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.