Long-term ozone exposure is positively associated with telomere length in critically ill patients

Chronic air pollutant exposure has been associated with development of Acute Respiratory Distress Syndrome (ARDS) in patients at risk, particularly from severe trauma. We recently reported that shorter peripheral blood leukocyte (PBL) telomere length (TL) was associated with worse outcomes and higher severity of ARDS in critically ill patients. Since most major air pollutants are potent oxidants that can induce cellular oxidative stress, and oxidative stress can accelerate telomere shortening, we hypothesized that higher levels of chronic air pollutant exposure would be associated with shorter telomere length in critically ill patients including patients with ARDS.

PBL-TL was measured in genomic DNA collected on the morning of ICU day 2 in 772 critically ill patients enrolled in a prospective observational study. Exposures to air pollutants including ozone (warm-season only), particulate matter < 2.5 µm (PM_2.5), particulate matter < 10 µm (PM₁₀), CO, NO₂ and SO₂, were estimated by weighted average of daily levels from all monitors within 50 km of each patient's residential address for the 3 years prior to admission. Associations of each air pollutant exposure and PBL-TL were investigated by multivariable linear regression models adjusting for age, ethnicity, sex, smoking history, alcohol abuse, insurance status, median household income, history of malignancy and APACHE II.

Contrary to our hypothesis, TL increased across exposure quartiles in both ozone and PM_2.5 analyses (p < 0.05). In a regression model controlling for potential confounders, long term ozone exposure was significantly associated with an increase in TL in the entire cohort (0.31 kb per 10 ppb), as well as in subgroups with sepsis, trauma and ARDS (all p < 0.05). In multivariable models, entire-year exposure to PM_2.5, PM₁₀, CO, NO₂ and SO₂ was not associated with TL after adjustment for potential confounders. In an analysis restricted to warm-season levels to assess the effect of seasonality, higher warm-season PM_2.5 and CO exposures were independently associated with longer TL.

Long-term exposure to ozone is associated with longer peripheral blood TL in critically ill patients. Further studies are needed to investigate the potential underlying mechanisms for this unexpected positive association between telomere length and air pollution exposure in critical illness.