Increased Parkinson Disease Risk Associated With Nitrogen Dioxide Exposure

Despite identifying a role of air pollutants in PD, no evidence for the association between the risk of PD and exposure to particulate matters, ozone, sulfur dioxide, or carbon monoxide were observed.

Results from a retrospective cohort study published in JAMA Neurology using over 750,000 total person-years of follow-up identified a statistically significant association between nitrogen dioxide (NO2) exposure and Parkinson disease (PD) risk.1

Lead author Sungyang Jo, MD, Department of Neurology, University of Ulsan College of Medicine, and colleagues also concluded that, “this finding suggests the role of air pollutants in PD development, advocating for the need to implement a targeted public health policy.” The authors collected data on exposure levels to particulate matters (PM2.5 and PM10), NO2, ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO) in 78,830 Korean individuals older than 40 years old without PD who lived in Seoul between January 2002 and December 2006. Each participant was followed-up annually from January 2007 to December 2015, adding up to 757,704 total person-years of follow-up.

Exposure to NO2 was found to be associated with an increase in risk of PD (hazard ratio [HR] for highest vs lowest quartile, 1.41 [95% CI, 1.02-1.95]; P trend = .045), whereas no statistically significant association was observed between exposure to PM2.5, PM10, O3, SO2, or CO and PD incidence. The association was robust even after adjusting for age, sex, insurance type, comorbidities, and lifestyle.

The exposure levels were estimated based on the participants’ residential address at the district level, while time-varying 5-year mean air pollutant exposure was calculated to evaluate long-term exposure to air pollution for each individual. NO2 exposure levels in the fourth quartile, or greater than 0.038 ppm, showed a statistically significant increase with incident PD using multivariable Cox regression models with cubic splines.

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In sensitivity analyses for NO2, researchers found a positive association between high exposure and incident PD in the 1-year lag analysis (HR for highest vs lowest quartile, 1.34 [95% CI, 0.97-1.84]; P trend = 0.48), but not in the 2-year lag analysis (HR for highest vs lowest quartile, 1.17 [95% CI, 0.86-1.58]; P trend = .16).

The most common preexisting comorbidities for the 338 individuals with incident PD were hypertension (n = 158; 46.7%) diabetes (n = 102; 30.2%) dyslipidemia (n = 93; 27.5%), and ischemic heart disease (n = 51; 15.1%). The mean age of those who developed incident PD was 66.5 years (standard deviation [SD], 9.7) compared to 54.4 years for the entire study population.

There were a number of limitations to the study identified by the authors, including the reference exposure based on district-level measurements, lack of occupational exposure to air pollutions such as heavy metals and pesticides, and the inability to investigate the long lag period in exposure.

In a related editorial, Earl R. Dorsey, MD, MBA, professor of neurology and director of the Center for Human Experimental Therapeutics, University of Rochester Medical Center, and colleagues reviewed data from previous studies that examined the connection between air pollution and incident PD.2 Included was the research by Jo et al, noting that establishing a link between air pollution and PD is challenging for 4 reasons.

The first is that quantifying individual exposure is difficult, with personal monitors of air pollution differing substantially from public monitoring data. Secondly, accounting for interactions and confounding factors can be challenging, especially considering patients normally are exposed to a mixture of impurities. The third was the extended time between exposure and outcome, which they noted was similar to that of smoking and lung cancer. Lastly, they noted that PD diagnosis is imperfect, and that many individuals have the disease but have never been identified.

The role of pesticides and industrial chemicals in PD have been doubted previously; however, Dorsey et al concluded, “Multiple independent investigations and preclinical studies confirmed their critical role. We suspect that as more studies like this one are conducted and published, the fog will lift and reveal that air pollution does contribute to Parkinson disease. Uncovering this potential linkage may help prevent this malady, improve our health, and protect future generations.”

REFERENCES
Jo S, Kim YJ, Park KW, et al. Association of NO2 and other air pollution exposures with the risk of Parkinson disease. JAMA Neurol. Published online June 1, 2021. doi: 10.1001/jamaneurol.2021.1335
Dorsey ER, Okun MS, Tanner CM. Bad air and Parkinson disease – the fog may be lifting. JAMA Neurol. Published online May 17, 2021. doi: 10.1001/jamaneurol.2021.0863