RT Journal Article SR Electronic T1 Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 1130 OP 1136 DO 10.1136/thoraxjnl-2015-207886 VO 71 IS 12 A1 Farzad Moazed A1 Ellen L Burnham A1 R William Vandivier A1 Cecilia M O'Kane A1 Murali Shyamsundar A1 Umar Hamid A1 Jason Abbott A1 David R Thickett A1 Michael A Matthay A1 Daniel F McAuley A1 Carolyn S Calfee YR 2016 UL http://thorax.bmj.com/content/71/12/1130.abstract AB 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 μg 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 μg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1β (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 non-smokers, 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.