Effect of pirfenidone on wound healing in lung transplant patients

Mortensen, Amber; Cherrier, Lauren; Walia, Rajat

doi:10.1186/s40248-018-0129-4

Cited by 22 publications

(19 citation statements)

References 16 publications

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“…Open questions remain regarding the continuation of antifibrotic therapy prior to lung transplantation. Data from small cohort studies suggest that antifibrotic drugs can be safely continued until lung transplantation [151,152] and pirfenidone and nintedanib may also decrease the waiting-list mortality due to their disease progression attenuating effects [153]. Genetic markers such as shorter telomere length can also impact the post-transplantation prognosis by increasing the risk of post-transplant infections such as viral cytomegalovirus and thereby increasing the risks of allograft rejection.…”

Section: Developments In Lung Transplantationmentioning

confidence: 99%

The therapy of idiopathic pulmonary fibrosis: what is next?

et al. 2019

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease, characterised by progressive scarring of the lung and associated with a high burden of disease and early death. The pathophysiological understanding, clinical diagnostics and therapy of IPF have significantly evolved in recent years. While the recent introduction of the two antifibrotic drugs pirfenidone and nintedanib led to a significant reduction in lung function decline, there is still no cure for IPF; thus, new therapeutic approaches are needed. Currently, several clinical phase I–III trials are focusing on novel therapeutic targets. Furthermore, new approaches in nonpharmacological treatments in palliative care, pulmonary rehabilitation, lung transplantation, management of comorbidities and acute exacerbations aim to improve symptom control and quality of life. Here we summarise new therapeutic attempts and potential future approaches to treat this devastating disease.

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Section: Developments In Lung Transplantationmentioning

confidence: 99%

The therapy of idiopathic pulmonary fibrosis: what is next?

et al. 2019

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“…The exact mechanism of action of pirfenidone may be from the inhibition of transforming growth factor beta (TGF-b) [23]. A few case reports describe the safety of pirfenidone use as a bridge to lung transplantation [24,25].…”

Section: Studies On Ofev/esbriet Prior To Lung Transplantationmentioning

confidence: 99%

“…Mortensen et al reported the largest retrospective analysis of 18 IPF patients who took pirfenidone prior to lung transplantation [25]. Only one patient developed sternal dehiscence that was more related to a surgical issue.…”

Section: Studies On Ofev/esbriet Prior To Lung Transplantationmentioning

confidence: 99%

Lung Transplant for Interstitial Lung Diseases

Nokes¹,

Golts²,

Afshar³

2019

Interstitial Lung Diseases

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Lung transplant is an important treatment modality for select cases of advanced interstitial lung disease. However, the pre-and postoperative management requires several unique considerations. The decision to transplant is based largely on clinical severity of illness and the lung allocation score. Transplant improves overall mortality across the interstitial lung diseases, though not all ILD subtypes experience equal benefit from lung transplant. Broadly speaking, there is no difference in benefit between single-and bilateral-lung transplants, though we will discuss some important clinical nuances to this decision as well. Lastly, there are a number of immunosuppression, coagulation, and malignancy risk considerations that must be carefully understood in caring for the lung transplant patient. This chapter will provide a general overview of the indications for lung transplant, risk stratification for lung transplant across the interstitial lung diseases, as well as general postoperative management details.

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“…Sternal wound and airway complications, including anastomotic dehiscence, have been reported in up to 35% of patients after lung transplantation resulting in serious morbidity as well as death. 6 For these reasons, the standard surgical dogma has been to hold antifibrotic agents at the time of listing to prevent such complications. This assumption was primarily based on the mechanistic understanding of pirfenidone's and nintenanib's mechanism of action but not on data-driven clinical science.…”

mentioning

confidence: 99%

“…Only 1 of the patients developed a sternal wound complication, thought not to be related to pirfenidone, and there were no reported airway complications. 6 Cumulatively, such retrospective evidence suggests that pirfenidone may not truly interfere with wound or airway healing post-transplant.…”

mentioning

confidence: 99%

Commentary: Antifibrotic agents in the postoperative period: Friends or foes?

Mannem

Krupnick

2019

The Journal of Thoracic and Cardiovascular Surgery

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Pirfenidone is a Food and Drug Administration-approved drug for idiopathic pulmonary fibrosis (IPF) and can delay the progression of lung disease over time. The underlying mechanism of pirfenidone is not completely understood, but it displays both anti-inflammatory and antifibrotic effects. 1 Thus, pirfenidone's mechanism of action has been postulated to involve the inhibition of production and activation of transforming growth factor (TGF)-b. Amelioration of TGF-b is thought to inhibit collagen deposition and fibrosis. However, recent data in both animals and humans demonstrate clinically important anti-inflammatory effects of pirfenidone as well, including the decrease in acute exacerbations of IPF, as outlined in the accompanying article in this issue of the Journal. 2,3 IPF is the leading indication for lung transplantation in the United States. With the development and clinical use of 2 Food and Drug Administration-approved antifibrotic agents, pirfenidone and nintedanib, the pretransplant management of IPF has changed dramatically. Little is known about the antifibrotic effects of these drugs in the immediate postoperative period. Saito and colleagues, 2 from Kyoto University in Japan, key in on the anti-inflammatory effects of pirfenidone using an acute lung transplantation rat model. They hypothesize that pirfenidone may offer a unique preventative treatment option for ischemiareperfusion injury (IRI) and primary graft dysfunction (PGD). 2 Because PGD is the leading cause of early postlung transplant mortality and increases the risk of chronic allograft dysfunction in lung transplant recipients, any methods to ameliorate this condition would be a welcome addition to current perioperative management. 4 In their novel article, Saito and colleagues 2 clearly show promising results in an IRI model treated with pirfenidone, including an increase in lung compliance, a decrease in the mean airway pressures, an improvement in oxygenation, and a decrease in lung edema. They also demonstrate an improvement in other parameters of lung injury, including perivascular edema and neutrophil infiltration. 2 Although it is clear that TGF-b is a profibrogenic cytokine, with the deleterious side effect of pulmonary fibrosis, it also plays a major role in would healing. 5 Thus, its inhibition in the perioperative period is a topic of major controversy. Sternal wound and airway complications, including anastomotic dehiscence, have been reported in up to 35% of patients after lung transplantation resulting in serious morbidity as well as death. 6 For these reasons, the standard surgical dogma has been to hold antifibrotic agents at the time of listing to prevent such complications. This assumption was primarily based on the mechanistic understanding of pirfenidone's and nintenanib's mechanism of action but not on data-driven clinical science. In the past several years, small retrospective reports have been published arguing against such theoretic complications of the antifibrotic agents continued in the perioperative period. De...

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Effect of pirfenidone on wound healing in lung transplant patients

Cited by 22 publications

References 16 publications

The therapy of idiopathic pulmonary fibrosis: what is next?

The therapy of idiopathic pulmonary fibrosis: what is next?

Lung Transplant for Interstitial Lung Diseases

Commentary: Antifibrotic agents in the postoperative period: Friends or foes?

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