Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplantation Outcome

Dotan, Yaniv; Vaidy, Anika; Shapiro, William B.; Zhao, Huaqing; Dass, Chandra; Toyoda, Yoshiya; Marchetti, Nathaniel; Shenoy, Kartik; Cordova, Francis; Criner, Gerard J.; Mamary, A.J.

doi:10.1016/j.chest.2018.06.027

Cited by 32 publications

(29 citation statements)

References 24 publications

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“…This is of interest, since pirfenidone might counteract further progression of the disease and AE‐IPF on the waiting list . Patients with IPF transplanted during AE‐IPF had significantly worse short‐term and long‐term survival compared with patients transplanted during stable IPF, which should be avoided …”

Section: Discussionmentioning

confidence: 99%

Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation

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et al. 2019

American Journal of Transplantation

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Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx. K E Y W O R D Sclinical research/practice, critical care/intensive care management, lung (allograft) function/ dysfunction, lung (native) function/dysfunction, lung disease, lung transplantation/ pulmonology, organ transplantation in general

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Section: Discussionmentioning

confidence: 99%

Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation

Veit

Leuschner

Sisic³

et al. 2019

American Journal of Transplantation

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“…This increased absolute decline can potentially be a predictor of rapid subclinical deterioration leading to clinical respiratory failure and hospitalisation for AE-IPF. Since the mortality of AE-IPF with respiratory failure is up to 90% for patients with AE-IPF and respiratory failure requiring mechanical ventilation [ 1 , 3 , 5 –], fastening the process of evaluation and early listing for patients with rapid decline of FVC might prevent lung transplantation during AE-IPF, which has been shown by our group to have worse short- and long-term outcomes [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis

et al. 2020

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BackgroundIdiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation.MethodsRetrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings.ResultsOut of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage.ConclusionsLung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

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“…Lung transplantation is another potential therapy for AE-IPF. Recently, post-transplantation survival among IPF patients including AE-IPF was reported [24]. In the study, IPF patients who transplanted lung during AE-IPF had significantly worse short-term and long-term survival compared to stable patients after lung transplantation.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

2019

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Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an acute respiratory worsening of unidentifiable cause that sometimes develops during the clinical course of IPF. Although the incidence of AE-IPF is not high, prognosis is poor. The pathogenesis of AE-IPF is not well understood; however, evidence suggests that coagulation abnormalities and inflammation are involved. Thrombomodulin is a transmembranous glycoprotein found on the cell surface of vascular endothelial cells. Thrombomodulin combines with thrombin, regulates coagulation/fibrinolysis balance, and has a pivotal role in suppressing excess inflammation through its inhibition of high-mobility group box 1 protein and the complement system. Thus, thrombomodulin might be effective in the treatment of AE-IPF, and we and other groups found that recombinant human soluble thrombomodulin improved survival in patients with AE-IPF. This review summarizes the existing evidence and considers the therapeutic role of thrombomodulin in AE-IPF.

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Effect of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplantation Outcome

Cited by 32 publications

References 24 publications

Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation

Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis

Therapeutic Role of Recombinant Human Soluble Thrombomodulin for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

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