Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 μg/m3 at rest, 10 and 25 μg/m3 with exercise, and 50 μg/m3 with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 μg/m3 UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 μg/m3 UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4+ T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed.

Rationale: Zinc oxide is a common, biologically active constituent of particulate air pollution as well as a workplace toxin. Ultrafine particles (Ͻ 0.1 m diameter) are believed to be more potent than an equal mass of inhaled accumulation mode particles (0.1-1.0 m diameter). Objectives: We compared exposure-response relationships for respiratory, hematologic, and cardiovascular endpoints between ultrafine and accumulation mode zinc oxide particles. Methods: In a human inhalation study, 12 healthy adults inhaled 500 g/m 3 of ultrafine zinc oxide, the same mass of fine zinc oxide, and filtered air while at rest for 2 hours. Measurements and Main Results: Preexposure and follow-up studies of symptoms, leukocyte surface markers, hemostasis, and cardiac electrophysiology were conducted to 24 hours post-exposure. Induced sputum was sampled 24 hours after exposure. No differences were detected between any of the three exposure conditions at this level of exposure. Conclusions: Freshly generated zinc oxide in the fine or ultrafine fractions inhaled by healthy subjects at rest at a concentration of 500 g/m 3 for 2 hours is below the threshold for acute systemic effects as detected by these endpoints.Keywords: air pollution; metal fume fever; particulate matter, ultrafine; zinc Ambient air pollution particles occur in three major size distributions. Common combustion processes generate some primary ultrafine particles (Ͻ 0.1 m diameter), which can rapidly coalesce into larger accumulation mode particles (0.1-1.0 m diameter). The third fraction is the coarse mode particles, from 1 to 100 m in diameter, which are often generated by mechanical breakdown of the earth's crustal minerals. A given mass of ultrafine particles has a markedly higher ratio of total surface area to weight than does the same mass of accumulation mode particles. In experimental animals, inhaled ultrafine particles exhibit greater lung inflammatory and systemic activity than an equal mass of larger particles, and these particles may also have greater effects in adult human subjects (1-3). With ambient particle air pollution exposure, certain respiratory effects have been more closely associated with the number of ultrafine particles than with the total mass of particle exposure (4).Zinc is a common element in the earth's crust and an essential mineral in human nutrition. Zinc oxide may be found in ambient air particles from combustion sources (5-7), and it is generated in high concentrations in industrial processes, such as brass founding and welding or cutting galvanized sheet metal. Actual exposures of welders and others depend on the conditions in the workplace, but the permissible exposure limit for occupational exposure to zinc oxide in the United States is 5.0 mg/m 3 respirable dust. Zinc is one of several transition metals that have been proposed to contribute to the biological activity of ambient combustion particles. Freshly generated zinc oxide causes a selflimited, febrile, and inflammatory response known as metal fume fever, subtle findings ...

BackgroundDiabetes confers an increased risk for cardiovascular effects of airborne particles.ObjectiveWe hypothesized that inhalation of elemental carbon ultrafine particles (UFP) would activate blood platelets and vascular endothelium in people with type 2 diabetes.MethodsIn a randomized, double-blind, crossover trial, 19 subjects with type 2 diabetes inhaled filtered air or 50 μg/m3 elemental carbon UFP (count median diameter, 32 nm) by mouthpiece for 2 hr at rest. We repeatedly measured markers of vascular activation, coagulation, and systemic inflammation before and after exposure.ResultsCompared with air, particle exposure increased platelet expression of CD40 ligand (CD40L) and the number of platelet-leukocyte conjugates 3.5 hr after exposure. Soluble CD40L decreased with UFP exposure. Plasma von Willebrand factor increased immediately after exposure. There were no effects of particles on plasma tissue factor, coagulation factors VII or IX, or D-dimer.ConclusionsInhalation of elemental carbon UFP for 2-hr transiently activated platelets, and possibly the vascular endothelium, in people with type 2 diabetes.

Objective-Arginine deficiency may contribute to microvascular dysfunction, but previous studies suggest that arginine supplementation may be harmful in sepsis. Systemic arginine availability can be estimated by measuring the ratio of arginine to its endogenous inhibitors, asymmetric and symmetric dimethylarginine. We hypothesized that the arginine to dimethylarginine (Arg/DMA) ratio is reduced in patients with severe sepsis and associated with severity of illness and outcomes.Design-Case-control and prospective cohort study This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptCrit Care Med. Author manuscript; available in PMC 2012 June 1. Conclusions-The Arg/DMA ratio is associated with severe sepsis, severity of illness, and clinical outcomes. The Arg/DMA ratio may be a useful biomarker, and interventions designed to augment systemic arginine availability in severe sepsis may still be worthy of investigation.