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.
- Tobacco and the lung
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Contributors FM, MAM, DFM and CSC: study conception and design; ELB, RWV, CMO, MS, UH, JA, DRT and DFM: data acquisition; FM, MAM, DFM, CSC: data analysis and interpretation. FM, MAM, DFM and CSC: drafted the manuscript. All authors participated in critically revising the manuscript, saw and approved the final version of the manuscript. FM takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding Supported by Northern Ireland R&D Office; UK Intensive Care Society (DFM); NHLBI HL51856 (MAM), HL110969 (CSC), HL126345-01 (FM) and R24 AA019661 (ELB). Some research reported in this publication was supported by grant number 1P50CA180890 from the National Cancer Institute and Food and Drug Administration Center for Tobacco Products (CSC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.
Competing interests None declared.
Ethics approval Queen's University Belfast and University of Colorado institutional review boards.
Provenance and peer review Not commissioned; externally peer reviewed.
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