title: Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease.
abstract: BACKGROUND
  The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised.
  
  
  OBJECTIVE
  To determine the risk factors of symptomatic NSAID-induced small intestinal injuries, including diaphragm disease.
  
  
  METHODS
  Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double-balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5'-nuclease assays.
  
  
  RESULTS
  Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID-induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID-induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05-8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04-24.40, P = 0.002, respectively). The combination of aspirin and non-aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34-1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55-108.36, P = 0.018, respectively).
  
  
  CONCLUSIONS
  The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishihara
authors.forename: N
authors.initials: N
authors.lastname: Ohmiya
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Funasaka
authors.forename: R
authors.initials: R
authors.lastname: Miyahara
authors.forename: E
authors.initials: E
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Kawashima
authors.forename: A
authors.initials: A
authors.lastname: Itoh
authors.forename: Y
authors.initials: Y
authors.lastname: Hirooka
authors.forename: O
authors.initials: O
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: H
authors.initials: H
authors.lastname: Goto
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001241:Aspirin / Q000009:adverse effects; D053704:Capsule Endoscopy; D016022:Case-Control Studies; D065729:Cytochrome P-450 CYP2C9; D003964:Diaphragm / Q000187:drug effects; D004008:Diclofenac / Q000009:adverse effects; D058582:Double-Balloon Enteroscopy; D005260:Female; D006801:Humans; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D007421:Intestine, Small / Q000187:drug effects / Q000293:injuries*; D008297:Male; D000077239:Meloxicam; D008875:Middle Aged; D010894:Piroxicam / Q000009:adverse effects / Q000031:analogs & derivatives; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013843:Thiazines / Q000009:adverse effects; D013844:Thiazoles / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; C065946:ampiroxicam; D010894:Piroxicam; D004008:Diclofenac; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C059451:lornoxicam; D001241:Aspirin; D000077239:Meloxicam