,1.08] for PM<sub>2.5</sub> and PM<sub>10</sub>, respectively, with respiratory disease). For cardiorespiratory
impacts associated with long-term AAP exposure a 10 μg/m<sup>3</sup> increase in SO<sub>2</sub> was associated with a higher incidence of major cardiovascular disease (HR 1.07, [95% CI 1.02, 1.12]) and respiratory disease (1.11 [1.04, 1.19]), specifically chronic obstructive pulmonary disease (COPD) and pneumonia (1.24 [1.08, 1.44] and 1.12 [1.03, 1.23], respectively). Ozone (O<sub>3</sub>) was associated with risk of major cardiovascular disease (1.02 [1.01, 1.03]) including all-type stroke, as well as ischaemic stroke specifically (1.04 [1.02, 1.05], 1.04 [1.02, 1.06], respectively). There were no differences in associated risk of cardio-respiratory
disease across population subgroups examined.</p>
<p><b>Conclusions:</b> In this adult Chinese population both acute and chronic exposure to AAP appeared associated with higher risk of incident cardio-respiratory disease. This suggests that current disease burden estimates which incorporate only mortality as an outcome are likely to underestimate the actual burden of AAP exposure in China.</p>
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