Treating Frailty in Lung Transplant Candidates (PREHAB)

Lung transplantation aims to extend survival, reduce disability, and improve health-related quality of life for persons suffering from advanced lung diseases. Despite rigorous candidacy screening practices, improvements in surgical and medical management, and iterative advancements in organ allocation policies, nearly 20% of adults awaiting lung transplantation die or are removed from the waiting list due to disease progression prior to receiving a suitable donor offer1. After lung transplantation, nearly the same proportion of patients dies within the first post-operative year2. Notably, serious morbidity after transplantation is increasing, with resultant disability and associated decrements in health-related quality of life3,4. Although known risk factors for death are already incorporated into lung allocation in the United States (Lung Allocation Score [LAS]), persistently high mortality and increasing morbidity underscore the need to identify novel risk factors for poor outcomes in order to maximize the individual and societal benefit of lung transplantation5.

Frailty- measured by simple, non-invasive clinic based instruments- is an independent risk factor for disability, perioperative complications, and mortality in older medical6-9 and surgical populations10-13. Conceptualized first in the field of geriatrics, frailty is defined as a generalized vulnerability to stressors resulting from an accumulation of physiologic deficits across multiple interrelated systems14. These deficits, in turn, deplete the body's physiologic reserves, resulting in a "state-of-risk" for disproportionate declines in health status following exposure to an additional stressor such as major surgery. Drawing from the geriatrics experience, frailty has become recognized more recently as a risk factor for poor outcomes in solid organ transplantation. Specifically, frailty has been found to be associated with delayed graft function and mortality in kidney transplant recipients and waitlist mortality in liver transplant candidates15-17.

The evaluation of geriatric derived measures is particularly important in contemporary lung transplantation. Indeed, older patients are the fastest growing group of lung transplant candidates in the U.S18. Compared to 8% in 2004, patients aged 65 now account for 30% of annual new recipients, outnumbering those aged 50; those aged 60 account for over half of all new transplants19. This rapid trend has outpaced the evidence base, risk stratification tools, and society guidelines needed to identify which older candidates will do well after lung transplantation. Absent better information, transplant programs have resorted to either ad hoc and admittedly arbitrary chronological age cutoffs or "eyeball tests" of fitness for transplant.

The investigators recently identified frailty as prevalent in lung transplant candidates and independently associated with delisting or death on the waitlist18. Very recently, studies in other populations suggest frailty may be reversible through targeted exercise and nutrition programs. While pulmonary rehabilitation programs may achieve similar goals, a substantial proportion of patients cannot access these programs due to geography or insurance limitations. The investigator's overarching hypothesis is that treating frailty with a home-based intervention before transplant may 1) reduce the risk of death or delisting for becoming too debilitated before transplant and 2) may reduce complications, disability, and possibly mortality after lung transplantation. This proposal seeks to generate critical pilot data needed to inform a larger intervention to treat frailty in lung transplant candidates.

Inclusion criteria

• Adult lung transplant candidates in the UCSF Lung Transplant Program aged >=50
• Ability to understand and speak English or lives with a family member who has the ability to understand and speak English.
• A diagnosis of chronic obstructive pulmonary disease (COPD) or pulmonary fibrosis (PF).
• A supplemental oxygen requirement with exercise that can be delivered safely at home using their home oxygen concentrator (as determined by clinically available six-minute walk distance test)
• Waitilisted or soon to be waitlisted for lung transplantation at UCSF
• Short Physical Performance Battery (SPBB) frailty score of 9 or less (range 0 - 12; lower scores = worse frailty).
• Must be an outpatient.
• Willing and able to come to UCSF Parnassus Campus for 1 day in-person training program.

Exclusion criteria

• Inability to speak or understand English or does not live with a family member who has the abilty to understand and speak English.
• Subject does not possess home oxygen equipment (if supplemental oxygen is required for exercise)
• Already or soon to be enrolled in a traditional hospital based pulmonary rehabilitation program
• Lives alone.
• A diagnosis of primary or secondary pulmonary hypertension. Diagnosis will be determined by clinically available right heart catheterization pulmonary arterial mean pressure >= 30 mm Hg or transthoracic echocardiogram pulmonary arterial systolic pressure > 50 mm Hg or report of moderate right ventricular dysfunction or worse. These tests are performed as part of routine clinical care in the lung transplant program. Echocardiograms are repeated every 6 months while patients are listed for transplantation.