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Tsukada A, Katagiri D, Izumi S, Terada-Hirashima J, Shimizu Y, Uemura Y, Toda M, Yasuma T, Gabazza CND, Fujimoto H, Kobayashi T, Gabazza EC, Sugiyama M, Noiri E, Abe S, Azuma A, Sugiyama H. Inflammatory and Coagulation Marker Changes in PMX-DHP-Treated COVID-19 Patients. Cureus 2025; 17:e78836. [PMID: 40084335 PMCID: PMC11904442 DOI: 10.7759/cureus.78836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2025] [Indexed: 03/16/2025] Open
Abstract
Introduction Direct hemoperfusion using polymyxin B-immobilized polystyrene fiber column (PMX-DHP) removes endotoxin and inflammatory mediators from the blood. This study aimed to evaluate the changes in the levels of cytokines, coagulation factors, and a microbiota-derived proapoptotic peptide in COVID-19 patients treated with PMX-DHP. Methods We conducted a multicenter, prospective, single-arm interventional study of 21 oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. PaO2/FiO2 (P/F) ratio and biomarkers of inflammation, fibrosis, coagulation, and microbiota-derived peptide were analyzed on PMX-DHP treatment days 1, 4, and 15. Results The P/F ratio significantly improved on Day 4 (87.1, 95% CI: 14.8-159.3) and Day 15 (140.6, 95% CI: 56.2-224.9) compared to baseline values. Among the inflammatory cytokines, IL-8 and IL-10 levels significantly decreased on Day 15 (-8.5, 95% CI: -13.4 to -3.5) and Day 4 (-2.3, 95% CI: -5.2 to 0.5) respectively compared to baseline values. Regarding coagulation markers, levels of thrombomodulin increased on Day 4 (1.1, 95% CI: 0.4-1.7) and Day 15 (0.8, 95% CI: 0.3-1.4), and those of tissue plasminogen activator-plasminogen activator-1 significantly decreased on Day 15 (-35.1, 95% CI: -57.6 to -12.6). Microbiota-derived corisin levels significantly decreased on Day 4 (-1740.6, 95% CI: -2860.2 to -621.0) and Day 15 (-1436.7, 95% CI: -2615.8 to -257.6). Conclusion Our study revealed improvement in the P/F ratio and the time course of various biomarkers in COVID-19 patients treated with PMX-DHP.
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Affiliation(s)
- Akinari Tsukada
- Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, JPN
| | - Daisuke Katagiri
- Nephrology, National Center for Global Health and Medicine, Tokyo, JPN
| | - Shinyu Izumi
- Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, JPN
| | | | - Yosuke Shimizu
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, JPN
| | - Yukari Uemura
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, JPN
| | - Masaaki Toda
- Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JPN
| | - Taro Yasuma
- Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JPN
| | | | - Hajime Fujimoto
- Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JPN
| | - Tetsu Kobayashi
- Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JPN
| | | | - Masaya Sugiyama
- Viral Pathogenesis and Controls, National Center for Global Health and Medicine, Tokyo, JPN
| | - Eisei Noiri
- National Center Biobank Network, National Center for Global Health and Medicine, Tokyo, JPN
| | - Shinji Abe
- Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, JPN
| | - Arata Azuma
- Respiratory Medicine, Nippon Medical School, Musashi Kosugi Hospital, Kawasaki, JPN
| | - Haruhito Sugiyama
- Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, JPN
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Abe S, Azuma A, Saito Y, Hayashi H, Kashiwada T, Tanaka T, Baba T, Sekine A, Kitamura H, Okuda R, Ikeda S, Ogura T. Direct hemoperfusion with polymyxin B immobilized fiber column (PMX) treatment for acute exacerbation of idiopathic pulmonary fibrosis: A prospective multicenter cohort study. Respir Investig 2025; 63:102-108. [PMID: 39672072 DOI: 10.1016/j.resinv.2024.11.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 09/29/2024] [Accepted: 11/28/2024] [Indexed: 12/15/2024]
Abstract
BACKGROUND The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is extremely poor. However, recent clinical reports suggest that direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) treatment may have beneficial effects in patients with AE-IPF. The aim of this multicenter prospective study was to investigate the effectiveness and safety of PMX treatment in AE-IPF. METHODS We conducted a prospective study of patients with AE-IPF treated by PMX at two institutions in Japan. Each patient received 2-3 sessions of PMX treatment with a target duration of 6-24 h. The primary endpoint was the survival rate at day 28 after the PMX treatment. RESULTS The survival rate of the patients on day 28 after PMX treatment was 65% [95% confidence interval (CI): 40.3-81.5%]. The lower limit of 95% CI in the study was higher than the survival rate of 40%, which was the upper limit of the survival rate in AE-IPF receiving conventional treatments, as reported previously. The survival rate of the patients 12 weeks after PMX was 50% (95% CI: 27.1-69.2%). The changes in the difference between alveolar and arterial oxygen tension and the partial pressure of arterial oxygen/fraction of inspired oxygen improved as the number of PMX sessions increased, and significant improvements were observed at the end of the second PMX session. The safety of PMX was clinically acceptable. CONCLUSIONS This prospective multicenter study suggests that PMX treatment is safe for patients with AE-IPF and may improve their oxygenation and prognosis.
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Affiliation(s)
- Shinji Abe
- Department of Respiratory Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjyuku-ku, Tokyo, 160-0023, Japan.
| | - Arata Azuma
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Yoshinobu Saito
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Hiroki Hayashi
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Takeru Kashiwada
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Toru Tanaka
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Tomohisa Baba
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan
| | - Akimasa Sekine
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan
| | - Hideya Kitamura
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan
| | - Ryo Okuda
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan
| | - Satoshi Ikeda
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan
| | - Takashi Ogura
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan
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3
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Luo X, Xiang F. Acute exacerbation of idiopathic pulmonary fibrosis a narrative review primary focus on treatments. J Thorac Dis 2024; 16:4727-4741. [PMID: 39144320 PMCID: PMC11320219 DOI: 10.21037/jtd-23-1565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 05/17/2024] [Indexed: 08/16/2024]
Abstract
Background and Objective Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia, which is the commonest type of idiopathic interstitial pneumonia in the clinic. For most patients, the course of the disease is slow and prolonged, but a percentage of them develop an acute respiratory worsening during the disease, known as an acute exacerbation of IPF (AE-IPF). The updated guidelines define AE-IPF as an acute worsening of dyspnea in an IPF patient within 1 month and exclude other conditions such as left heart failure and pulmonary embolism. However, the prevention and treatment of AE-IPF are still unclear. Based on the high mortality rate caused by AE, in this article, we will focus on the latest research advances in AE-IPF treatment strategies and provide a comprehensive review of its pathogenesis, risk factors, clinical features, and diagnosis. Methods This study searched for relevant literature published from 2018 to 2023 in the PubMed database. The search terms used were as follows: "Acute exacerbation", "Idiopathic pulmonary fibrosis", "Biomarker", "Pathogenesis", "Treatment", "HRCT", "Antifibrotic", "Infection", "Immunosuppressant", "Autoantibody", "Oxygen therapy", "Hemoperfusion", "Inflammation". Key Content and Findings The review found that corticosteroids are still the primary treatment strategy at present, although there is some controversy regarding the dosing and tapering of corticosteroids. However, corticosteroids combined with intravenous cyclophosphamide have been shown to be detrimental to the prognosis of patients with AE-IPF. Given its deadly high mortality rate, early intervention is crucial. Pirfenidone and nintedanib have been proven to reduce incidence of AE. Meanwhile, in the future, the lung microbiome may also be a break-through. Conclusions This study reviewed the pathogenesis and risk factors of AE-IPF and updated the current and potential treatment strategies regarding AE-IPF. The pathogenesis of AE-IPF is not exact, multiple mechanisms may be involved simultaneously. Corticosteroids remain the mainstream treatment modality in the medical treatment of AE-IFP. Many other treatment modalities have been proposed in succession, but no clear conclusions can be drawn about the effectiveness and safety of these interventions.
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Affiliation(s)
- Xiaohui Luo
- Department of Pulmonary and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fei Xiang
- Department of Pulmonary and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Tachibana Y, Hara M, Hashisako M, Yamano Y, Kataoka K, Kondoh Y, Johkoh T, Morimoto S, Bychkov A, Fukuoka J. Squamous metaplasia is an indicator of acute exacerbation in patients with usual interstitial pneumonia / idiopathic pulmonary fibrosis. Respir Investig 2024; 62:631-637. [PMID: 38723442 DOI: 10.1016/j.resinv.2024.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 04/10/2024] [Accepted: 04/26/2024] [Indexed: 06/25/2024]
Abstract
BACKGROUND Acute exacerbation (AE) is a potentially lethal event in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF). However, to date, no pathological predictors of AE have been identified. This retrospective study aimed to elucidate the pathological features that could predict AE in patients with UIP. METHODS We reviewed the pathological findings of 91 patients with UIP/IPF and correlated these findings with AE events. Thirteen histological variables related to acute lung injury were evaluated by three independent observers and classified as positive or negative. The patients' clinical data during follow-up were collected and reviewed for AE. A recursive partition using the Gini index for the prediction of AE was performed, with each pathological finding as a candidate for branching. RESULTS Twenty patients (22%) developed AE during the median follow-up duration of 40 months. Thirty-eight patients died (15 due to AE and 23 for other reasons). The median time interval from surgical lung biopsy to AE onset was 497 (interquartile range: 901-1657) days. Histologically, squamous metaplasia was positively associated with AE (odds ratio: 4.7, P = 0.015) and worse event-free survival in patients with UIP (P = 0.04). Leaf scoring based on the Gini index for recursive partition, including five positive findings (squamous metaplasia, neutrophilic infiltration, septal widening, Kuhn's hyaline, and fibrin), showed a sensitivity of 90% with a specificity of 74.7% (area under curve: 0.89). CONCLUSIONS We found that squamous metaplasia is an important histopathological finding that predicts AE events and tends to unfavorable outcome in patients with UIP/IPF.
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Affiliation(s)
- Yuri Tachibana
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashicho, Kamogawa-shi, Chiba, 2960041, Japan
| | - Masatake Hara
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan
| | - Mikiko Hashisako
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan
| | - Yasuhiko Yamano
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwakecho, Seto-shi, Aichi, 4898642, Japan
| | - Kensuke Kataoka
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwakecho, Seto-shi, Aichi, 4898642, Japan
| | - Yasuhiro Kondoh
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwakecho, Seto-shi, Aichi, 4898642, Japan
| | - Takeshi Johkoh
- Department of Radiology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki-shi, Hyogo, 6608511, Japan
| | - Shimpei Morimoto
- Clinical Research Center, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, Nagasaki-shi, 8528501, Japan
| | - Andrey Bychkov
- Department of Pathology, Kameda Medical Center, 929, Higashicho, Kamogawa-shi, Chiba, 2960041, Japan
| | - Junya Fukuoka
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashicho, Kamogawa-shi, Chiba, 2960041, Japan.
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Katagiri D, Tsukada A, Izumi S, Shimizu Y, Terada-Hirashima J, Uemura Y, Kusaba Y, Takasaki J, Takoi H, Tamura-Nakano M, Hojo M, Takano H, Noiri E, Abe S, Azuma A, Sugiyama H. Blood perfusion with polymyxin B immobilized columns in patients with COVID-19 requiring oxygen therapy. Sci Rep 2024; 14:12550. [PMID: 38822071 PMCID: PMC11143350 DOI: 10.1038/s41598-024-63330-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 05/28/2024] [Indexed: 06/02/2024] Open
Abstract
Extracorporeal blood purification with polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP), is reported to be effective in treating COVID-19 pneumonitis with oxygen demand. This multicenter prospective study evaluated the efficacy and safety of PMX-DHP in oxygen-requiring patients with COVID-19 admitted between September 28, 2020, and March 31, 2022. The primary endpoint was the percentage of clinical improvement 15 days after treatment. The secondary endpoint was the percentage of worsened disease status. Data from the COVID-19 patient registry were used for the synthetic control group. The improvement rate on Day 15 did not differ between PMX-treated patients and controls; however, the deterioration rate was 0.38 times lower in the PMX-treated group, and the death rates on Day 29 were 0 and 11.1% in the PMX-treated and control groups, respectively. The PMX group showed a 0.73 times higher likelihood for reduced intensive care demand, as 16.7% of PMX-treated patients and 22.8% of controls worsened. After treatment blood oxygenation improved, urinary β2-microglobulin and liver-type fatty acid-binding protein showed significant decreases, and IL-6 decreased once during treatment but did not persist. In this study, PMX treatment effectively prevented the worsening of COVID-19 pathology, accompanied by improved oxygenation. PMX treatment to remove activated cells may effectively improve patient outcomes.
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Affiliation(s)
- Daisuke Katagiri
- Department of Nephrology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Akinari Tsukada
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Shinyu Izumi
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
| | - Yosuke Shimizu
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Junko Terada-Hirashima
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yukari Uemura
- Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yusaku Kusaba
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Jin Takasaki
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroyuki Takoi
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Miwa Tamura-Nakano
- Communal Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masayuki Hojo
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Hideki Takano
- Department of Nephrology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
| | - Eisei Noiri
- National Center Biobank Network, National Center for Global Health and Medicine, Tokyo, Japan
| | - Shinji Abe
- Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
| | - Arata Azuma
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
- Mihara General Hospital, Pulmonary Medicine and Clinical Research Center, Saitama, Japan
| | - Haruhito Sugiyama
- Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
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Bando M, Homma S, Date H, Kishi K, Yamauchi H, Sakamoto S, Miyamoto A, Goto Y, Nakayama T, Azuma A, Kondoh Y, Johkoh T, Nishioka Y, Fukuoka J, Miyazaki Y, Yoshino I, Suda T. Japanese guidelines for the treatment of idiopathic pulmonary fibrosis 2023:Revised edition. Respir Investig 2024; 62:402-418. [PMID: 38484504 DOI: 10.1016/j.resinv.2024.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/08/2024] [Accepted: 02/22/2024] [Indexed: 04/20/2024]
Abstract
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines." Because new evidence had accumulated, we formulated the "Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition)." While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.
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Affiliation(s)
- Masashi Bando
- Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
| | - Sakae Homma
- Department of Respiratory Medicine, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Hiroshi Date
- Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kazuma Kishi
- Department of Respiratory Medicine, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Hiroyoshi Yamauchi
- Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Susumu Sakamoto
- Department of Respiratory Medicine, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Atsushi Miyamoto
- Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Yoshihito Goto
- Clinical Research Center, National Hospital Organization Kyoto Medical Center, 1-1, Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, Kyoto, 612-8555, Japan
| | - Takeo Nakayama
- Department of Health Informatics, Graduate School of Medicine and School of Public Health, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto, Kyoto, 606-8501, Japan
| | - Arata Azuma
- Pulmonary Medicine, Tokorozawa Mihara General Hospital, 2-2934-3 Mihara-cho, Tokorozawa-shi, Saitama, 359-0045, Japan; Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Yasuhiro Kondoh
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi, 489-8642, Japan
| | - Takeshi Johkoh
- Department of Radiology, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, Hyogo, 660-8511, Japan
| | - Yasuhiko Nishioka
- Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
| | - Junya Fukuoka
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Yasunari Miyazaki
- Department of Respiratory Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Ichiro Yoshino
- Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital, 852 Hatakeda, Narita City, Chiba, 286-8520, Japan; Department of General Thoracic Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan
| | - Takafumi Suda
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatus, 431-3192, Japan
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Enomoto N. Relationship between idiopathic interstitial pneumonias (IIPs) and connective tissue disease-related interstitial lung disease (CTD-ILD): A narrative review. Respir Investig 2024; 62:465-480. [PMID: 38564878 DOI: 10.1016/j.resinv.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 01/17/2024] [Accepted: 03/14/2024] [Indexed: 04/04/2024]
Abstract
While idiopathic interstitial pneumonia (IIP) centering on idiopathic pulmonary fibrosis (IPF) is the most prevalent interstitial lung disease (ILD), especially in the older adult population, connective tissue disease (CTD)-related ILD is the second most prevalent ILD. The pathogenesis of IPF is primarily fibrosis, whereas that of other ILDs, particularly CTD-ILD, is mainly inflammation. Therefore, a precise diagnosis is crucial for selecting appropriate treatments, such as antifibrotic or immunosuppressive agents. In addition, some patients with IIP have CTD-related features, such as arthritis and skin eruption, but do not meet the criteria for any CTD, this is referred to as interstitial pneumonia with autoimmune features (IPAF). IPAF is closely associated with idiopathic nonspecific interstitial pneumonia (iNSIP) and cryptogenic organizing pneumonia (COP). Furthermore, patients with iNSIP or those with NSIP with OP overlap frequently develop polymyositis/dermatomyositis after the diagnosis of IIP. Acute exacerbation of ILD, the most common cause of death, occurs more frequently in patients with IPF than in those with other ILDs. Although acute exacerbation of CTD-ILD occurs at a low rate of incidence, patients with rheumatoid arthritis, microscopic polyangiitis, or systemic sclerosis experience more acute exacerbation of CTD-ILD than those with other CTD. In this review, the features of each IIP, focusing on CTD-related signatures, are summarized, and the pathogenesis and appropriate treatments to improve the prognoses of patients with various ILDs are discussed.
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Affiliation(s)
- Noriyuki Enomoto
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan; Health Administration Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.
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8
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Enomoto N. Pathological Roles of Pulmonary Cells in Acute Lung Injury: Lessons from Clinical Practice. Int J Mol Sci 2022; 23:ijms232315027. [PMID: 36499351 PMCID: PMC9736972 DOI: 10.3390/ijms232315027] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/23/2022] [Accepted: 11/26/2022] [Indexed: 12/05/2022] Open
Abstract
Interstitial lung diseases (ILD) are relatively rare and sometimes become life threatening. In particular, rapidly progressive ILD, which frequently presents as acute lung injury (ALI) on lung histopathology, shows poor prognosis if proper and immediate treatments are not initiated. These devastating conditions include acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), clinically amyopathic dermatomyositis (CADM), epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced lung injury, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection named coronavirus disease 2019 (COVID-19). In this review, clinical information, physical findings, laboratory examinations, and findings on lung high-resolution computed tomography and lung histopathology are presented, focusing on majorly damaged cells in each disease. Furthermore, treatments that should be immediately initiated in clinical practice for each disease are illustrated to save patients with these diseases.
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Affiliation(s)
- Noriyuki Enomoto
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan; ; Tel.: +81-53-435-2263; Fax: +81-53-435-2354
- Health Administration Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
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9
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Horio Y, Takihara T, Takahashi F, Enokida K, Nakamura N, Tanaka J, Tomomatsu K, Niimi K, Tajiri S, Hayama N, Ito Y, Oguma T, Asano K. Prognosis of acute exacerbation in idiopathic pulmonary fibrosis with pulmonary emphysema: a retrospective cohort study in Japan. BMJ Open 2022; 12:e062236. [PMID: 36123101 PMCID: PMC9486357 DOI: 10.1136/bmjopen-2022-062236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES To analyse the clinical characteristics and prognosis of acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema. DESIGN A multicentre retrospective cohort study SETTING: Two university hospitals in Japan PARTICIPANTS: Patients admitted to hospitals due to AE of IPF diagnosed based on a multidisciplinary discussion. INTERVENTIONS None PRIMARY AND SECONDARY OUTCOME MEASURES: 90-day mortality rate METHODS: We retrospectively analysed consecutive patients with AE of IPF, with or without pulmonary emphysema, admitted to two university hospitals between 2007 and 2018. RESULTS Among 62 patients (median age, 75 years; 48 men) admitted for AE of IPF, 29 patients (46%) presented with concomitant pulmonary emphysema. There was no significant difference in the arterial partial oxygen pressure/fraction of inhaled oxygen (P/F) ratio or other laboratory and radiographic data between patients with and without emphysema. The 90-day mortality rate was significantly lower in patients with emphysema than in those with IPF alone (23% vs 52%, p=0.03). The median survival time was significantly longer in patients with emphysema than in those with IPF alone (405 vs 242 days, p=0.02). CONCLUSION Patients with IPF and emphysema had better short-term survival after AE than those with non-emphysematous IPF.
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Affiliation(s)
- Yukihiro Horio
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Takahisa Takihara
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Fuminari Takahashi
- Department of Medicine, Tokai University Oiso Hospital, Naka-gun, Kanagawa, Japan
| | - Keito Enokida
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Noriko Nakamura
- Department of Radiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Jun Tanaka
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Katsuyoshi Tomomatsu
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Kyoko Niimi
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Sakurako Tajiri
- Department of Medicine, Tokai University Oiso Hospital, Naka-gun, Kanagawa, Japan
| | - Naoki Hayama
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Yoko Ito
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Tsuyoshi Oguma
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Koichiro Asano
- Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
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10
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Ohashi K, Ito R, Koda R, Iino N, Takada T. Serum cytokine changes induced by direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute respiratory failure. Respir Investig 2022; 60:585-594. [PMID: 35525835 DOI: 10.1016/j.resinv.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/28/2022] [Accepted: 04/12/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Polymyxin B-immobilized Fiber therapy (PMX-DHP) may improve the prognosis of patients with rapidly progressive interstitial lung diseases (ILDs). However, the mechanisms by which PMX-DHP ameliorates oxygenation are unclear. The present study aimed to clarify the changes in serum cytokine concentrations during PMX-DHP with steroid pulse therapy. METHODS Patients with acute respiratory failure (ARF) and rapidly progressive ILDs, acute exacerbation of idiopathic pulmonary fibrosis (IPF), or acute respiratory distress syndrome (ARDS), and treated with PMX-DHP were assessed, including patients with IPF. The serum concentrations of 38 cytokines were compared between the ARF and IPF groups before treatment. In the ARF group, cytokine levels were compared before, immediately after PMX-DHP, and the day after termination of steroid pulse therapy. RESULTS Fourteen ARF and eight IPF patients were enrolled. A comparison of the cytokine levels before treatment initiation revealed that EGF, GRO, IL-10, MDC, IL-12p70, IL-15, sCD40L, IL-7, IP-10, MCP-1, and MIP-1β were significantly different between the two groups. In the ARF group treated with PMX-DHP, the concentrations of MDC, IP-10, and TNF-α continuously decreased during treatment (P < 0.01). Further, the cytokine levels of GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 decreased after the entire treatment period, with no change observed during the steroid-only period (P < 0.01, except GRO and MCP-1). Although PMX-DHP significantly reduced eotaxin and GM-CSF serum levels (P < 0.01 and P < 0.05), these levels did not change after treatment. CONCLUSIONS PMX-DHP combined with steroid pulse therapy might reduce GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 levels in ARF, contributing to better oxygenation in the disorder.
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Affiliation(s)
- Kazumasa Ohashi
- Department of Respiratory Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Niigata, Japan
| | - Ryo Ito
- Department of Respiratory Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Niigata, Japan
| | - Ryo Koda
- Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Niigata, Japan
| | - Noriaki Iino
- Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Niigata, Japan
| | - Toshinori Takada
- Department of Respiratory Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-uonuma, Niigata, Japan.
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11
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Changes in Oxygenation and Serological Markers in Acute Exacerbation of Interstitial Lung Disease Treated with Polymyxin B Hemoperfusion. J Clin Med 2022; 11:jcm11092485. [PMID: 35566611 PMCID: PMC9105740 DOI: 10.3390/jcm11092485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/19/2022] [Accepted: 04/26/2022] [Indexed: 11/20/2022] Open
Abstract
Background: Polymyxin B direct hemoperfusion (PMX-DHP) has been tried in acute exacerbation of interstitial lung disease (AE-ILD) patients and has shown clinical benefit. In this study, we tried to investigate the change in oxygenation and serologic markers after PMX-DHP treatment in AE-ILD patients in Korea. Methods: We reviewed the medical records of twenty-two patients who were admitted for AE-ILD and underwent PMX-DHP treatment. Changes in vital signs and laboratory findings before and after treatment were compared and factors related to 90-day mortality were analyzed using the Cox regression model. Results: Of the 22 included patients, 11 (50%) patients were diagnosed with idiopathic pulmonary fibrosis. In AE-ILD patients treated with PMX-DHP, the 28-day mortality rate was 45.5% and the 90-day mortality rate was 72.7%. The P/F ratio before and after PMX-DHP treatment significantly improved in patients from baseline to 24 h (median (IQR), 116.3 (88.5–134.3) mmHg vs. 168.6 (115.5–226.8) mmHg, p = 0.001), and 48 h (116.3 (88.5–134.3) mmHg vs. 181.6 (108.9–232.0) mmHg, p = 0.003). Also, white blood cells (WBCs) and C-reactive protein (CRP) were decreased after PMX-DHP treatment. High acute physiology and chronic health evaluation II scores were associated with 90-day mortality. Conclusions: In patients with AE-ILD, PMX-DHP treatment was associated with an improved P/F ratio and lower WBC and CRP levels.
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12
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Charokopos A, Moua T, Ryu JH, Smischney NJ. Acute exacerbation of interstitial lung disease in the intensive care unit. World J Crit Care Med 2022; 11:22-32. [PMID: 35433309 PMCID: PMC8788209 DOI: 10.5492/wjccm.v11.i1.22] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 08/04/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Acute exacerbations of interstitial lung disease (AE-ILD) represent an acute, frequent and often highly morbid event in the disease course of ILD patients. Admission in the intensive care unit (ICU) is very common and the need for mechanical ventilation arises early. While non-invasive ventilation has shown promise in staving off intubation in selected patients, it is unclear whether mechanical ventilation can alter the exacerbation course unless it is a bridge to lung transplantation. Risk stratification using clinical and radiographic findings, and early palliative care involvement, are important in ICU care. In this review, we discuss many of the pathophysiological aspects of AE-ILD and raise the hypothesis that ventilation strategies used in acute respiratory distress syndrome might be implemented in AE-ILD. We present possible decision-making and management algorithms that can be used by the intensivist when caring for these patients.
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Affiliation(s)
- Antonios Charokopos
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Teng Moua
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Jay H Ryu
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Nathan J Smischney
- Department of Anesthesiology and Perioperative Medicine, Division of Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
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13
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Abstract
Acute exacerbation is a major cause of morbidity and mortality in patients with idiopathic pulmonary fibrosis. Although the real nature of it is still not clear and there is no proven effective therapy, progress has been made since the consensus definition and diagnostic criteria were proposed. The trial results of several new innovative therapies in idiopathic pulmonary fibrosis have suggested a potential for benefit in acute exacerbation of idiopathic pulmonary fibrosis, leading to double blind randomized clinical trials in this area. This article reviews the present knowledge on acute exacerbation of idiopathic pulmonary fibrosis, focusing on the triggering factors and treatment.
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14
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Oishi K, Azuma A, Abe S, Murata Y, Sakamoto K, Mimura Y, Asami-Noyama M, Kakugawa T, Hirano T, Matsunaga K. Improved Prognostic Prediction by Combination of Early Initiation of Polymyxin B Hemoperfusion with Modified Gender-Age-Physiology Index in Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Blood Purif 2021; 51:485-491. [PMID: 34518460 DOI: 10.1159/000518705] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 07/24/2021] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Respiratory failure from acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) has been reported to have beneficial effects on patients with AE-IPF. Whether patient characteristics influence the extent of this benefit remains unclear. METHODS We retrospectively examined the records of 30 patients with AE-IPF who underwent PMX-DHP. The favorable factors of survival were determined using Cox proportional hazards analyses. RESULTS The 1- and 12-month survival rates after PMX-DHP were 70.0% and 50.0%, respectively. The multivariate analysis revealed that low modified Gender-Age-Physiology (GAP) index (≤8 points) (hazard ratio [HR] 0.317, p = 0.015) and PMX-DHP received within 48 h of steroid pulse (HR 0.289, p = 0.012) were favorable factors. Notably, even in the patients with high modified GAP index (>8 points), that is, more advanced IPF, those who received PMX-DHP within 48 h of steroid pulse had a better prognosis than those who did after 48 h of the steroid pulse (p = 0.032). CONCLUSIONS Early PMX-DHP initiation in patients with AE-IPF, specifically within 48 h after the steroid pulse therapy, may improve prognosis regardless of the severity of chronic phase of IPF before AE-IPF.
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Affiliation(s)
- Keiji Oishi
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.,Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Arata Azuma
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Shinji Abe
- Department of Respiratory Medicine, Tokyo Medical University, Tokyo, Japan
| | - Yoriyuki Murata
- Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Kenji Sakamoto
- Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Yusuke Mimura
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan
| | - Maki Asami-Noyama
- Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Tomoyuki Kakugawa
- Department of Pulmonology and Gerontology, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Tsunahiko Hirano
- Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Kazuto Matsunaga
- Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Japan
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15
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Kikuchi R, Takoi H, Tsuji T, Nagatomo Y, Tanaka A, Kinoshita H, Ono M, Ishiwari M, Toriyama K, Kono Y, Togashi Y, Yamaguchi K, Yoshimura A, Abe S. Glasgow prognostic score for prediction of chemotherapy-triggered acute exacerbation interstitial lung disease in patients with small cell lung cancer. Thorac Cancer 2021; 12:1681-1689. [PMID: 33939332 PMCID: PMC8169307 DOI: 10.1111/1759-7714.13900] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/05/2021] [Accepted: 02/05/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Predicting the incidence of chemotherapy-triggered acute exacerbation of interstitial lung disease (AE-ILD) in patients with lung cancer is important because AE-ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation-based index composed of serum levels of C-reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE-ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. METHODS Medical records of patients who received platinum-based first-line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE-ILD and overall survival (OS) between GPS 0, 1, and 2. RESULTS Among our cohort of 31 patients, six (19.3%) experienced chemotherapy-triggered AE-ILD. The AE-ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE-ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). CONCLUSIONS Our results suggest that GPS 2 is both a predictor of risk of chemotherapy-triggered AE-ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy-tolerant patients from those at high risk of AE-ILD.
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Affiliation(s)
- Ryota Kikuchi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Hiroyuki Takoi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Takao Tsuji
- Respiratory CenterOtsuki Municipal Central HospitalOtsuki‐shiJapan
| | - Yoko Nagatomo
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Akane Tanaka
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Hayato Kinoshita
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Mariko Ono
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Mayuko Ishiwari
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Kazutoshi Toriyama
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Yuta Kono
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Yuki Togashi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Kazuhiro Yamaguchi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Akinobu Yoshimura
- Department of Clinical OncologyTokyo Medical University HospitalTokyoJapan
| | - Shinji Abe
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
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16
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Enomoto N, Naoi H, Aono Y, Katsumata M, Horiike Y, Yasui H, Karayama M, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Inui N, Nakamura Y, Suda T. Acute exacerbation of unclassifiable idiopathic interstitial pneumonia: comparison with idiopathic pulmonary fibrosis. Ther Adv Respir Dis 2021; 14:1753466620935774. [PMID: 32600180 PMCID: PMC7328360 DOI: 10.1177/1753466620935774] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is well known as
a life-threatening condition during its clinical course. However, the
clinical features and prognosis in AE of unclassifiable idiopathic
interstitial pneumonia (AE-UCIIP) remain to be elucidated. The aim of this
study was to clarify the clinical features and prognosis of AE-UCIIP
compared with those of AE-IPF. Methods: In 187 patients with UCIIP or IPF, 64 patients with AE-UCIIP or AE-IPF, who
were diagnosed and treated at our hospital, were retrospectively
evaluated. Results: A total of 24 patients with AE-UCIIP were significantly older
(p = 0.011), included more women
(p < 0.001) and never-smokers
(p < 0.001), and showed fewer lung lesions on
high-resolution computed tomography (p = 0.006) than 40
patients with AE-IPF. Incidence of AE-UCIIP was 10.29%/year and was
significantly higher than in AE-IPF (Gray’s test,
p = 0.008). Prognosis of AE-UCIIP was as poor as that of
AE-IPF (log-rank, p = 0.681). Percent-predicted forced
vital capacity (%FVC) [hazard ratio (HR) 0.934, p = 0.045],
and GAP stage within 12 months before AE (HR 3.530,
p = 0.023), and partial pressure arterial oxygen/fraction
of inspired oxygen (PaO2/FiO2) ratio at AE (HR 0.998,
p = 0.016) were significant prognostic factors.
Finally, commencement of long-duration (⩾12 h) direct hemoperfusion with a
polymyxin B-immobilised fibre column (PMX-DHP) within 2 days after admission
significantly improved survival (log-rank, p = 0.038) and
was a significant prognostic factor (HR 0.175, p = 0.0039)
in AE-UCIIP. Long-duration PMX-DHP showed favourable treatment effects even
in the combined group of patients with AE-UCIIP or AE-IPF (log-rank
p = 0.002; HR 0.328, p = 0.006). Conclusions: Patients with AE-UCIIP were older and included more women and never-smokers
than those with AE-IPF. Prognosis of AE-UCIIP was as poor as that of
AE-IPF. The reviews of this paper are available via the supplemental
material section.
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Affiliation(s)
- Noriyuki Enomoto
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.,Health Administration Center, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hyogo Naoi
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yuya Aono
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Mineo Katsumata
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasuoki Horiike
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hideki Yasui
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Masato Karayama
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Hironao Hozumi
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yuzo Suzuki
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kazuki Furuhashi
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tomoyuki Fujisawa
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Naoki Inui
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.,Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yutaro Nakamura
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Takafumi Suda
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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17
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Current therapies for patients with acute exacerbation of idiopathic pulmonary fibrosis. Chin Med J (Engl) 2021; 133:1470-1472. [PMID: 32558705 PMCID: PMC7339357 DOI: 10.1097/cm9.0000000000000864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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18
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Omote N, Matsuda N, Hashimoto N, Nishida K, Sakamoto K, Ando A, Nakahara Y, Nishikimi M, Higashi M, Matsui S, Hasegawa Y. High-flow nasal cannula therapy for acute respiratory failure in patients with interstitial pneumonia: a retrospective observational study. NAGOYA JOURNAL OF MEDICAL SCIENCE 2021; 82:301-313. [PMID: 32581409 PMCID: PMC7276417 DOI: 10.18999/nagjms.82.2.301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
High-flow nasal cannula (HFNC) oxygen is a therapy that has demonstrated survival benefits in acute respiratory failure (ARF). However, the role of HFNC in ARF due to interstitial pneumonia (IP) is unknown. The aim of this study was to compare the effects of HFNC therapy and non-invasive positive pressure ventilation (NPPV) in ARF due to IP. This retrospective observational study included 32 patients with ARF due to IP who were treated with HFNC (n = 13) or NPPV (n = 19). The clinical characteristics, intubation rate and 30-day mortality were analyzed and compared between the HFNC group and the NPPV group. Predictors of 30-day mortality were evaluated using a logistic regression model. HFNC group showed higher mean arterial blood pressure (median 92 mmHg; HFNC group vs 74 mmHg; NPPV group) and lower APACHEII score (median 22; HFNC group vs 27; NPPV group) than NPPV group. There was no significant difference in the intubation rate at day 30 between the HFNC group and the NPPV group (8% vs 37%: p = 0.069); the mortality rate at 30 days was 23% and 63%, respectively. HFNC therapy was a significant determinant of 30-day mortality in univariate analysis, and was confirmed to be an independent significant determinant of 30-day mortality in multivariate analysis (odds ratio, 0.148; 95% confidence interval, 0.025–0.880; p = 0.036). Our findings suggest that HFNC therapy can be a possible option for respiratory management in ARF due to IP. The results observed here warrant further investigation of HFNC therapy in randomized control trials.
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Affiliation(s)
- Norihito Omote
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.,Pulmonary, Critical Care and Sleep Medicine Section, Department of Internal Medicine, Yale University School of Medicine, New Haven, United States of America
| | - Naoyuki Matsuda
- Department of Emergency and Critical Care, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Naozumi Hashimoto
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuki Nishida
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Koji Sakamoto
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Akira Ando
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshio Nakahara
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuaki Nishikimi
- Department of Emergency and Critical Care, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michiko Higashi
- Department of Emergency and Critical Care, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shigeyuki Matsui
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshinori Hasegawa
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.,Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
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19
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Kershaw CD, Batra K, Torrealba JR, Terada LS. Characteristics and evaluation of acute exacerbations in chronic interstitial lung diseases. Respir Med 2021; 183:106400. [PMID: 33957435 DOI: 10.1016/j.rmed.2021.106400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 12/13/2020] [Accepted: 04/09/2021] [Indexed: 11/18/2022]
Abstract
Acute exacerbations of fibrosing interstitial lung disease (ILD) occur in both idiopathic pulmonary fibrosis (IPF) as well as non-IPF ILDs. An expert consensus definition has allowed for more frequent reporting of IPF exacerbations. The same is lacking for non-IPF ILD exacerbations. The incidence of non-IPF ILD exacerbations is likely less than in IPF, but the two entities share similar risk factors, such as increased frequency as physiologic derangements advance. The radiologic and histopathologic spectrum of acute ILD exacerbations extends from organizing pneumonia (OP) to the more treatment-refractory diffuse alveolar damage (DAD) pattern. Indeed, responsiveness to various therapies may depend on the relative components of these entities, favoring OP over DAD. There are no proven therapies for acute ILD exacerbations. Corticosteroids are a mainstay in any regimen although clear evidence of benefit does not exist. A variety of immunosuppressant agents have purported success in historical cohort studies - cyclophosphamide, cyclosporine A, and tacrolimus most commonly. Only one randomized controlled trial has been published, studying recombinant thrombomodulin for IPF exacerbation, but the primary outcome of survivor proportion at 90 days was not met. Other novel therapies for ILD exacerbations are still under investigation. The short and long-term prognosis of acute exacerbations of ILD is poor, especially in patients with IPF. Transplant referral should be considered early for both IPF as well as fibrosing non-IPF ILDs, given the unpredictability of the exacerbation event.
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Affiliation(s)
- Corey D Kershaw
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
| | - Kiran Batra
- Department of Radiology and Division of Pulmonary and Critical Care Medicine, Department of Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Jose R Torrealba
- Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
| | - Lance S Terada
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, UT Southwestern Medical Center, Dallas, TX, USA
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20
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Lee SI. Effectiveness of polymyxin B hemoperfusion in acute exacerbation of interstitial pneumonia: a retrospective analysis. SARCOIDOSIS, VASCULITIS, AND DIFFUSE LUNG DISEASES : OFFICIAL JOURNAL OF WASOG 2021; 38:e2021012. [PMID: 33867795 PMCID: PMC8050624 DOI: 10.36141/svdld.v38i1.9734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 02/05/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Acute exacerbation (AE) of interstitial pneumonia (IP) occurs commonly and has a poor prognosis. Polymyxin B hemoperfusion (PMX-DHP) has a beneficial effect on AE of some types of IPs, particularly idiopathic pulmonary fibrosis (IPF). However, little is known about the efficacy of PMX-DHP in the Korean population. The aim of this study was to examine the effectiveness of PMX-DHP in AE of IP. METHODS We conducted a retrospective study of 12 patients with AE of IP, including two patients with AE of IPF, who were treated with PMX-DHP at our center. Treatment with PMX-DHP was carried out once or twice. We collected and analyzed data on changes in oxygenation with PMX-DHP and survival after AE. RESULTS In patients with AE of IP, the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen, or the P/F ratio, had significantly improved at the end of the treatment with PMX-DHP (87.0 [80.3 - 130.9] to 200.6 [105.0 - 245.5] mmHg, p = 0.019). The white blood cell (WBC) count had significantly reduced at the end of the treatment (12,400 [8,860 - 20,287] to 6,800 [3,950 - 15,775]/mm3, p = 0.050). The 28-day and in-hospital mortality rates of patients after AE of IP were 41.7 % and 75.0 %, respectively. CONCLUSION PMX-DHP improved oxygenation and reduced the WBC count in patients with AE, with either steroids alone or steroids and cyclophosphamide. Further studies are required to verify the potential benefits of PMX-DHP for patients with AE of IP.
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Affiliation(s)
- Song-I Lee
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Republic of Korea
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21
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Kikuchi R, Takoi H, Tsuji T, Nagatomo Y, Tanaka A, Kinoshita H, Ono M, Ishiwari M, Toriyama K, Kono Y, Togashi Y, Yamaguchi K, Yoshimura A, Abe S. Glasgow Prognostic Score predicts chemotherapy-triggered acute exacerbation-interstitial lung disease in patients with non-small cell lung cancer. Thorac Cancer 2021; 12:667-675. [PMID: 33480111 PMCID: PMC7919129 DOI: 10.1111/1759-7714.13792] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 12/02/2020] [Accepted: 12/02/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy-triggered acute exacerbation (AE)-ILD. The Glasgow Prognostic Score (GPS), which is based on serum C-reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy-triggered AE-ILD and the prognosis in patients with NSCLC and pre-existing ILD. METHODS We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent-based treatment as first-line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0-2) and compared the incidence of chemotherapy-triggered AE-ILD and OS. RESULTS The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy-triggered AE-ILD. The median OS was at 11.5 months (95% confidence interval: 8.0-15.1). The incidence of chemotherapy-triggered AE-ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy-triggered AE-ILD and OS (P < 0.05). CONCLUSIONS GPS assessment of patients with NSCLC and pre-existing ILD is a valuable prognostic tool for predicting chemotherapy-triggered AE-ILD and OS. KEY POINTS SIGNIFICANT FINDINGS OF THE STUDY: We found that GPS 2 was an independent risk factor for chemotherapy-triggered AE-ILD and prognosis in patients with ILD associated with NSCLC. WHAT THIS STUDY ADDS GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE-ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy.
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Affiliation(s)
- Ryota Kikuchi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Hiroyuki Takoi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Takao Tsuji
- Respiratory CenterOtsuki Municipal Central HospitalYamanashiJapan
| | - Yoko Nagatomo
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Akane Tanaka
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Hayato Kinoshita
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Mariko Ono
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Mayuko Ishiwari
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Kazutoshi Toriyama
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Yuta Kono
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Yuki Togashi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Kazuhiro Yamaguchi
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
| | - Akinobu Yoshimura
- Department of Clinical OncologyTokyo Medical University HospitalTokyoJapan
| | - Shinji Abe
- Department of Respiratory MedicineTokyo Medical University HospitalTokyoJapan
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22
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Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock. Int J Mol Sci 2021; 22:ijms22042228. [PMID: 33672437 PMCID: PMC7926968 DOI: 10.3390/ijms22042228] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/17/2021] [Accepted: 02/18/2021] [Indexed: 12/11/2022] Open
Abstract
Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.
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Kim SY, Park JH, Kim HJ, Jang HJ, Kim HK, Kim SH, Lee JH. Direct hemoperfusion with polymyxin B-immobilized fiber column in a patient with acute exacerbation of idiopathic pulmonary fibrosis. Acute Crit Care 2020; 35:302-306. [PMID: 33423442 PMCID: PMC7808850 DOI: 10.4266/acc.2020.00038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 03/07/2020] [Indexed: 02/07/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterized by dyspnea and a worsening of the lung function. Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are defined by a clinically significant respiratory deterioration, that typically develops in less than 1 month, accompanied by new radiologic abnormalities on high-resolution computed tomography, including diffused and bilateral ground-glass opacification, along with an absence of other obvious clinical etiologies. Recently, AE-IPF has gained significant importance as a major cause of mortality and morbidity. However, despite the extremely poor prognosis of the condition, no well-validated therapeutic interventions are currently available. Therefore, novel treatment modalities are being investigated and applied in addition to conventional treatments. Among them, several studies have reported that a direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP), developed for endotoxin removal in septic shock, has an effect on AE-IPF. We describe two cases of PMX-DHP treatment with conflicting results. One patient successfully recovered via a PMX-DHP in severe AE-IPF that required extracorporeal membrane oxygenation (ECMO). PMX-DHP subsequently improved oxygenation (PaO2/FiO2 ratio) and decreased the levels of inflammatory markers (interleukin-6, C-reactive protein, and white blood cells). The patient dramatically recovered without the need for ECMO. PMX-DHP may be considered an alternative therapy in AE-IPF patients requiring mechanical ventilation or ECMO.
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Affiliation(s)
- Shin Young Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, St. Vincent’s Hospital, Suwon, Korea
| | - Jin Han Park
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hyo Jung Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hang Jea Jang
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hyun Kuk Kim
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Seung Hoon Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, St. Vincent’s Hospital, Suwon, Korea
| | - Jae Ha Lee
- Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
- Corresponding author Jae Ha Lee Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, 875 Haeun-daero, Haeundae-gu, Busan 48108, Korea Tel: +82-51-797-0457 Fax: +82-51-797-2210 E-mail:
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24
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Utsunomiya T, Mimura-Kimura Y, Yamamoto T, Aoe K, Oishi K, Kamei H, Matsunaga K, Yano M, Mimura Y. Cytokine Adsorption to Polymyxin B-Immobilized Fiber: An in vitro Study. Blood Purif 2020; 50:230-237. [PMID: 32894831 DOI: 10.1159/000510290] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/17/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are episodes of acute respiratory worsening characterized by diffuse alveolar damage superimposed on usual interstitial pneumonia. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) is reported to have beneficial effects on the respiratory status and outcome in patients with AE-IPF although its mechanism of action is not fully elucidated. OBJECTIVE To investigate whether and how the PMX-immobilized fiber (PMX-F) adsorbs cytokines because reduction of the serum levels of various cytokines has been noted in AE-IPF patients receiving PMX-DHP. METHODS The propensity of recombinant cytokines for adsorption onto PMX-F was examined by incubating cytokines with heparin-coated or uncoated PMX-F for 2 h at 37°C. Cytokines were quantitated by multiplex bead array assay or ELISA. RESULTS Interleukin (IL)-8, RANTES, platelet-derived growth factor-bb, and transforming growth factor-β were substantially adsorbed onto PMX-F without heparin coating. The adsorbed cytokines could be eluted with PMX sulfate, indicating that the PMX moiety is involved in cytokine adsorption. Importantly, although IL-1β, monocyte chemoattractant protein-1, fibroblast growth factor 2, and vascular endothelial growth factor-A were adsorbed onto PMX-F to lesser extents, the adsorption was enhanced by heparin coating of PMX-F. Furthermore, heparin-coated PMX-F acquired the capability to adsorb IL-6, IL-12, and tumor necrosis factor α. An affinity of heparin to PMX was determined (Kd = 0.061 ± 0.032 mg/mL), which accounts for the enhanced cytokine adsorption onto PMX-F upon heparin coating. CONCLUSIONS Various cytokines involved in inflammation, fibrosis, and vascular permeability were shown to be adsorbed onto PMX-F. Removal of multiple cytokines may be associated with positive impacts of PMX-DHP in patients with AE-IPF.
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Affiliation(s)
- Toshiaki Utsunomiya
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan.,Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yuka Mimura-Kimura
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan
| | - Takeshi Yamamoto
- Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Keisuke Aoe
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan
| | - Keiji Oishi
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan
| | - Haruhito Kamei
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan
| | - Kazuto Matsunaga
- Department of Respiratory Medicine and Infectious Disease, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Masafumi Yano
- Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yusuke Mimura
- Department of Clinical Research, National Hospital Organization Yamaguchi Ube Medical Center, Ube, Japan,
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25
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Kamiya H, Panlaqui OM. Systematic review and meta-analysis of prognostic factors of acute exacerbation of idiopathic pulmonary fibrosis. BMJ Open 2020; 10:e035420. [PMID: 32540889 PMCID: PMC7299085 DOI: 10.1136/bmjopen-2019-035420] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE To clarify prognostic factors of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). DESIGN A systematic review and meta-analysis. DATA SOURCES Medline, Embase and Science Citation Index Expanded were searched from 2002 through 1 March 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES The review included primary studies addressing the association between the outcomes such as all-cause mortality of AE of IPF and its potential prognostic factors, which were designated as any clinical information related to the outcomes. DATA EXTRACTION AND SYNTHESIS Two reviewers extracted relevant data independently and assessed risk of bias. Univariate results were pooled using a random-effect model if at least three studies were available. Prognostic factors were determined based on significant and consistent results on both univariate and multivariate analyses in the majority of studies. RESULTS Out of a total of 6763 articles retrieved, 37 were eligible and 31 potential prognostic factors for all-cause mortality were selected. Each study was subject to certain methodological shortcomings. The following five factors were statistically significant by a meta-analysis of univariate results, which was confirmed by multivariate analysis, that is, Acute Physiology and Chronic Health Evaluation (APACHE) II score (HR 1.10, 1.01 to 1.19), partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio (ORs 0.99 in two studies and HRs 0.31 and 0.99 in two studies, respectively), lactate dehydrogenase (LDH) (HRs 1.002, 1.003, 1.01 and 1.02), white blood cell (WBC) count (OR 1.38, 1.04 to 1.83) and oxygen therapy before AE (HRs 3.68, 1.05 to 12.9 and 2.34, 1.04 to 5.28) (multivariate analysis, 95% CI). CONCLUSIONS APACHE II score, PaO2/FiO2 ratio, LDH, WBC count and oxygen therapy before AE were deemed as prognostic factors of AE of IPF. Although there are some methodological limitations in this study, these findings are reliable due to consistent results by both univariate and multivariate analyses. PROSPERO REGISTRATION NUMBER CRD42018106172.
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Affiliation(s)
- Hiroyuki Kamiya
- School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia
| | - Ogee Mer Panlaqui
- Department of Intensive Care Medicine, Northern Hospital, Epping, Victoria, Australia
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26
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Gläser S, Glöckl R, Bonella F. [Treatment of complications and nonpharmacological management of idiopathic pulmonary fibrosis]. PNEUMOLOGE 2020; 17:186-196. [PMID: 32206051 PMCID: PMC7087706 DOI: 10.1007/s10405-020-00313-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Komplikationen der idiopathischen pulmonalen Fibrose (IPF) sind für einen relevanten Mortalitätsanteil verantwortlich. Als wichtigstes Beispiel ist diesbezüglich die akute Exazerbation anzuführen, deren Krankenhausletalität über 50 % beträgt bei einem mittleren Überleben von nur wenigen Monaten. Somit kommt der Betrachtung von Komplikationen eine große Bedeutung für Krankheitsverständnis sowie Therapieplanung zu. Des Weiteren ist in den letzten Jahren die Evidenz für pneumologische Rehabilitation bei IPF deutlich gestiegen und wird von der Amerikanischen und Europäischen Gesellschaft für Pneumologie (American Thoracic Society [ATS]/European Respiratory Society [ERS]) zur Verbesserung der körperlichen Leistungsfähigkeit, Lebensqualität und der Symptome empfohlen.
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Affiliation(s)
- S Gläser
- 1Klinik für Innere Medizin - Pneumologie und Infektiologie, Vivantes Kliniken Neukölln und Spandau, Forschungsbereich Pneumologie und Pneumologische Epidemiologie, Universitätsmedizin Greifswald, Greifswald, Deutschland
| | - R Glöckl
- 2Forschungsinstitut für Pneumologische Rehabilitation, Schön Klinik Berchtesgadener Land, Schönau am Königssee und Zentrum für Prävention und Sportmedizin, Technische Universität München, München, Deutschland
| | - F Bonella
- 3Zentrum für interstitielle und seltene Lungenerkrankungen, Klink für Pneumologie, Ruhrlandklinik, Universitätsmedizin Essen, Essen, Deutschland
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27
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Biondini D, Balestro E, Sverzellati N, Cocconcelli E, Bernardinello N, Ryerson CJ, Spagnolo P. Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF): an overview of current and future therapeutic strategies. Expert Rev Respir Med 2020; 14:405-414. [PMID: 31994940 DOI: 10.1080/17476348.2020.1724096] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF), the most common of the idiopathic interstitial pneumonias, is a disease with a poor prognosis, and a highly heterogeneous and unpredictable clinical course. While most patients experience a relatively slow clinical, functional and radiological deterioration, a significant minority develops episodes of acute respiratory worsening termed acute exacerbations of IPF (AE-IPF). AE-IPF cannot be predicted or prevented and precede approximately half of IPF-related deaths. An international working group has recently proposed new diagnostic criteria and definition of AE-IPF.Areas covered: Despite their clinical significance, the optimal treatment of AE-IPF remains undetermined. In this review, we discuss the huge unmet need for an improved understanding of AE-IPF, with emphasis on current and potential therapeutic strategies.Expert opinion: The recently revised definition and diagnostic criteria of AE-IPF will facilitate future research into the etiology, pathobiology and clinical management of these life-threatening events. Efforts should be made to identify patients at higher risk for AE-IPF and detect early signs of these events. Potential treatment options should be studied in randomized, controlled trials. To this end, the importance of international collaborations cannot be overemphasized.
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Affiliation(s)
- Davide Biondini
- Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Elisabetta Balestro
- Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Nicola Sverzellati
- Section of Diagnostic Imaging, Department of Surgery, University of Parma, Parma, Italy
| | - Elisabetta Cocconcelli
- Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Nicol Bernardinello
- Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Christopher J Ryerson
- Department of Medicine, University of British Columbia and Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, Canada
| | - Paolo Spagnolo
- Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
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Kamiya H, Panlaqui OM. A systematic review of the efficacy of direct hemoperfusion with a polymyxin B-immobilized fibre column to treat rapidly progressive interstitial pneumonia. SAGE Open Med 2019; 7:2050312119861821. [PMID: 31312451 PMCID: PMC6614938 DOI: 10.1177/2050312119861821] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 06/10/2019] [Indexed: 01/11/2023] Open
Abstract
Objectives Rapidly progressive interstitial pneumonia is a fatal disease with no established therapeutic options. The aim of this systematic review is to clarify the efficacy of interstitial pneumonia treatment utilizing direct hemoperfusion with a polymyxin B-immobilized fibre column. Methods All patients with adult-onset rapidly progressive interstitial pneumonia including acute exacerbation of underlying chronic interstitial pneumonia were eligible. Primary studies of any design, which compared outcomes of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment such as oxygenation and all-cause mortality with those of conventional therapy, were included. Electronic databases such as Medline and EMBASE were searched through October 7, 2018, and ICHUSHI, the largest database for medical articles in Japan, was also searched. Two reviewers independently extracted the relevant data and assessed the risk of bias in individual studies. The results were reported qualitatively due to substantial heterogeneity between studies. Results Out of 775 records retrieved, 10 reports were eligible and 8 of them were included for further analysis. They were all retrospective studies including a total of 327 patients and contained some risk of bias. There was variation in the administration method of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment such as the timing, frequency, duration and interval. Multivariate analyses of only two studies with historical controls demonstrated beneficial effects of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment over conventional therapy with all-cause mortality hazard ratios of 0.345 (95% confidence interval: 0.127-0.936) and 0.505 (95% confidence interval: 0.270-0.904), respectively. A significant difference of an improvement in the ratio of partial arterial oxygen pressure to the fraction of inspired oxygen in-between two treatment groups was also reported in two studies utilizing historical controls with mean differences of 56.8 and 57.5 mmHg, respectively. Conclusions There is currently insufficient data to support the use of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment for rapidly progressive interstitial pneumonia. It should be instituted for research purposes only until new evidence is available.
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Affiliation(s)
- Hiroyuki Kamiya
- School of Population and Global Health, The University of Western Australia, Perth, WA, Australia
| | - Ogee Mer Panlaqui
- Department of Intensive Care Medicine, Northern Hospital Epping, Epping, VIC, Australia
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29
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Spagnolo P, Tzouvelekis A, Bonella F. The Management of Patients With Idiopathic Pulmonary Fibrosis. Front Med (Lausanne) 2018; 5:148. [PMID: 30013972 PMCID: PMC6036121 DOI: 10.3389/fmed.2018.00148] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 04/30/2018] [Indexed: 12/14/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF), the most common form of fibrosing idiopathic interstitial pneumonia, is an inexorably progressive disease with a 5-year survival of ~20%. In the last decade, our understanding of disease pathobiology has increased significantly and this has inevitably impacted on the approach to treatment. Indeed, the paradigm shift from a chronic inflammatory disorder to a primarily fibrotic one coupled with a more precise disease definition and redefined diagnostic criteria have resulted in a massive increase in the number of clinical trials evaluating novel candidate drugs. Most of these trials, however, have been negative, probably because of the multitude and redundancy of cell types, growth factors and profibrotic pathways involved in disease pathogenesis. As a consequence, until recently IPF has lacked effective therapies. Finally, in 2014, two large phase 3 clinical trials have provided robust evidence that pirfenidone, a compound with anti-fibrotic, anti-oxidant and anti-inflammatory properties, and nintedanib, a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor receptors are able to slow down functional decline and disease progression with an acceptable safety profile. While this is a major achievement, neither pirfenidone nor nintedanib cures IPF and most patients continue to experience disease progression and/or exacerbation despite treatment. Therefore, in recent years increasingly more attention has been paid to preservation of quality of life and, in the advanced phase of the disease, palliation of symptoms. Lung transplantation, the only curative treatment, remains a viable option for only a minority of highly selected patients. The unmet medical need in IPF remains high, and more efficacious and better tolerated drugs are urgently needed. However, a truly effective therapeutic approach should also address quality of life and highly prevalent concomitant conditions and complications of IPF.
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Affiliation(s)
- Paolo Spagnolo
- Respiratory Disease Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
| | - Argyris Tzouvelekis
- Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece
| | - Francesco Bonella
- Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany
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30
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Ohshimo S, Costabel U, Shime N. An emerging frontier in the treatment of acute exacerbation of idiopathic pulmonary fibrosis. Respir Investig 2018; 56:97-99. [PMID: 29548662 DOI: 10.1016/j.resinv.2017.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Affiliation(s)
- Shinichiro Ohshimo
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
| | - Ulrich Costabel
- Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Essen, Germany.
| | - Nobuaki Shime
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
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Leuschner G, Behr J. Acute Exacerbation in Interstitial Lung Disease. Front Med (Lausanne) 2017; 4:176. [PMID: 29109947 PMCID: PMC5660065 DOI: 10.3389/fmed.2017.00176] [Citation(s) in RCA: 108] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 10/02/2017] [Indexed: 12/13/2022] Open
Abstract
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field.
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Affiliation(s)
- Gabriela Leuschner
- Department of Internal Medicine V, Ludwig Maximilians University, Comprehensive Pneumology Center (CPC-M), German Center for Lung Research (DZL), Munich, Germany
| | - Jürgen Behr
- Department of Internal Medicine V, Ludwig Maximilians University, Comprehensive Pneumology Center (CPC-M), German Center for Lung Research (DZL), Munich, Germany.,Asklepios Fachkliniken München-Gauting, Gauting, Germany
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Kang HS, Cho KW, Kwon SS, Kim YH. Prognostic significance of Glasgow prognostic score in patients with acute exacerbation of idiopathic pulmonary fibrosis. Respirology 2017; 23:206-212. [DOI: 10.1111/resp.13184] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 07/03/2017] [Accepted: 07/28/2017] [Indexed: 01/16/2023]
Affiliation(s)
- Hye S. Kang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine; The Catholic University of Korea; Seoul Republic of Korea
| | - Kang W. Cho
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine; The Catholic University of Korea; Seoul Republic of Korea
| | - Soon S. Kwon
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine; The Catholic University of Korea; Seoul Republic of Korea
| | - Yong H. Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine; The Catholic University of Korea; Seoul Republic of Korea
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Direct hemoperfusion with polymyxin B-immobilized fiber for the treatment of the acute exacerbation of idiopathic pulmonary fibrosis in patients requiring invasive mechanical ventilation. Respir Investig 2017; 55:318-322. [PMID: 28942888 DOI: 10.1016/j.resinv.2017.05.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Revised: 04/14/2017] [Accepted: 05/25/2017] [Indexed: 11/23/2022]
Abstract
The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) in individuals undergoing invasive mechanical ventilation is known to be poor. We describe the cases of three men, who were former smokers and required mechanical ventilation, whose AE-IPF was treated with direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). In all cases, we successfully weaned the patients from mechanical ventilation. Two of the patients survived for more than 180 days after development of AE-IPF. PMX-DHP may improve the prognosis of severe respiratory failure in patients with AE-IPF.
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Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013. J Artif Organs 2017; 20:244-251. [PMID: 28600615 DOI: 10.1007/s10047-017-0968-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 05/31/2017] [Indexed: 01/11/2023]
Abstract
To clarify the clinical status of blood purification therapy (BPT) in critical care in Japan, we conducted a cohort study using data from a nationwide registry of the Japan Society for Blood Purification in Critical Care in 2013. We enrolled 2227 patients treated with BPT (female, 39.1%; mean age, 65.5 ± 12.1 years) in the intensive care units of 43 facilities. Patient characteristics, modes of BPT, and survival rate for each disease were investigated. In total, BPT was performed 3053 times. Continuous renal replacement therapy (CRRT) (57.9%) was the most common mode of BPT, followed by intermittent renal replacement therapy (20.2%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX-DHP) (11.5%). Nafamostat mesilate (84.9%) was most frequently used as the anticoagulant. The 28-day survival rate was 56.8% in all patients. The most common mode for acute kidney injury (AKI) and multiple organ failure was CRRT, while PMX-DHP and CRRT were most common for sepsis. There was no significant difference in survival rates among AKI stages 1-3. Survival rate (38.3%) was significantly lower in patients with acute lung injury (ALI) than in those with multiple organ failure (41.8%) and those with sepsis (46.6%). Multivariate regression analysis revealed that the APACHE II score and the presence of acute ALI and acute hepatic failure were significantly associated with death. This large-scale cohort study showed the clinical status of BPT in Japan. Further investigations are required to clarify the efficacy of BPT for critically ill patients.
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Ichiyasu H, Horio Y, Masunaga A, Migiyama Y, Sakamoto Y, Jodai T, Ideguchi H, Okabayashi H, Hamada S, Yoshida C, Hirosako S, Okamoto S, Kohrogi H. Efficacy of direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) in rapidly progressive interstitial pneumonias: results of a historical control study and a review of previous studies. Ther Adv Respir Dis 2017; 11:261-275. [PMID: 28554260 PMCID: PMC5933632 DOI: 10.1177/1753465817708950] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) therapy has been approved for sepsis-associated acute respiratory distress syndrome, but its efficacy for other rapidly progressive interstitial pneumonias (RPIPs) is unclear. The purpose of this study was to examine the efficacy of PMX-DHP therapy for acute respiratory failure in patients with RPIPs, when compared with a historical control receiving conventional treatment without PMX-DHP. METHODS This study comprised 77 patients with RPIPs in our institute between January 2002 and December 2015. The initial 36 patients between January 2002 and March 2007 were treated without PMX-DHP (historical control group), and the following 41 patients between April 2007 and December 2015 were treated with PMX-DHP (PMX-DHP group) once daily for two successive days concurrently with corticosteroids and/or immunosuppressive agents. The 90-day mortality and clinical factors were compared between the groups. Cox proportional hazards models were constructed to analyze 90-day mortality and identify predictors. RESULTS The 90-day mortality rate was significantly lower in the PMX-DHP group than in the controls (41.5% versus 66.7%, p = 0.019). PMX-DHP therapy was significantly associated with mortality (hazard ratio 0.505; 95% confidence interval, 0.270-0.904; p = 0.032). There were significant differences in the serial changes in the PaO2/FiO2 ratio, SOFA score, and blood neutrophil counts from days 0-5 after PMX-DHP between the survivor and non-survivor groups ( p = 0.015, p < 0.001, p = 0.035, respectively). The improved PaO2/FiO2 ratio on day 3 significantly correlated with the change in blood neutrophil counts (rs = -0.431, p = 0.006). CONCLUSIONS PMX-DHP therapy may be effective in RPIPs patients accompanied by acute respiratory failure and is expected to reduce mortality rates.
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Affiliation(s)
- Hidenori Ichiyasu
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Yuko Horio
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Aiko Masunaga
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Yohei Migiyama
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Yasumiko Sakamoto
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Takayuki Jodai
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Hideharu Ideguchi
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Hiroko Okabayashi
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Shohei Hamada
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Chieko Yoshida
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Susumu Hirosako
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Shinichiro Okamoto
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
| | - Hirotsugu Kohrogi
- Department of Respiratory Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
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The Role of Infection in Interstitial Lung Diseases: A Review. Chest 2017; 152:842-852. [PMID: 28400116 PMCID: PMC7094545 DOI: 10.1016/j.chest.2017.03.033] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 03/22/2017] [Accepted: 03/25/2017] [Indexed: 02/02/2023] Open
Abstract
Interstitial lung disease (ILD) comprises an array of heterogeneous parenchymal lung diseases that are associated with a spectrum of pathologic, radiologic, and clinical manifestations. There are ILDs with known causes and those that are idiopathic, making treatment strategies challenging. Prognosis can vary according to the type of ILD, but many exhibit gradual progression with an unpredictable clinical course in individual patients, as seen in idiopathic pulmonary fibrosis and the phenomenon of "acute exacerbation"(AE). Given the often poor prognosis of these patients, the search for a reversible cause of respiratory worsening remains paramount. Infections have been theorized to play a role in ILDs, both in the pathogenesis of ILD and as potential triggers of AE. Research efforts thus far have shown the highest association with viral pathogens; however, fungal and bacterial organisms have also been implicated. This review aims to summarize the current knowledge on the role of infections in the setting of ILD.
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