Acute Inflammatory Responses in the Airways and Peripheral Blood After Short-Term Exposure to Diesel Exhaust in Healthy Human Volunteers

TLDR

Particulate matter, especially diesel exhaust, is linked to cardiovascular and respiratory mortality, yet the biological mechanisms underlying its toxicity remain unclear. The study aimed to assess the acute impact of diesel exhaust on human airways. Fifteen healthy volunteers were exposed to air or diluted diesel exhaust for one hour with intermittent exercise, after which lung function was measured and airway lavage and bronchial biopsies were obtained six hours later. Despite unchanged lung function, diesel exhaust exposure induced marked pulmonary and systemic inflammation, evidenced by increased neutrophils, B cells, mast cells, T cells, ICAM‑1/VCAM‑1 expression in bronchial tissue, and elevated neutrophils and platelets in peripheral blood.

Abstract

Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.