Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias IV immunoglobulin for acute exacerbation of fibrotic IIPs

Main Article Content

Hisao Higo
Hirohisa Ichikawa
Naoki Nakamura
Masanori Fujii
Katsuhiro Matsuoka
Shoko Seki
Takamasa Wada
Noriyuki Suzaki
Takuya Nagata
Yukako Arakawa
Yoshihiro Mori
Masaomi Marukawa
Katsuyuki Kiura
Yoshinobu Maeda
Nobuaki Miyahara

Keywords

Intravenous immunoglobulin, Acute exacerbation, Idiopathic pulmonary fibrosis, Idiopathic interstitial pneumonia

Abstract

Background and aim: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF.


Methods: We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500–1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital.


Results: This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3–5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02–0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06–1.33, p < 0.01) were independently associated with 90-day mortality.


Conclusions: The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

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References

1. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2018, 198:e44-e68.
2. Collard HR, Ryerson CJ, Corte TJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med 2016, 194:265-275.
3. Natsuizaka M, Chiba H, Kuronuma K, et al. Epidemiologic survey of Japanese patients with idiopathic pulmonary fibrosis and investigation of ethnic differences. Am J Respir Crit Care Med 2014, 190:773-779.
4. Park IN, Kim DS, Shim TS, et al. Acute exacerbation of interstitial pneumonia other than idiopathic pulmonary fibrosis. Chest 2007, 132:214-220.
5. Miyazaki Y, Tateishi T, Akashi T, Ohtani Y, Inase N, Yoshizawa Y. Clinical predictors and histologic appearance of acute exacerbations in chronic hypersensitivity pneumonitis. Chest 2008, 134:1265-1270.
6. Kondoh Y, Azuma A, Inoue Y, et al. Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial. American Journal of Respiratory and Critical Care Medicine 2020, 201:1110-1119.
7. Naccache JM, Jouneau S, Didier M, et al. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2022, 10:26-34.
8. Song JW, Hong SB, Lim CM, Koh Y, Kim DS. Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome. Eur Respir J 2011, 37:356-363.
9. Oishi K, Mimura-Kimura Y, Miyasho T, et al. Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis. Cytokine 2013, 61:84-89.
10. Arai T, Tachibana K, Sugimoto C, et al. High-dose prednisolone after intravenous methylprednisolone improves prognosis of acute exacerbation in idiopathic interstitial pneumonias. Respirology 2017, 22:1363-1370.
11. Homma S, Sakamoto S, Kawabata M, et al. Cyclosporin treatment in steroid-resistant and acutely exacerbated interstitial pneumonia. Intern Med 2005, 44:1144-1150.
12. Ding J, Chen Z, Feng K. Procalcitonin-guided antibiotic use in acute exacerbations of idiopathic pulmonary fibrosis. Int J Med Sci 2013, 10:903-907.
13. Gelfand EW: Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med 2012, 367:2015-2025.
14. Alejandria MM, Lansang MA, Dans LF, Mantaring JB 3rd. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev 2013:CD001090.
15. Masaoka T. Combination therapy of antibiotics and intravenous immunoglobulin. Nihon Rinsho 2001, 59:781-784.
16. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022, 205:e18-e47.
17. Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013, 188:733-748.
18. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013, 48:452-458.
19. Kishaba T, Tamaki H, Shimaoka Y, Fukuyama H, Yamashiro S. Staging of acute exacerbation in patients with idiopathic pulmonary fibrosis. Lung 2014, 192:141-149.
20. Enomoto N, Chida K, Suda T, et al. An exploratory trial of intravenous immunoglobulin therapy for idiopathic pulmonary fibrosis: a preliminary multicenter report. Clinical Respiratory Journal 2016, 10:746-755.
21. Huapaya JA, Hallowell R, Silhan L, et al. Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease. Respir Med 2019, 154:6-11.
22. Molina V, Haj-Yahia S, Solodeev I, Levy Y, Blank M, Shoenfeld Y. Immunomodulation of experimental pulmonary fibrosis by intravenous immunoglobulin (IVIG). Autoimmunity 2006, 39:711-717.
23. Oda K, Ishimoto H, Yamada S, et al. Autopsy analyses in acute exacerbation of idiopathic pulmonary fibrosis. Respiratory Research 2014, 15.
24. Wootton SC, Kim DS, Kondoh Y, et al. Viral infection in acute exacerbation of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011, 183:1698-1702.
25. Donahoe M, Valentine VG, Chien N, et al. Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis. PLoS One 2015, 10:e0127771.