Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation.

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Recipient Age Impacts Long-Term Survival in Adult Subjects with Cystic Fibrosis after Lung Transplantation.

Lung transplant is an effective treatment option providing survival benefit in patients with cystic fibrosis (CF). Several studies have suggested survival benefit in adults compared with pediatric patients with CF undergoing lung transplant. However, it remains unclear whether this age-related disparity persists in adult subjects with CF.

Using Bronchoscopic Lung Cryobiopsy and a Genomic Classifier in the Multidisciplinary Diagnosis of Diffuse Interstitial Lung Diseases.

Background: Challenges remain for establishing a specific diagnosis in cases of interstitial lung disease (ILD). Bronchoscopic lung cryobiopsy (BLC) has impacted the diagnostic impression and confidence of multidisciplinary discussions (MDDs) in the evaluation of ILD. Reports indicate that a genomic classifier (GC) can distinguish usual interstitial pneumonia (UIP) from non-UIP.

National Heart, Lung, and Blood Institute and American Association for Thoracic Surgery Workshop Report: Identifying collaborative clinical research priorities in lung transplantation.

This report summarizes the discussion and recommendations from the June 2017 NHLBI-AATS Workshop on Identifying Collaborative Clinical Research Priorities in Lung Transplantation.

Lung transplantation: indications and contraindications.

The selection of appropriate recipients for lung transplantation is an evolving discipline. As experience with the procedure has developed over the last decades, the identification of transplant candidates has also changed as transplant centers strive to safely provide the therapy to as many patients possible. The International Society for Heart and Lung Transplantation (ISHLT) has developed three editions of recipient selection guidelines.

Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study.

Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA.

Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.

Rationale: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted.

Effect of Transplant Center Volume on Cost and Readmissions in Medicare Lung Transplant Recipients.

Rationale: Although lung transplant recipient survival is better at higher volume centers, the effect of center volume on admission cost and early hospital readmission is unknown.

Objectives: To understand the association between transplant center volume and recipient risk-adjusted transplant admission cost, in-hospital mortality, and early hospital readmission in lung transplant recipients.

Methods: Medicare lung transplant recipients from May 4, 2005 to December 31, 2011 were identified through linkage of transplant registry and Medicare administrative claims.

Addressing inherited predisposition for breast cancer in transplant recipients.

Consideration of prophylactic mastectomy surgery following transplantation requires complex medical decision-making, and bias against elective surgery exists because of concern for post-operative complications. Prevention of cancer in transplant recipients is of utmost importance, given the risks of treating malignancy in an immunosuppressed patient. We present a patient case and review of the literature to support a thorough pre-transplantation evaluation of family history and consideration of prophylactic interventions to safeguard the quality of life of transplant recipients.

Noninvasive monitoring of infection and rejection after lung transplantation.

The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.

Heart-lung vs. double-lung transplantation for idiopathic pulmonary arterial hypertension.

Patients with idiopathic pulmonary arterial hypertension (IPAH) have improved survival after heart-lung transplantation (HLT) and double-lung transplantation (DLT). However, the optimal procedure for patients with IPAH undergoing transplantation remains unclear. We hypothesized that critically ill IPAH patients, defined by admission to the intensive care units (ICU), would demonstrate improved survival with HLT vs.

Increased resource use in lung transplant admissions in the lung allocation score era.

Rationale: In 2005, the lung allocation score (LAS) was implemented to prioritize organ allocation to minimize waiting-list mortality and maximize 1-year survival. It resulted in transplantation of older and sicker patients without changing 1-year survival. Its effect on resource use is unknown.

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.

The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation.

Temporal response of the human virome to immunosuppression and antiviral therapy.

There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with posttransplant therapies that combine immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients) and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma.

Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation.

Introduction: Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability.

Variation in PTX3 is associated with primary graft dysfunction after lung transplantation.

Rationale: Elevated long pentraxin-3 (PTX3) levels are associated with the development of primary graft dysfunction (PGD) after lung transplantation. Abnormalities in innate immunity, mediated by PTX3 release, may play a role in PGD pathogenesis.

Objectives: Our goal was to test whether variants in the gene encoding PTX3 are risk factors for PGD.

Persistent racial disparities in survival after heart transplantation.

Background: Racial and ethnic disparities are well documented in many areas of health care, but have not been comprehensively evaluated among recipients of heart transplants.

Methods And Results: We performed a retrospective cohort study of 39075 adult primary heart transplant recipients from 1987 to 2009 using national data from the United Network of Organ Sharing and compared mortality for nonwhite and white patients using the Cox proportional hazards model. During the study period, 8082 nonwhite and 30 993 white patients underwent heart transplantation.

Racial disparities in survival after lung transplantation.

Context: Racial disparities have not been comprehensively evaluated among recipients of lung transplantation.

Objectives: To describe the association between race and lung transplant survival and to determine whether racial disparities have changed in the modern (2001-2009) compared with the historical (1987-2000) transplant eras.

Design, Setting, And Patients: A retrospective cohort study of 16 875 adults who received primary lung transplants from October 16, 1987, to February 19, 2009, was conducted using data from the United Network of Organ Sharing.