Cyclosporin A Followed by the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis with Corticosteroid

Inase, Naohiko; Sawada, Megumi; Ohtani, Yoshio; Miyake, Shuji; Isogai, Susumu; Sakashita, Hiroyuki; Miyazaki, Yasunari; Yoshizawa, Yasuyuki

doi:10.2169/internalmedicine.42.565

Cited by 90 publications

(55 citation statements)

References 21 publications

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“…Interestingly, immunosuppressive peptidyl-prolyl isomerase inhibitors like FK506 have been ascribed potent antifibrotic effects in lung fibrosis (40)(41)(42)(43). FK506 suppresses collagen synthesis and expression of the TGF-b 1 receptor in dermal and lung fibroblasts, but the underlying mechanisms are largely unclear (41,44,45).…”

Section: Discussionmentioning

confidence: 99%

FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis

Staab-Weijnitz

Fernandez

Knüppel

et al. 2015

Am J Respir Crit Care Med

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Rationale: Increased abundance and stiffness of the extracellular matrix, in particular collagens, is a hallmark of idiopathic pulmonary fibrosis (IPF). FK506-binding protein 10 (FKBP10) is a collagen chaperone, mutations of which have been indicated in the reduction of extracellular matrix stiffness (e.g., in osteogenesis imperfecta).Objectives: To assess the expression and function of FKBP10 in IPF. Methods:We assessed FKBP10 expression in bleomycininduced lung fibrosis (using quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunofluorescence), analyzed microarray data from 99 patients with IPF and 43 control subjects from a U.S. cohort, and performed Western blot analysis from 6 patients with IPF and 5 control subjects from a German cohort. Subcellular localization of FKBP10 was assessed by immunofluorescent stainings. The expression and function of FKBP10, as well as its regulation by endoplasmic reticulum stress or transforming growth factor-b 1 , was analyzed by small interfering RNA-mediated loss-of-function experiments, quantitative reverse transcriptase-polymerase chain reaction, Western blot, and quantification of secreted collagens in the lung and in primary human lung fibroblasts (phLF). Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF.Measurements and Main Results: FKBP10 expression was up-regulated in bleomycin-induced lung fibrosis and IPF. Immunofluorescent stainings demonstrated localization to interstitial (myo)fibroblasts and CD68 1 macrophages. Transforming growth factor-b 1 , but not endoplasmic reticulum stress, induced FKBP10 expression in phLF. The small interfering RNA-mediated knockdown of FKBP10 attenuated expression of profibrotic mediators and effectors, including collagens I and V and a-smooth muscle actin, on the transcript and protein level. Importantly, loss of FKBP10 expression significantly suppressed collagen secretion by phLF.Conclusions: FKBP10 might be a novel drug target for IPF.

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Section: Discussionmentioning

confidence: 99%

FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis

Staab-Weijnitz

Fernandez

Knüppel

et al. 2015

Am J Respir Crit Care Med

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“…CsA is an immunomodulatory drug that plays a role in inhibiting the activation of helper T cells and alveolar macrophages (14), and has been used to treat several types of pulmonary interstitial diseases (15)(16)(17). The pathogenesis of OP remains speculative.…”

Section: Discussionmentioning

confidence: 99%

Adjunctive Effects of Cyclosporine and Macrolide in Rapidly Progressive Cryptogenic Organizing Pneumonia with no Prompt Response to Steroid

et al. 2011

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Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. However, it can rapidly worsen and lead to respiratory failure that is refractory to corticosteroids. Adjunctive drugs have been used in refractory cases with various outcomes, but treatment experience is still lacking. We present a case of rapidly progressive COP accompanying air leak syndrome, which showed no prompt response to corticosteroids alone but gradual improvement with the addition of cyclosporine and macrolide. This case report supports the existing literature suggesting that an early therapeutic trial of this drug combination might be considered in COP patients whose condition worsens despite corticosteroid administration.

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“…Both approaches are typically followed by a rapid taper and cessation of prednisone within several weeks, based on the rationale that chronic prednisone use is likely harmful in IPF [9]. Several other investigational agents have been studied in AE-IPF including polymyxin B-immobilised fibre cartridge [61][62][63][64], tacrolimus [65] and cyclosporine [66][67][68]; however, there are currently insufficient data to support the routine use of these medications.…”

Section: Managementmentioning

confidence: 99%

Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm

et al. 2015

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The goal of this review is to summarise the clinical features, management, and prognosis of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). AE-IPF has previously been defined based on clinical and radiological features that include the subacute onset of dyspnoea, bilateral ground glass changes on chest high-resolution computed tomography, and the absence of an identifiable aetiology. The annual incidence of AE-IPF is typically reported at 5-15%, but is less common in mild disease. Features of diffuse alveolar damage are present when a biopsy is performed. Idiopathic pulmonary fibrosis (IPF) patients with acute respiratory worsening are often initially treated with high dose corticosteroids and antimicrobials; however, there are no clear data to support these therapies, and the short-term mortality of AE-IPF is ∼50%. Recent studies have shown that the features and prognosis of AE-IPF are similar to other causes of acute respiratory worsening, including infection, aspiration, air pollution and mechanical injury to the alveolar epithelium. Based on this emerging evidence, we propose a novel approach to the classification of acute respiratory worsening events in patients with IPF that focuses on clinical and radiological findings consistent with an underlying pathobiology of diffuse alveolar damage. @ERSpublications A review summarising the features, management, and prognosis of acute exacerbations of idiopathic pulmonary fibrosis

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Cyclosporin A Followed by the Treatment of Acute Exacerbation of Idiopathic Pulmonary Fibrosis with Corticosteroid

Cited by 90 publications

References 21 publications

FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis

FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis

Adjunctive Effects of Cyclosporine and Macrolide in Rapidly Progressive Cryptogenic Organizing Pneumonia with no Prompt Response to Steroid

Acute exacerbation of idiopathic pulmonary fibrosis: shifting the paradigm

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