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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Respirol. Mar 28, 2015; 5(1): 1-3
Published online Mar 28, 2015. doi: 10.5320/wjr.v5.i1.1
Polymyxin B-immobilized fiber columns: A column to breathe new life into the treatment of interstitial lung disease?
Katsuaki Asakawa, Toshinori Takada, Division of Respiratory Medicine, Niigata University Medical and Dental Hospital, Niigata 951-8520, Japan
Toshinori Takada, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata 951-8520, Japan
Author contributions: Asakawa K and Takada T equally contributed to this paper.
Conflict-of-interest: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Toshinori Takada, MD, PhD, Professor, Director of the Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata 951-8520, Japan. ttakada@med.niigata-u.ac.jp
Telephone: +81-25-2270379 Fax: +81-25-2270417
Received: December 4, 2014
Peer-review started: December 7, 2014
First decision: December 26, 2014
Revised: January 6, 2015
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: March 28, 2015
Processing time: 109 Days and 1.5 Hours

Abstract

Acute exacerbations of idiopathic pulmonary fibrosis (IPF) is a severe respiratory condition with high mortality rate. Direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX-DHP) was originally introduced for the treatment of septic shock. Application of PMX-DHP to the treatment of acute exacerbations of IPF may improve oxygenation and survival of the patients with the disease. In addition to acute exacerbations of IPF, PMX-DHP has been applied to acute respiratory failure from various causes; an amyopathic dermatomyositis patient who developed rapidly progressive interstitial lung disease (ILD) with elevated anti-CADM-140/MDA5 autoantibody and a patient with severe amiodarone pulmonary toxicity. It is also demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive ILDs in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. Although the incidence of acute exacerbations of IPF is too low for proper randomization, in order to test the effects of PMX-DHP on the disease, a cohort or case-control analytic study needs to be conducted, preferably from more than one center or research group.

Key Words: Acute exacerbation; Idiopathic pulmonary fibrosis; Polymyxin B; Hemoperfusion; Interstitial lung disease

Core tip: Application of direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX-DHP) to the treatment of acute exacerbations of idiopathic pulmonary fibrosis may improve oxygenation and survival of the patients with the disease. PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with rapidly progressive interstitial lung diseases in a case-control setting. PMX treatment decreases not only various circulating molecules but also inflammatory cells, in particular activated monocytes, producing such mediators. In order to test the effects of PMX-DHP on the disease, a cohort or case-control analytic study needs to be conducted, preferably from more than one center or research group.



PMX-DHP TO BREATHE NEW LIFE INTO THE TREATMENT OF ILD

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial lung disease (ILD) of unknown cause that usually affects middle-aged and older adults. Although the natural history of IPF was thought to be a steady, gradual, and predictable decline in lung function over years, some patients may experience an accelerated phase of rapid clinical decline. When these acute declines develop without clinically apparent infection, left heart failure, pulmonary embolism, or other identifiable cause, the episodes of acute deterioration have been termed acute exacerbations of IPF[1]. In spite of the intensified therapy with broad-spectrum antibiotics, high dose glucocorticoids, and mechanical ventilation, the hospital mortality rate was as high as 78% in one study[2]. The estimates of incidence and mortality rates of acute exacerbation of IPF are discordant among different studies, probably due to substantial variations in the definition of acute exacerbation. Among them Japanese patients with IPF seem to suffer from acute exacerbation much more frequently than patients of other ethnic backgrounds[3-6].

Direct hemoperfusion through a membranous polymyxin B fiber column (PMX-DHP) is an extracorporeal technique to effectively reduce blood endotoxin levels during sepsis. The addition of PMX-DHP to conventional therapy reduced mortality in a population with severe sepsis and/or septic shock due to intra-abdominal Gram-negative infections[7]. PMX-DHP also improved the circulatory disturbance, oxygenation, and mortality in patients with ARDS[8,9]. Since then, PMX-DHP has been applied to rapidly progressive ILDs associated with various disorders (Table 1). Seo et al[10] applied PMX-DHP to the treatment of acute exacerbations of IPF for the first time. They successfully treated 4 of 6 patients through administration of PMX-DHP in addition to glucocorticoid therapy. The results of a study of a large and diverse cohort treated with PMX-DHP demonstrated that PMX-DHP might improve oxygenation and survival in IPF patients with acute exacerbation[11]. In addition to acute exacerbations of IPF, PMX-DHP has been applied to acute respiratory failure from various causes. An amyopathic dermatomyositis patient who developed rapidly progressive ILD with elevated anti-CADM-140/MDA5 autoantibody was successfully treated with PMX-DHP after being resistant to combined steroid and immunosuppressant therapy[12]. A patient with severe amiodarone pulmonary toxicity was also successfully treated with PMX-DHP and completely recovered, in which the patient’s severe respiratory failure improved with the reduction of amiodarone and monodesethylamiodarone serum levels[13]. Hara et al[14] reported that PMX-DHP would be a safe and effective therapy for rapidly progressive ILDs of different etiologies resistant to initial high-dose glucocorticoid therapy. Since all of these previous reports were observational case series without controls, case-control studies were needed. We then tried to determine the effects of PMX-DHP on the prognosis of the patients with rapidly progressive ILDs in a case-control setting. A retrospective study of the clinical records of consecutive 26 patients with acute exacerbation of IPF or rapidly progressive ILDs treated in our institute demonstrated that PMX-DHP performed on the first day of steroid pulse therapy may improve the prognosis of patients with these diseases[15].

Table 1 Representative reports of PMX-DHP for the treatment of intersititial lung diseases.
Ref.Publication yearCase
Comments
nUnderlying disease
Seo et al[10]20066IPF, acute exacerbationThe first trial
Abe et al[11]2012160IPF, acute exacerbation (73)The largest cohort study
Teruya et al[12]20131Amyopathic dermatomyositisDecrease in anti-CADM140/MDA5
antibody titer observed
Sato et al[13]20131Amiodarone lung injuryReduction of amiodarone and its derivative observed
Hara et al[14]201133Rapidly progressive ILDDecrease in serum MCP-1 observed
Resistant to steroid pulse therapy
Takada et al[15]201426IPF, acute exacerbationThe first case-control study
Rapidly progressive ILD

PMX treatment decreases not only various circulating molecules including monocyte chemotactic protein 1, metalloproteinase (MMP) -9, tissue inhibitor of MMP-1, neutrophil elastase, interleukin (IL)-8, IL-9, IL-12, IL-17, PDGF, and VEGF[9,14,16,17] but also inflammatory cells, in particular activated monocytes, producing such mediators[18,19]. These results suggest that removal of proinflammatory, profibrotic, and proangiogenic cytokines by PMX-fibers may improve oxygenation in the patients with rapidly progressive ILD or acute exacerbations of IPF. If the removal of these molecules were delayed, acute lung injury would progress into irreversible fibrosis resulting in fatal respiratory failure. The improved prognosis seen in the patients treated with the simultaneous administration of PMX-DHP with steroid pulse therapy may support this hypothesis.

Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients[20]. Although the best evidence is obtained from properly designed randomized controlled trials, the incidence of acute exacerbations of IPF is too low for proper randomization. In order to test the effects of PMX-DHP on the disease, a cohort or case-control analytic study needs to be conducted, preferably from more than one center or research group. Furthermore, a prospective study with predetermined eligibility criteria and outcome measures should be designed.

Footnotes

P- Reviewer: Tanabe S S- Editor: Tian YL L- Editor: A E- Editor: Lu YJ

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