Idiopathic pulmonary fibrosis acute exacerbations: where are we now?

Papiris, Spyros; Kagouridis, Konstantinos; Kolilekas, Likurgos; Bouros, Demosthenes; Manali, Effrosyni D.

doi:10.1586/17476348.2014.896206

Cited by 12 publications

(6 citation statements)

References 25 publications

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“…It is common sense that a single academic center like ours could never support by itself such a trial but needs the scientific, technical and financial support of the international scientific community and of official medical institutions that could conduct a multi-center trial designed and empowered to provide definitive answers to this already long lasting and crucial for IPF patients debate. We are convinced that our proposal reflects not only our view but also the evolving view of other experts that treat IPF-AE patients worldwide [ 21 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 61%

“…However, to our opinion it is difficult to understand why in the majority of cases the authors do not consider the use of antibiotics as a treatment for IPF-AE and they do not consider it to be a determinant of outcome even when they use antibiotics, although experts opinion recommend the use of antibiotics in all cases of IPF-AE [ 20 ] and this reflects common practice worldwide. In our opinion the use of antibiotics is of cardinal importance to judge IPF-AE studies results and to treat IPF-AE and this is the main reason why it was included as the major therapeutic strategy in our treating protocol [ 6 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

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Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach

et al. 2015

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BackgroundIdiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF’s most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology. Guidelines recommend high-dose steroids treatment despite unproven benefit. We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome.MethodsWe studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013. Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad-spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration. Patients were followed-up for survival; post-discharge none received immunosuppression.ResultsTwenty-four out of 85 admissions (28 %) fulfilled IPF-AE criteria. IPF-AE were analyzed both as unique events and as unique patients. As unique events 50 % survived; 3 out of 12 (25 %) in the group previously treated with immunosuppression whereas nine out of 12 (75 %) in the group not receiving immunosuppression (p = 0.041). As unique patients 35.3 % survived; 3 out of 6 (50 %) in the never treated group whereas three out of 11 (27.3 %) in the group receiving immunosuppression (p = 0.685). The history of immunosuppression significantly and adversely influenced survival (p = 0.035). Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022). Post-discharge, our IPF-AE survivors had an 83 % 1-year survival.ConclusionsBy applying the above mentioned protocol half of our patients survived. The history of immunosuppression before IPF-AE adversely influences survival. Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach

et al. 2015

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“…It is known that acute lung injury is a pathology that may serve as a trigger for a number of pulmonary fibrotic conditions, such as pulmonary emphysema, chronic obstructive pulmonary disease, interstitial pneumonia, and idiopathic pulmonary fibrosis [23][24][25][26]; on the other hand, acute exacerbations are one of the complications of pulmonary fibrosis [27][28][29]. Pathological fibrosis is associated with increments in molecules such as FLIP, allowing unremitted accumulation of myofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Forefront: MiR-34a-Knockout Mice with Wild Type Hematopoietic Cells, Retain Persistent Fibrosis Following Lung Injury

Bulvik

Biton²,

Berkman

et al. 2020

IJMS

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MicroRNAs (miRs) are known to limit gene expression at the post-transcriptional level and have important roles in the pathogenesis of various conditions, including acute lung injury (ALI) and fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). In this study, we found increased levels of miR-34 at times of fibrosis resolution following injury, in myofibroblasts from Bleomycin-treated mouse lungs, which correlates with susceptibility to cell death induced by immune cells. On the contrary, a substantial downregulation of miR-34 was detected at stages of evolution, when fibroblasts resist cell death. Concomitantly, we found an inverse correlation between miR-34 levels with that of the survival molecule FLICE-like inhibitory protein (FLIP) in lung myofibroblasts from humans with IPF and the experimental model. Forced upregulation of miR-34 with miR-34 mimic in human IPF fibrotic-lung myofibroblasts led to decreased cell survival through downregulation of FLIP. Using chimeric miR-34 knock-out (KO)-C57BL/6 mice with miR34KO myofibroblasts but wild-type (WT) hematopoietic cells, we found, in contrast to WT mice, increased and persistent FLIP levels with a more severe fibrosis and with no signs of resolution as detected in pathology and collagen accumulation. Moreover, a mimic of miR-34a decreased FLIP expression and susceptibility to cell death was regained in miR-34KO fibroblasts. Through this study, we show for the first time an inverse correlation between miR-34a and FLIP expression in myofibroblasts, which affects survival, and accumulation in lung fibrosis. Reprogramming fibrotic-lung myofibroblasts to regain susceptibility to cell-death by specifically increasing their miR34a and downregulating FLIP, may be a useful strategy, enabling tissue regeneration following lung injury.

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“…Few studies have evaluated the outcome of patients with AE-IPF receiving mechanical ventilation in the ICU, and in addition they all share important limitations (see Table 2 ): single-centered and retrospective analysis; limited number of patients included; unclear or unreported mode of ventilation and setting; and heterogeneous use of drugs [ 4 , 39 – 42 ]. Overall, the available data are consistent in stating that invasive mechanical ventilation cannot significantly modify the poor prognosis of these patients [ 9 ].…”

Section: Respiratory Assistancementioning

confidence: 99%

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

et al. 2018

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Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

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Idiopathic pulmonary fibrosis acute exacerbations: where are we now?

Cited by 12 publications

References 25 publications

Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach

Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach

Forefront: MiR-34a-Knockout Mice with Wild Type Hematopoietic Cells, Retain Persistent Fibrosis Following Lung Injury

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

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