The University of Southampton
University of Southampton Institutional Repository

Health effects of acute exposure to air pollution. Part I: healthy and asthmatic subjects exposed to diesel exhaust

Health effects of acute exposure to air pollution. Part I: healthy and asthmatic subjects exposed to diesel exhaust
Health effects of acute exposure to air pollution. Part I: healthy and asthmatic subjects exposed to diesel exhaust
The purpose of this study was to assess the impact of short-term exposure to diluted diesel exhaust on inflammatory parameters in human airways. We previously exposed control subjects for 1 hour to a high ambient concentration of diesel exhaust (particle concentration 300 pg/m3--a level comparable with that found in North Sea ferries, highway underpasses, etc). Although these exposures did not have any measurable effect on standard indices of lung function, there was a marked neutrophilic inflammatory response in the airways accompanied by increases in blood neutrophil and platelet counts. Endothelial adhesion molecules were upregulated, and the expression of interleukin 8 messenger RNA (IL-8 mRNA*) was increased in a pattern consistent with neutrophilia. Individuals with asthma have inflamed airways and are clinically more sensitive to air pollutants than are control subjects.
The present study was designed to assess whether this clinical sensitivity can be explained by acute neutrophilic inflammation or an increase in allergic airway inflammation resulting from diesel exhaust exposure. For this study, we used a lower concentration of diesel exhaust (100 microg/m3 PM10) for a 2-hour exposure. At this concentration, both the control subjects and those with asthma demonstrated a modest but statistically significant increase in airway resistance following exposure to diesel exhaust. This increase in airway resistance was associated with an increased number of neutrophils in the bronchial wash (BW) fluid obtained from control subjects (median after diesel exhaust 22.0 vs median after air 17.2; P = 0.015), as well as an increase in lymphocytes obtained through bronchoalveolar lavage (BAL) (15.0% after diesel exhaust vs 12.3% after air; P = 0.017). Upregulation of the endothelial adhesion molecule P-selectin was noted in bronchial biopsy tissues from control subjects (65.4% of vessels after diesel exhaust vs 52.5% after air). There was also a significant increase in IL-8 protein concentrations in BAL fluid and IL-8 mRNA gene expression in the bronchial biopsy tissues obtained from control subjects after diesel exhaust exposure (median IL-8 expression 65.7% of adenine phosphoribosyl transferase [APRT] gene expression value after diesel exhaust vs 51.0% after air; P = 0.007). There were no significant changes in total protein, albumin, or other soluble inflammatory markers in the BW or BAL fluids. Red and white blood cell counts in peripheral blood were unaffected by diesel exhaust exposure. Airway mucosal biopsy tissues from subjects with mild asthma (defined as forced expiratory volume in 1 second [FEV1] greater than or equal to 70% of the predicted value) showed eosinophilic airway inflammation after air exposure compared with the airways of the corresponding control subjects. However, among the subjects with mild asthma, diesel exhaust did not induce any significant change in airway neutrophils, eosinophils, or other inflammatory cells; cytokines; or mediators of inflammation. The only clear effect of diesel exhaust on the airways of subjects with asthma was a significant increase in IL-10 staining in the biopsy tissues.
This study demonstrated that modest concentrations of diesel exhaust have clear-cut inflammatory effects on the airways of nonasthmatic (or control) subjects. The data suggest a direct effect of diesel exhaust on IL-8 production leading to upregulation of endothelial adhesion molecules and neutrophil recruitment. Despite clinical reports of increased susceptibility of patients with asthma to diesel exhaust and other forms of air pollution, it does not appear that this susceptibility is caused either directly by induction of neutrophilic inflammation or indirectly by worsening of preexisting asthmatic airway inflammation. The increased level of IL-10 after diesel exhaust exposure in airways of subjects with asthma suggests that this pollutant may induce subtle changes in airway immunobiology. This is an important topic for further investigation. Other possible explanations for the apparent lack of response to diesel exhaust among subjects with asthma include (1) the time course of the response to diesel may differ from the response to allergens, which peaks 6 to 8 hours after exposure; (2) a different type of inflammation may occur that was not detectable by the standard methods used in this study; and (3) the increased sensitivity of patients with asthma to particulate air pollution may reflect the underlying bronchial hyperresponsiveness found in asthma rather than any specific increase in inflammatory responses.
1041-5505
1-30
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Sandström, Thomas
77a4c11d-a84f-4a52-9bfe-4ec83f62363a
Frew, Anthony J.
4887b766-67c6-4d69-940d-4c06c0890b76
Stenfors, Nikolai
69c8966c-e8f8-40f8-b8b2-8e4f918953f0
Nördenhall, Charlotta
8b58ae29-9426-401e-af4a-0b1bc329da99
Salvi, Sundeep
606fe69f-eda6-465b-8a55-f4514397b3ca
Blomberg, Anders
b19c0008-dc79-425d-a05b-2fda60f020cf
Helleday, Ragnberth
26fa403b-f9f0-41fd-9332-78bc493b78e5
Söderberg, Margaretha
60a87849-085a-4eba-b127-48abb24ee887
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Sandström, Thomas
77a4c11d-a84f-4a52-9bfe-4ec83f62363a
Frew, Anthony J.
4887b766-67c6-4d69-940d-4c06c0890b76
Stenfors, Nikolai
69c8966c-e8f8-40f8-b8b2-8e4f918953f0
Nördenhall, Charlotta
8b58ae29-9426-401e-af4a-0b1bc329da99
Salvi, Sundeep
606fe69f-eda6-465b-8a55-f4514397b3ca
Blomberg, Anders
b19c0008-dc79-425d-a05b-2fda60f020cf
Helleday, Ragnberth
26fa403b-f9f0-41fd-9332-78bc493b78e5
Söderberg, Margaretha
60a87849-085a-4eba-b127-48abb24ee887

Holgate, Stephen T., Sandström, Thomas, Frew, Anthony J., Stenfors, Nikolai, Nördenhall, Charlotta, Salvi, Sundeep, Blomberg, Anders, Helleday, Ragnberth and Söderberg, Margaretha (2003) Health effects of acute exposure to air pollution. Part I: healthy and asthmatic subjects exposed to diesel exhaust. Health Effects Institute Research Report, (112), 1-30.

Record type: Article

Abstract

The purpose of this study was to assess the impact of short-term exposure to diluted diesel exhaust on inflammatory parameters in human airways. We previously exposed control subjects for 1 hour to a high ambient concentration of diesel exhaust (particle concentration 300 pg/m3--a level comparable with that found in North Sea ferries, highway underpasses, etc). Although these exposures did not have any measurable effect on standard indices of lung function, there was a marked neutrophilic inflammatory response in the airways accompanied by increases in blood neutrophil and platelet counts. Endothelial adhesion molecules were upregulated, and the expression of interleukin 8 messenger RNA (IL-8 mRNA*) was increased in a pattern consistent with neutrophilia. Individuals with asthma have inflamed airways and are clinically more sensitive to air pollutants than are control subjects.
The present study was designed to assess whether this clinical sensitivity can be explained by acute neutrophilic inflammation or an increase in allergic airway inflammation resulting from diesel exhaust exposure. For this study, we used a lower concentration of diesel exhaust (100 microg/m3 PM10) for a 2-hour exposure. At this concentration, both the control subjects and those with asthma demonstrated a modest but statistically significant increase in airway resistance following exposure to diesel exhaust. This increase in airway resistance was associated with an increased number of neutrophils in the bronchial wash (BW) fluid obtained from control subjects (median after diesel exhaust 22.0 vs median after air 17.2; P = 0.015), as well as an increase in lymphocytes obtained through bronchoalveolar lavage (BAL) (15.0% after diesel exhaust vs 12.3% after air; P = 0.017). Upregulation of the endothelial adhesion molecule P-selectin was noted in bronchial biopsy tissues from control subjects (65.4% of vessels after diesel exhaust vs 52.5% after air). There was also a significant increase in IL-8 protein concentrations in BAL fluid and IL-8 mRNA gene expression in the bronchial biopsy tissues obtained from control subjects after diesel exhaust exposure (median IL-8 expression 65.7% of adenine phosphoribosyl transferase [APRT] gene expression value after diesel exhaust vs 51.0% after air; P = 0.007). There were no significant changes in total protein, albumin, or other soluble inflammatory markers in the BW or BAL fluids. Red and white blood cell counts in peripheral blood were unaffected by diesel exhaust exposure. Airway mucosal biopsy tissues from subjects with mild asthma (defined as forced expiratory volume in 1 second [FEV1] greater than or equal to 70% of the predicted value) showed eosinophilic airway inflammation after air exposure compared with the airways of the corresponding control subjects. However, among the subjects with mild asthma, diesel exhaust did not induce any significant change in airway neutrophils, eosinophils, or other inflammatory cells; cytokines; or mediators of inflammation. The only clear effect of diesel exhaust on the airways of subjects with asthma was a significant increase in IL-10 staining in the biopsy tissues.
This study demonstrated that modest concentrations of diesel exhaust have clear-cut inflammatory effects on the airways of nonasthmatic (or control) subjects. The data suggest a direct effect of diesel exhaust on IL-8 production leading to upregulation of endothelial adhesion molecules and neutrophil recruitment. Despite clinical reports of increased susceptibility of patients with asthma to diesel exhaust and other forms of air pollution, it does not appear that this susceptibility is caused either directly by induction of neutrophilic inflammation or indirectly by worsening of preexisting asthmatic airway inflammation. The increased level of IL-10 after diesel exhaust exposure in airways of subjects with asthma suggests that this pollutant may induce subtle changes in airway immunobiology. This is an important topic for further investigation. Other possible explanations for the apparent lack of response to diesel exhaust among subjects with asthma include (1) the time course of the response to diesel may differ from the response to allergens, which peaks 6 to 8 hours after exposure; (2) a different type of inflammation may occur that was not detectable by the standard methods used in this study; and (3) the increased sensitivity of patients with asthma to particulate air pollution may reflect the underlying bronchial hyperresponsiveness found in asthma rather than any specific increase in inflammatory responses.

This record has no associated files available for download.

More information

Published date: 2003

Identifiers

Local EPrints ID: 27112
URI: http://eprints.soton.ac.uk/id/eprint/27112
ISSN: 1041-5505
PURE UUID: e8697b02-ee5e-40ef-8ac2-b295118df342

Catalogue record

Date deposited: 26 Apr 2006
Last modified: 08 Jan 2022 03:50

Export record

Contributors

Author: Thomas Sandström
Author: Anthony J. Frew
Author: Nikolai Stenfors
Author: Charlotta Nördenhall
Author: Sundeep Salvi
Author: Anders Blomberg
Author: Ragnberth Helleday
Author: Margaretha Söderberg

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×