We obtained the articles for this Review by searching PubMed for articles published from Jan 1, 1986, to Jan 25, 2019, using the individual search terms “IPF”, “idiopathic pulmonary fibrosis”, “lung transplantation”, “antifibrotic”, “pirfenidone”, “nintedanib”, “transplant listing”, “PPFE”, “telomeropathy”, “lung allocation score”, “ECMO”, “extra-corporeal life support”, “single lung transplant”, “bilateral lung transplant”, and “ex vivo lung perfusion”; we also searched the term “IPF” in
ReviewLung transplantation for idiopathic pulmonary fibrosis
Introduction
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring lung disease of unknown cause. It has a poor prognosis with a median survival of 3·8 years (95% CI 3·5–3·8) from time of diagnosis in adults aged 65 years or older.1 IPF is characterised by a usual interstitial pneumonia pattern on high-resolution CT scanning, as defined by basal predominant reticulation, traction bronchiectasis and honeycombing. Histologically, these features are represented by heterogenous paraseptal fibrosis, architectural distortion, and fibroblastic foci.2
The antifibrotic drugs pirfenidone3 and nintedanib4 slow the rate of lung function decline, but despite treatment, the usual course of the condition is for patients to progress inexorably to end-stage respiratory failure, secondary pulmonary hypertension, and death. Comorbidities including cardiac disease and gastro-oesophageal reflux contribute to the disease burden, and acute exacerbations accelerate decline towards death. When medical options have been exhausted, the only treatment with the potential to improve quality of life and survival is lung transplantation.
In this Review, we consider the indications and specific challenges associated with lung transplantation in IPF. We discuss modifiable patient factors and perioperative management strategies that can be used to optimise outcomes. We address the discordance between transplantation referral criteria for IPF and the realities of organ availability, and describe novel technological approaches to support patients until organs become available. Finally, accurately predicting IPF disease course remains a challenge; therefore, we consider methods of ensuring that the most suitable patients with IPF are referred for lung transplantation at the most appropriate time.
Section snippets
When to consider referral for transplantation
The poor prognosis and the potential for accelerated decline in IPF mean that early referral is recommended.5 Robust survival data for IPF in the era of antifibrotic therapy are awaited, given the low mortality in clinical trials. Although pooled analyses of clinical trials have demonstrated a beneficial effect of pirfenidone6 and nintedanib7 on mortality, clinical trials exclude patients with comorbidities and advanced disease—ie, the patient group with the highest mortality. Real-world
Pulmonary hypertension
Perhaps the most important comorbidity is pulmonary hypertension, evident in up to 85% of patients with IPF on the US transplant waiting list,20 and underestimated by transthoracic echocardiography,21 leaving right heart catheterisation as the only accurate diagnostic method (figure 1). No proven benefits have been reported for interventions to treat pulmonary hypertension in the preoperative period, but accurate assessment of mean pulmonary artery pressure and right ventricular function is
Current indications and timing
Patients listed for lung transplantation are generally accepted as being those for whom no other treatment option is available, who have a greater than 50% chance of death within 2 years without transplantation, and a projected postoperative survival of at least 5 years. The ISHLT provides recommendations for transplant listing of appropriate patients with interstitial lung disease (panel 2).5
Palliative care for patients with IPF awaiting lung transplantation
Early palliative care referral is recommended as an adjunct to disease-focused care in IPF.51 The UK
Organ allocation
The first successful isolated lung transplantation, performed in 1983, was for pulmonary fibrosis.69 Since then, limited donor organ availability, uptake of less than 30% of organs offered for transplant, and a broadening of the indications for lung transplantation have resulted in demand exceeding supply and contributed to mortality on the waiting list. Historically, patients with IPF have had higher waiting list mortality than patients with other common indications for transplantation, with
Single versus bilateral lung transplant
The surgical procedures used for lung transplantation are SLT, BSSLT (figure 3), bilateral lobar transplantation, and heart-lung transplantation. Little evidence exists regarding the merits of SLT versus BSSLT in IPF, but in most cases, BSSLT is done, and the percentage of bilateral transplants is increasing.77 According to reports from the ISHLT database, 39% of patients with IPF receive an SLT and 61% receive a BSSLT.77
Across all lung transplantation indications, the advantages of BSSLT are
Future directions
IPF remains an unpredictable disease of unknown cause. In coming years, a more sophisticated understanding of the interaction between host genetics and environmental influences should allow a more nuanced definition of IPF disease endotypes. Not all patients with IPF appear to progress at the same rate and treatment responses vary between individuals. Integrating novel molecular biomarkers with radiological modelling95 and deep learning algorithms96 could allow physicians to better identify
Search strategy and selection criteria
References (97)
- et al.
Idiopathic pulmonary fibrosis in US Medicare beneficiaries aged 65 years and older: incidence, prevalence, and survival, 2001–11
Lancet Respir Med
(2014) - et al.
A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation
J Heart Lung Transplant
(2015) - et al.
Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis
Lancet Respir Med
(2017) - et al.
Nintedanib in patients with idiopathic pulmonary fibrosis: combined evidence from the TOMORROW and INPULSIS trials
Respir Med
(2016) - et al.
Risk factors for acute exacerbation of idiopathic pulmonary fibrosis—extended analysis of pirfenidone trial in Japan
Respir Investig
(2015) A survey of clinical practice of lung transplantation in North America
Chest
(2004)- et al.
The registry of the International Society for Heart and Lung Transplantation: thirtieth adult lung and heart-lung transplant report—2013; focus theme: age
J Heart Lung Transplant
(2013) - et al.
Is there an age limit to lung transplantation?
Ann Thorac Surg
(2015) - et al.
Prevalence and outcomes of pulmonary arterial hypertension in advanced idiopathic pulmonary fibrosis
Chest
(2006) - et al.
Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis
J Heart Lung Transplant
(2005)
Effect of pulmonary hypertension on survival in patients with idiopathic pulmonary fibrosis after lung transplantation: an analysis of the United Network of Organ Sharing registry
J Heart Lung Transplant
Coronary revascularization in lung transplant recipients with concomitant coronary artery disease
Am J Transplant
How important is coronary artery disease when considering lung transplant candidates?
J Heart Lung Transplant
Antacid therapy and disease outcomes in idiopathic pulmonary fibrosis: a pooled analysis
Lancet Respir Med
Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial
Lancet Respir Med
Fundoplication after lung transplantation prevents the allograft dysfunction associated with reflux
Ann Thorac Surg
J Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease
Ann Thorac Surg
Lung cancer in patients with idiopathic pulmonary fibrosis: clinical characteristics and impact on survival
Respir Med
Lung cancer in idiopathic pulmonary fibrosis patients diagnosed during or after lung transplantation
Respir Med Case Rep
Functional associations of pleuroparenchymal fibroelastosis and emphysema with hypersensitivity pneumonitis
Respir Med
Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post-lung transplantation survival
J Heart Lung Transplant
Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial
Lancet Respir Med
Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy
J Heart Lung Transplant
Pirfenidone in restrictive allograft syndrome after lung transplantation: a case series
Am J Transplant
Palliative care in interstitial lung disease: living well
Lancet Respir Med
Body mass index and mortality in patients with idiopathic pulmonary fibrosis
Chest
Idiopathic pulmonary fibrosis: effects and optimal management of comorbidities
Lancet Respir Med
Palliative care and location of death in decedents with idiopathic pulmonary fibrosis
Chest
Pulmonary rehabilitation improves long-term outcomes in interstitial lung disease: a prospective cohort study
Respir Med
Lung transplantation in the United States, 1999–2008
Am J Transplant
Lung allocation score predicts survival in lung transplantation patients with pulmonary fibrosis
Ann Thorac Surg
Survival benefit of lung transplantation for patients with idiopathic pulmonary fibrosis
J Thorac Cardiovasc Surg
Extracorporeal life support as a bridge to lung transplantation
Clin Chest Med
Awake extracorporeal membrane oxygenation as bridge to lung transplantation: a 9-year experience
Ann Thorac Surg
Improved results treating lung allograft failure with venovenous extracorporeal membrane oxygenation
Ann Thorac Surg
Single- versus double-lung transplantation in pulmonary fibrosis: impact of age and pulmonary hypertension
Ann Thorac Surg
what is the optimal transplant for older patients with idiopathic pulmonary fibrosis?
Ann Thorac Surg
Survival after single versus bilateral lung transplantation for high-risk patients with pulmonary fibrosis
Ann Thorac Surg
Staging of bilateral lung transplantation for high-risk patients with interstitial lung disease: one lung at a time
Am J Transplant
A review of lung transplant donor acceptability criteria
J Heart Lung Transplant
A decade of living lobar lung transplantation: perioperative complications after 253 donor lobectomies
Am J Transplant
Deep learning for classifying fibrotic lung disease on high-resolution computed tomography: a case-cohort study
Lancet Respir Med
Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline
Am J Respir Crit Care Med
A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis
N Engl J Med
Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis
N Engl J Med
Predicting life Expectancy for pirfenidone in idiopathic pulmonary fibrosis
J Manag Care Spec Pharm
Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry
Eur Respir J
Prognostic implications of physiologic and radiographic changes in idiopathic interstitial pneumonia
Am J Respir Crit Care Med
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