Abstract Body (Do not enter title and authors here): Background: Individuals with chronic obstructive pulmonary disease (COPD) have been shown to be more susceptible to air pollution-induced cardiovascular effects. However, the mediators linking lung pathology of COPD and cardiovascular responses to air pollution remain poorly understood. We hypothesize that nitrated fatty acids, which exhibit both anti-inflammatory and cardioprotective activities, may act as such mediators.
Methods: In a randomized crossover study, 40 healthy, 40 COPD, and 39 ischemic heart disease (IHD) adults underwent a 2-hour walk in a more-polluted street or a less-polluted park. Urine voids were collected before, and 24 h after the walk for the measurement of nitrated conjugated linoleic acids (NO2-cLA). Blood pressure and arterial stiffness were measured before and at 3h, 4h, 6h, and 24h after the walk using a Vicorder. Cardiac electrical activity was continuously monitored for 24 hours using Holter devices. Induced sputum samples were collected from a subgroup of 59 participants (17 healthy, 33 COPD, and 9 IHD) at 24 h after walk for measurements of inflammatory biomarkers.
RESULTS: Baseline NO₂-cLA levels were 2.56 (95%CI: 1.20 to 5.43)-fold higher among COPD participants than in healthy participants, accompanied by higher fractional exhaled nitric oxide and sputum myeloperoxidase levels. In COPD but not healthy or IHD participants, walking in the street, compared to the park, led to 57.7% (95%CI: 7.6% to 80.6%) decrease in NO₂-cLA levels, in associations with exposure to black carbon and ultrafine particles during the 2-hour walk. The decrease in NO₂-cLA level among COPD patients was associated with increased pulse wave velocity (PWV) at 3h, decreased pNN50 at 12h – 21h, and decreased QTc at 12 h – 22h. In COPD patients, walking in the street, compared to the park, led to increased PWV (at 3h, 5h, 6h, and 24h), decreased pNN50 (at 5h, 9h, 12h, 13h, and 23h), and decreased QTc (at 12h – 20 h). In IHD patients, the street walk led to increased PWV (at 3h, 5h, and 24h), decreased pNN50 (at 3h,7h, 10h, 14h, 17h, 23h, and 24h), and decreased QTc (at 17h). In healthy participants, the street walk increased PWV at 24h only.
CONCLUSIONS: Nitrated fatty acids may have partially mediated cardiovascular responses to air pollution in COPD patients, explaining their susceptibility.