Subphenotypes of frailty in lung transplant candidates.

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.

Mobile health technology to improve emergent frailty after lung transplantation.

We evaluated the feasibility, safety, and efficacy of a mHealth-supported physical rehabilitation intervention to treat frailty in a pilot study of 18 lung transplant recipients. Frail recipients were defined by a short physical performance battery (SPPB score ≤7). The primary intervention modality was Aidcube, a customizable rehabilitation mHealth platform. Our primary aims included tolerability, feasibility, and acceptability of use of the platform, and secondary outcomes were changes in SPPB and in scores of physical activity, and disability measured using the Duke Activity Status Index (DASI) and Lung Transplant-Value Life Activities (LT-VLA). Notably, no adverse events were reported. Subjects reported the app was easy to use, usability improved over time, and the app enhanced motivation to engage in rehabilitation. Comments highlighted the complexities of immediate post-transplant rehabilitation, including functional decline, pain, tremor, and fatigue. At the end of the intervention, SPPB scores improved a median of 5 points from a baseline of 4. Physical activity and patient-reported disability also improved. The DASI improved from 4.5 to 19.8 and LT-VLA score improved from 2 to 0.59 at closeout. Overall, utilization of a mHealth rehabilitation platform was safe and well received. Remote rehabilitation was associated with improvements in frailty, physical activity and disability. Future studies should evaluate mHealth treatment modalities in larger-scale randomized trials of lung transplant recipients.

Discharge frailty following lung transplantation.

INTRODUCTION: Frailty at listing for lung transplant has been associated with waitlist and post-transplant mortality. Frailty trajectories following transplant, however, have been less well characterized, including whether recipient frailty improves. The objective of this study was to identify prevalence and risk factors for frailty at discharge and to evaluate changes in frail recipients enrolled in an outpatient physical therapy program. METHODS: This was a single-center prospective cohort study of lung transplant recipients. Enrollees completed a short physical performance battery (SPPB) to assess frailty at listing and at initial hospital discharge. RESULTS: Of the 111 enrolled recipients, none were frail at listing and 18 (16.2%) were prefrail. At discharge, however, 60 (54.1%) patients were frail. Discharge frailty was associated with prefrailty at listing, acute kidney injury post-transplant, and longer intensive care unit stay. Among the 35 patients who were frail at discharge and who were enrolled in an outpatient PT program, the median improvement in SPPB was 6 points (IQR = 5-7 points), and 85.7% became not frail over a median of 6 weeks. CONCLUSION: Discharge frailty is common following lung transplantation. In most frail patients, an intensive outpatient physical therapy program is associated with improvement in frailty, as assessed by the SPPB.

Rehabilitation Characteristics and Outcomes for Lung Transplantation for COVID-19: A Case Series.

OBJECTIVE: Severe coronavirus disease 2019 (COVID-19) can result in irreversible lung damage, with some individuals requiring lung transplantation. The purpose of this case series is to describe the initial experience with the rehabilitation and functional outcomes of 9 patients receiving a lung transplant for COVID-19. METHODS: Nine individuals, ranging in age from 37 to 68 years, received bilateral orthotopic lung transplantation (BOLT) for COVID-19 between December 2020 and July 2021. Rehabilitation was provided before and after the transplant, including in-hospital rehabilitation, postacute care inpatient rehabilitation, and outpatient rehabilitation. RESULTS: Progress with mobility was limited in the pretransplant phase despite rehabilitation efforts. Following transplantation, 2 individuals expired before resuming rehabilitation, and 2 others had complications that delayed their progress. The remaining 5 experienced clinically important improvements in mobility and walking capacities. CONCLUSION: Considerable rehabilitation resources are required to care for individuals both before and after BOLT for COVID-19. Rehabilitation can have a profound impact on both functional and clinical outcomes for this unique patient population. IMPACT: There is limited literature on the rehabilitation efforts and outcomes for patients who received BOLT for COVID-19. Occupational therapists and physical therapists play an important role during the pretransplant and posttransplant recovery process for this novel patient population. LAY SUMMARY: Patients with a bilateral orthotopic lung transplant due to COVID-19 require a unique rehabilitation process. They have significant difficulties with activities of daily living and functional mobility across the pretransplant and posttransplant continuum of care, but progressive gains in functional performance may be possible with a comprehensive multidisciplinary rehabilitation program.

Development of the Lung Transplant Frailty Scale (LT-FS).

BACKGROUND: Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty scale for lung transplantation with improved performance characteristics. METHODS: We measured the short physical performance battery (SPPB), fried frailty phenotype (FFP), Body Composition, and serum Biomarkers representative of putative frailty mechanisms. We applied a 4-step established approach (identify frailty domain variable bivariate associations with the outcome of waitlist delisting or death; build models sequentially incorporating variables from each frailty domain cluster; retain variables that improved model performance ability by c-statistic or AIC) to develop 3 candidate "Lung Transplant Frailty Scale (LT-FS)" measures: 1 incorporating readily available clinical data; 1 adding muscle mass, and 1 adding muscle mass and research-grade Biomarkers. We compared construct and predictive validity of LT-FS models to the SPPB and FFP by ANOVA, ANCOVA, and Cox proportional-hazard modeling. RESULTS: In 342 lung transplant candidates, LT-FS models exhibited superior construct and predictive validity compared to the SPPB and FFP. The addition of muscle mass and Biomarkers improved model performance. Frailty by all measures was associated with waitlist disability, poorer HRQL, and waitlist delisting/death. LT-FS models exhibited stronger associations with waitlist delisting/death than SPPB or FFP (C-statistic range: 0.73-0.78 vs. 0.57 and 0.55 for SPPB and FFP, respectively). Compared to SPPB and FFP, LT-FS models were generally more strongly associated with delisting/death and improved delisting/death net reclassification, with greater improvements with increasing LT-FS model complexity (range: 0.11-0.34). For example, LT-FS-Body Composition hazard ratio for delisting/death: 6.0 (95%CI: 2.5, 14.2), SPPB HR: 2.5 (95%CI: 1.1, 5.8), FFP HR: 4.3 (95%CI: 1.8, 10.1). Pre-transplant LT-FS frailty, but not SPPB or FFP, was associated with mortality after transplant. CONCLUSIONS: The LT-FS is a disease-specific physical frailty measure with face and construct validity that has superior predictive validity over established measures.

Causes, Preventability, and Cost of Unplanned Rehospitalizations Within 30 Days of Discharge After Lung Transplantation.

BACKGROUND: Unplanned rehospitalizations (UR) within 30 days of discharge are common after lung transplantation. It is unknown whether UR represents preventable gaps in care or necessary interventions for complex patients. The objective of this study was to assess the incidence, causes, risk factors, and preventability of UR after initial discharge after lung transplantation. METHODS: This was a single-center prospective cohort study. Subjects completed a modified short physical performance battery to assess frailty at listing and at initial hospital discharge after transplantation and the State-Trait Anxiety Inventory at discharge. For each UR, a study staff member and the patient's admitting or attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely preventable) to rate readmission preventability. A total sum score of 2 or higher defined a preventable UR. RESULTS: Of the 90 enrolled patients, 30 (33.3%) had an UR. The single most common reasons were infection (7 [23.3%]) and atrial tachyarrhythmia (5 [16.7%]). Among the 30 URs, 9 (30.0%) were deemed preventable. Unplanned rehospitalization that happened before day 30 were more likely to be considered preventable than those between days 30 and 90 (30.0% versus 6.2%, P = 0.04). Discharge frailty, defined as short physical performance battery less than 6, was the only variable associated with UR on multivariable analysis (odds ratio, 3.4; 95% confidence interval, 1.1-11.8; P = 0.04). CONCLUSIONS: Although clinicians do not rate the majority of UR after lung transplant as preventable, discharge frailty is associated with UR. Further research should identify whether modification of discharge frailty can reduce UR.

Implementation of an Early Mobility Pathway in Neurointensive Care Unit Patients With External Ventricular Devices.

BACKGROUND: Patients with an external ventricular drain (EVD) may not be readily mobilized because of concerns of catheter dislodgment and/or inappropriate cerebrospinal fluid drainage. Delayed mobilization may result in longer hospital stays and an increased risk for complications related to immobility. We aimed to determine the safety, feasibility, and outcome of an EVD mobilization protocol in patients with subarachnoid hemorrhage (SAH). METHODS: A multidisciplinary group developed a formal algorithm for the mobilization of patients with SAH with EVDs. Outcome measures included intensive care unit (ICU) length of stay (LOS), day to first mobilization, and discharge disposition. Patients were prospectively enrolled during a 12-month period and compared with a historical control group of patients with SAH for the preceding 12-month period. RESULTS: Thirty-nine of 45 (86.7%) patients were women. Mean age did not differ significantly between the preintervention (n = 19) and postintervention (n = 26) groups (59.6 vs 55.7). Number of EVD device days did not differ significantly between groups (16.3 vs 15, P = .422]. Of 101 attempted postintervention mobilization sessions, six were aborted for increased lethargy (1), pain (1), elevated intracranial pressure (1), drain malfunction (1), and hypotension (2). Twenty-four sessions were attempted but never initiated because of worsening neurologic examination (10), pulmonary instability (2), hemodynamic instability (2), medical instability (3), and provider request (1). No patient experienced catheter dislodgment. Mean ICU LOS was not different between groups (20.7 vs 18.2, P = .262). The day of first mobilization was significantly earlier in the postintervention group (18.7 vs 6.5, P < .0001). The percentage of patients discharged home or to acute rehabilitation was higher in the postintervention group (63.2% vs 88.5%, P = .018], when accounting for Hunt and Hess grade. CONCLUSIONS: The mobilization of patients with EVDs is safe and feasible; it may be associated with earlier mobilization, reduced ICU LOS, and better discharge disposition. No major complications were attributable to early mobilization.