Received Lung Transplantation Research Articles

Ambient Air Pollution Exposure and Outcomes in Patients Receiving Lung Transplant

Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood. To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants. This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023. Zip code-level annual PM2.5 exposure was constructed using previously published North American estimates. The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality. Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code's annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable. In this study, elevated zip code-level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.

Clinical outcomes of lung transplant recipients with pre-transplant Mycobacterium avium complex infection.

Lung transplant recipients (LTRs) are at risk for Mycobacterium avium complex (MAC) infections, in part due to the presence of structural lung disease pre-transplant and relatively higher levels of immunosuppression post-transplant. There is a lack of data regarding outcomes of LTR with MAC infections pre-transplant. This is a single-center retrospective analysis of patients who received lung transplants (LTs) from 2013 to 2020 with 1) evidence of MAC on culture or polymerase chain reaction before or at the time of transplant or 2) granulomas on explant pathology and positive acid-fast bacillus stains with no other mycobacteria identified. Patients were deemed to have MAC pulmonary disease (MAC-PD) if they met the American Thoracic Society/Infectious Disease Society of America criteria. Fourteen patients (14/882, 2%) met inclusion criteria. Seven patients (7/14, 50%) had pre-transplant MAC-PD, four of whom had cavitary disease. None of the 14 patients had smear-positive cultures at the time of transplant. Two patients in our cohort received treatment for MAC before transplant. Thirteen patients were bilateral LTR (13/14, 93%). One single LTR was the sole patient to receive MAC treatment post-transplant. No patients developed MAC-PD after transplant. The bilateral LTR in our cohort did not develop MAC-PD despite not receiving MAC treatment post-transplant. It is possible source control was achieved with native lung explantation. Our observations suggest patients may not uniformly require pre- or post-transplant MAC treatment if they are smear-negative and undergo bilateral LT.

Utilizing Generalized Linear Mixed Effects Models for Prediction of Bone Mineral Decrease After Lung Transplant - A Preliminary Study.

Recipients of lung transplants are at heightened risk of developing low bone mineral density (BMD). They also have increased risk of developing osteoporosis-related fractures. This rate of BMD decline is not well characterized. The aim of this manuscript is to characterize the rate of BMD decrease after lung transplant. This is a preliminary retrospective cohort study of 200 patients who received lung transplants. Each patient had pre-transplant dual energy X-ray absorptiometry (DXA) and post-transplant DXA scans on the same DXA scanner. The BMD at each lumbar vertebra, total hip, and femoral neck were recorded. Generalized linear mixed effects models with random intercepts and random slopes were used to model the rate of change of BMD after transplant, adjusting for time since transplant, sex, and sex*time interaction. We found that men had higher baseline BMD than women at all sites (P<0.05 for all). The rate of BMD decrease was fastest at the femoral neck (P<0.05). Men lost BMD at a faster rate (-5.23 x10-5 g/cm2/day) than women at the femoral neck (-2.22 x10-5 g/cm2 /day). BMD decreases after lung transplant and occurs faster in men than women.

Lung Donation and Transplant Recipient Outcomes at Independent vs Hospital-Based Donor Care Units

Centralizing deceased organ donor management and organ recovery into donor care units (DCUs) may mitigate the critical organ shortage by positively impacting donation and recipient outcomes. To compare donation and lung transplant outcomes between 2 common DCU models: independent (outside of acute-care hospitals) and hospital-based. This is a retrospective cohort study of Organ Procurement and Transplantation Network deceased donor registry and lung transplant recipient files from 21 US donor service areas with an operating DCU. Characteristics and lung donation rates among deceased donors cared for in independent vs hospital-based DCUs were compared. Eligible participants included deceased organ donors (aged 16 years and older) after brain death, who underwent organ recovery procedures between April 26, 2017, and June 30, 2022, and patients who received lung transplants from those donors. Data analysis was conducted from May 2023 to March 2024. Organ recovery in an independent DCU (vs hospital-based DCU). The primary outcome was duration of transplanted lung survival (through December 31, 2023) among recipients of lung(s) transplanted from cohort donors. A Cox proportional hazards model stratified by transplant year and program, adjusting for donor and recipient characteristics was used to compare graft survival. Of 10 856 donors in the starting sample (mean [SD] age, 42.8 [15.2] years; 6625 male [61.0%] and 4231 female [39.0%]), 5149 (primary comparison group) underwent recovery procedures in DCUs including 1466 (28.4%) in 11 hospital-based DCUs and 3683 (71.5%) in 10 independent DCUs. Unadjusted lung donation rates were higher in DCUs than local hospitals, but lower in hospital-based vs independent DCUs (418 donors [28.5%] vs 1233 donors [33.5%]; P < .001). Among 1657 transplant recipients, 1250 (74.5%) received lung(s) from independent DCUs. Median (range) duration of follow-up after transplant was 734 (0-2292) days. Grafts recovered from independent DCUs had shorter restricted mean (SE) survival times than grafts from hospital-based DCUs (1548 [27] days vs 1665 [50] days; P = .04). After adjustment, graft failure remained higher among lungs recovered from independent DCUs than hospital-based DCUs (hazard ratio, 1.85; 95% CI, 1.28-2.65). In this retrospective analysis of national donor and transplant recipient data, although lung donation rates were higher from deceased organ donors after brain death cared for in independent DCUs, lungs recovered from donors in hospital-based DCUs survived longer. These findings suggest that further work is necessary to understand which factors (eg, donor transfer, management, or lung evaluation and acceptance practices) differ between DCU models and may contribute to these differences.

Comparison of the Effects of Multiple Frailty and Nutritional Indexes on Postoperative Outcomes in Critically Ill Patients Undergoing Lung Transplantation.

Background and Objective: Lung transplantation is the only life-extending therapy for end-stage pulmonary disease patients, but its risks necessitate an understanding of outcome predictors, with the frailty index and nutritional status being key assessment tools. This study aims to evaluate the relationship between preoperative frailty and nutritional indexes and the postoperative mortality rate in patients receiving lung transplants, and to determine which measure is a more potent predictor of outcomes. Materials and Methods: This study reviewed 185 adults who received lung transplants at a single medical center between January 2013 and May 2023. We primarily focused on postoperative 7-year overall survival. Other outcomes measured were short-term mortalities, acute rejection, kidney complications, infections, and re-transplantation. We compared the predictive abilities of preoperative nutritional and frailty indicators for survival using receiver operating characteristic curve analysis and identified factors affecting survival through regression analyses. Results: There were no significant differences in preoperative nutritional indicators between survivors and non-survivors. However, preoperative frailty indicators did differ significantly between these groups. Multivariate analysis revealed that the American Society of Anesthesiologists Class V, clinical frailty scale, and Charlson Comorbidity Index (CCI) were key predictors of 7-year overall survival. Of these, the CCI had the strongest predictive ability with an area under the curve of 0.755, followed by the modified frailty index at 0.731. Conclusions: Our study indicates that for critically ill patients undergoing lung transplantation, frailty indexes derived from preoperative patient history and functional autonomy are more effective in forecasting postoperative outcomes, including survival, than indexes related to preoperative nutritional status.

Impact of Blood Products Transfusion on Patients in the Immediate Post-Lung Transplant Period: A Cohort Study.

BACKGROUND Anemia is common in post-transplant patients. Blood product transfusion is associated with mortality and rejection in solid organ transplants. In lung transplant recipients, transfusion predisposes to primary graft dysfunction (PGD). The adverse effects and associated mortality of perioperative transfusions in lung transplant recipients have not been evaluated. This study examined the effects of perioperative blood transfusions in lung transplant recipients. MATERIAL AND METHODS We conducted a retrospective study of the effects of blood product transfusions in patients who received single- or double-lung transplantation at Houston Methodist Hospital between August 2017 and September 2019. Univariable and multiple logistic regression modeling were used to determine the characteristics associated with single events as well as a composite outcome within 30 days (including mortality, acute myocardial infarction, acute stroke, lower respiratory tract infection, urinary tract infection, surgical site infections, or PGD). RESULTS A total of 232 patients received lung transplants between December 2015 and September 2019 at our center. Univariable analysis revealed an increased risk of PGD (P<0.001), more mechanical ventilation days (P<0.001), more ICU days post-transplant (P<0.001), and greater need for ECMO support (P=0.001) in patients who received blood product transfusions. In univariate analysis, the composite outcome was also more common (P=0.01) in patients who received any transfusion perioperatively. A total of 7 patients died within 30 days from transplant, and they were all in the transfused group. CONCLUSIONS Among lung transplant recipients, PGD, ICU days, need for mechanical ventilation and ECMO support, and total composite events were significantly greater in patients who received blood transfusion perioperatively.

Evaluation of the Current Urgency-Based Lung Allocation System in Korea with Simulation of the Eurotransplant Lung Allocation Score.

Due to the shortage of lung donors relative to the number of patients waiting for lung transplantation (LTx), more than one-third of patients on the waitlist have died without receiving LTx in Korea. Therefore, the importance of fair and effective allocation policies has been emphasized. This study investigated the characteristics of the current urgency-based allocation system in Korea by simulating the Eurotransplant lung allocation score (ET-LAS) using a nationwide multi-institutional registry for LTx in Korea. This study used data from the Korean Organ Transplantation Registry (KOTRY), along with additional retrospective data for ET-LAS calculation. A total of 194 patients were included in this study between January 2015 and December 2019. The Korean urgency definition classifies an LTx candidate as having statuses 0-3 according to urgency. The ET-LAS was analyzed according to the Korean urgency status. In total, 92 patients received lung transplants at status 0, 85 at status 1, and 17 at status 2/3. The ET-LAS showed a bimodal distribution with distinct peaks corresponding to status 0 and non-status 0. There was no significant difference in the ET-LAS among non-status 0 patients. In logistic and decision tree analyses, oxygen supplementation methods, particularly oxygen masks and high-flow nasal cannulas, were significantly associated with a high ET-LAS (≥50) among non-status 0 patients. Simulation of the ET-LAS with KOTRY data showed that the Korean urgency definition may not allocate lungs by urgency, especially for patients in non-status 0; therefore, it needs to be revised.

The role of coronary artery disease in lung transplantation

Abstract Background Coronary artery disease (CAD) is a common comorbidity in patients suffering from terminal lung disease and a recurrent problem in pre-transplant evaluation. While historically, CAD has been treated as a contraindication for lung transplantation, data from multiple small studies suggests that CAD in well selected patients might not be associated with a worse outcome. In its 2020 consensus document for the selection of lung transplant candidates, the International Society for Heart and Lung Transplantation states that CAD should not be considered an absolute contraindication but a potential marker for an unfavourable phenotype. However, data backing up this decision is limited and in parts inconclusive. Purpose This study aims to provide solid data on the relevance of pre-existing CAD in the setting of lung transplantation. Furthermore, defining cardiovascular risk factors and their effect in this unique population is required to support evidence-based risk stratification. Methods 1003 patients receiving lung transplantation between January 2000 and August 2021 were included in this study. The median follow up was 3.24 years [1.30, 4.82]. Plaque formation in the coronary arteries was identified by coronary angiography in 230 patients. A relevant CAD defined by stenosis &amp;gt;50% or previous percutaneous coronary intervention/coronary artery bypass graft was present in 104 patients. Results Baseline characteristics of the CAD group differed significantly from the non-CAD group in terms of Age at Transplantation [y] (60.28 [56.71, 63.24] vs. 53.96 [44.45, 59.85], p&amp;lt;0.001), Sex [male] (74.0% vs. 52.3%, p&amp;lt;0.001) and BMI [kg/m2] (24.13 [21.25, 27.41] vs 22.22 [19.37, 25.62], p&amp;lt;0.001) as well as the abundance of cardiovascular risk factors including hypertension (67.3% vs 32.1%, p&amp;lt;0.001) and smoking (67.3% vs 40.9%, p&amp;lt;0.001). Therefore 1:1 propensity score matching was performed, resulting in 98 matched pairs. Matching variables, including demographics, cardiovascular risk factors, results from the right heart catheter and lung testing, were well balanced without significant differences between the groups. The primary endpoint overall survival was similar in the matched groups: HR=0.94, 95% CI 0.64-1.39, p=0.77. Graph 1 pictures the corresponding Kaplan – Meier curves. In addition, no significant differences in intrahospital mortality between patients with and without CAD (8.2% vs 5.1%, p=0.566) could be detected. Furthermore, there was no significant difference in the occurrence of myocardial infarction (6.1% vs 4.1%, p=0.745) or stroke (2.0% vs 5.1%, p=0.441) post transplantation. Conclusion The finding of this study provides further evidence indicating that CAD itself may not be associated with worse short – or long-term survival following lung transplantation. Careful evaluation and patient selection can allow patients suffering from CAD to successfully undergo lung transplantation without inferior survival.Survival Analysis

Factors Influencing the quality of life of lung transplant patients

Purpose : This study aimed to identify the factors affecting the quality of life of lung transplant patients.Method : The participants were patients who received lung transplants at a general hospital in City Y. Data were collected through structured questionnaires from June 2023 to August 2023. General characteristics, lung transplantation-related characteristics, quality of life, functional disability, treatment compliance, social support, anxiety, and depression—were measured. For data analysis, hierarchical multiple regression was performed using SPSS/WIN 29.0.Results : In the final model, quality of life was associated with income, self-help group attendance, functional disability, social support, treatment compliance, and anxiety and depression. Together, they explained 61.2% of the total variance in the results.Conclusion : Our findings suggest that improving lung transplant patients’ quality of life requires active intervention in stress management to perform treatment instructions well, a social support system that can help them financially, and encouraging and participating in social activities as patients.

Suspected Legionella Transmission from a Single Donor to Two Lung Transplant Recipients — Pennsylvania, May 2022

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor’s cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care–associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May–June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

Lung Allocation Score Exceptions in Persons with Cystic Fibrosis Undergoing Lung Transplant.

Rationale: Lung transplantation can extend the lives of individuals with advanced cystic fibrosis (CF). Until March 2023, the Lung Allocation Score (LAS) was used in the United States to determine transplant priority. Certain clinical events or attributes ("risk events") that are not included in the LAS (e.g., massive hemoptysis) are relatively common and prognostically important in CF and may prompt an exception request to increase priority for donor lungs. The new Lung Composite Allocation Score (CAS) also allows for exceptions based on the same principles. Objectives: To evaluate the frequency of LAS exceptions in persons with CF (PwCFs) listed for lung transplantation and assess whether LAS exceptions are associated with improved waitlist outcomes for PwCFs compared with similarly "at-risk" individuals without LAS exceptions. Methods: A merged dataset combining data from the CF Foundation Patient Registry and the Organ Procurement and Transplantation Network (2005-2019) was used to identify PwCFs listed for lung transplantation. We compared waitlist outcomes between PwCFs with a LAS exception versus those without an exception despite having a risk event. Risk events were defined as an episode of massive hemoptysis, pneumothorax, at least three moderate/severe pulmonary exacerbations, and/or a decrease in forced expiratory volume in 1 second by ⩾30% predicted (absolute) in the prior 12 months. Analyses were performed using competing risk regression with time to transplantation as the primary outcome and death without a transplant as a competing risk. Results: Of 3,538 listings from 3,309 candidates, 2% of listings (n = 81) had at least one exception. Candidates with an exception and those with a risk event but no exception received lung transplants more slowly than people without an exception or risk event (subdistribution hazard ratio [95% confidence interval]: LAS exception cohort, 0.66 [0.52-0.85]; risk event cohort without exceptions, 0.79 [0.72-0.86]). There was no difference between those with LAS exceptions and those at risk without LAS exceptions: subdistribution hazard ratio, 0.84 (0.66-1.08). Conclusions: LAS exceptions are rare in PwCFs listed for lung transplantation. LAS exceptions resulted in a similar time to transplantation for PwCFs compared with similarly at-risk individuals. As we enter the CAS era, these LAS-based results are pertinent to improve risk stratification among PwCFs being considered for lung transplantation.

Exercise-Induced Electrocardiography Changes in Pulmonary Arterial Hypertension

Cardiopulmonary exercise testing (CPET) is an important tool in assessing the functional status of patients with pulmonary arterial hypertension (PAH). During CPET, continuous electrocardiography (ECG) is used as a marker of exercise-induced ischemia or arrhythmia. We hypothesize that ECG changes with exercise may be an early indicator of clinical worsening in PAH and could predict adverse outcomes. Clinical, hemodynamic, and CPET data of 155 children and young adult patients with PAH who underwent CPET between 2012 and 2019 in our pulmonary hypertension (PH) center were included in this retrospective analysis. ECGs were analyzed for ST depressions and T-wave inversions, along with coincident hemodynamic data. These data were correlated with adverse outcomes divided into 2 categories: severe worsening (death or receiving lung transplant) and mild to moderate worsening (PAH medication escalation, hospitalization, shunt creation, or listing for lung transplant). The median age was 19years (range 7 to 40years), 69% were female, and the average follow-up time was 5years (range 1 to 8years). A total of 63 patients (41%) had at least 1 adverse outcome. A total of 39 patients (25%) demonstrated significant ST-T-wave changes with exercise. Patients with ST-T-wave changes were 20% more likely to die or need lung transplant than those without. The multiple linear regression found that ST-T-wave changes were a predictor of elevated mean pulmonary arterial pressure (mPAP) found on catheterization (R=0.489, p=0.003), although not of pulmonary vascular resistance index (R=-0.112, p=0.484). An mPAP of 55mm Hg was the most sensitive and specific point in identifying when ST-T-wave changes with exercise begin to appear. In conclusion, ST-T-wave changes on exercise ECG are significantly associated with adverse outcomes in PH in a medium-term follow-up study, and the presence of ST-T-wave changes correlates with higher mPAP. These ECG changes with exercise may be used as early indicators of clinical worsening in PH and predictors of adverse outcomes.

Suspected Legionella Transmission from a Single Donor to Two Lung Transplant Recipients - Pennsylvania, May 2022.

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor's cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care-associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May-June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

Racial Disparities in Waiting List Outcomes of Patients Listed for Lung Transplantation

BackgroundThe Lung Allocation Score, implemented in 2005, prioritized lung transplant candidates by medical urgency rather than waiting list time and was expected to improve racial disparities in transplant allocation. We evaluated whether racial disparities in lung transplant persisted after 2005. MethodsWe identified all wait-listed adult lung transplant candidates in the United States from 2005 through 2021 using the Scientific Registry of Transplant Recipients. We evaluated the association between race and receipt of a transplant by using a multivariable competing risk regression model adjusted for demographics, socioeconomic status, Lung Allocation Score, clinical measures, and time. We evaluated interactions between race and age, sex, socioeconomic status, and Lung Allocation Score. ResultsWe identified 33,158 candidates on the lung transplant waiting list between 2005 and 2021: 27,074 White (82%), 3350 African American (10%), and 2734 Hispanic (8%). White candidates were older, had higher education levels, and had lower Lung Allocation Scores (P < .001). After multivariable adjustment, African American and Hispanic candidates were less likely to receive lung transplants than White candidates (African American: adjusted subhazard ratio, 0.86; 95% CI, 0.82-0.91; Hispanic: adjusted subhazard ratio, 0.82; 95% CI, 0.78-0.87). Lung transplant was significantly less common among Hispanic candidates aged >65 years (P = .003) and non-White candidates from higher-poverty communities (African-American: P = .013; Hispanic: P =.0036). ConclusionsDespite implementation of the Lung Allocation Score, racial disparities persisted for wait-listed African American and Hispanic lung transplant candidates and differed by age and poverty status. Targeted interventions are needed to ensure equitable access to this life-saving intervention.

Influence of De Novo Malignancies on Long-Term Survival after Lung Transplantation.

(1) Background: Malignancies are an important cause of mortality after solid organ transplantation. The purpose of this study was to analyze the incidence of malignancies in patients receiving lung transplants (LT) and their influence on patients' survival. (2) Methods: Review of consecutive LT from 1994 to 2021. Patients with and without malignancies were compared by univariable and multivariable analyses. Survival was compared with Kaplan-Meier and Cox regression analysis. (3) Results: There were 731 LT malignancies developed in 91 patients (12.4%) with related mortality of 47% (n = 43). Native lung cancer, digestive and hematological malignancies were associated with higher lethality. Malignancies were more frequent in males (81%; p = 0.005), transplanted for emphysema (55%; p = 0.003), with cyclosporine-based immunosuppression (58%; p < 0.001), and receiving single LT (65%; p = 0.011). Survival was worse in patients with malignancies (overall) and with native lung cancer. Risk factors for mortality were cyclosporine-based immunosuppression (OR 1.8; 95%CI: 1.3-2.4; p < 0.001) and de novo lung cancer (OR 2.6; 95%CI: 1.5-4.4; p < 0.001). (4) Conclusions: Malignancies are an important source of morbidity and mortality following lung transplantation that should not be neglected. Patients undergoing single LT for emphysema are especially at higher risk of mortality due to lung cancer in the native lung.

Long-Term Safety, Outcome, and Clinical Effects of Subcutaneous and Intravenous Treprostinil Treatment in Patients with Severe Chronic Pulmonary Arterial Hypertension

Background: Current guidelines recommend treatment with parenteral prostacyclin analogs in patients with severe pulmonary arterial hypertension (PAH), who have insufficient response to treatment. Real-life data are sought to help physicians in treatment decisions and clinical care of patients. Objective: This study analyzed safety, clinical effects, and long-term outcomes of subcutaneous (sc) and/or intravenous (iv) treprostinil via different pump systems in consecutive patients with PAH. Methods: Thirty-seven patients with severe progressive PAH despite dual combination therapy (20 female, mean age: 52.3 ± 15 years, mean pulmonary vascular resistance: 12.1 ± 5.1 WU) were initiated with add-on treprostinil sc and were routinely clinically assessed. Changes in clinical parameters, adverse events, and outcome were analyzed retrospectively. Results: In 24 of 37 patients, treprostinil administration was continued iv via implantation of LENUS Pro® pump after 3 ± 1.3 months, 6 patients continued with sc therapy, and 7 discontinued treatment. After 3, 6, 9, and 12 months of treprostinil treatment, patients showed a significant improvement in mean 6-min walk distance and tricuspid annular plane systolic excursion compared to baseline. In 8 of the 24 patients, iv pumps required surgical revision. During a mean follow-up of 2.82 ± 1.95 years, 12 patients died, four received lung transplantation. Transplant-free survival after 1, 2, and 3 years was 85.7%, 69.2%, and 65.3%, respectively. Conclusion: sc treprostinil as add-on to double combination treatment significantly improved exercise capacity and right heart function. In most patients, treprostinil could be continued via more tolerable iv administration approach (LENUS Pro® pump), showing reasonable overall survival with respect to the severity of PAH.

Factors associated with quality of life in patients receiving lung transplantation: a cross-sectional study

BackgroundWith improved prognosis after lung transplantation (LTx), improving health-related quality of life (HRQL) in patients who have undergone LTx is a key goal. Although HRQL is improved significantly after transplantation, it is poorer than that in ordinary healthy people. However, the factors associated with poor HRQL remain unclear. This cross-sectional study aimed to identify the factors associated with poor HRQL in patients who have undergone LTx.MethodsBetween December 2018 and May 2022, 80 patients who had undergone LTx completed St. George’s Respiratory Questionnaire (SGRQ) as a disease-specific quality of life measure, the Short Form-12 (SF-12) as a generic quality of life measure, and modified Medical Research Council (mMRC) scale of dyspnea. The groups were assigned according to the median SGRQ-total score and the Japanese population standard for SF-12, and those with good HRQL were compared with those with poor HRQL. Independent factors were evaluated using multivariate analysis.ResultsWith regard to the SGRQ, there were significant differences in the forced expiratory volume in 1 s (FEV1) (P = 0.041), use of bronchodilators (P = 0.026), 6-min walk distance (6MWD) (P < 0.001), and Mmrc (P < 0.001) between better and poorer HRQL. For the SF-12 physical component summary score (PCS), age (P = 0.017), sex (P = 0.011), FEV1 (P < 0.001), forced vital capacity (FVC) (P < 0.001), diagnosis (P = 0.011), handgrip force (P = 0.003), 6MWD (P < 0.001), and Mmrc (P < 0.001) varied. Multivariate analyses revealed that Mmrc was the only independent factor in the SGRQ (P < 0.001, odds ratio [OR] = 6.65, 95% confidence interval [CI]: 2.49–17.74) and SF-12 PCS (P = 0.001, OR = 0.185, 95% CI: 0.07–0.52). There were significant correlations between the SGRQ-Total score and SF-12 PCS (correlation coefficient = -0.612, P < 0.001).ConclusionsDyspnea may be an independent factor of poor disease-specific and generic HRQL in LTx patients. The management of dyspnea may improve the HRQL in patients who have undergone LTx.

Transplantation of initially rejected donor lungs using ex vivo lung perfusion: A 5-year experience.

Ex vivo lung perfusion (EVLP) is a method for the evaluation and reconditioning of high-risk donor lungs to increase the pool of potential donor lungs. We reviewed all consecutive patients who received lung transplants from May 2012 to May 2017 with follow-up until July 2021. EVLP was used in lungs initially rejected due to inadequate oxygenation but without other contraindications. Lungs with improved oxygenation levels above the threshold were transplanted. The primary endpoint was the time to graft failure, which was defined as the time from surgery to death or re-transplantation, whichever occurred first. The secondary outcome was freedom from chronic lung allograft dysfunction. A total of 157 patients underwent transplantation during the study period. Thirty-nine patients received EVLP-treated donor lungs. Restricted mean graft survival time up to 7 years is 5.14 years for non-EVLP and 4.19 for EVLP, the difference being -0.95 (confidence interval [CI]-1.93 to 0.04, p = .059). The hazard ratio is 1.66 (CI 1.00-2.75, p = .046). Chronic lung allograft dysfunction was the highest contributor to mortality in both groups. There were significant differences in freedom from chronic lung allograft dysfunction at 12 and 24 months of follow-up (p = .005 and p = .030, respectively). Subgroup analyses revealed that the first patients who received EVLP in 2012-2013 had a substantially worse 5-year graft survival than those who received EVLP more recently in 2016-2017 (14.3% vs. 60.0%). For the latter, the 5-year graft survival was observed to be remarkably close to the non-EVLP group (60.8%). Long-term survival was significantly lower, and lung function was poorer among recipients in the EVLP group than in the non-EVLP group. However, the outcome of patients who received EVLP-treated lungs was observed to improve steadily after the first 2 years after EVLP was introduced in Denmark.

(371) Testosterone Levels after Lung Transplant: An Analysis of the TriNetX Research Network

Abstract Introduction Men with end stage organ dysfunction or failure are more likely to have low testosterone. In the case of men with heart and kidney failure, improvement in testosterone levels are seen after successful transplantation. Limited data exists regarding the natural course of serum testosterone after lung transplant. Objective To report incidence of low testosterone in men prior to lung transplant and to determine changes in testosterone levels after transplantation. Methods We compiled all clinical data from the TriNetX research network, a globally federated health research network (with waiver from Western IRB) that provides de-identified clinical information from 58 heath care organizations, and over 80 million patients located within the United States. We selected male patients (aged ≥ 18) with a history of lung transplant and testosterone levels recorded before and after transplantation. All men who had a recorded prescription for testosterone therapy were excluded. For all patients, we collected clinical information including demographics, comorbidities, laboratory findings, and medication use. Patients were stratified by testosterone levels and grouped into those who had low serum testosterone versus those with normal levels, with a cut-off point of 300 ng/dL. Patient characteristics were compared using descriptive statistics. Propensity score matching was performed between the two groups to normalize differences in pre-operative characteristics. Mean serum testosterone levels before and after transplantation was compared using a paired T test to determine change in serum testosterone levels after successful transplantation. Results A total of 37 men were identified with history of lung transplant, and testosterone levels recorded before and after transplant. Average serum testosterone level in the year prior to lung transplantation was 301.57 +/− 163.25. After transplantation, average serum testosterone was 332.37 +/− 200.92, for a mean difference of 30.80 (p = 0.4815). Prior to transplantation, 24 (65%) men met criteria for low serum testosterone. After transplantation 17 (46%) men demonstrated serum testosterone less than 300 ng/dl. Among men with low serum testosterone, average testosterone levels in the year prior to lung transplantation was 203.29 +/− 66.57, and was 332.37 +/− 200.92 after transplantation (p = 0.0057). Conclusions Among men with low serum testosterone receiving lung transplant, transplantation was associated with rescue of low testosterone levels. Further research incorporating a larger cohort is required to determine which patients recover endocrine function after lung transplant and whether etiology of chronic lung disease results in different outcomes after transplantation with regards to serum androgen level and function. Disclosure No

Computed tomography body composition and clinical outcomes following lung transplantation in cystic fibrosis

BackgroundLow muscle mass is common in patients approaching lung transplantation and may be linked to worse post-transplant outcomes. Existing studies assessing muscle mass and post-transplant outcomes include few patients with cystic fibrosis (CF).MethodsBetween May 1993 and December 2018, 152 adults with CF received lung transplants at our institution. Of these, 83 met inclusion criteria and had usable computed tomography (CT) scans. Using Cox proportional hazards regression, we evaluated the association between pre-transplant thoracic skeletal muscle index (SMI) and our primary outcome of death after lung transplantation. Secondary outcomes, including days to post-transplant extubation and post-transplant hospital and intensive care unit (ICU) length of stay, were assessed using linear regression. We also examined associations between thoracic SMI and pre-transplant pulmonary function and 6-min walk distance.ResultsMedian thoracic SMI was 26.95 cm2/m2 (IQR 23.97, 31.32) for men and 22.83 cm2/m2 (IQR 21.27, 26.92) for women. There was no association between pre-transplant thoracic SMI and death after transplant (HR 1.03; 95% CI 0.95, 1.11), days to post-transplant extubation, or post-transplant hospital or ICU length of stay. There was an association between pre-transplant thoracic SMI and pre-transplant FEV1% predicted (b = 0.39; 95% CI 0.14, 0.63), with higher SMI associated with higher FEV1% predicted.ConclusionsSkeletal muscle index was low for men and women. We did not identify a significant relationship between pre-transplant thoracic SMI and post-transplant outcomes. There was an association between thoracic SMI and pre-transplant pulmonary function, confirming the potential value of sarcopenia as a marker of disease severity.