Meaningful survival benefit for single lung transplantation in idiopathic pulmonary fibrosis patients over 65 years of age
Peter RiddellJana KleinerováDonna EatonDavid HealyHossein JavadpourJim McCarthyLars NölkeKaren RedmondJim Egan
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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that results in progressive respiratory failure and death. Antifibrotic therapy has been shown to slow disease progression [1, 2]. For many patients [3], lung transplantation is the only intervention recognised to provide significant survival benefit [4]. IPF commonly affects older patients, with a median age at diagnosis of 66 years old [5]. Without transplantation, the median survival from diagnosis is 2–4 years [5]. However, registry data indicates impaired outcomes following lung transplantation for older patients 6]. These data have prompted many centres in Europe to avoid offering transplantation to older IPF patients. This study demonstrates a clinically meaningful survival benefit of lung transplantation for IPF patients aged ≥65 years Introduction: Idiopathic Pulmonary Fibrosis (IPF) is a unique type of interstitial pneumonia in which progressive fibrosis can ultimately result in respiratory failure and death. The median survival of IPF remains dismal despite newer anti-fibrotic therapies. Lung transplantation is the only modality currently known to enhance survival for patients with IPF.Areas covered: Since IPF is predominantly a disorder of the elderly, determination of the impact of co-morbidities is crucial for risk stratification of the individual patient. We review the potential effect of anti-fibrotic therapy in the pre and post-transplant period; and also discuss the factors that need to be considered in deciding between single lung and bilateral lung transplantation.Expert commentary: Early referral to a transplant center is recommended for patients with IPF due to the high waiting list mortality. Evaluation of the transplant candidate should also be directed specifically at identifying co-morbidities that portend higher risk. While there has been a universal trend favoring bilateral lung transplantation over single lung transplantation for IPF, there are inherent pros and cons for both strategies and decisions should be individualized. Further studies are required to deduce the efficacy and safety of anti-fibrotic drugs in the immediate pre-and post-lung transplantation period.
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(1) Background: This paper aims to assess temporal trends (2016-2020) in incidence, patient's characteristics, complications, length of hospital stay (LOHS) and in-hospital mortality (IHM) among patients with and without idiopathic pulmonary fibrosis (IPF) undergoing lung transplantation (LTx). We also analyse the effect of the COVID-19 pandemic on LTx in these populations. (2) Methods: A retrospective, population-based observational study was conducted using the Spanish National Hospital Discharge Database. Multivariable adjustment was conducted with logistic regression to analyse the IHM. (3) Results: We identified 1777 admissions for LTx during the study period, of which 573 (32.2%) were performed in patients with IPF. The number of hospital admissions for LTx rose from 2016 to 2020, both in patients with and without IPF, but a marked reduction was observed from year 2019 to year 2020. Over time, the proportion of single LTx decreased and bilateral LTx increased significantly in both groups. The incidence of LTx complications increased significantly over time along with the increase in the incidence of IPF. No significant differences in the incidence of complications or in the IHM between patients with and without IPF were found. Suffering any complication of the LTx and pulmonary hypertension were conditions positively associated with IHM in patients with and without IPF. The IHM remained stable from 2016 to 2020 in both study populations and was not affected by the COVID pandemic. (4) Conclusions: Patients with IPF account for almost a third of all lung transplants. The number of LTx increased over time in patients with and without IPF, but a marked reduction was observed from 2019 to 2020. Although the proportion of LTx complications increased significantly over time in both groups, the IHM did not change. IPF was not associated with increased complications or IHM after LTx.
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Pulmonary involvement is common in connective tissue disease (CTD), and respiratory failure is a major cause of morbidity and mortality in CTD-related interstitial lung disease (CTD-ILD). Lung transplantation is thus important for these patients. However, survival, outcomes, and management of these patients after transplantation have been debated. The aim of this study was to evaluate the outcomes for CTD-ILD compared to those for idiopathic pulmonary fibrosis (IPF) after lung transplantation.We performed a single-centre retrospective study of 62 patients with CTD-ILD or IPF who underwent lung transplantation at a tertiary hospital in South Korea between October 2012 and October 2016.Patients with CTD-ILD (n=15) were younger (46 vs. 60 years, P=0.001) and were less likely to be male (33.3% vs. 76.6%, P=0.004) than were patients with IPF (n=47). The 1-year cumulative survival rate was 80.0% for CTD-ILD and 59.6% for IPF (log-rank P=0.394). There was no difference in the cumulative survival rate (log-rank P=0.613) of age- and sex-matched patients with CTD-ILD (n=15) and IPF (n=15). The incidence of primary graft dysfunction was similar (P=0.154), and 2 (18.2%) patients developed possible CTD flare.Patients with CTD-ILD and those with IPF who underwent lung transplantation had similar survival rates.
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Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease with a poor prognosis of 2.5 to 5 years. IPF is not responsive to medicinal treatment and lung transplantation is the only therapeutic option to prolong life. Objective: The aim of this study was to examine waiting list mortality of IPF in the Netherlands. Methods: Data were retrospectively collected from September 1989 till June 2010 of all IPF patients registered for lung transplantation in the Netherlands. Patients were included after revision of the diagnosis based on the IPF criteria set by the ATS/ERS. Clinical data and lung function measurements were collected at the time of screening. Results: 167 IPF patients were referred for lung transplantation. After evaluation for contraindications and screening, 90 patients were listed for lung transplantation. During the waiting list period 33.3% of IPF patients (n=30) died compared to 13.8% in Cystic Fibrosis (CF) (p = 0.0018) and 16.3% in Chronic Obstructive Pulmonary Disease (COPD) (p = 0.003). Analysis of lung function showed a mean FVC%-predicted of 51.1% (SD 19.0) and mean DLco%-predicted of 27.1% (SD 9.4) at time of screening. Five patients were taken off the list due to new comorbidities and deterioration of physical condition, 51 were transplanted and 4 IPF patients were still on the waiting list. Conclusions: This study revealed a significantly higher waiting list mortality for IPF compared to COPD and CF. DLco%-predicted at time of screening was considerably lower than international guidelines for lung transplantation. This indicates that timing of referral of IPF for lung transplantation can be improved.
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We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT).We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group).The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group.EVL-CT may predict the outcome of the early phase after lung transplantation.
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Idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (INSIP) are two related diseases involving varying degrees of pulmonary fibrosis with no effective cure. Bone morphogenetic protein 3 (BMP3) is a member of the transforming growth factor-β (TGF-β) super-family, which has not been implicated in pulmonary fibrosis previously. In this study, we aimed to investigate the potential role of BMP3 playing in pulmonary fibrosis from clinical diagnosis to molecular signaling regulation. RNA sequencing was performed to explore the potential biomarker of IIP patients. The expression of BMP3 was evaluated in 83 cases of IPF and INSIP by immunohistochemistry. The function of BMP3 was investigated in both fibroblast cells and a bleomycin-induced murine pulmonary fibrosis model. The clinical relevance of BMP3 expression were analyzed in 47 IIP patients, which were included in 83 cases and possess more than five-year follow-up data. Both RNA-sequencing and immunohistochemistry staining revealed that BMP3 was significantly down-regulated in lung tissues of patients with IPF and INSIP. Consistently, lower expression of BMP3 also was found in pulmonary fibrotic tissues of bleomycin-induced mice model. Up-regulation of BMP3 prevented pulmonary fibrosis processing through inhibiting cellular proliferation of fibroblasts as well as TGF-β1 signal transduction. Finally, the relatively higher expression of BMP3 in IPF patients was associated with less/worse mortality. Intravenous injection of recombinant BMP3. Taken together, our results suggested that the low expression level of BMP3 may indicate the unfavorable prognosis of IPF patients, targeting BMP3 may represent a novel potential therapeutic method for pulmonary fibrosis management.
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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that results in progressive respiratory failure and death. Antifibrotic therapy has been shown to slow disease progression [1, 2]. For many patients [3], lung transplantation is the only intervention recognised to provide significant survival benefit [4]. IPF commonly affects older patients, with a median age at diagnosis of 66 years old [5]. Without transplantation, the median survival from diagnosis is 2–4 years [5]. However, registry data indicates impaired outcomes following lung transplantation for older patients 6]. These data have prompted many centres in Europe to avoid offering transplantation to older IPF patients. This study demonstrates a clinically meaningful survival benefit of lung transplantation for IPF patients aged ≥65 years
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