Urban airborne particle exposure impairs human lung and blood Mycobacterium tuberculosis immunity.

RATIONALE: Associations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored. OBJECTIVES: To examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis. METHODS: Cellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis. MEASUREMENTS AND MAIN RESULTS: In vitro exposure of AM to PM2.5 did not affect M. tuberculosis phagocytosis. High in vivo-acquired AM PM burden reduced constitutive, M. tuberculosis and PM-induced interleukin-1ß production in freshly isolated BAC but not in autologous PBMC while it reduced constitutive production of tumour necrosis factor-alpha in both BAC and PBMC. Further, PM burden was positively correlated with constitutive, PM, M. tuberculosis and purified protein derivative (PPD)-induced interferon gamma (IFN-γ) in BAC, and negatively correlated with PPD-induced IFN-γ in PBMC. CONCLUSIONS: Inhalation exposure to urban air pollution PM impairs important components of the protective human lung and systemic immune response against M. tuberculosis. PM load in AM is correlated with altered M. tuberculosis-induced cytokine production in the lung and systemic compartments. Chronic PM exposure with high constitutive expression of proinflammatory cytokines results in relative cellular unresponsiveness.

Concentrations of urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in women exposed to woodsmoke in a cookstove intervention study in San Marcos, Peru.

Nearly half of the world's population is exposed to household air pollution (HAP) due to long hours spent in close proximity to unvented cooking fires. The effect of woodsmoke exposure on oxidative stress was examined by investigating the association between woodsmoke exposure and biomarkers of DNA oxidation (8-hydroxy-2'-deoxyguanosine [8-OHdG]) and lipid peroxidation (8-isoprostane) among control and intervention stove users. HAP exposure assessment was conducted within the framework of a community-randomized controlled trial of 51 communities in San Marcos Province, Cajamarca Region, Peru. The first morning urine voids after 48h HAP exposure assessment from a subset of 45 control and 39 intervention stove users were analyzed for 8-OHdG and 8-isoprostane. General linear models and correlation analyses were performed. Urinary oxidative stress biomarkers ranged from 11.2 to 2270.0µg/g creatinine (median: 132.6µg/g creatinine) for 8-OHdG and from 0.1 to 4.5µg/g creatinine (median: 0.8µg/g creatinine) for 8-isoprostane among all study subjects (n=84). After controlling for the effects of traffic in the community and eating food exposed to fire among all subjects, cooking time was weakly, but positively associated with urinary 8-OHdG (r=0.29, p=0.01, n=80). Subjects' real-time personal CO exposures were negatively associated with 8-OHdG, particularly the maximum 30-second CO exposure during the sampling period (r=-0.32, p=0.001, n=73). 48h time integrated personal PM2.5 was negatively, but marginally associated with urinary 8-isoprostane (r=-0.21, p=0.09, n=69) after controlling for the effect of distance of homes to the road. Urinary 8-isoprostane levels reported in the available literature are comparable to results found in the current study. However there were relatively high levels of urinary 8-OHdG compared to data in the available literature for 8-OHdG excretion. Results suggest a sustained systemic oxidative stress among these Peruvian women chronically exposed to wood smoke.