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Original research
Risk of drug-induced interstitial lung disease in hospitalised patients: a nested case–control study
  1. Taisuke Jo1,2,
  2. Nobuaki Michihata2,
  3. Hayato Yamana2,
  4. Kojiro Morita3,4,
  5. Miho Ishimaru3,4,
  6. Yasuhiro Yamauchi1,
  7. Wakae Hasegawa1,
  8. Hirokazu Urushiyama1,
  9. Kazuaki Uda4,
  10. Hiroki Matsui4,
  11. Kiyohide Fushimi5,
  12. Hideo Yasunaga4,
  13. Takahide Nagase1
  1. 1Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  2. 2Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  3. 3Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
  4. 4Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
  5. 5Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan
  1. Correspondence to Dr Taisuke Jo, Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; jo-taisuke{at}umin.ac.jp

Abstract

Introduction Information on drug-induced interstitial lung disease (DILD) is limited due to its low incidence. This study investigated the frequencies of drug categories with potential risk in patients developing DILD during hospitalisation and analysed the risk of developing DILD associated with each of these drugs.

Methods Using a Japanese national inpatient database, we identified patients without interstitial pneumonia on admission who developed DILD and required corticosteroid therapy during hospitalisation from July 2010 to March 2016. We conducted a nested case–control study; four controls from the entire non-DILD patient cohort were matched to each DILD case on age, sex, main diagnosis, admission year and hospital. We defined 42 classified categories of drugs with 216 generic names as drugs with potential risk of DILD, and we identified the use of these drugs during hospitalisation for each patient. We analysed the association between each drug category and DILD development using conditional logistic regression analyses.

Results We retrospectively identified 2342 patients who developed DILD. After one-to-four case–control matching, 1541 case patients were matched with 5677 control patients. Six drug categories were significantly associated with the increased occurrence of DILD. These included epidermal growth factor receptor inhibitors (OR: 16.84, 95% CI 9.32 to 30.41) and class III antiarrhythmic drugs (OR: 7.01, 95% CI 3.86 to 12.73). Statins were associated with reduced risk of DILD (OR: 0.68, 95% CI 0.50 to 0.92).

Conclusions We demonstrated significant associations between various drug categories and DILD. Our findings provide useful information on drug categories with potential risk to help physicians prevent and treat DILD.

  • clinical epidemiology
  • drug induced lung disease

Data availability statement

Data are available upon reasonable request. Data cannot be made publicly available for ethical reasons as the data are patient data. Data are available to interested researchers upon reasonable request to the corresponding author, pending ethical approval.

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Data availability statement

Data are available upon reasonable request. Data cannot be made publicly available for ethical reasons as the data are patient data. Data are available to interested researchers upon reasonable request to the corresponding author, pending ethical approval.

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Footnotes

  • Contributors TJ: conception and design, data analysis and interpretation, and manuscript writing. NM, HYam, YY, WH, UH: conception and design, data analysis and interpretation, and final approval of the manuscript. KM, MI, KU, KF, HM: data collection, data analysis and final approval of the manuscript. HYas: conception and design, data collection, data analysis and interpretation, and manuscript writing. TN: conception and design and final approval of the manuscript.

  • Funding This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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