Indoor particulate matter concentrations and air cleaner intervention association with biomarkers in former smokers with COPD

Background: Indoor pollutants have been associated with worse clinical outcomes in chronic obstructive pulmonary disease (COPD). Elevated biomarkers are associated with ambient pollution exposure, however the association with indoor pollution remains unclear. Methods: Former smokers with spirometry-confirmed COPD were randomized to portable air cleaner or placebo. Indoor particulate matter (PM_2.5, PM₁₀, and ultrafine particles [UFP; PM_<0.1]) and biomarkers were measured longitudinally at pre-specified intervals and course PM fraction (PM_10-2.5) was calculated. Biomarkers were categorized based on associations with biologic mechanisms: inflammation (white blood cell count, interleukin [IL]-6, IL-8, IL-1β, tumor necrosis factor-α, interferon-γ, serum amyloid A), platelet activation (P-selectin, CD40 ligand [CD40L], 11-dehdydro-thromboxane-B2 [11dTxB2]), endothelial dysfunction (Vascular Cell Adhesion Molecule [VCAM]-1, Intercellular Adhesion Molecule [ICAM]-1), and oxidative stress (thiobarbituric acid reactive substances [TBARS], 8-hydroxydeoxyguanosine, 8-isoprostane). Associations between PM concentrations and each biomarker were analyzed using multivariable linear mixed models. An intention-to-treat analysis was performed to evaluate the air cleaner intervention on the biomarker levels longitudinally. Results: Fifty-eight participants were randomized to each group. Finer PM was more strongly associated with higher IL-8 (mean difference per doubling: UFP 13.9% [p = 0.02], PM_2.5 6.8% [p = 0.002], PM_10-2.5 5.0% [p = 0.02]) while interferon-γ was associated with UFP and IL-1β with PM_10-2.5. UFP and PM_2.5 were associated with elevated levels of the oxidative stress biomarkers TBARS and 8-isoprostane respectively. For platelet activation markers, UFP was associated with higher 11dTxB2 while PM_2.5 was associated with higher P-selectin and CD40L. Pollutants were not associated with biomarkers of endothelial dysfunction. In intention-to-treat analysis there was no association of the air cleaner intervention with any of the biomarkers. Discussion: Among former smokers with COPD, elevated levels of indoor air pollutants, particularly ultrafine particles (PM_<0.1), were associated with elevated biomarkers of inflammation, platelet activation, and oxidative stress. However, an air cleaner intervention that reduced PM did not significantly reduce biomarker levels.