New Grant to Study Chronic Rejection, the ‘Achilles’ Heel’ of Lung Transplant, in Patients with Cystic Fibrosis

Patients with cystic fibrosis (CF) are living longer and healthier lives; however, for those who receive a lung transplant, chronic rejection of lung transplant is the leading cause of mortality for these patients. Investigators at Cleveland Clinic entered a new phase of CF research following the renewal of a prestigious consortium grant and designation as the sole biorepository site and coordinating center for 15 participating institutions.

The Cystic Fibrosis Lung Transplant Consortium (CFLTC), sponsored by the Cystic Fibrosis Foundation (CFF), was first launched in 2016. The goal was to develop a collaborative research network among institutions with strong CF and lung transplant programs to accelerate investigations into chronic lung allograft dysfunction (CLAD), a common complication following lung transplant that is the leading cause of mortality after lung transplant.

Maryam Valapour, MD, MPP, a lung transplant pulmonologist in Cleveland Clinic’s Respiratory Institute and primary investigator of the consortium grant, explains that “chronic rejection is the Achilles’ heel of lung transplantation.” She notes, “As a field, we’ve made great strides in improving short-term survival after transplant, but long-term survival is much less understood.”

Given the relatively low patient volumes for lung transplant at centers across the U.S., a single institution experience is not powered to address the complex issues of long-term outcomes for these patients. Recently, a movement within the field acknowledged that a broader, multi-institutional network is necessary to design statistically significant studies.

Collaboration with internal and external CF partners

Four years ago, Cleveland Clinic was one of 10 institutions that received an initial grant from the CFLTC. This grant funded programs well-positioned to investigate and improve outcomes in CF patients, with a primary focus on issues of access to transplant and improving survival after transplant. Four years later, this goal is still central to the aims of the CFLTC. In the 2020 award cycle, 15 institutions received new research awards, offering access and funding to a network of collaborators.

The maturation of these programs since the first award cycle has prompted a new direction for CF lung transplant research. As biorepository efforts grew at the local level, so too did the need to centralize and coordinate data at the multi-institutional level. After a competitive grant review process, Cleveland Clinic was chosen as the biorepository coordinating site for the consortium. The award will enable the team of investigators to build a prospective, longitudinal dataset and biorepository to study CF lung transplant recipients.

Cleveland Clinic will provide oversight of an administrative, biospecimen and data management cores to better understand the pathogenesis of CLAD and develop new therapies to improve outcomes for CF and lung transplant patients.

Dr. Valapour, who is also the senior staff for lung transplantation for the United States Scientific Registry of Transplant Recipients, partnered with scientists at the Cleveland Clinic Lerner Research Institute, Suzy Comhair, PhD, Associate Staff and Director of the Human Biorepository Core and Gerry Beck, PhD, Quantitative Health Sciences, to lead this ambitious initiative.

“This collaboration reinforces that every clinical or scientific problem has multiple components to it, and the only way we can study it – and solve it – is to examine it from different contexts,” says Dr. Valapour. “This cannot be done through one lens.”

Making an impact on care

With an average post-transplant life expectancy of 6.7 years, lung transplant patients tend to have a shorter survival time compared to patients who receive other types of organ transplant. Dr. Valapour notes, “At the end of the day, transplants should have a significant impact on long-term survival. This is true on an individual level and also on a broader, societal level.”

“There is increasing interest in harnessing collaboration and developing large-scale mechanisms for centers to come together and conduct studies to better understand mortality in these patients,” says Dr. Valapour. “We are honored to be recognized as a leader in this way, and we are hopeful about the future of this research to improve the survival of lung transplant patients.”