Journal
THORAX
Volume 71, Issue 12, Pages 1130-1136Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/thoraxjnl-2015-207886
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Funding
- Northern Ireland RD Office
- UK Intensive Care Society
- NHLBI [HL51856, HL110969, HL126345-01, R24 AA019661]
- National Cancer Institute [1P50CA180890]
- Food and Drug Administration Center for Tobacco Products
- MRC [MR/L002736/1, G1100196] Funding Source: UKRI
- Medical Research Council [G1100196, MR/L002736/1] Funding Source: researchfish
- National Institute for Health Research [CS-2014-14-027] Funding Source: researchfish
- Public Health Agency [CDV/3778/08] Funding Source: researchfish
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Rationale Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. Objective To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. Methods We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 mu g LPS inhalation (n=30). Measurements and main results After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 mu g/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1 beta (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than nonsmokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). Conclusions Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products.
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