Skip to main content

Advertisement

SpringerLink
Log in

Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRA

  • Original Article
  • Published:
Modern Rheumatology

Abstract

Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case–control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003;62:722–7.

    Article  CAS  PubMed  Google Scholar 

  2. Gochuico BR, Avila NA, Chow CK, Novero LJ, Wu HP, Ren P, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008;168:159–66.

    Article  CAS  PubMed  Google Scholar 

  3. Young A, Koduri G, Batley M, Kulinskaya E, Gough A, Norton S, et al. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology (Oxford). 2007;46:350–7.

    Article  CAS  Google Scholar 

  4. Winthrop KL. Serious infections with antirheumatic therapy: are biologicals worse? Ann Rheum Dis. 2006;65(Suppl 3):iii54–7.

    Article  PubMed  Google Scholar 

  5. Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Ann Rheum. 2006;54:628–34.

    CAS  Google Scholar 

  6. Evans RB, Ettensohn DB, Fawaz-Estrup F, Lally EV, Kaplan SR. Gold lung: recent developments in pathogenesis, diagnosis, and therapy. Semin Arthritis Rheum. 1987;16:196–205.

    Article  CAS  PubMed  Google Scholar 

  7. Negishi M, Kaga S, Kasama T, Hashimoto M, Fukushima T, Yamagata N, et al. Lung injury associated with bucillamine therapy. Ryumachi. 1992;32:135–9.

    CAS  PubMed  Google Scholar 

  8. McCurry J. Japan deaths spark concerns over arthritis drug. Lancet. 2004;363:461.

    Article  PubMed  Google Scholar 

  9. Carroll GJ, Thomas R, Phatouros CC, Atchison MH, Leslie AL, Cook NJ, et al. Incidence, prevalence and possible risk factors for pneumonitis in patients with rheumatoid arthritis receiving methotrexate. J Rheumatol. 1994;21:51–4.

    CAS  PubMed  Google Scholar 

  10. Bartram SA. Experience with methotrexate-associated pneumonitis in northeastern England: comment on the article by Kremer et al. Arthritis Rheum. 1998;41:1327–8.

    Article  CAS  PubMed  Google Scholar 

  11. Kremer JM, Alarcón GS, Weinblatt ME, Kaymakcian MV, Macaluso M, Cannon GW, et al. Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. Arthritis Rheum. 1997;40:1829–37.

    Article  CAS  PubMed  Google Scholar 

  12. Golden MR, Katz RS, Balk RA, Golden HE. The relationship of preexisting lung disease to the development of methotrexate pneumonitis in patients with rheumatoid arthritis. J Rheumatol. 1995;22:1043–7.

    CAS  PubMed  Google Scholar 

  13. Yazici Y, Sokka T, Kautiainen H, Swearingen C, Kulman I, Pincus T. Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities. Ann Rheum Dis. 2005;64:207–11.

    Article  CAS  PubMed  Google Scholar 

  14. Swierkot J, Szechiński J. Methotrexate in rheumatoid arthritis. Pharmacol Rep. 2006;58:473–92.

    CAS  PubMed  Google Scholar 

  15. Yamanaka H, Inoue E, Tanaka E, Nakajima A, Taniguchi A, Terai C, et al. Influence of methotrexate dose on its efficacy and safety in rheumatoid arthritis patients: evidence based on the variety of prescribing approaches among practicing Japanese rheumatologists in a single institute-based large observational cohort (IORRA). Mod Rheumatol. 2007;17:98–105.

    Article  CAS  PubMed  Google Scholar 

  16. Brown KK. Rheumatoid lung disease. Proc Am Thorac Soc. 2007;4:443–8.

    Article  PubMed  Google Scholar 

  17. Wolfe F, Caplan L, Michaud K. Rheumatoid arthritis treatment and the risk of severe interstitial lung disease. Scand J Rheumatol. 2007;36:172–8.

    Article  CAS  PubMed  Google Scholar 

  18. Rajasekaran BA, Shovlin D, Lord P, Kelly CA. Interstitial lung disease in patients with rheumatoid arthritis: a comparison with cryptogenic fibrosing alveolitis. Rheumatology (Oxford). 2001;40:1022–5.

    Article  CAS  Google Scholar 

  19. Ochi S, Harigai M, Mizoguchi F, Iwai H, Hagiyama H, Oka T, et al. Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid arthritis: autopsy findings with a mosaic pattern of acute and organizing diffuse alveolar damage. Mod Rheumatol. 2006;16:316–20.

    Article  PubMed  Google Scholar 

  20. Takano T, Ohe Y, Kusumoto M, Tateishi U, Yamamoto S, Nokihara H, et al. Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib. Lung Cancer. 2004;45:93–104.

    Article  PubMed  Google Scholar 

  21. Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, et al. Severe acute interstitial pneumonia and gefitinib. Lancet. 2003;361:137–9.

    Article  PubMed  Google Scholar 

  22. Takeuchi T, Tatsuki Y, Nogami Y, Ishiguro N, Tanaka Y, Yamanaka H, et al. Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:189–94.

    Article  CAS  PubMed  Google Scholar 

  23. Kaur N, Mahl TC. Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases. Dig Dis Sci. 2007;52:1481–4.

    Article  CAS  PubMed  Google Scholar 

  24. Matsuda Y, Singh G, Yamanaka H, Tanaka E, Urano W, Taniguchi A, et al. Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis. Arthritis Rheum. 2003;49:784–8.

    Article  PubMed  Google Scholar 

  25. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–24.

    Article  CAS  PubMed  Google Scholar 

  26. Prevoo ML, van‘t Hof MA, van Leeuwen MA, van de Putte LB, Kuper HH, van Riel PL. Modified disease activity scores that include 28-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–8.

    Article  CAS  PubMed  Google Scholar 

  27. Carson CW, Cannon GW, Egger MJ, Ward JR, Clegg DO. Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate. Semin Arthritis Rheum. 1987;16:186–95.

    Article  CAS  PubMed  Google Scholar 

  28. Maskell NA, Waine DJ, Lindley A, Pepperell JC, Wakefield AE, Miller RF, et al. Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study. Thorax. 2003;58:594–7.

    Article  CAS  PubMed  Google Scholar 

  29. Shimizu A, Oka H, Matsuda T, Ozaki S. (1–>3)-beta-d glucan is a diagnostic and negative prognostic marker for Pneumocystis carinii pneumonia in patients with connective tissue disease. Clin Exp Rheumatol. 2005;23:678–80.

    CAS  PubMed  Google Scholar 

  30. Roos JC, Chilvers ER, Ostor AJ. Interstitial pneumonitis and anti-tumor necrosis factor-alpha therapy. J Rheumatol. 2007;34:238–9.

    PubMed  Google Scholar 

  31. Villeneuve E, St-Pierre A, Haraoui B. Interstitial pneumonitis associated with infliximab therapy. J Rheumatol. 2006;33:1189–93.

    PubMed  Google Scholar 

  32. Sihvonen S, Korpela M, Laippala P, Mustonen J, Pasternack A. Death rates and causes of death in patients with rheumatoid arthritis: a population-based study. Scand J Rheumatol. 2004;33:221–7.

    Article  CAS  PubMed  Google Scholar 

  33. Searles G, McKendry RJ. Methotrexate pneumonitis in rheumatoid arthritis: potential risk factors. Four case reports and a review of the literature. J Rheumatol. 1987;14:1164–71.

    CAS  PubMed  Google Scholar 

  34. Alarcón GS, Kremer JM, Macaluso M, Weinblatt ME, Cannon GW, Palmer WR, et al. Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med. 1997;127:356–64.

    PubMed  Google Scholar 

  35. Ohosone Y, Okano Y, Kameda H, Fujii T, Hama N, Hirakata M, et al. Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis. J Rheumatol. 1997;24:2299–303.

    CAS  PubMed  Google Scholar 

  36. Saag KG, Kolluri S, Koehnke RK, Georgou TA, Rachow JW, Hunninghake GW, et al. Rheumatoid arthritis lung disease. Determinants of radiographic and physiologic abnormalities. Arthritis Rheum. 1996;39:1711–9.

    Article  CAS  PubMed  Google Scholar 

  37. Scott TE, Wise RA, Hochberg MC, Wigley FM. HLA-DR4 and pulmonary dysfunction in rheumatoid arthritis. Am J Med. 1987;82:765–71.

    Article  CAS  PubMed  Google Scholar 

  38. Schernthaner G, Scherak O, Kolarz G, Kummer F. Seropositive rheumatoid arthritis associated with decreased diffusion capacity of the lung. Ann Rheum Dis. 1976;35:258–62.

    Article  CAS  PubMed  Google Scholar 

  39. Jurik AG, Davidsen D, Graudal H. Prevalence of pulmonary involvement in rheumatoid arthritis and its relationship to some characteristics of the patients. A radiological and clinical study. Scand J Rheumatol. 1982;11:217–24.

    Article  CAS  PubMed  Google Scholar 

  40. Tuomi T, Heliövaara M, Palosuo T, Aho K. Smoking, lung function, and rheumatoid factors. Ann Rheum Dis. 1990;49:753–6.

    Article  CAS  PubMed  Google Scholar 

  41. Popper MS, Bogdonoff ML, Hughes RL. Interstitial rheumatoid lung disease. A reassessment and review of the literature. Chest. 1972;62:243–50.

    Article  CAS  PubMed  Google Scholar 

  42. Hakala M. Poor prognosis in patients with rheumatoid arthritis hospitalized for interstitial lung fibrosis. Chest. 1988;93:114–8.

    Article  CAS  PubMed  Google Scholar 

  43. Davidson C, Brooks AG, Bacon PA. Lung function in rheumatoid arthritis. A clinic survey. Ann Rheum Dis. 1974;33:293–7.

    Article  CAS  PubMed  Google Scholar 

  44. Lee HK, Kim DS, Yoo B, Seo JB, Rho JY, Colby TV, et al. Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease. Chest. 2005;127:2019–27.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The IORRA cohort was supported by nonrestricted research grants from 36 pharmaceutical companies: Abbott Japan Co., Ltd., Asahikasei Kuraray Medical Co., Ltd., Asahikasei Pharma Corporation, Astellas Pharma Inc., AstraZeneca K.K., Banyu Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Fine Chemical Co., Ltd., Daiichi Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., GlaxoSmithKline K.K., Janssen Pharmaceutical K.K., Japan Tobacco Inc., Kaken Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co., Ltd., Mitsubishi Chemical Medience Corporation, Mitsuibishi Tanabe Pharma Corporation, Nippon Chemiphar Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi-Aventis K.K, Santen Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Sekisui Medical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Torii Pharmaceutical Co., Ltd., Toyama Chemical Co., Ltd., UCB Japan Co., Ltd., Wyeth K.K., and Zeria Pharmaceutical Co., Ltd.

Author information

Authors and Affiliations

  1. Institute of Rheumatology, Tokyo Women’s Medical University, 10-22 Kawada-cho, Shinjyuku-ku, Tokyo, 162-0054, Japan

    Kumi Shidara, Daisuke Hoshi, Eisuke Inoue, Toru Yamada, Ayako Nakajima, Atsuo Taniguchi, Masako Hara, Shigeki Momohara, Naoyuki Kamatani & Hisashi Yamanaka

Authors
  1. Kumi Shidara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daisuke Hoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eisuke Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toru Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ayako Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Atsuo Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Masako Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shigeki Momohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Naoyuki Kamatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hisashi Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kumi Shidara.

About this article

Cite this article

Shidara, K., Hoshi, D., Inoue, E. et al. Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRA. Mod Rheumatol 20, 280–286 (2010). https://doi.org/10.1007/s10165-010-0280-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10165-010-0280-z

Keywords

Search

Navigation