title: Cigarette smoking impairs pancreatic duct cell bicarbonate secretion.
abstract: OBJECTIVE
  To compare pancreatic duct cell function in smokers (current and past) and never smokers by measurement of secretin-stimulated peak bicarbonate concentration ([HCO3-]) in endoscopic collected pancreatic fluid (PF).
  
  
  METHODS
  This retrospective study was cross-sectional in design, recording demographic information (age, gender, etc.), smoking status (former, current, never), alcohol intake, clinical data (imaging, endoscopy), and laboratory results (peak PF [HCO3-]) from subjects evaluated for pancreatic disease at a tertiary pancreas center. Univariate and multivariate statistical analysis (SAS Version 9.2, Cary, NC, USA) was performed to assess the relationship between cigarette smoking and secretin-stimulated pancreatic fluid bicarbonate concentration.
  
  
  RESULTS
  A total of 131 subjects underwent pancreatic fluid collection (endoscopic pancreatic function test, ePFT) for bicarbonate analysis: 25.2% (33 out of 131) past smokers, 31.3% (41 out of 131) current smokers, and 43.5% (57 out of 131) were never smokers. Measures of Association: The mean peak PF [HCO3-] in never smokers (81.3 ± 18.5 mEq/L) was statistically higher (indicating better duct cell function) when compared to past smokers (66.8 ± 24.7 mEq/L, P=0.005) and current smokers (70.0 ± 20.2 mEq/L, P=0.005). However, the mean peak [HCO3-] in past smokers was not statistically different from that in current smokers (P=0.575), and therefore, the two smoking groups were combined to form a single "smokers cohort". When compared to the never smokers, the smokers cohort was older (P=0.037) and had a greater proportion of subjects with definite chronic pancreatitis imaging (P=0.010), alcohol consumption ≥20 g/day (P=0.012), and abnormal peak PF [HCO3-] (P<0.001). Risk-Based Estimates: Cigarette smoking (risk ratio, RR: 2.2, 95% CI: 1.3-3.5; P<0.001), diagnosis of definite chronic pancreatitis imaging (RR: 2.2, 95% CI: 1.6-3.2; P<0.001) and alcohol consumption ≥20 g/day (RR: 1.6, 95% CI: 1.1-2.4; P=0.033) were all associated with low mean peak PF [HCO3-] (indicating duct cell secretory dysfunction). Multivariate Analysis: Smoking (odds ratio, OR: 3.8, 95% CI: 1.6-9.1; P=0.003) and definite chronic pancreatitis imaging (OR: 5.7, 95% CI: 2.2-14.8; P<0.001) were determined to be independent predictors of low peak PF [HCO3-], controlling for age, gender, and alcohol intake. Furthermore there was no interaction between smoking status and alcohol intake in predicting duct cell dysfunction (P=0.571).
  
  
  CONCLUSIONS
  Measurement of pancreatic fluid bicarbonate in smokers reveals that cigarette smoking (past and current) is an independent risk factor for pancreatic duct cell secretory dysfunction (low PF [HCO3-]). Furthermore, the risk of duct cell dysfunction in subjects who smoked was approximately twice the risk (RR: 2.2) in never smokers. Further in depth, translational research approaches to pancreatic fluid analysis may help unravel mechanisms of cigarette smoking induced pancreatic duct cell injury.
authors.affiliation: Center for Pancreatic Disease, Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kadiyala
authors.forename: Linda S
authors.initials: LS
authors.lastname: Lee
authors.forename: Peter A
authors.initials: PA
authors.lastname: Banks
authors.forename: Shadeah
authors.initials: S
authors.lastname: Suleiman
authors.forename: Joao A
authors.initials: JA
authors.lastname: Paulo
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jessica
authors.initials: J
authors.lastname: Rosenblum
authors.forename: Nisha I
authors.initials: NI
authors.lastname: Sainani
authors.forename: Koenraad
authors.initials: K
authors.lastname: Mortele
authors.forename: Darwin Lewis
authors.initials: DL
authors.lastname: Conwell
mesh_terms: D000328:Adult; D000428:Alcohol Drinking; D001639:Bicarbonates / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010183:Pancreatic Ducts / Q000378:metabolism* / Q000473:pathology; D010186:Pancreatic Function Tests; D010189:Pancreatic Juice / Q000737:chemistry; D050500:Pancreatitis, Chronic / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001639:Bicarbonates