Pulmonary infections following immunosuppressive treatments during hospitalization worsen the short-term vital prognosis for patients with connective tissue disease-associated interstitial pneumonia

Abstract

Objective. Connective tissue disease-associated interstitial pneumonia (CTD-IP) significantly affects the mortality of patients with CTD. The purpose of the present study is to identify causes and risk factors for death during hospitalization for immunosuppressive treatment of CTD-IP.

Methods. A multicenter, retrospective study was conducted that collected data from patients with CTD who had been hospitalized for commencing or intensifying immunosuppressive treatment of CTD-IP using a standardized case report form. Risk factors were identified using the Cox proportional hazard regression model.

Results. A total of 322 CTD-IP patients were enrolled with rheumatoid arthritis (n = 84), systemic lupus erythematosus (n = 13), polymyositis (n = 33), dermatomyositis (n = 69), systemic sclerosis (n = 55), mixed connective tissue disease (n = 21), microscopic polyangiitis (n = 19), and overlap syndrome (n = 28). Of the 42patients who died during hospitalization, 22 died from CTD-IP, 15 from CTD-IP and pulmonary infection, 2 from pulmonary infection, and 3 from other causes. Age ≥ 65 years and development of pulmonary infections after commencing or intensifying immunosuppressive treatments were identified as risk factors for death during hospitalization after adjusting for covariates.

Conclusion. Careful consideration of the benefit–risk balance of immunosuppressive treatment for CTD-IP is indispensable for improving the short-term vital prognosis of these patients.

Keywords:

• Connective tissue disease
• Interstitial
• pneumonia
• Immunosuppressive treatments
• Pulmonary infections
• Vital prognosis

Acknowledgements

This work was supported by a grant-in-aid from the Ministry of Health, Labour and Welfare, Japan (H23-meneki-sitei-016 and H19-meneki-ippan-009 to N. Miyasaka, H22-meneki-ippann-001 to M. Harigai) and by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (#20390158 to M. Harigai, #19590530 to R. Koike, and #50277141 to M. Tanaka). This work was also supported by the grant from the Japanese Ministry of Education, Global Center of Excellence (GCOE) Program, “International Research Center for Molecular Science in Tooth and Bone Diseases” (to N. Miyasaka).

Other members of the investigators group of this study were as follows: Yoshiya Tanaka, M.D. Ph.D. (The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan), Kazuhiko Yamamoto, M.D., Ph.D. (Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo), Hirofumi Amano, M.D., Ph.D. (Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine), Koichi Amano, M.D., Ph.D. (Department of Rheumatology & Clinical Immunology, Saitama Medical Center, Saitama Medical University), Naohiko Inase, M.D., Ph.D. (Department of Respiratory Medicine, University Hospital of Medicine, Tokyo Medical & Dental University), Yuichiro Fujieda, M.D., Ph.D., Takashi Kurita, M.D., Ph.D., and Hiromi Hagiwara, M.D. (Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine).

Conflict of interest

Nishioka Y has received research grants from Chugai Pharmaceutical Co. Ltd. and Mitsubishi Tanabe Pharmaceutical Co. Ltd., Miyasaka N has received research grants from Abbott Japan Co. Ltd., Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co. Ltd., Dainihon-Sumitomo Pharma Co. Ltd., Daiichi-Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K. Ltd., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd., and received Consulting fee or honorarium from Abbott Japan Co. Ltd., Bristol Myers Squibb, Janssen Pharmaceutical KK, and Otsuka Pharmaceutical Co. Ltd. Harigai M has received research grants from Abbvie Japan Co. Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis K.K., Santen Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., and UCB Japan.