Nitrated Fatty Acids and Susceptibility of COPD to Air Pollution: Evidence from a Randomized Crossover Study

Previous studies documented increased nitrative stress and susceptibility to air pollution among individuals with chronic inflammatory conditions. This study examines the role of anti-inflammatory and cardioprotective nitrated fatty acids (i.e., NO₂-cLA) in chronic obstructive pulmonary disease (COPD)'s and ischemic heart disease (IHD)'s susceptibility to air pollution. In a randomized crossover study, 40 healthy, 40 COPD, and 39 IHD adults underwent a 2 h walk in a more polluted street or a less polluted park. We measured urinary NO₂-cLA before and 24 h after the walk, as well as respiratory inflammatory biomarkers, lung function, airway resistance, and arterial stiffness. Baseline NO₂-cLA levels were 2.56 (95% CI: 1.20-5.43)-fold higher among COPD participants than healthy participants, which can be explained by higher fractional exhaled nitric oxide and sputum myeloperoxidase levels. Among COPD but not healthy or IHD participants, the street walk, compared to park, led to a 57.7% (95% CI: 7.6-80.6%) decrease in NO₂-cLA levels and sputum biomarker changes indicative of decreased neutrophil inflammation and proresolving responses. Decreased NO₂-cLA levels were associated with exposure to black carbon and ultrafine particles and worsened lung function and arterial stiffness. Taken together, nitrated fatty acids partially mediate COPD patients' cardiorespiratory responses to air pollution, explaining their susceptibility.