Tacrolimus Treatment Effectively Inhibits Progression of Obliterative Airway Disease Even at Later Stages of Disease Development

Hollmén, Maria; Tikkanen, Jussi; Nykänen, Antti; Koskinen, Petri; Lemström, Karl

doi:10.1016/j.healun.2008.05.018

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…In addition, the mRNA expression of pro-inflammatory cytokines MCP-1, IL-6, and HO-1 was also significantly reduced in mVHL -/-recipients. However, even low-dose tacrolimus preventing T-cell signal transduction and IL-2 production 21 did not delay the development of OAD in the mHIF-1α -/-recipients. There are a few plausible mechanisms of action by which myeloid cell-specific VHL deficiency reduced OAD in our study.…”

Section: Figurementioning

confidence: 83%

“…The degree of airway occlusion may be regulated by tacrolimus immunosuppression in a dose-dependent fashion. 21 In the second phase, the recipients received tacrolimus 0.75 mg/kg daily subcutaneously that reduces OAD development, and tracheal allografts exhibit approximately 30% luminal occlusion at 30 days. The dose was based on our previous dose-response study with this animal model.…”

Section: Drug Regimensmentioning

confidence: 99%

“…The dose was based on our previous dose-response study with this animal model. 21 Tacrolimus was provided by Astellas.…”

Section: Drug Regimensmentioning

confidence: 99%

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Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

Ropponen

Keränen

Raissadati

et al. 2016

The Journal of Heart and Lung Transplantation

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Section: Figurementioning

confidence: 83%

Section: Drug Regimensmentioning

confidence: 99%

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Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

Ropponen

Keränen

Raissadati

et al. 2016

The Journal of Heart and Lung Transplantation

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“…This concurs with results in animal experiments, where VEGF-α was found to have a limiting influence on fibrotic remodelling of the lung. This is most likely because of its positive effect on the recruitment of macrophages, as these contribute significantly to "airway clearance" of necrotic/apoptotic cells and infectious agents and thus reduce local inflammation and subsequent fibrosis [38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Obliterative airway remodelling in transplanted and non-transplanted lungs

et al. 2010

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Obliterative airway remodelling is a morphological sequence in a variety of pulmonary diseases. Notably, bronchiolitis obliterans represents one of the key complications of lung transplantation, induced by (immigrating) myofibroblasts. A comparative expression analysis of obliterative airway remodelling in transplanted and non-transplanted patients has not been reported so far. Obliterated and unremodelled airways from explanted lungs (n = 19) from patients suffering from chronic allograft dysfunction, infection, graft-versus-host disease and toxic exposure were isolated by laser-assisted microdissection. Airways from lung allografts harvested shortly before and after transplantation (n = 4) as well as fibroblastic foci from lungs with interstitial pulmonary fibrosis (n = 4) served as references. Pre-amplified cDNA was analysed by quantitative real-time RT-PCR for expression of fibrosis, inflammation and apoptosis-associated genes. Composition of infiltrating cells and protein expression were assessed by conventional histology and immunohistochemistry. Bronchiolitis obliterans in transplanted patients showed a significant increase of BMP-7 expression (p = 0.0141 compared with controls), while TGF-beta1 and FGF-2 as well as BMP-4 and BMP-7 were up-regulated in fibroblastic foci in interstitial pulmonary fibrosis (p < 0.0424 compared with controls). Regarding other fibrosis-associated genes (BMP-6, SMAD-3, CASP-3 and CASP-9, FASLG, NF-KB1, IL-1 and IL-2) as well as cellularity and cellular composition, no significant differences between obliterative airway remodelling in transplanted and non-transplanted patients could be shown. Obliterative airway remodelling in lung allografts and in non-transplanted patients share many morphological and genetic traits. BMPs, especially BMP-7, warrant further investigation as possible markers for the aggravation of airway remodelling.

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“…Data from lung transplantation literature suggests that these agents are likely to be beneficial by decreasing the rate of progression of BOS. [73,74] Current recommendations for BOS therapy include: high dose systemic corticosteroids (1mg/kg/day) for a protracted course with expected “improvements” in 8–20%, of which most are likely transient given the poor overall survival. [1,75–77] Azithromycin and inhaled steroids have been tested in small clinical trials of patients with BOS after HCT with evidence for some benefit by pulmonary function tests.…”

Section: Clinical Assessment Of Bos After Hctmentioning

confidence: 99%

Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation—An Increasingly Recognized Manifestation of Chronic Graft-versus-Host Disease

Chien

Duncan

Williams

et al. 2010

Biology of Blood and Marrow Transplantation

166

167

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Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious, and often fatal lung allo-reaction that can occur following allogeneic hematopoietic stem cell transplantation (HCT) or allogeneic lung transplantation. Current estimates in the literature suggest that approximately 2–3% of all allogeneic HCT recipients and 6% of patients who develop chronic GVHD will develop this syndrome. However, based on newer data it is likely that the true incidence of BOS is higher. Unfortunately, the survival and treatment of patients with BOS after HCT has not improved over the last 20 years. Attempts at clinical trials have been hindered by the lack of uniform diagnostic criteria and inability to detect the syndrome at a reversible stage in its natural history. Recently, the NIH consensus project for criteria in chronic GVHD has made recommendations regarding the diagnosis of BOS and monitoring of lung disease among long term survivors. Although a rare and poorly understood manifestation of chronic GVHD, BOS occurs commonly after lung transplantation and is similar in pathology, clinical presentation, radiographic presentation, and presumed immunologic pathogenesis. This review describes the current understanding of the epidemiology and pathogenesis of BOS and presents information on evaluations and therapies for patients with BOS after HCT.

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Tacrolimus Treatment Effectively Inhibits Progression of Obliterative Airway Disease Even at Later Stages of Disease Development

Cited by 18 publications

References 27 publications

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse

Obliterative airway remodelling in transplanted and non-transplanted lungs

Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation—An Increasingly Recognized Manifestation of Chronic Graft-versus-Host Disease

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