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Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation
  1. Farzad Moazed1,
  2. Ellen L Burnham2,
  3. R William Vandivier2,
  4. Cecilia M O'Kane3,
  5. Murali Shyamsundar3,
  6. Umar Hamid3,
  7. Jason Abbott4,
  8. David R Thickett5,
  9. Michael A Matthay1,4,6,
  10. Daniel F McAuley3,
  11. Carolyn S Calfee1,4,6
  1. 1Department of Medicine, UCSF, San Francisco, California, USA
  2. 2Department of Medicine, University of Colorado, Aurora, Colorado, USA
  3. 3Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK
  4. 4Cardiovascular Research Institute, UCSF, San Francisco, California, USA
  5. 5Lung Injury and Fibrosis Treatment Programme, University of Birmingham, Birmingham, UK
  6. 6Department of Anesthesia, UCSF, San Francisco, California, USA
  1. Correspondence to Dr Farzad Moazed, Department of Medicine, Division of Pulmonary and Critical Care Medicine, UCSF, 505 Parnassus Ave, M1097, San Francisco, CA 94143-0111, USA; farzad.moazed{at}


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.

  • ARDS
  • Tobacco and the lung

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