Frailty and clinical benefits with lung transplantation.

BACKGROUND: The Fried frailty phenotype is associated with morbidity and mortality in lung transplant (LTx) candidates, but its clinical application and association with post-transplant outcomes are not well defined. We assessed 2 alternate frailty indices in LTx candidates and evaluated associations of frailty with early post-transplant outcomes and 1-year mortality. METHODS: Frailty was prospectively evaluated in 50 LTx candidates using the Fried and 2 alternate phenotypic indices, one using variables readily available to clinicians and one using variables from an existing data set. Agreement between indices and associations with related measures were assessed to establish validity. The data set index was then applied retrospectively to 221 LTx patients. Post-transplant outcomes were compared between frail and non-frail patients using t-tests and multivariable regression analysis. RESULTS: Frailty prevalence among the 3 indices was 26% to 30%, and the κ agreement was 0.38 to 0.41. All indices had moderate correlations with London Chest Activity of Daily Living (r = 0.48-0.62) and Short-Physical Performance Battery (r = -0.43 to -0.52). In the retrospective cohort, frail LTx candidates had a worse St. George's Respiratory Questionnaire total score (73 ± 12vs 62 ± 12, p < 0.001). Frail candidates had a larger improvement with transplant in the St. George's Respiratory Questionnaire (-52 ± 19vs -43 ± 18, p = 0.002) and 6-minute walk distance (191 ± 119vs 129 ± 94m, p = 0.001). Frailty was not associated with hospital length of stay or 1-year mortality. CONCLUSIONS: There was good construct validity and acceptable agreement among the frailty indices. Despite significant disability pre-transplant, frail LTx candidates derived significant benefit with transplantation.

Preoperative expectations for health-related quality of life after lung transplant.

How patients' health-related quality of life (HRQL) after lung transplant compares to their preoperative expectations is unclear. As part of a previously published prospective cohort study, we compared 328 subjects' expectations for their post-transplant HQRL with and without chronic lung allograft dysfunction (CLAD) to their actual HRQL scores after transplant, using the visual analog scale (VAS) and standard gamble (SG). Subjects' expectations were considered met when the absolute difference between the expected and actual scores (the "expectation error") was <0.1 units, based on the minimally important difference for VAS and SG. On average, subjects' post-transplant HRQL without CLAD met their expectations (mean expectation error: -0.09 units [VAS] and +0.02 units [SG]) and subjects' post-transplant HRQL with CLAD met or exceeded their expectations (mean expectation error: +0.08 units [VAS] and +0.19 units [SG]). When subjects developed CLAD stages 1 and 2, their HRQL was better than they expected (mean expectation error of each disease group: >+0.1 units). When subjects developed CLAD stage 3, their HRQL was as they expected (mean expectation error of each disease group except COPD and CF: within ± 0.1 units). Patients' expectations for their HRQL after transplant are at least met and may be exceeded.

Evaluation of Skeletal Muscle Function in Lung Transplant Candidates.

BACKGROUND: Lung transplantation (LTx) is offered to older and more complex patients who may be at higher risk of skeletal muscle dysfunction, but the clinical implications of this remain uncertain. The study aims were to characterize deficits in skeletal muscle mass, strength and physical performance, and examine the associations of these deficits with clinical outcomes. METHODS: Fifty LTx candidates (58% men; age, 59 ± 9 years) were prospectively evaluated for skeletal muscle deficits: muscle mass using bioelectrical impedance, quadriceps, respiratory muscle and handgrip strength, and physical performance with the Short Physical Performance Battery. Comparisons between number of muscle deficits (low muscle mass, quadriceps strength and physical performance) and 6-minute walk distance (6MWD), London Chest Activity of Daily Living Questionnaire, and quality of life were assessed using one-way analysis of variance. Associations with pretransplant and posttransplant delisting/mortality, hospital duration, and 3-month posttransplant 6MWD were evaluated using Fisher exact test and Spearman correlation. RESULTS: Deficits in quadriceps strength (n = 27) and physical performance (n = 24) were more common than muscle mass (n = 8). LTx candidates with 2 or 3 muscle deficits (42%) compared with those without any deficits (26%) had worse 6MWD = -109 m (95% confidence interval [CI], -175 to -43), London Chest Activity of Daily Living Questionnaire = 18 (95% CI, 7-30), and St. George's Activity Domain = 12 (95% CI, 2-21). Number of muscle deficits was associated with posttransplant hospital stay (r = 0.34, P = 0.04), but not with delisting/mortality or posttransplant 6MWD. CONCLUSIONS: Deficits in quadriceps muscle strength and physical performance are common in LTx candidates and further research is needed to assess whether modifying muscle function pretransplant can lead to improved clinical outcomes.

Thoracic muscle cross-sectional area is associated with hospital length of stay post lung transplantation: a retrospective cohort study.

Low muscle mass is common in lung transplant (LTx) candidates; however, the clinical implications have not been well described. The study aims were to compare skeletal muscle mass in LTx candidates with controls using thoracic muscle cross-sectional area (CSA) from computed tomography and assess the association with pre- and post-transplant clinical outcomes. This was a retrospective, single-center cohort study of 527 LTx candidates [median age: 55 IQR (42-62) years; 54% male]. Thoracic muscle CSA was compared to an age- and sex-matched control group. Associations between muscle CSA and pre-transplant six-minute walk distance (6MWD), health-related quality of life (HRQL), delisting/mortality, and post-transplant hospital outcomes and one-year mortality were evaluated using multivariable regression analysis. Muscle CSA for LTx candidates was about 10% lower than controls (n = 38). Muscle CSA was associated with pre-transplant 6MWD, but not HRQL, delisting or pre- or post-transplant mortality. Muscle CSA (per 10 cm2 difference) was associated with shorter hospital stay [0.7 median days 95% CI (0.2-1.3)], independent of 6MWD. In conclusion, thoracic muscle CSA is a simple, readily available estimate of skeletal muscle mass predictive of hospital length of stay, but further study is needed to evaluate the relative contribution of muscle mass versus functional deficits in LTx candidates.

Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation.

RATIONALE: The average age of lung transplant recipients is increasing, and the mix of recipient indications for transplantation is changing. OBJECTIVES: To determine whether the health-related quality-of-life (HRQL) benefit of lung transplantation differs by recipient age and diagnosis. METHODS: In this prospective cohort study, we obtained serial HRQL measurements in adults with advanced lung disease who subsequently underwent lung transplantation (2004-2012). HRQL assessments included the St. George's Respiratory Questionnaire, 36-Item Short-Form Health Survey (SF-36), EQ-5D, Standard Gamble, and Visual Analog Scale for current health. We used linear mixed effects models for associations between age or diagnosis and changes in HRQL with transplantation. To address potential survivorship bias, we fitted Markov models to the distribution of discrete post-transplant health states (HRQL better than pretransplant, not better, or dead) and estimated quality-adjusted life-years post-transplant. MEASUREMENTS AND MAIN RESULTS: A total of 430 subjects were listed, 387 were transplanted, and 326 provided both pretransplant and post-transplant data. Transplantation conferred large improvements in all HRQL measures: St. George's change of -47 units (95% confidence interval, -48 to -44), 36-Item Short-Form Health Survey physical component summary score of 17.7 (16.5-18.9), EQ-5D of 0.27 (0.24-0.30), Standard Gamble of 0.48 (0.44-0.51), and Visual Analog of 44 (42-47). Age was not associated with meaningful differences in the HRQL benefits of transplantation. There was less HRQL benefit in interstitial lung disease than in cystic fibrosis. CONCLUSIONS: Lung transplantation confers large HRQL benefits, which vary by recipient diagnosis, but do not differ substantially in older recipients.

Pulmonary rehabilitation in lung transplant candidates.

BACKGROUND: While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. METHODS: This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. RESULTS: The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p < 0.0001); biceps resistance training, 18 lbs. × reps (n = 286; p < 0.0001); and quadriceps resistance training, 15 lbs. × reps (n = 278; p < 0.0001). HRQL measures declined. A greater final 6MWD prior to transplant correlated with a shorter length of stay in the hospital (n = 207; p = 0.003). CONCLUSIONS: Exercise capacity and training volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes.