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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.

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.

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.

Purpose Palliative care (PC) has been shown to improve outcomes for seriously ill patients but has not been fully integrated into the care of lung transplant patients. Little is known about the palliative care needs for this population. Our goal was to describe adult lung transplant candidates’ perspectives of their PC needs. Methods Prospective, cross-sectional study; Pre-lung transplant patients from a large, single-center adult lung transplant program between February and October 2019, rated their PC needs using an adapted version of the Needs at the End-of-Life Screening Tool (NEST- 13). Each item was scored on a 10-point scale with higher scores indicating greater needs. Results The sample included 113 lung transplant candidates. Most (66.3%) were undergoing evaluation, 18.4% were waitlisted, and 15.3% had completed evaluation testing but were not yet listed. Almost 74% of the participants undergoing pre-transplant evaluation were outpatient and 26.2% were inpatients. Participants were predominantly middle-aged (mean: 55.5 years, SD:13.6), Caucasian (83.0%) and female (58.0%). The highest-rated PC needs were “difficulty being as physically active as you would like” (mean= 7.9; SD= 2.5), “suffer from physical symptoms” (mean= 7.4; SD= 2.5), “have to miss or cut back on work due to your illness” (mean=6.2; SD= 3.2), “distressed by the thought your life might end” (mean=5.1; SD= 3.6), and “difficulty preparing family and friends for possibility of losing you” (mean= 4.8; SD= 3.8). Psychiatric symptoms were not rated as a significant need. Participants reported that spirituality is important but did not report difficulty meeting this need. Only 7.1% reported seeing a PC specialist and many (48.2%) were unsure what a PC specialist is. Despite concerns regarding end-of-life, 60.7% indicated that they had not discussed their views on death and dying with their health care team. Conclusion Lung transplant candidates have significant PC needs, particularly related to their physical symptoms, restrictions on their daily activities, and end-of-life concerns. More research is needed to test the effectiveness of PC in meeting the physical and psychosocial needs of lung transplant patients and to examine the most effective approaches for integrating PC into regular, ongoing lung transplant care.

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.

RationaleFrailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.ObjectivesTo examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.MethodsIn 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 resultsOf 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.ConclusionsFrailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

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.

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.

Background: Venous thromboembolism (VTE) is common after lung transplantation. We aimed to review our experience with VTE in lung transplant recipients, while paying attention to the use of sirolimus, a novel immunosuppressive agent that may have prothrombotic effects. Methods: A retrospective review of lung transplant recipients at the University of Pennsylvania from 2000 to 2006 was performed. Demographic data, acute and chronic rejection and survival were included. Clinically apparent VTE episodes and sirolimus utilization were noted. Results: 59/278 (21.2%) of patients developed VTE. There were no baseline differences in patients with and without VTE. Patients more than three months post-transplant had a higher rate of VTE on sirolimus vs. off (1.98% vs. 0.32% per month on vs. off sirolimus; p

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.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).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%; p0.001). 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.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.

Background The role of nurses in cardiothoracic transplantation has evolved over the last 25 years. Transplant nurses work in a variety of roles in collaboration with multidisciplinary teams to manage complex pre- and post-transplantation issues. There is lack of clarity and consistency regarding required qualifications to practice transplant nursing, delineation of roles and adequate levels of staffing. Methods A consensus conference with workgroup sessions, consisting of 77 nurse participants with clinical experience in cardiothoracic transplantation, was arranged. This was followed by subsequent discussion with the ISHLT Nursing, Health Science and Allied Health Council. Evidence and expert opinions regarding key issues were reviewed. A modified nominal group technique was used to reach consensus. Results Consensus reached included: (1) a minimum of 2 years nursing experience is required for transplant coordinators, nurse managers or advanced practice nurses; (2) a baccalaureate in nursing is the minimum education level required for a transplant coordinator; (3) transplant coordinator–specific certification is recommended; (4) nurse practitioners, clinical nurse specialists and nurse managers should hold at least a master's degree; and (5) strategies to retain transplant nurses include engaging donor call teams, mentoring programs, having flexible hours and offering career advancement support. Future research should focus on the relationships between staffing levels, nurse education and patient outcomes. Conclusions Delineation of roles and guidelines for education, certification, licensure and staffing levels of transplant nurses are needed to support all nurses working at the fullest extent of their education and licensure. This consensus document provides such recommendations and draws attention to areas for future research.

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.

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.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 of200 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.Academic medical center.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%; p0.001). 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; p0.001). The median HLOS in 30-day survivors was 47 days in patients with PGF vs 15 days in those without PGF (p0.001), and the mean duration of mechanical ventilation was 15 days in patients with PGF vs 1 day in those without PGF (p0.001). 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).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.

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.

Background Malignancy is a well-recognized complication of solid-organ transplantation. Although a variety of malignancies have been reported in lung transplant recipients, a paucity of information exists regarding the incidence and clinical course of bronchogenic carcinoma in this patient population. Methods We conducted a retrospective cohort study of our lung transplant experience at the University of Pennsylvania. Results We identified 6 patients with bronchogenic carcinoma detected at the time of, or developing after, transplantation. The incidence of bronchogenic carcinoma was 2.4%. All patients with lung cancer had a history of smoking, with an average of 79 ± 39 pack-years. A total of 5 patients had chronic obstructive pulmonary disease, and 1 had idiopathic pulmonary fibrosis. Lung cancers were all of non–small-cell histology and first developed in native lungs. Three patients had bronchogenic carcinoma at the time of surgery. The remaining 3 patients were diagnosed between 280 and 1,982 days post-transplantation. Of the 6 patients, 4 presented with a rapid course suggestive of an infectious process. The 1- and 2-year survival rates after diagnosis were 33% and 17%, respectively. Conclusion Lung transplant recipients are at risk for harboring or developing bronchogenic carcinoma in their native lungs. Rapid progression to locally advanced or metastatic disease commonly occurs, at times mimicking an infection. Bronchogenic carcinoma should be considered in the differential diagnosis of pleuroparenchymal processes involving the native lung.

A 50-year-old woman underwent single lung transplantation for advanced chronic obstructive pulmonary disease. Shortly after the procedure, it was discovered that the donor suffered from both a renal cell carcinoma and a spindle-cell sarcoma of the ascending aorta, which had metastasized to the spleen. The patient was emergently listed for a retransplantation and underwent bilateral lung transplantation after a new donor became available 4 days after the initial transplantation procedure. After 24 months, the patient is without evidence of malignancy. This case illustrates the role of immediate retransplantation for patients who have inadvertently received thoracic organs from donors harboring occult malignancies.

This study was undertaken to evaluate the efficacy of high resolution computed tomography (HRCT) in predicting the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Fifty lung transplant patients who were clinically stable and without evidence of BOS were evaluated for the presence of four HRCT features reported to be associated with bronchiolitis obliterans: mosaic attenuation on inspiratory CT (mosaic perfusion), mosaic attenuation on expiratory CT (air trapping), bronchiectasis, and tree-in-bud opacities. CT exams were part of an annual surveillance process with the hope of predicting subsequent development of BOS. Diagnosis of BOS was made in 9 of 50 patients as indicated by a fall in FEV1 of greater than 20% of a stable baseline. None of the radiographic features associated with clinically established BOS were both sensitive and specific in the prediction of BOS. Air trapping demonstrated moderate sensitivity (56%, 5/9) and moderate specificity (76%, 35/46) for prediction of BOS in the year following the CT exam. Bronchiectasis, the most reliable indicator of the presence of BOS was a poor predictor of subsequent BOS with an 11% (1/9) sensitivity but had high specificity (96%, 44/46). No high resolution CT features accurately predicted the development of BOS.

We studied lung mechanics and small airways function in 15 patients after double-lung (DL) transplantation. Patients were classified as stable (DL-S, n = 11), or having obliterative bronchiolitis syndrome (DL-OBS, n = 4). We performed pulmonary function tests (PFT), measured slope of phase 3 of the single-breath nitrogen test (N2SP3), and obtained pressure-volume curves and values: chord compliance (Cst,L), specific chord compliance (SCst,L), and elastic recoil pressure at 90% TLC. PFT showed mild restrictive pattern in DL-S and severe obstructive lung disease in DL-OBS. The N2SP3 measurement indicated small airways dysfunction in 82% of DL-S and in all DL-OBS patients. The Cst,L was 0.24 +/- 0.08 L/cm H2O in DL-S and 0.16 +/- 0.05 L/cm H2O in DL-OBS, both lower than control subjects 0.34 +/- 0. 09 L/cm H2O (p < 0.01; p < 0.001). Moreover, SCst,L was 0.09 +/- 0. 03 cm H2O-1 in DL-S, and 0.05 +/- 0.02 cm H2O-1 in DL-OBS, significantly lower than control subjects 0.12 +/- 0.02 cm H2O-1 (p < 0.05; p < 0.001). Elastic recoil at 90% TLC was normal in 14 of 15 patients. We found a linear correlation between N2SP3 and FEV1, and between FEV1 and Cst,L and SCst,L for combined DL-S and DL-OBS. Reduced compliance near FRC with normal elastic recoil at high lung volumes does not suggest changes in lung parenchyma. We speculate that structural or functional alterations in small airways may have contributed to low compliance measurements. Of special concern are our findings that DL-S had significant small airways dysfunction and reduced compliance in a pattern similar to the DL-OBS, only smaller in magnitude.

The finding of a pulmonary infiltrate on chest radiograph may represent a spectrum of pathologic entities in the acutely ill hospitalized adult. Timely intervention depends on the advanced practice nurse's ability to devise a differential diagnosis based on the characteristics of the infiltrate and the clinical setting. Pulmonary infiltrates are described as interstitial or alveolar, diffuse or focal. Their presentation may be chronic or acute in nature. Understanding the nuances of chest radiographic interpretation provides the foundation on which the infiltrate is described and is therefore the first step in establishing the differential diagnosis. Thorough clinical assessment and thoughtful requisition of diagnostic studies are used to discriminate the disorders found in the differential diagnosis. Using an organized approach to describe the radiographic abnormality and define its clinical context, the advanced practice nurse can efficiently establish a diagnosis so that the work of treatment may begin.

Objective: Traditionally, despite ventilation/perfusion mismatch, single lung transplantation has been the mainstay for end-stage chronic obstructive pulmonary disease. We tested the hypothesis that bilateral sequential lung transplantation has better short- and intermediate-term results than single lung transplantation for chronic obstructive pulmonary disease.Methods: One hundred twenty-six consecutive lung transplants have been performed from November 1991 to March 1996. Seventy-six have been for chronic obstructive pulmonary disease. The diagnosis of this disease includes emphysema (80.3%), α1-antitrypsin deficiency (9.2%), lymphangioleiomyomatosis (7.9%), and obliterative bronchiolitis (2.6%). Twenty-nine transplants have been bilateral and 47 have been single. Mean age was 55.3 for patients having single lung transplantation and 48.8 for those having bilateral lung transplantation (p = 0.001). The distribution of the diagnoses was similar between the two groups. At 6 months, there were 29 survivors of single lung transplantation and 20 survivors of bilateral lung transplantation, with complete data for evaluation. Pulmonary function tests and 6-minute walk tests were evaluated at a mean of 15.4 and 12.8 months after transplantation, respectively.Results: Sixty-day mortality was 21.3% for single lung transplantation versus only 3.45% for bilateral lung transplantation (p = 0.03). Additionally, Kaplan-Meier analysis revealed 1- and 2-year survivals of 71.1% and 63.3% for single lung transplantation versus 90% and 90% for bilateral lung transplantation, respectively. Multiple major morbidities were analyzed. Primary graft failure was significantly reduced in the bilateral group (p = 0.049). Both 6-minute walk tests and forced expiratory volume in 1 second were improved from baseline by both single and bilateral lung transplantation (p = 0.001).Conclusions: Bilateral lung transplantation improves forced expiratory volume in 1 second and 6-minute walk tests significantly over single lung transplantation (p < 0.0001). Both perioperative mortality and Kaplan-Meier survival (to 3 years) are significantly improved when bilateral rather than single lung transplantation is used for chronic obstructive pulmonary disease in our series (p < 0.05). This is probably the result of significantly reduced primary graft failure. (J Thorac Cardiovasc Surg 1997;113:520-8)

Lung transplantation through controlled donation after circulatory death (cDCD) has slowly gained universal acceptance with reports of equivalent outcomes to those through donation after brain death. In contrast, uncontrolled DCD (uDCD) lung use is controversial and requires ethical, legal and medical complexities to be addressed in a limited time. Consequently, uDCD lung use has not previously been reported in the United States. Despite these potential barriers, we present a case of a patient with multiple gunshot wounds to the head and the body who was unsuccessfully resuscitated and ultimately became an uDCD donor. A cytomegalovirus positive recipient who had previously consented for CDC high-risk, DCD and participation in the NOVEL trial was transplanted from this uDCD donor, following 3 hours of ex vivo lung perfusion. The postoperative course was uneventful and the recipient was discharged home on day 9. While this case represents a “best-case scenario,” it illustrates a method for potential expansion of the lung allograft pool through uDCD after unsuccessful resuscitation in hospitalized patients.

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.

s S15 that the new Lung Transplantation allocation rules implemented in France since 2007 (HELT) allows a rapid organ procurement for patients at imminent risk of death, and is feasible with an acceptable survival (74% at 1 year).

A fundamental goal of lung transplantation is the regaining of functional capacity, yet little is known about what factors are associated with the achievement of this goal. The aim of this study is to test the association of clinical risk factors with functional status 1 year following lung transplantation. We conducted a cohort study of 321 lung transplants and assessed functionality by the distance achieved during a standard 6-min walk test (6MWT). Preoperative recipient risk factors were evaluated for association with functional status and adjusted for confounding using multivariable linear regression models. In these multivariable analyses, recipient female gender (p < 0.001), recipient pretransplant body mass index (BMI) of greater than 27 kg/m2 (p = 0.017) and shorter pretransplant 6MWT distances (p = 0.006) were independently associated with shorter distances achieved during 6MWT after lung transplant, while cystic fibrosis (CF) (p = 0.003), and bilateral lung transplant (p = 0.014) were independently associated with longer distances achieved. Approximately 51% of the variance in 6MWT distance was explained by these risk factors in the linear regression models (R2= 0.51). These findings may have implications in patient counseling, selection, procedure choice, and may lead to interventions aimed at improving the functional outcomes of lung transplantation.

A few publications have reported on the role of variables affecting blood component usage during lung transplantation.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.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; p0.001). 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; p0.001), 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 others2.00; FFP, ES = 19.18 vs CF = 5.72 vs others2.00; PLT, ES = 4.73 vs CF = 1.22 vs others0.40; p0.001). A regression model identified variables predictive of blood product usage, including the number of lungs transplanted, CPB status, disease and patient age.Patients receiving double-lung transplantations, on CPB, or transplanted for ES and CF exhibited a very highly statistically significant demand (p0.001) 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.

Doppler echocardiography is commonly used to estimate systolic nose PH in patients with advanced lung disease is preferable. pulmonary artery pressure and to diagnose pulmonary hypertension, Doppler echocardiography (DE) has gained popularity in but data relating to its utility in patients with advanced lung disease the last 2 decades for noninvasive estimation of systolic pulare limited. In a cohort study of 374 lung transplant candidates, the monary artery pressure (sPAP) from the peak velocity of a performance characteristics of echocardiography compared with tricuspid regurgitant jet. Studies in patients with cardiac disright heart catheterization in the determination of systolic pulmo- ease have revealed a significant statistical correlation benary artery pressure and diagnosis of pulmonary hypertension were tween sPAP estimated by DE and that measured by RHC investigated. The prevalence of pulmonary hypertension was 25% (6‐9). However, in patients with chronic pulmonary disease, in the study population. Estimation of systolic pulmonary artery pres- DE has been reported to perform variably in the assessment sure by echocardiography was possible in 166 patients (44%). The of sPAP (10‐12). Despite a close correlation between DEcorrelation between systolic pulmonary artery pressure estimated estimated and directly measured sPAP, several studies have by echocardiography and measured by cardiac catheterization was revealed that such estimations were possible in only a minorgood (r 0.69, p 0.0001). However, 52% of pressure estimations ity of patients with chronic lung disease (11‐14). More imporwere found to be inaccurate (more than 10 mm Hg difference tantly, by focusing exclusively on the correlation between compared with measured pressure), and 48% of patients were mis- estimated and measured pressures, previous studies have classified as having pulmonary hypertension by echocardiography. largely ignored the important issue of the true accuracy of Sensitivity, specificity, and positive and negative predictive values DE estimation of sPAP. That is, if DE were to consistently of systolic pulmonary artery pressure estimation for diagnosis of overestimate or underestimate sPAP by a constant value, pulmonary hypertension were 85%, 55%, 52%, and 87%, respectively. correlation would be high, but the accuracy of the estimation In conclusion, despite a statistically significant correlation with directly measured values, estimation of systolic pulmonary artery pres- would be dictated by the magnitude of discrepancy. It is the sure by echocardiography is frequently inaccurate in patients with accuracy of estimation that defines the clinical utility of DE in advanced lung disease and leads to considerable overdiagnosis of such circumstances as evaluation of patients for lung volume pulmonary hypertension. reduction surgery or lung transplantation. Patients with advanced lung disease referred for lung

Background Antithymocyte globulin is frequently used as a component of induction therapy in thoracic organ transplantation. This study evaluates the utility of monitoring peripheral CD3 lymphocytes to rationally adjust antithymocyte globulin therapy in this patient population. Methods A total of 17 heart and 19 lung transplant recipients received antithymocyte globulin (ATGAM or thymoglobulin) as induction therapy or to treat steroid-resistant acute or chronic rejection. Absolute CD3 counts were maintained between 50 and 100 cells/microl. Results With CD3 monitoring, the doses of antithymocyte globulin were reduced from 10-15 mg/kg to 1-5 mg/kg during the course of therapy. The total amount of antithymocyte globulin given to each CD3 monitored patient was reduced by 48%. Dose reduction did not alter the number of acute rejection or infectious episodes, and hematological side effects were infrequent. Conclusion CD3 monitoring of antithymocyte globulin therapy in thoracic organ recipients reduced the amount of drug received by each patient, while maintaining CD3 counts less than 100 cells/microl.

To characterize the course of patients with advanced sarcoidosis who have been listed for lung transplantation and to identify prognostic factors for death while they are on the waiting list.Retrospective cohort study.Tertiary-care university hospital.Forty-three patients with sarcoidosis who have been listed for lung transplantation at the University of Pennsylvania Medical Center.A multivariable explanatory analysis using a Cox proportional hazards model was performed to determine risk factors that are independently associated with mortality while patients await transplantation.Twenty-three of the 43 patients (53%) died while awaiting transplantation. The survival rate of listed patients (as determined by the Kaplan-Meier method) was 66% at 1 year, 40% at 2 years, and 31% at 3 years. In a univariate analysis, the following factors were significantly associated with death on the waiting list: PaO(2)or = 60 mm Hg (relative risk [RR], 3.4; 95% confidence interval [CI], 1.2 to 9.3); mean pulmonary artery pressureor = 35 mm Hg (RR, 3.2; 95% CI, 1.1 to 9.5); cardiac indexor = 2 L/min/m(2) (RR, 2.8; 95% CI, 1.2 to 6.6), and right atrial pressure (RAP)or = 15 mm Hg (RR, 7.6; 95% CI, 3.0 to 19.3). Multivariable analysis revealed that RAPor = 15 mm Hg was the only independent prognostic variable (RR, 5.2; 95% CI, 1.6 to 16.7; p = 0.006). Twelve patients underwent lung transplantation. Survival after transplantation determined by the Kaplan-Meier method was 62% at both 1 and 2 years, and 50% at 3 years.Patients with advanced sarcoidosis awaiting lung transplantation have a high mortality rate with a median survival of2 years. Mortality is most closely linked to elevated RAP. While earlier referral may diminish the mortality rate of patients on the waiting list for transplantation, further improvements in posttransplantation outcomes will be necessary to ensure that this procedure truly bestows a survival benefit.

There is controversy regarding the transplant procedure of choice in chronic obstructive pulmonary disease. We reviewed our intermediate-term outcomes with single lung transplantation (SLT) versus bilateral lung transplantation (BLT).We retrospectively reviewed 130 patients with chronic obstructive pulmonary disease: 84 underwent SLT, 46 BLT. The mean age was 51.1 +/- 1.2 years for those who underwent BLT and 56.2 +/- 0.7 years for those who underwent SLT (p0.0001). Male patients represented 65% of the BLT group and 46% of the SLT group (p = 0.04). Spirometry and 6-minute walk tests were obtained preoperatively and at 3- to 6-month intervals. Posttransplant survival and survival from time of onset of bronchiolitis obliterans syndrome were calculated by Kaplan-Meier method. The mean follow-up was 32.4 months.The 90-day mortality rate was 13.0% For BLT and 15.5% for SLT (p = 0.71). Actuarial survival rates at 1, 3, and 5 years were 82.6%, 74.6%, and 61.9% for BLT and 72.2%, 63.4%, and 57.4% for SLT; the favorable survival trend with BLT did not achieve statistical significance. There were no differences in preoperative spirometry or 6-minute walk tests. The improvements in forced expiratory volume in one second, forced vital capacity (FVC), and 6 MWT were significantly greater following BLT. The incidence of bronchiolitis obliterans syndrome was 22.4% in SLT and 22.2% in BLT; survival following onset of bronchiolitis obliterans syndrome was similar.For patients with chronic obstructive pulmonary disease, BLT is associated with superior lung function, exercise tolerance, and a trend toward enhanced survival. Younger candidates may be best suited for BLT. Given the limited donor lungs, SLT remains the preferred alternative for all other patients.

To determine the incidence of primary graft failure (PGF) following lung transplantation, assess possible risk factors, and characterize its effect on outcomes.Retrospective review of 100 consecutive patients undergoing lung transplantation at the University of Pennsylvania Medical Center. Fifteen patients meeting diagnostic criteria for PGF (PGF+ group) were compared with 85 patients without this complication (PGF- group).The incidence of PGF was 15%. There was no significant difference in age, sex, underlying pulmonary disease, preoperative pulmonary artery systolic pressure, type of transplant, allograft ischemic times, use of cardiopulmonary bypass, or use of postoperative prostaglandin E1 infusion between the PGF+ and PGF- groups. Induction therapy with antilymphocyte globulin was used less frequently in the PGF+ group (p0.005). Duration of mechanical ventilatory support was 36+/-43 days vs 4+/-6 days for the PGF+ and PGF- groups, respectively (p0.0001). Hospital stay was significantly longer in the PGF+ group, averaging 75+/-105 days, compared with 27+/-38 days in the PGF group (p0.005). One-year actuarial survival for the PGF+ group was only 40% compared with 69% for the PGF- group (p0.005). Five of the six PGF+ survivors were ambulatory by 1 year; three were completely independent while two continued to require assistance with activities of daily living. Six-minute walk test distance among the ambulatory patients averaged 883+/-463 feet (range, 200 to 1,223 feet) compared with 1513+/-424 feet for the PGF- group (p0.005). Among the subset of survivors who underwent single lung transplantation for COPD, the mean percent predicted FEV1 at 1 year was 43% for the PGF+ group and 55% for the PGF- groups, but this difference was not statistically significant.PGF is a devastating postoperative complication, occurring in 15% of patients in the current series, and it is associated with a high mortality rate, lengthy hospitalization, and protracted and often compromised recovery among survivors.

calculated. Actual transplant benefit was calculated by subtracting predicted waiting list siurvival from actual post-transplant survival The predicted values of post-transplant survival and transplant benefit were compared with the actual values for our group of patients. Results: Thirty-one transplants were performed with actual 1-year survival of 87.1%. Predicted and actual results can be seen on the Table. Actual results for post-transplant survival and transplant benefit showed higher variability than predicted results. The actual benefit was better than the predicted benefit (17.7 99.2; median 47.5; IR: 36.5, 57.9; range: -308, 106; p 0.008). There were no statistical differences in LAS and other variables between survivors and nonsurvivors. Conclusions: Patients transplanted under LAS experience significant transplant benefit as a group, although precise predictions for individual patients are difficult. Larger studies will assess whether LAS is associated with post-transplant outcomes.

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.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.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.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.

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. J Thorac Cardiovasc Surg 2002;124:241-9