Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways.Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10) 108 mg?m -3 ) and lung function and airway inflammation were assessed.Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin-8 (IL-8) protein in lavage fluid, increased IL-8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their preexisting eosinophilic airway inflammation. Epithelial staining for the cytokine IL-10 was increased after DE in the asthmatic group.Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 mm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses. Numerous epidemiological studies have demonstrated clear associations between increased ambient particulate matter (PM) concentrations and indices of pulmonary and cardiac morbidity and mortality within the general population [1]. These adverse effects appear to be magnified in populations with pre-existing respiratory disease, such as asthma [2]. During PM pollution episodes, asthmatic subjects demonstrate increased respiratory symptoms, bronchoconstriction, medication use, bronchial hyperreactivity and emergency care visits [2,3]. The mechanism underlying this difference remains unclear.Exposure to particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10) at concentrations above the USA National Air Quality Standards of 150 mg?m -3 (24 h average) occurs frequently in many cities throughout the world, due to a combination of vehicle traffic and industrial processes. The transport sector, especially diesel-powered vehicles, is a major source of urban PM pollution. Diesel exhaust (DE) is a complex mixture containing carbonaceous particles, oxides of nitrogen, carbon monoxide, aldehydes and other volatile organic carbon species. In addition, DE particles may act as vectors for the delivery to the lung of toxic materials, including heavy metal ions, hydrocarbons and allergens [4,5].The authors have previously shown airway inflammatory responses in healthy volunteers exposed to DE at a PM10 concentration of 300 mg?m -3 [6,7]...

We have previously demonstrated that short-term exposure to diesel exhaust (DE) for 1 h induced a marked leukocytic infiltration in the airways of healthy human volunteers involving neutrophils, lymphocytes, and mast cells along with increases in several inflammatory mediators. We hypothesized that the leukocyte infiltration and the various inflammatory responses induced by DE were mediated by enhanced chemokine and cytokine production by resident cells of the airway tissue and lumen. To investigate this, 15 healthy human volunteers were exposed to diluted DE and air on two separate occasions for 1 h each in an exposure chamber. Fiberoptic bronchoscopy was performed 6 h after each exposure to obtain endobronchial biopsies and bronchial wash (BW) cells. Using reverse transcriptase/polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR ELISA), a novel and sensitive technique to quantify relative amounts of cytokine mRNA gene transcripts, and immunohistochemical staining with computer-assisted image analysis to quantify expression of cytokine protein in the bronchial tissue, we have demonstrated that DE enhanced gene transcription of interleukin-8 (IL-8) in the bronchial tissue and BW cells along with increases in IL-8 and growth-regulated oncogene-alpha (GRO-alpha) protein expression in the bronchial epithelium, and an accompanying trend toward an increase in IL-5 mRNA gene transcripts in the bronchial tissue. There were no significant changes in the gene transcript levels of interleukin-1B (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimulating factor (GM-CSF) either in the bronchial tissue or BW cells after DE exposure at this time point. These observations suggest an underlying mechanism for DE-induced airway leukocyte infiltration and offer a possible explanation for the association observed between ambient levels of particulate matter and various respiratory health outcome indices noted in epidemiological studies.

Particulate matter (PM) pollution has been associated with negative health effects, including exacerbations of asthma following exposure to PM peaks. The aim of the present study was to investigate the effects of short-term exposure to diesel exhaust (DE) in asthmatics, by specifically addressing the effects on airway hyperresponsiveness, lung function and airway inflammation.Fourteen nonsmoking, atopic asthmatics with stable disease, on continuous treatment with inhaled corticosteroids, were included. All were hyperresponsive to methacholine. Each subject was exposed to DE (particles with a 50% cut-off aerodynamic diameter of 10 mm (PM10) 300 mg?m -3 ) and air during 1 h on two separate occasions. Lung function was measured before and immediately after the exposures. Sputum induction was performed 6 h, and methacholine inhalation test 24 h, after each exposure.Exposure to DE was associated with a significant increase in the degree of hyperresponsiveness, as compared to after air, of 0.97 doubling concentrations at 24 h after exposure (pv0.001). DE also induced a significant increase in airway resistance (p~0.004) and in sputum levels of interleukin (IL)-6 (p~0.048). No changes were detected in sputum levels of methyl-histamine, eosinophil cationic protein, myeloperoxidase and IL-8.This study indicated that short-term exposure to diesel exhaust, equal to high ambient levels of particulate matter, is associated with adverse effects in asthmatic airways, even in the presence of inhaled corticosteroid therapy. The increase in airway responsiveness may provide an important link to epidemiological findings of exacerbations of asthma following exposure to particulate matter. Eur Respir J 2001; 17: 909-915.

The adverse health effects of particulate matter pollution are of increasing concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway inflammation was detected following exposure to diesel exhaust (DE). The present study was conducted in order to evaluate the time kinetics of the inflammatory response following exposure to DE using induced sputum from healthy volunteers.Fifteen healthy nonsmoking volunteers were exposed to DE particles with a 50% cut-off aerodynamic diameter of 10 mm 300 mg . m -3 and air for 1 h on two separate occasions. Sputum induction with hypertonic saline was performed 6 and 24 h after each exposure. Analyses of sputum differential cell counts and soluble protein concentrations were performed.Six hours after exposure to DE, a significant increase was found in the percentage of sputum neutrophils (37.7 versus 26.2% p=0.002) together with increases in the concentrations of interleukin-6 (12.0 versus 6.3 pg . mL -1 , p=0.006) and methylhistamine (0.11 versus 0.12 mg . L -1 , p=0.024). Irrespective of exposure, a significant increase was found in the percentage of sputum neutrophils at 24 as compared to 6 h, indicating that the procedure of sputum induction itself may change the composition of sputum.This study demonstrates that exposure to diesel exhaust induces inflammatory response in healthy human airways, represented by an early increase in interleukin -6 and methylhistamine concentration and the percentage of neutrophils. Induced sputum provides a safe tool for the investigation of the inflammatory effects of diesel exhaust, but care must be taken when interpreting results from repeated sputum inductions. Eur Respir J 2000; 15: 1046±1051. The adverse health effects of particulate matter (PM) pollution are of increasing concern as several epidemiological studies have revealed an association between elevations in ground level PM concentrations and increased morbidity and mortality from cardiovascular and respiratory causes [1±7].Recently, attention has been directed towards the particulate air pollution emitted from diesel engines. The number of diesel-powered cars is rising and diesel engines emit up to 100 times more particles than petrol engines [8,9]. Diesel exhaust (DE) particles contain a carbonaceous core, which adsorbs various metals and organic compounds on its surface. Consequently, the biological effects of DE may be explained by not only the gases and pure particles but also by these surface components.The number of studies investigating the effects of DE has increased during recent years. In working environments, exposure to DE has been associated with various symptoms related to the eyes and airways [10±12]. In experimental chamber studies, DE has been shown to cause airway symptoms [13] and to induce an acute inflammatory response in human airways as reflected in bronchoalveolar lavage [14,15] and bronchial biopsy [16] samples. Further, local nasal challenge with DE particles has been reported to enhance immunoglobulin E production in the ...

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To obtain information on the real-time events occurring within human respiratory tract lining fluids (RTLFs) during ozone exposure, sequential nasal lavage was performed on 13 human volunteers exposed on separate occasions to 0.2 parts per million O 3 and filtered air (2-h exposures, with intermittent exercise).Nasal lavage was performed and blood samples obtained at four time points throughout each exposure: pre-exposure (Pre-E), 1 h into exposure (1h-E), immediately postexposure (0h-PE) and 1 h post-exposure (1h-PE). Endobronchial mucosal biopsies were obtained at 1.5 h-post exposure (1.5 h-PE).Nasal RTLF neutrophilia was not apparent during, or 1.5 h after, O 3 exposure. Furthermore, activation of the pre-existing neutrophil population did not occur. Airway permeability was not altered by this O 3 exposure regimen. Sequential lavage resulted in significant washout of RTLF ascorbic acid, reduced glutathione, extracellular superoxide dismutase and myeloperoxidase at 1h-E, 0h-PE and 1.5h-PE relative to baseline Pre-E values. In contrast, RTLF uric acid (UA), total protein and albumin concentrations did not display washout kinetics. Of the antioxidants examined, only UA was clearly depleted by O 3 , concentrations, falling by 6.22 mmol . L -1 at 1h-E, compared with 1.61 mmol . L -1 (p<0.01) during control air exposure. The establishment of a new pseudo-steady-state concentration of RTLF UA (70% of Pre-E values) during the second hour of O 3 exposure was coincident with a small but significant increase in plasma UA concentration (19.27 (O 3 ) versus 1.95 mmol . L -1 (air), p<0.05).These data demonstrate that inhalation of 0.2 parts per million O 3 results in the depletion of nasal respiratory tract lining fluid uric acid and that this regional loss of uric acid leads to a small increase in plasma uric acid concentration. Whilst the reaction of uric acid with inspired O 3 may confer protection locally, the role of upper airway uric acid as a sink for inhaled O 3 is not supported by these findings.

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