Lung transplantation in idiopathic pulmonary fibrosis

Kumar, Anupam; Kapnadak, Siddhartha G.; Girgis, Reda E.; Raghu, Ganesh

doi:10.1080/17476348.2018.1462704

Cited by 54 publications

(35 citation statements)

References 69 publications

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“…Idiopathic pulmonary fibrosis (IPF) is a specific form of interstitial pneumonia that leads to progressive, irreversible scarring of the lung and death due to respiratory failure within five years in approximately 50% of the patients [1]. Survival rate has not been improved by the recent introduction of two antifibrotic drugs, thus lung transplantation remains the only effective treatment [2]. Clinical and functional worsening are generally proportional to the spreading of the histopathological pattern UIP (usual interstitial pneumonia), which is characterized by patchy areas of dense fibrosis with basal and subpleural predominance causing extensive remodeling of lung architecture [3,4].…”

Section: Introductionmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

2019

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Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung, which leads to extensive parenchymal scarring and death from respiratory failure. The most accepted hypothesis for IPF pathogenesis relies on the inability of the alveolar epithelium to regenerate after injury. Alveolar epithelial cells become apoptotic and rare, fibroblasts/myofibroblasts accumulate and extracellular matrix (ECM) is deposited in response to the aberrant activation of several pathways that are physiologically implicated in alveologenesis and repair but also favor the creation of excessive fibrosis via different mechanisms, including epithelial–mesenchymal transition (EMT). EMT is a pathophysiological process in which epithelial cells lose part of their characteristics and markers, while gaining mesenchymal ones. A role for EMT in the pathogenesis of IPF has been widely hypothesized and indirectly demonstrated; however, precise definition of its mechanisms and relevance has been hindered by the lack of a reliable animal model and needs further studies. The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.

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Section: Introductionmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

2019

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“…Idiopathic pulmonary fibrosis (IPF) is a multifactorial disease that is characterized by progressive worsening in lung function, an unfavorable prognosis and subsequent death for respiratory failure ( Martinez et al., 2017 ). Continued research efforts are needed to identify better and innovative pharmacological treatments, since there is little evidence from randomized clinical trials of disease progression retardation with current medications and only lung transplantation prolongs the survival ( Varone et al., 2017 ; Kumar et al., 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive degenerative lung disease leading to respiratory failure and death. Although anti-fibrotic drugs are now available for treating IPF, their clinical efficacy is limited and lung transplantation remains the only modality to prolong survival of IPF patients. Despite its limitations, the bleomycin (BLM) animal model remains the best characterized experimental tool for studying disease pathogenesis and assessing efficacy of novel potential drugs. In the present study, the effects of oropharyngeal (OA) and intratracheal (IT) administration of BLM were compared in C57BL/6 mice. The development of lung fibrosis was followed in vivo for 28 days after BLM administration by micro-computed tomography and ex vivo by histological analyses (bronchoalveolar lavage, histology in the left lung to stage fibrosis severity and hydroxyproline determination in the right lung). In a separate study, the antifibrotic effect of Nintedanib was investigated after oral administration (60 mg/kg for two weeks) in the OA BLM model. Lung fibrosis severity and duration after BLM OA and IT administration was comparable. However, a more homogeneous distribution of fibrotic lesions among lung lobes was apparent after OA administration. Quantification of fibrosis by micro-CT based on % of poorly aerated tissue revealed that this readout correlated significantly with the standard histological methods in the OA model. These findings were further confirmed in a second study in the OA model, evaluating Nintedanib anti-fibrotic effects. Indeed, compared to the BLM group, Nintedanib inhibited significantly the increase in % of poorly aerated areas (26%) and reduced ex vivo histological lesions and hydroxyproline levels by 49 and 41%, respectively. This study indicated that micro-computed tomography is a valuable in vivo technology for lung fibrosis quantification, which will be very helpful in the future to better evaluate new anti-fibrotic drug candidates.

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“…The average post-transplant survival of these patients is lower than other diagnostic groups such as cystic fibrosis or COPD. Pulmonary fibrosis patients have higher mortality within 90 days and in the first year after transplantation [ 50 , 51 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

Lung Transplantation in Idiopathic Pulmonary Fibrosis

et al. 2018

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Despite the advances in recent years in the treatment of idiopathic pulmonary fibrosis (IPF), it continues to be a progressive disease with poor prognosis. In selected patients, lung transplantation may be a treatment option, with optimal results in survival and quality of life. Currently, pulmonary fibrosis is the main cause of lung transplantation. However, mortality on the waiting list of these patients is high, since many patients are referred to the transplant units with advanced disease. There is not a parameter that can predict the survival of a specific patient. Different variables are to be considered in order to decide the right time to send them to a transplant unit. It is also very difficult to decide when to include these patients on the waiting list. Every patient diagnosed with IPF, without contraindications for surgery, should be referred early to a transplant unit for assessment. A uni or bilateral transplantation will be decided based on the characteristics of the patient and the experience of each center. The post-transplant survival of recipients with IPF is lower than that observed in other diseases, such as cystic fibrosis or chronic obstructive pulmonary disease as a consequence of their older age and the frequent presence of associated comorbidity. Post-transplant follow-up must be tight in order to assure optimal level of immunosuppressive treatment, detect complications associated with it, and avoid graft rejection. The main cause of long-term mortality is late graft dysfunction as a consequence of chronic rejection. Other complications, such as infections and tumors, must be considered.

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Lung transplantation in idiopathic pulmonary fibrosis

Cited by 54 publications

References 69 publications

Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

Quantification of Lung Fibrosis in IPF-Like Mouse Model and Pharmacological Response to Treatment by Micro-Computed Tomography

Lung Transplantation in Idiopathic Pulmonary Fibrosis

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