Effects of ultrafine carbon particles in healthy subjects and subjects with asthma
Annette Peters GSF-National Research Center for Environment and Health Institute of Epidemiology, Neuherberg, Germany
Particulate air pollution has been associated with acute and chronic health effects due to respiratory and cardiovascular disease exacerbation (1;2). New air quality standards have been introduced in Europe to control particulate matter with an aerodynamic diameter less then 10 µm (PM10) (3). However, particles in ambient air are a complex mixture and might be quite divers in terms of their chemical composition and their sizes. In particular, ultrafine particles defined as particles with a diameter less than 100 nm represent a class of particles which has been implicated to have health effects independent of those of PM10 (4). Their smallness results in large number concentrations and large surface areas at relatively low mass concentrations.
Frampton and colleagues have assessed in a recent report the impact of ultrafine carbon particles on humans with and without asthma (5). The particles were laboratory generated and provide therefore a model to study the potential health impacts of ultrafine particles being otherwise chemically inert. The controlled exposure setting allows comparing the physiological responses of the subjects to exposures to filtered air in the absence of other potential confounding factors. The authors first compared the deposition efficiency of the ultrafine particle number concentrations between healthy and asthmatic subjects and found that the deposition fraction at rest was 21% higher in subjects with asthma than in subjects without asthma (5;6). During exercise there was no difference observed, but exercise increased the deposition fraction 33% in non-asthmatics and only 13% in asthmatics. Larger differences were observed for the total mass deposited, but here the results for the asthmatics were highly variable and the differences between non-asthmatics and asthmatics were not statistically significant.
No substantial differences were observed with respect to symptoms, pulmonary function, markers of airway inflammation, soluble markers of systemic inflammation or coagulation (5;7). Blood leukocyte counts and adhesion molecule profiles of blood leukocytes were altered (5). Exercise which was part of the protocols did alter the blood cell count and the adhesion molecule profiles. This response in turn was modified by ultrafine particle exposures. Part of the study protocol that did not include exercise did not observe convincing differences between the physiological markers assessed during ultrafine particle exposure and air exposure. Breathing 25 µg/m3 ultrafine carbon particles was associated with reductions in blood monocytes and activation of T lymphocytes in healthy females. In all subjects, monocyte expression of intercellular adhesion molecule-1 (ICAM-1) was reduced. In asthmatic subjects, breathing 10 µg/m3 ultrafine carbon particles was associated with reduced numbers of blood eosinophils and CD4+ T lymphocytes, and CD11b expression was reduced on monocytes and eosinophils, and ICAM-1 expression was reduced on polymorphonuclear leukocytes. The results point towards endothelial activation in the absence of signs of airway inflammation or systemic inflammation as it could be detected by acute phase proteins. ECG analyses of healthy subjects showed transient reductions in parasympathetic influence on heart rate variability and a reduced repolarization (QT) interval. In asthmatic subjects, ECG analyses showed decreased QT variability, but no effect on the QT interval.
The study is unique in the aspect that the physiological responses to ultrafine carbon particles are studied in a controlled setting. The subjects involved are healthy young individuals or young volunteers with mild asthma. The particle mass concentrations delivered were low with respect to mass concentrations (10 µg/m3 or 25 µg/m3), but the number concentrations are comparable to those measured at very busy roads. The new evidence by Frampton and colleagues suggests in particularly, that endothelial activation might take place in absence of signs of lung inflammation or activation of cells in the lung. Three mechanisms have been discussed as potentially being responsible for the observed associations between ambient air pollution and cardiovascular disease exacerbation (8): (a) pulmonary inflammation that may lead to systemic inflammation, (b) translocation of ultrafine particles that may lead to endothelial activation and effects on other organs and (c) modifications of the autonomic control through activation of irritant receptors. The data presented by Frampton and colleagues suggests that there was no evidence for pulmonary or systemic inflammation. There seemed to be evidence for endothelial activation and modulation of the exercise induced responses. The changes observed in the ECG recordings might in addition point to a modification in the autonomic control of the heart. Evidence has been provided that ultrafine particles may be translocated through the air-blood barrier (9), and that the translocation of particles may be enhanced by histamine and oxidative stress (10). There exists the potential that subjects with asthma experience more translocation of particles than healthy subjects. Therefore, one might speculate that the associations observed by Frampton and colleagues might have been induced by ultrafine particles entering the blood. Frampton and colleagues speculate that particles in the blood stream might exhibit anti-inflammatory properties either via NO synthesis or sequestration of soluble cytokines. In addition, in vitro studies have observed the formation of pro-inflammatory and anti-inflammatory lipid mediators (11). Particles in the ambient air are a complex mixture with potentially reactive chemicals on the surface of the particles. Therefore, the absence of other signs of inflammation in the study by Frampton and colleagues (5) might be due to the fact that the particles can generally be considered as being chemically inert and that their potential in inducing oxidative stress was lower than the potential of ambient particles. Furthermore, the effects might be different and more pronounced in subjects with severer stages of cardio-pulmonary disease as indicated by earlier epidemiological studies in subjects with asthma and coronary artery disease (12;13). The study by Frampton and colleagues highlights the challenge to disentangle the role of particle properties that induce health effects and of the host susceptibility that might enhance the pathophysiological responses. However, the fact that study observed effects of exposure to ultrafine carbon particles in healthy subjects and mild asthmatics indicates that the ultrafine particle number concentrations in the ambient air might be of serious concern for subjects with underlying disease in urban areas where particles are more reactive.
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PD Dr. Annette Peters GSF-National Research Center for Environment and Health Institute of Epidemiology 85764 Neuherberg Germany Email: firstname.lastname@example.org