© 2008 American Thoracic Society doi: 10.1164/rccm.200710-1527ED
Reducing Exposure to Airborne ParticlesA Novel Strategy to Improve Cardiovascular Health
The University of Edinburgh
University of Rochester
The University of Edinburgh In the last decade, evidence accumulated to suggest that inhaled particles have effects beyond the lungs and may exert an important influence on the cardiovascular system. Exposure to particulate air pollution is associated with a range of serious cardiovascular problems, including hospital admissions with angina, myocardial infarction, and heart failure (1), and long-term exposure increases lifetime risk of death from coronary heart disease (2). Understanding the mechanisms that underpin these associations is necessary if we are to develop strategies to protect individuals at risk and reduce the burden of air pollution on cardiovascular health. Inhaled particles can provoke an inflammatory response in the lungs with the consequent release of prothrombotic and inflammatory cytokines into the circulation, which may lead to detrimental effects on the cardiovascular system (3). A substantial body of work confirms the inflammatory nature of particulate matter (PM) (4), and controlled-exposure studies have identified adverse effects of particulates on endothelial function, fibrinolysis, and thrombogenesis (5–7). As such, particulate air pollution may influence the development, progression, and clinical manifestations of atherothrombosis. Although these adverse cardiovascular effects may be mediated through the lung, translocation of the ultrafine or nanoparticulate fraction of PM directly into the bloodstream has been advanced as an alternative mechanism. This also has implications for "engineered" nanoparticles in the nanotechnology industry, which may pose similar hazards (8). Nanoparticles have a diameter of less than 0.1 µm, and are able to penetrate to the terminal bronchioles and proximal alveoli. Within the nanoparticulate fraction, inhaled particles with a diameter of 20 nm have the greatest pulmonary deposition, with up to 50% retained in the alveolar region. Previous clinical studies have assessed deposition (9), translocation, and the systemic distribution of inhaled nanoparticles (10, 11) using a model of technetium Tc 99m–labeled carbon nanoparticles, "Technegas," which is used routinely in clinical practice for radionuclide lung ventilation imaging in Europe. Nemmar and colleagues were the first to use this model to assess translocation into the systemic circulation, and their findings were provocative (10). In a small study, they suggested that inhaled insoluble nanoparticles were capable of rapid translocation into the bloodstream with accumulation of activity over the liver and spleen, suggesting clearance through the endoreticular system. However, the presence of minute quantities of oxygen or sodium chloride can result in the generation of soluble species of 99mTc. Replication of this study, with close attention to the generation of 99mTc-labeled nanoparticles, failed to demonstrate translocation of these particles into the circulation (11). Gamma camera imaging may not have been sufficiently sensitive to detect small quantities of particulate outside the lungs in healthy subjects and it remained uncertain whether subjects with impaired pulmonary function would be more susceptible to particle translocation. In this issue of the Journal (pp. 426–431), Möller and colleagues develop the Technegas model to minimize contamination of the aerosol by soluble activity (12). A simple modification to remove sodium chloride improved the accuracy of this technique and allowed meaningful comment on retention of inhaled nanoparticles at intervals up to 2 days after inhalation. Möller and colleagues report that 96% of nanoparticles deposited in the peripheral airways are retained at 48 hours. Critically, pulmonary retention was not reduced in smokers or patients with emphysema who might have been expected to have greater airway permeability. Single nanoparticles are not readily phagocytosed by alveolar macrophages and can be moved into the interstitium with longer term retention likely. These findings could have implications for the nanotechnology industry as more reactive inhaled nanoparticles may have the potential to initiate interstitial inflammatory lung disease. The fact that elemental carbon nanoparticles are not readily cleared from the peripheral airways in humans and do not translocate in any measurable amount does not necessarily mean that other nanoparticles behave similarly. Indeed, inhaled nanoparticles can gain direct access into the circulation in animal models as demonstrated both by direct observation and more sensitive labeling techniques (8). The major unresolved question is whether nanoparticles translocate in sufficient numbers to exert a significant influence on vascular endothelial or myocardial function. Whether mediated via direct or indirect effects, controlled exposures to ultrafine particles, such as elemental carbon and diesel exhaust, result in acute impairment of vascular and myocardial function (6, 13, 14). It is presently unknown if repeated exposure to lower concentrations of ambient particulate exerts a cumulative effect on vascular function. The article by Bräuner and colleagues in this issue of the Journal (pp. 419–425) used a novel interventional study design to determine whether particulate air pollution encountered in the homes of those living near major roads impacts the regulation of vascular function (15). In a double-blind, randomized crossover study, particle filtration for 48 hours using an indoor air filtration system reduced exposure to fine particles by two-thirds and was associated with improvements in vascular function. The study design is pertinent as the majority of elderly or susceptible persons spend most of their time within or in the vicinity of the home. The concept of a simple and practical intervention to reduce personal exposure to airborne particles with the potential to prevent the adverse vascular effects of particulate air pollution is enticing. In comparison to mainstream techniques, such as plethysmography and flow-mediated vasodilatation, the technique used by Bräuner and colleagues to measure endothelial function was unusual, has not been robustly validated with clinical endpoint trials, and did not measure endothelium-independent vasoreactivity. As such, the precise mechanism whereby indoor particulate air pollution alters vascular function remains to be established. However, if these improvements in vascular function are sustained and validated, then particle filtration may well become an important public health strategy in the future. These two studies together make an important contribution to our understanding of the cardiopulmonary effects of ultrafine PM. Airborne particles pervade all aspects of modern life with our reliance on the combustion of fossil fuels and the increasing importance of emerging nanotechnologies. Further studies addressing the impact of particle filtration on cardiovascular health are urgently required if we are to develop effective strategies to protect our increasingly urban populations. FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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