title: Cigarette Smoke Exposure and the Acute Respiratory Distress Syndrome.
abstract: OBJECTIVE
  The association between cigarette smoke exposure and the acute respiratory distress syndrome in patients with the most common acute respiratory distress syndrome risk factors of sepsis, pneumonia, and aspiration has not been well studied. The goal of this study was to test the association between biomarker-confirmed cigarette smoking and acute respiratory distress syndrome in a diverse cohort.
  
  
  METHODS
  Prospective cohort.
  
  
  METHODS
  Tertiary care center.
  
  
  METHODS
  Four hundred twenty-six critically ill patients with acute respiratory distress syndrome risk factors (excluding trauma and transfusion)
  
  
  METHODS
  : None.
  
  
  RESULTS
  We obtained smoking histories and measured urine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol (a biomarker of cigarette smoke exposure) on urine samples obtained at the time of study enrollment. The association between cigarette smoke exposure and acute respiratory distress syndrome differed based on acute respiratory distress syndrome risk factor (p < 0.02 for interaction). In patients with nonpulmonary sepsis as the primary acute respiratory distress syndrome risk factor (n = 212), 39% of those with acute respiratory distress syndrome were current smokers by history compared with 22% of those without acute respiratory distress syndrome (odds ratio, 2.28; 95% CI, 1.24-4.19; p = 0.008). Likewise, cigarette smoke exposure as measured by urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was significantly associated with acute respiratory distress syndrome in this group. The increased risk of acute respiratory distress syndrome in nonpulmonary sepsis was restricted to patients with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol levels consistent with active smoking and was robust to adjustment for other acute respiratory distress syndrome predictors. Cigarette smoke exposure as measured by history or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was not associated with acute respiratory distress syndrome in patients with other risk factors (e.g., pneumonia and aspiration).
  
  
  CONCLUSIONS
  Cigarette smoking measured both by history and biomarker is associated with an increased risk of acute respiratory distress syndrome in patients with nonpulmonary sepsis. This finding has important implications for tobacco product regulation and for understanding the pathogenesis of acute respiratory distress syndrome.
authors.affiliation: 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA. 2Department of Anesthesia, University of California San Francisco, San Francisco, CA. 3Division of Hospital Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA. 4Department of Medicine, Vanderbilt University, Nashville, TN. 5Department of Medicine, Louisiana State University School of Medicine, New Orleans, LA. 6Department of Surgery, Vanderbilt University, Nashville, TN. 7Center for Tobacco Control Research and Education, University of California San Francisco, San Francisco, CA. 8Division of Clinical Pharmacology and Experimental Therapeutics, University of California San Francisco, San Francisco, CA. 9Departments of Medicine and of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Calfee
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: Kirsten N
authors.initials: KN
authors.lastname: Kangelaris
authors.forename: Edward D
authors.initials: ED
authors.lastname: Siew
authors.forename: David R
authors.initials: DR
authors.lastname: Janz
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bernard
authors.forename: Addison K
authors.initials: AK
authors.lastname: May
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
authors.forename: Christopher
authors.initials: C
authors.lastname: Havel
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology; D015415:Biomarkers; D016638:Critical Illness; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009602:Nitrosamines / Q000652:urine; D015995:Prevalence; D011446:Prospective Studies; D011725:Pyridines / Q000652:urine; D044469:Racial Groups; D012128:Respiratory Distress Syndrome / Q000453:epidemiology*; D012307:Risk Factors; D018805:Sepsis / Q000453:epidemiology*; D012907:Smoking / Q000453:epidemiology*; D062606:Tertiary Care Centers; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000032:analysis*
chemical_list: D015415:Biomarkers; D009602:Nitrosamines; D011725:Pyridines; D014028:Tobacco Smoke Pollution; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol