The Supportive Care Needs of Primary Caregivers of Lung Transplant Candidates.

CONTEXT: Caring for people with advanced illness has an impact on caregivers' physical, psychological, and emotional health. Patients being evaluated for lung transplantation or those on the transplant waitlist are required to have identified social support. However, little is known about the caregivers' specific supportive care needs. OBJECTIVE: The aim of this study was to determine the supportive care needs of informal caregivers of patients who are being evaluated for or awaiting lung transplantation. METHODS: A cross sectional survey of the caregivers of lung transplant candidates using the Carers' Support Needs Assessment Tool (CSNAT) was conducted. RESULTS: The sample (n = 78) included caregivers from a single-center academic institution in the United States. Participants were predominantly Caucasian and female, mean age 58 years (SD:13). Most were the patient's spouse or partner and over half reported needs in the following areas: what to expect in the future; who to call with healthcare concerns; financial, legal and work issues; and caregivers' feelings and worries. When asked if they need more support in these areas, up to one-third indicated they needed "quite a bit more" or "very much more," with substantial needs regarding what to expect in the future, who to call with healthcare concerns, and financial, legal, or work issues. CONCLUSION: A substantial portion of lung transplant caregivers express need for more support. Future research should focus on testing strategies to promote regular assessment of these needs and examining the effectiveness of interdisciplinary interventions to address them.

The palliative care needs of lung transplant candidates.

BACKGROUND: Little is known about the palliative care needs of patients awaiting lung transplantation. The aim of this study was to describe these needs in patients undergoing evaluation for or awaiting lung transplantation. METHODS: Cross-sectional survey using an adapted version of the Needs at the End-of-life Screening Tool (NEST-13) at a US-based transplant program. RESULTS: Among the 111 participants, 83.5% were White, 60.0% were female, and almost three-quarters had either restrictive or obstructive lung disease. The greatest palliative care needs included difficulty being physically active (mean: 7.9/10; SD: 2.6; median: 9.0), physical symptoms (mean: 7.4/10; SD: 2.6; median: 8.0), missing work due to illness (mean: 6.2/10; SD: 4.0; median: 8.0), and concerns that life might end (mean: 5.1/10; SD: 3.6; median: 5.0). Participants reported that religious/spiritual beliefs contribute to their sense of purpose (mean: 4.1/10; SD: 3.9) but had few unmet needs in this area (mean: 0.9/10; median: 0.0). Only 6.4% reported seeing a palliative care specialist, and 48.2% were unsure what a palliative care specialist is. CONCLUSION: There are substantial palliative care needs among lung transplant candidates, particularly physical symptoms and end-of-life concerns. These findings support integrating palliative care and end-of-life discussions in the management of lung transplant candidates.

An Integrative Review of the Role of Palliative Care in Lung Transplantation.

BACKGROUND: Lung transplant patients experience significant physical symptoms and psychological stress that affect their quality of life. Palliative care is an interdisciplinary specialty associated with improved symptom management and enhanced quality of life. Little, however, is known about the palliative care needs of lung transplant patients and the role it plays in their care. AIM: The aim of this integrative review was to synthesize the literature describing the palliative care needs, the current role, and factors influencing the integration of palliative care in the care of lung transplant patients. DESIGN/DATA SOURCES: We searched PubMed, Scopus, CINAHL, and Embase to identify English-language, primary studies focused on palliative care in adult lung transplantation. Study quality was evaluated using Strengthening the Report of Observational studies in Epidemiology and Consolidated Criteria for Reporting Qualitative Research criteria. RESULTS: Seven articles were included in the review. Most were single-center, descriptive studies. Two studies used qualitative and 5 used quantitative methodologies. Collectively, these studies suggest that palliative care is typically consulted for physical and psychological symptom management, although consultation is uncommon and often occurs late in the lung transplant process. We found no studies that systematically assessed palliative needs. Misperceptions about palliative care, communication challenges, and unrealistic patient/family expectations are identified barriers to the integration. While limited, evidence suggests that palliative care can be successfully integrated into lung transplant patient management. CONCLUSIONS: Empirical literature about palliative care in lung transplantation is sparse. Further research is needed to define the needs and opportunities for integration into the care of these patients.

Frailty phenotypes and mortality after lung transplantation: A prospective cohort study.

Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score-adjusted Cox models. We calculated postestimation marginalized standardized risks for 1-year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1- and 4-year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6-36.0 and aHR 3.8; 95%CI: 1.8-8.0, respectively). Each 1-point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08-1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%-21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1-13.2) but not over longer follow-up. Preoperative frailty is associated with an increased risk of death after lung transplantation.

Missing Domains of Lung Transplant Patient Selection.

The goal of consistent, predictable, and improved outcomes has continued to elude the scientific community in the 30 years since lung transplantation became the procedure of choice for patients with terminal, nonmalignant lung disease. BACKGROUND: Although there is consensus regarding disease-specific indications for lung transplant, ambiguity remains regarding how patient-specific attributes should influence lung transplant candidacy. This study had 3 aims (1) to establish the missing domains of the interdisciplinary assessment of the lung transplant candidate, (2) to have these domains validated by an international panel of lung transplant experts, and (3) to recommend the next step for inclusion of these domains into the lung transplant candidate selection process. METHODS: Three levels of evidence were reviewed. A search for standards and guidelines, a comprehensive literature review, and a validation of domains by experts were conducted. RESULTS: Seven domains of patient attributes were identified as relevant to lung transplant patient selection: cognitive performance, frailty, psychological factors, self-efficacy, social support, quality of life, and sociodemographic factors. Within each domain, several elements were identified to be incorporated in the process of patient assessment. CONCLUSION: Assessment of the missing domains and elements should be incorporated into the interdisciplinary lung transplant evaluation process. Standardized recognition and reporting of the patient-specific attributes will inform the work of individual transplant programs and the international transplant community. Further study is needed to associate these patient attributes with transplant outcomes. Improved understanding is needed regarding how nurses assess lung transplant candidates and how they communicate their findings within interdisciplinary settings.

Frailty Phenotypes, Disability, and Outcomes in Adult Candidates for Lung Transplantation.

RATIONALE: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation. OBJECTIVES: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates. METHODS: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively. MEASUREMENTS AND MAIN RESULTS: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB. CONCLUSIONS: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

Cognitive function, mental health, and health-related quality of life after lung transplantation.

RATIONALE: Cognitive and psychiatric impairments are threats to functional independence, general health, and quality of life. Evidence regarding these outcomes after lung transplantation is limited. OBJECTIVES: Determine the frequency of cognitive and psychiatric impairment after lung transplantation and identify potential factors associated with cognitive impairment after lung transplantation. METHODS: In a retrospective cohort study, we assessed cognitive function, mental health, and health-related quality of life using a validated battery of standardized tests in 42 subjects post-transplantation. The battery assessed cognition, depression, anxiety, resilience, and post-traumatic stress disorder (PTSD). Cognitive function was assessed using the Montreal Cognitive Assessment, a validated screening test with a range of 0 to 30. We hypothesized that cognitive function post-transplantation would be associated with type of transplant, cardiopulmonary bypass, primary graft dysfunction, allograft ischemic time, and physical therapy post-transplantation. We used multivariable linear regression to examine the relationship between candidate risk factors and cognitive function post-transplantation. MEASUREMENTS AND MAIN RESULTS: Mild cognitive impairment (score, 18-25) was observed in 67% of post-transplant subjects (95% confidence interval [CI]: 50-80%) and moderate cognitive impairment (score, 10-17) was observed in 5% (95% CI, 1-16%) of post-transplant subjects. Symptoms of moderate to severe anxiety and depression were observed in 21 and 3% of post-transplant subjects, respectively. No transplant recipients reported symptoms of PTSD. Higher resilience correlated with less psychological distress in the domains of depression (P < 0.001) and PTSD (P = 0.02). Prolonged graft ischemic time was independently associated with worse cognitive performance after lung transplantation (P = 0.001). The functional gain in 6-minute-walk distance achieved at the end of post-transplant physical rehabilitation (P = 0.04) was independently associated with improved cognitive performance post-transplantation. CONCLUSIONS: Mild cognitive impairment was present in the majority of patients after lung transplantation. Prolonged allograft ischemic time may be associated with cognitive impairment. Poor physical performance and cognitive impairment are linked, and physical rehabilitation post-transplant and psychological resilience may be protective against the development of long-term impairment. Further study is warranted to confirm these potential associations and to examine the trajectory of cognitive function after lung transplantation.

University of Pennsylvania Lung Transplantation: update 2012.

The University of Pennsylvania is committed to providing the highest level of longitudinal care to patients with end stage lung disease who pursue and undergo lung transplantation. Since 1991, the Penn Lung Transplant Program has performed over 800 lung, heart/lung, lung/liver, and redo lung transplants. As a result of this experience, we believe in a careful, deliberate approach to patients throughout all phases of care and encourage active participation of patients and their support systems throughout this process. We aim to continue to be leaders in the field of transplant related research, with goals of improving short- and long-term outcomes and safely allowing this procedure to be made available to more patients who need it. This chapter provides an overview of our program structure and philosophy towards patient evaluation, as well as highlights the unique aspects of our program.

Post-transplant lymphoproliferative disorder after lung transplantation: a review of 35 cases.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation. The risk of developing PTLD varies depending on a number of factors, including the organ transplanted and the degree of immunosuppression used. METHODS: We report a retrospective analysis of 35 patients with PTLD treated at our center after lung transplantation. Of 705 patients who received allografts, 34 (4.8%) developed PTLD. One patient underwent transplantation elsewhere and was treated at our center. RESULTS: PTLD involved the allograft in 49% of our patients and the gastrointestinal (GI) tract lumen in 23%. Histologically, 39% of tumors were monomorphic and 48% polymorphic. The time to presentation defined the location and histology of disease. Of 17 patients diagnosed within 11 months of transplantation, PTLD involved the allograft in 12 (71%) and the GI tract in 1 (p = 0.01). This "early" PTLD was 85% polymorphic (p = 0.006). Conversely, of the 18 patients diagnosed more than 11 months after transplant, the lung was involved in 5 (28%) and the GI tract in 7 (39%; p = 0.01). "Late" PTLD was 71% monomorphic (p = 0.006). Median overall survival after diagnosis was 18.57 months. Overall survival did not differ between all lung transplant recipients and those who developed PTLD. CONCLUSIONS: PTLD is an uncommon complication after lung transplantation, and its incidence declined remarkably in the era of modern immunosuppression. We report several factors that are important for predisposition toward, progression of, and treatment of PTLD after lung transplantation.

Lung transplant outcomes in white and African American recipients: special focus on acute and chronic rejection.

BACKGROUND: The effects of lung transplant recipient race on post-transplant outcomes have not been adequately evaluated. This cohort study seeks to determine the characteristics of African American lung transplant recipients and the effects of African American race on post-transplant outcomes, particularly acute and chronic rejection, compared with white recipients, at a single center. METHODS: There were 485 first-time lung transplantations (431 white, 47 African American, 5 Hispanic and 2 Asian recipients) performed at the University of Pennsylvania between 1991 and 2006. All white and African American recipients were compared based on pre-transplant diagnoses and post-transplant survival. The cohort from 1998 to 2006 (239 white and 25 African American recipients) was also compared based on acute rejection score (ARS) and development of bronchiolitis obliterans syndrome (BOS). RESULTS: Chronic obstructive pulmonary disease was the most common diagnosis leading to lung transplantation in both groups, but sarcoidosis was a much more common indication in African American recipients (white, 1%; African American, 28%; p < 0.001). Survival was similar in the two groups (white vs African American groups: 1 month, 90.0% vs 87.2%; 1 year, 74.9% vs 74.5%; 5 years, 52.3% vs 50.5%, respectively; p = 0.84). Freedom from BOS at 3 years (white, 60.3%; African American, 62.8%; p = 0.30) and ARS per biopsy (white, 0.83 +/- 0.82; African American, 0.63 +/- 0.77; p = 0.31) were similar in both groups. CONCLUSIONS: White and African American patients seek lung transplantation for different diseases, but post-transplant outcomes were found to be similar. Larger, multi-center studies are needed to confirm these results.

Effects of lung allocation score on waiting list rankings and transplant procedures.

The effect of the new lung allocation score on ranking of patients on the waiting list and the number of transplants performed is not known. We assessed this effect on our lung transplant program and conducted a simulation of lung transplants for the first few months of the new system, using the old waiting lists. Patients with idiopathic pulmonary fibrosis had improved rankings and patients with emphysema had worse rankings, but the number of transplants for each disease category did not change significantly compared with the simulated transplants.

Multiple variables affecting blood usage in lung transplantation.

BACKGROUND: A few publications have reported on the role of variables affecting blood component usage during lung transplantation. METHODS: Transfusion records for lung transplantation patients at the Hospital of the University of Pennsylvania (November 1991 to July 2004) were reviewed. Bivariate analyses and regression models were used to correlate usage of packed red blood cells (RBC), fresh-frozen plasma (FFP) and platelets (PLT) with variables such as disease, number of pulmonary lobes (1 or 2), cardiopulmonary bypass (CPB) status and time on bypass. RESULTS: Among 376 patients examined during the study period, blood product usage (in units) was significantly higher in double- than in single-lung recipients (RBC, 5.76 vs 1.21; FFP, 5.55 vs 1.10; PLT, 1.15 vs 0.16; p < 0.001). Patients on CPB also used significantly more units (RBC, 8.28 vs 1.45; FFP, 9.70 vs 0.73; PLT, 1.86 vs 0.14; p < 0.001), correlating with time on bypass. Patients transplanted for Eisenmenger syndrome (ES) and cystic fibrosis (CF) received significantly more blood products than those transplanted for other diseases (RBC, ES = 17.91 vs CF = 7.31 vs all others <2.00; FFP, ES = 19.18 vs CF = 5.72 vs others <2.00; PLT, ES = 4.73 vs CF = 1.22 vs others <0.40; p < 0.001). A regression model identified variables predictive of blood product usage, including the number of lungs transplanted, CPB status, disease and patient age. CONCLUSIONS: Patients receiving double-lung transplantations, on CPB, or transplanted for ES and CF exhibited a very highly statistically significant demand (p < 0.001) for more blood products. Additional selected variables differentially predicted usage. These data will help transplant surgeons and transfusion medicine specialists better anticipate and prepare blood products for use in lung transplantation.

Impact of primary graft failure on outcomes following lung transplantation.

STUDY OBJECTIVES: Primary graft failure (PGF) is a severe acute lung injury syndrome that occurs following lung transplantation. We compared the clinical outcomes of patients who developed PGF with those who did not. METHODS: We conducted a retrospective cohort study including 255 consecutive lung transplant procedures. PGF was defined as (1) diffuse alveolar opacities developing within 72 h of transplantation, (2) an arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio of < 200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction. PGF was tested for acceptance with 30-day and all-cause hospital mortality rates, overall survival, hospital length of stay (HLOS), duration of mechanical ventilation, and best 6-min walk test (6MWT) distance achieved within 12 months. SETTING: Academic medical center. RESULTS: The overall incidence of PGF was 11.8% (95% confidence interval [CI], 7.9 to 15.9%). The all-cause mortality rate at 30 days was 63.3% in patients with PGF and 8.8% in patients without PGF (relative risk [RR], 7.15; 95% CI, 4.34 to 11.80%; p < 0.001). A total of 73.3% of patients with PGF died during hospitalization vs 14.2% of patients without PGF (RR, 5.18%; 95% CI, 3.51 to 7.63; p < 0.001). The median HLOS in 30-day survivors was 47 days in patients with PGF vs 15 days in those without PGF (p < 0.001), and the mean duration of mechanical ventilation was 15 days in patients with PGF vs 1 day in those without PGF (p < 0.001). By 12 months, a total of 28.5% of survivors with PGF achieved a normal age-appropriate 6MWT distance vs 71.4% of survivors without PGF at 12 months (p = 0.014). The median best 6MWT distance achieved within the first 12 months was 1,196 feet in patients with PGF vs 1,546 feet in those without PGF (p = 0.009). CONCLUSIONS: PGF has a significant impact on mortality, HLOS, and duration of mechanical ventilation following lung transplantation. Survivors of PGF have a protracted recovery with impaired physical function up to 1 year following transplantation.

Association between pulmonary fibrosis and coronary artery disease.

BACKGROUND: Pulmonary fibrosis and atherosclerosis have many similarities at the histopathologic level. Moreover, fibrotic lung diseases exhibit systemic effects and have the potential to affect the vasculature beyond the lung. The existence of a relationship between the two, however, has not been studied. METHODS: To investigate whether fibrotic lung disorders may predispose to atherosclerosis, we conducted a cross-sectional study of 630 patients referred for lung transplantation evaluation at a university hospital. We compared the prevalence of angiographic coronary artery disease (CAD) in patients with fibrotic vs nonfibrotic lung diseases. RESULTS: Fibrotic lung diseases were associated with an increased prevalence of CAD compared with nonfibrotic diseases after adjustment for traditional risk factors (odds ratio, 2.18; 95% confidence interval, 1.17-4.06). The magnitude and significance of this association were maintained when only nongranulomatous fibrotic disease or its subset, idiopathic pulmonary fibrosis, was examined. The strength of the relationship between fibrotic disorders and CAD increased when multivessel disease was analyzed (odds ratio, 4.16; 95% confidence interval, 1.46-11.9). No significant association was detected for granulomatous fibrotic disorders (odds ratio, 1.56; 95% confidence interval, 0.47-5.16; P =.47), although this subgroup had fewer cases of CAD for analysis. CONCLUSIONS: These findings support an association between fibrotic lung disorders and CAD. Further research is necessary to confirm this relationship and to explore the pathologic processes underlying, and potentially linking, these 2 conditions.

Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease.

Doppler echocardiography is commonly used to estimate systolic pulmonary artery pressure and to diagnose pulmonary hypertension, but data relating to its utility in patients with advanced lung disease are limited. In a cohort study of 374 lung transplant candidates, the performance characteristics of echocardiography compared with right heart catheterization in the determination of systolic pulmonary artery pressure and diagnosis of pulmonary hypertension were investigated. The prevalence of pulmonary hypertension was 25% in the study population. Estimation of systolic pulmonary artery pressure by echocardiography was possible in 166 patients (44%). The correlation between systolic pulmonary artery pressure estimated by echocardiography and measured by cardiac catheterization was good (r = 0.69, p < 0.0001). However, 52% of pressure estimations were found to be inaccurate (more than 10 mm Hg difference compared with measured pressure), and 48% of patients were misclassified as having pulmonary hypertension by echocardiography. Sensitivity, specificity, and positive and negative predictive values of systolic pulmonary artery pressure estimation for diagnosis of pulmonary hypertension were 85%, 55%, 52%, and 87%, respectively. In conclusion, despite a statistically significant correlation with directly measured values, estimation of systolic pulmonary artery pressure by echocardiography is frequently inaccurate in patients with advanced lung disease and leads to considerable overdiagnosis of pulmonary hypertension.

Cardiopulmonary bypass for bilateral sequential lung transplantation in patients with chronic obstructive pulmonary disease without adverse effect on lung function or clinical outcome.

OBJECTIVE: The use of cardiopulmonary bypass in lung transplantation remains controversial. Previous studies have concluded that cardiopulmonary bypass is deleterious, but these studies were confounded by the inclusion of patients with different diagnoses undergoing single- and double-lung transplantation with elective or emergency use of bypass. The goal of this study was to determine whether cardiopulmonary bypass has deleterious effects on lung function or clinical outcome by analyzing the cases of patients with a single disease entity and elective use of bypass for bilateral sequential lung transplantation. METHODS: A retrospective review of 50 patients with chronic obstructive pulmonary disease who underwent bilateral sequential lung transplantation was performed. Fourteen patients who underwent elective cardiopulmonary bypass for 218.3 +/- 75.4 minutes were compared to 36 control patients. RESULTS: After the operation, the bypass and nonbypass groups were not significantly different with respect to median duration of mechanical ventilation (1 day vs 1 day, P =.76), median stay in the intensive care unit (4 days vs 4 days, P =.44), median hospital stay (15.5 days vs 16 days, P =.74), mean increase in serum creatinine level (1.4 +/- 1.9 mg/dL vs 0.9 +/- 1.0 mg/dL, P =.33), and mean ratio of Pao(2) to fraction of inspired oxygen at 1 hour (376.6 +/- 123 vs 357.0 +/- 218, P =.75), at 24 hours (309.9 +/- 92 vs 350.6 +/- 122, P =.26), and at 48 hours (335.0 +/- 144 vs 316.2 +/- 120, P =.64). Late outcome markers compared between the bypass and nonbypass groups were the following: 1-year percentage predicted forced expiratory volume in 1 second (76.1% +/- 17.0% vs 85.3% +/- 21.7%, P =.24), 30-day mortality (7.1% vs 8.3%, P >.999), 1-year survival (85.7% vs 80.1%, P =.66), 3-year survival (64.3% vs 58.3%, P =.70), and the prevalence of bronchiolitis obliterans syndrome (0% vs 36.1%, P =.01). CONCLUSION: Cardiopulmonary bypass appears to have no deleterious effect on early lung function or clinical outcome. We hope that this pilot study removes some of the unwarranted fear of the use of bypass in lung transplantation for chronic obstructive pulmonary disease.