Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease

M. Ishihara, Naoki Omiya, M. Nakamura, K. Funasaka, R. Miyahara, E. Ohno, H. Kawashima, A. Itoh, Y. Hirooka, O. Watanabe, T. Ando, H. Goto

Research output: Contribution to journalArticle

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Abstract

Background The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. Aim 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). Conclusion The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

Original languageEnglish
Pages (from-to)538-547
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume40
Issue number5
DOIs
Publication statusPublished - 01-01-2014

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Non-Steroidal Anti-Inflammatory Agents
Diaphragm
Anti-Inflammatory Agents
meloxicam
Wounds and Injuries
Pharmaceutical Preparations
Aspirin
Double-Balloon Enteroscopy
Diclofenac
Proton Pump Inhibitors
Endoscopy
Single Nucleotide Polymorphism
Comorbidity
Multivariate Analysis
Cytochrome P-450 CYP2C9

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Ishihara, M. ; Omiya, Naoki ; Nakamura, M. ; Funasaka, K. ; Miyahara, R. ; Ohno, E. ; Kawashima, H. ; Itoh, A. ; Hirooka, Y. ; Watanabe, O. ; Ando, T. ; Goto, H. / Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease. In: Alimentary Pharmacology and Therapeutics. 2014 ; Vol. 40, No. 5. pp. 538-547.
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abstract = "Background The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. Aim 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). Conclusion The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.",
author = "M. Ishihara and Naoki Omiya and M. Nakamura and K. Funasaka and R. Miyahara and E. Ohno and H. Kawashima and A. Itoh and Y. Hirooka and O. Watanabe and T. Ando and H. Goto",
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Ishihara, M, Omiya, N, Nakamura, M, Funasaka, K, Miyahara, R, Ohno, E, Kawashima, H, Itoh, A, Hirooka, Y, Watanabe, O, Ando, T & Goto, H 2014, 'Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease', Alimentary Pharmacology and Therapeutics, vol. 40, no. 5, pp. 538-547. https://doi.org/10.1111/apt.12858

Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease. / Ishihara, M.; Omiya, Naoki; Nakamura, M.; Funasaka, K.; Miyahara, R.; Ohno, E.; Kawashima, H.; Itoh, A.; Hirooka, Y.; Watanabe, O.; Ando, T.; Goto, H.

In: Alimentary Pharmacology and Therapeutics, Vol. 40, No. 5, 01.01.2014, p. 538-547.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Risk factors of symptomatic NSAID-induced small intestinal injury and diaphragm disease

AU - Ishihara, M.

AU - Omiya, Naoki

AU - Nakamura, M.

AU - Funasaka, K.

AU - Miyahara, R.

AU - Ohno, E.

AU - Kawashima, H.

AU - Itoh, A.

AU - Hirooka, Y.

AU - Watanabe, O.

AU - Ando, T.

AU - Goto, H.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. Aim 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). Conclusion The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

AB - Background The aetiology for nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injuries has not been well characterised. Aim 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). Conclusion The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.

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