PT - JOURNAL ARTICLE AU - Moazed, Farzad AU - Burnham, Ellen L AU - Vandivier, R William AU - O'Kane, Cecilia M AU - Shyamsundar, Murali AU - Hamid, Umar AU - Abbott, Jason AU - Thickett, David R AU - Matthay, Michael A AU - McAuley, Daniel F AU - Calfee, Carolyn S TI - Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation AID - 10.1136/thoraxjnl-2015-207886 DP - 2016 Dec 01 TA - Thorax PG - 1130--1136 VI - 71 IP - 12 4099 - http://thorax.bmj.com/content/71/12/1130.short 4100 - http://thorax.bmj.com/content/71/12/1130.full SO - Thorax2016 Dec 01; 71 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.