title: Role of Salmonella enterica exposure in Chilean Crohn's disease patients.
abstract: OBJECTIVE
  To study the association between exposure to Salmonella enterica (SE) and Crohn's disease (CD) and its clinical implications in Chilean patients.
  
  
  METHODS
  Ninety-four unrelated Chilean CD patients from CAREI (Active Cohort Registry of Inflammatory Bowel Disease) presenting to a single inflammatory bowel disease (IBD) unit of a University Hospital were prospectively included in this study. A complete clinical evaluation, including smoking history, was performed at the initial visit, and all the important data of clinical evolution of CD were obtained. Blood samples from these CD patients and 88 healthy sex- and age-matched control subjects were analyzed for exposure to SE and for their NOD2/CARD15 gene status using the presence of anti-Salmonella lipopolysaccharide antibodies [immunoglobulin-G type (IgG)] and polymerase chain reaction (PCR), respectively. We also evaluated exposure to SE in 90 sex- and age-matched patients without CD, but with known smoking status (30 smokers, 30 non-smokers, and 30 former smokers).
  
  
  RESULTS
  CD patients comprised 54 females and 40 males, aged 35.5 ± 15.2 years at diagnosis with a mean follow-up of 9.0 ± 6.8 years. CD was inflammatory in 59 patients (62.7%), stricturing in 24 (25.5%) and penetrating in 15 (15.5%). Thirty cases (31.9%) had lesions in the ileum, 29 (30.8%) had ileocolonic lesions, 32 (34.0%) had colonic lesions and 23 (24.4%) had perianal disease. Sixteen CD patients (17%) were exposed to SE compared to 15 (17%) of 88 healthy control subjects (P = 0.8). Thirty-one CD patients (32.9%) were smokers, and 7 (7.4%) were former smokers at diagnosis. In the group exposed to SE, 10 of 16 patients (62.5%) were active smokers compared to 21 of 78 patients (26.9%) in the unexposed group (P = 0.01). On the other hand, 10 of 31 smoking patients (32%) were exposed to SE compared to 5 of 56 nonsmoking patients (9%), and one of the seven former smokers (14%) (P = 0.01). In the group of 90 patients without CD, but whose smoking status was known, there was no difference in exposure to SE [3 of 30 smokers (10%), 5 of 30 non-smokers (16%), and 5 of 30 former smokers (16%); P = 0.6]. There were no differences in disease severity between CD patients with and those without anti-SE IgG antibodies, estimated as the appearance of stricturing [2 (12.5%) vs 22 (28.2%); P = 0.2] or penetrating lesions [2 (12.5%) vs 13 (16.6%); P = 1.0]; or the need for immunosuppressants [11 (68.7%) vs 55 (70.5%); P = 1.0], anti-tumor necrosis factor therapy [1 (6.2%) vs 7 (8.9%); P = 1.0], hospitalization [13 (81.2%) vs 58 (74.3%); P = 0.7], or surgery [3 (18.7%) vs 12 (15.3%); P = 0.3), respectively]. No other factors were associated with SE, including NOD2/CARD15 gene status. Seventeen CD patients (18%) had at least one mutation of the NOD2/CARD15 gene.
  
  
  CONCLUSIONS
  Our study found no association between exposure to SE and CD. We observed a positive correlation between SE exposure and cigarette smoking in Chilean patients with CD, but not with disease severity.
authors.affiliation: Manuel Alvarez-Lobos, Patricio Ibañez, Carlos Quintana, CAREI Group (Active Cohort Registry of Inflammatory Bowel Disease), Department of Gastroenterology, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 6510260, Chile.
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez-Lobos
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Pizarro
authors.forename: Christian E
authors.initials: CE
authors.lastname: Palavecino
authors.forename: Abner
authors.initials: A
authors.lastname: Espinoza
authors.forename: Valentina P
authors.initials: VP
authors.lastname: Sebastián
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alvarado
authors.forename: Patricio
authors.initials: P
authors.lastname: Ibañez
authors.forename: Carlos
authors.initials: C
authors.lastname: Quintana
authors.forename: Orlando
authors.initials: O
authors.lastname: Díaz
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Kalergis
authors.forename: Susan M
authors.initials: SM
authors.lastname: Bueno
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002677:Chile / Q000453:epidemiology; D003424:Crohn Disease / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D012480:Salmonella Infections / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology / Q000628:therapy; D019779:Salmonella enterica / Q000276:immunology / Q000472:pathogenicity*; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
keywords: Crohn’s disease; Environmental factors; Infection; Salmonella; Smoking; Tobacco