Proinflammatory doses of diesel exhaust in healthy subjects fail to elicit equivalent or augmented airway inflammation in subjects with asthma

• Published in: Thorax Vol. 66; no. 1; pp. 12 - 19
• Main Authors: Behndig, Annelie F, Larsson, Nirina, Brown, Joanna L, Stenfors, Nikolai, Helleday, Ragnberth, Duggan, Sean T, Dove, Rosamund E, Wilson, Susan J, Sandstrom, Thomas, Kelly, Frank J, Mudway, Ian S, Blomberg, Anders
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group 01.01.2011; BMJ Publishing Group LTD
• Subjects: Adolescent; Adult; Aerosols; Allergies; Asthma; Asthma - etiology; Asthma - physiopathology; Automobiles; Biological and medical sciences; Bronchial Provocation Tests - methods; Bronchoconstrictor Agents; Bronchoscopy; Cardiology. Vascular system; Chronic obstructive pulmonary disease, asthma; Epidemiologic Methods; Female; Forced Expiratory Volume; Humans; Inflammation; Inflammation Mediators - analysis; Inflammation Mediators - toxicity; Inhalation Exposure - adverse effects; Inhalation Exposure - analysis; Male; Medical sciences; Methacholine Chloride; Neutrophil Infiltration; Nitric oxide; Nitric Oxide - metabolism; Peak Expiratory Flow Rate; Pneumology; Steroids; Vehicle Emissions - analysis; Vehicle Emissions - toxicity; Young Adult; Human; Lung disease; Healthy subject; Respiratory disease; Inflammation; Posology; Asthma; Exhaust; Respiratory tract; Bronchus disease; Anesthesia; Obstructive pulmonary disease; Circulatory system; Cardiology; Dose
• ISSN: 0040-6376; 1468-3296; 1468-3296
• DOI: 10.1136/thx.2010.140053

BackgroundExposure to traffic-derived air pollutants, particularly diesel emissions, has been associated with adverse health effects, predominantly in individuals with pre-existing respiratory disease. Here the hypothesis that this heightened sensitivity reflects an augmentation of the transient inflammatory response previously reported in healthy adults exposed to diesel exhaust is examined.Methods32 subjects with asthma (mild to moderate severity) and 23 healthy controls were exposed in a double-blinded crossover control fashion to both filtered air and diesel exhaust (100 μg/m3 PM10) for 2 h. Airway inflammation was assessed by bronchoscopy 18 h postexposure. In addition, lung function, fraction of exhaled nitric oxide and bronchial reactivity to metacholine were examined in the subjects with asthma.ResultsIn healthy control subjects a significant increase in submucosal neutrophils (p=0.004) was observed following the diesel challenge. Significant increases in neutrophil numbers (p=0.01), and in the concentrations of interleukin 6 (p=0.03) and myeloperoxidase (p=0.04), were also seen in bronchial wash after diesel, relative to the control air challenge. No evidence of enhanced airway inflammation was observed in the subjects with asthma following the diesel exposure.ConclusionsExposure to diesel exhaust at concentrations consistent with roadside levels elicited an acute and active neutrophilic inflammation in the airways of healthy subjects. This response was absent in subjects with asthma, as was evidence supporting a worsening of allergic airway inflammation.