Associations of long-term nitrogen dioxide exposure with a wide spectrum of diseases: a prospective cohort study of 0·5 million Chinese adults.

Background: Little evidence is available on the long-term health effects of nitrogen dioxide (NO) in low-income and middle-income populations. We investigated the associations of long-term NO exposure with the incidence of a wide spectrum of disease outcomes, based on data from the China Kadoorie Biobank.

Methods: This prospective cohort study involved 512 724 Chinese adults aged 30-79 years recruited from ten areas of China during 2004-08. Time-varying Cox regression models yielded adjusted hazard ratios (HRs) for the associations of long-term NO exposure with aggregated disease incidence endpoints classified by 14 ICD-10 chapters, and incidences of 12 specific diseases selected from three key ICD-10 chapters (cardiovascular, respiratory, and musculoskeletal diseases) found to be robustly associated with NO in the analyses of aggregated endpoints. All models were stratified by age-at-risk (in 1-year scale), study area, and sex, and were adjusted for education, household income, smoking status, alcohol intake, cooking fuel type, heating fuel type, self-reported health status, BMI, physical activity level, temperature, and relative humidity.

Findings: The analysis of 512 709 participants (mean baseline age 52·0 years [SD 10·7]; 59·0% female and 41·0% male) included approximately 6·5 million person-years of follow-up. Between 5285 and 144 852 incident events were recorded for each of the 14 aggregated endpoints. Each 10 μg/m higher annual average NO exposure was associated with higher risks of chapter-specific endpoints, especially cardiovascular (n=144 852; HR 1·04 [95% CI 1·02-1·05]), respiratory (n=73 232; 1·03 [1·01-1·05]), musculoskeletal (n=54 409; 1·11 [1·09-1·14]), and mental and behavioural (n=5361; 1·12 [1·05-1·21]) disorders. Further in-depth analyses on specific diseases found significant positive supra-linear associations with hypertensive disease (1·08 [1·05-1·11]), lower respiratory tract infection (1·03 [1·01-1·06]), arthrosis (1·15 [1·09-1·21]), intervertebral disc disorders (1·13 [1·09-1·17]), and spondylopathies (1·05 [1·01-1·10]), and linear associations with ischaemic heart disease (1·03 [1·00-1·05]), ischaemic stroke (1·08 [1·06-1·11]), and asthma (1·15 [1·04-1·27]), whereas intracerebral haemorrhage (1·00 [0·95-1·06]), other cerebrovascular disease (0·98 [0·96-1·01]), acute upper respiratory infection (1·03 [0·96-1·09]), and chronic lower respiratory disease (0·98 [0·95-1·02]) showed no significant association. NO exposure showed robust null association with external causes (n=32 907; 0·98 [0·95-1·02]) as a negative control.

Interpretation: In China, long-term NO exposure was associated with a range of diseases, particularly cardiovascular, respiratory, and musculoskeletal diseases. These associations underscore the pressing need to implement the recently tightened WHO air quality guidelines.

Funding: Wellcome Trust, UK Medical Research Council, Cancer Research UK, British Heart Foundation, National Natural Science Foundation of China, National Key Research and Development Program of China, Sino-British Fellowship Trust, and Kadoorie Charitable Foundation.