Purpose: It is not known whether outcomes after COVID-19 meaningfully differ for single-lung (SL) and double-lung (DL) transplant recipients. We describe a cohort of SL and DL recipients who were diagnosed with COVID-19.

Purpose: Recent studies suggest 10oC cold storage for extended periods of time in lung transplants may offer equivalent or better clinical outcomes and improve operational efficiency. In the present study, we report on our experience successfully implementing a 10oC cold storage protocol in a high-volume transplant center using existing hospital refrigeration resources

Purpose Multiorgan transplants have increased over the last two decades. Post-transplant survival data has not yet been reported on lung-kidney recipients despite the growth in numbers. In this study we compared post-transplant survival between lung-kidney and lung transplant recipients. Methods We conducted a retrospective cohort study using the UNOS registry to analyze post-transplant survival for lung-kidney compared with lung transplant recipients from May 2005-June 2021. We used multivariable Cox proportional hazard regression analysis to compare post-transplant survival and Kaplan-Meier to estimate unadjusted 1- and 5-year survival. Covariates were selected using a directed acyclic graph and included age, single/double transplant, gender, mechanical support at transplant, lung allocation score, and transplant center volume. Results Since 2005, the number of patients waitlisted and transplanted with simultaneous lung-kidney has increased in the US, reaching 19 transplants in 2021. There was no significant difference in post-transplant survival between the lung-kidney and lung groups in the unadjusted or adjusted analyses (1.04, 95%CI: 0.76-1.43). However, there was violation of the proportional hazards assumption with trends towards decreased survival at 1-year post-transplant and towards improved long term survival in lung-kidney recipients. The 1- and 5-year survival was 78% (95%CI: 0.68-0.86) and 61% (95%CI: 0.48-0.72) for lung-kidney recipients, respectively. This compared with 86% (95%CI: 0.86-0.87) 1-year and 55% (95%CI: 0.54-0.55) 5-year survival in lung alone recipients. Conclusion There is no significant difference in post-transplant survival between lung and lung-kidney transplant recipients, but there is a trend towards reduced early post-transplant survival in the lung-kidney group. Simultaneous lung-kidney transplant is a viable therapeutic option for appropriately selected patients with end-stage lung disease who have concurrent advanced kidney disease.

Purpose Despite data supporting single lung transplant (SLT) as viable option for patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), practice patterns vary across U.S. transplant centers. In this study, we investigate changes in use of SLT vs double lung transplant (DLT) at U.S. centers over the last 17 years. Methods Using the UNOS registry, we conducted a retrospective cohort study from May 2005 - December 2021 describing the frequency of SLT and DLT in COPD and ILD. COPD included emphysema/COPD and alpha-1 anti-trypsin. ILD included chronic hypersensitivity pneumonitis, non-specific interstitial pneumonia, and idiopathic pulmonary fibrosis. We divided the study period into eras: 2005-2009, 2010-2015, and 2016-2021. Yearly trends were compared using cuzick's test. We used multivariable logistic regression to evaluate the association between era and odds of undergoing DLT. Covariates were selected using a directed acyclic graph, including pulmonary arterial hypertension, age, lung allocation score and extracorporeal membrane oxygenation support. Results The frequency of SLT for both COPD and ILD have steadily decreased in the U.S., from 45.6% and 52.4% in 2005 to 17.6% and 26.6% in 2021, respectively, p <0.001. Compared to the earliest era (2005-2009), subjects in the most recent era (2016-2021) were significantly more likely to receive a DLT (COPD adjusted OR 2.94, 95%CI: 2.57-3.37; ILD adjusted OR 3.6, 95%CI: 3.21-4.05). Centers had varied practice across eras; in the earliest era (2005-2009), 49.2% and 42.9% of transplant centers performed majority single lung transplant for COPD and ILD respectively. Compared with the current era (2016-2021) where only 15.6% and 17.9% of centers performed majority SLT for COPD and ILD recipients. Conclusion Fewer patients with COPD and ILD are undergoing SLT despite a worsening organ shortage. In 2005, nearly half of centers performed majority SLT for these patients, now most transplant centers in the U.S. perform DLT for these patients.

SLT, these data should be interpreted with caution given small patient numbers and lack of statistical power.Future research should be focused on and powered to assess differences in outcomes for SLT with and without the use of CLES.

Purpose Single (SLT) or double lung transplant (DLT) for COPD patients remains controversial. Which patients derive the greatest benefits from DLT is unknown. In this study, we investigate whether age alters the benefit of DLT on survival and hospital-free days (HFD). Methods Using the UNOS registry, we conducted a retrospective cohort study of 6,767 COPD transplant recipients from 2005-2020. Four age groups (<50, 50-65, 65-70, and >70 years) were made using cubic splines. A multivariable flexible parametric survival model was used to compare transplant survival for SLT vs DLT across age groups, with subgroup analysis by left and right laterality. We compared HFD at 90 days using negative binomial regression. Results SLT was associated with decreased transplant survival compared with DLT (HR=1.25, CI 1.13-1.39). Relative to DLT, left SLT was associated with lower transplant survival (HR=1.36, CI 1.21-1.52) than right SLT (HR=1.14, CI 1.01-1.28). The predicted 5-yr survival was 58% for DLT, 55% for right SLT and 50% for left SLT. The survival benefit of DLT did not vary significantly with age. Age 65-70 and age > 70 were the most important predictors of survival; the predicted 5-yr survival for ages <50, 50-65, 65-70 and >70 were 58%, 57%, 51% and 40%, respectively. SLT was associated with more HFD, 67 vs 63 days for SLT and DLT (IRR=1.06, CI 1.01-1.12) and this did not vary significantly by age. Increasing age group was associated with fewer HFD, 69, 66, 62 and 60 days, respectively. Conclusion SLT recipients, particularly left SLT, have reduced transplant survival, but SLT recipients have more HFD compared to DLT. These effects did not vary significantly with age. Age is the most important predictor of transplant survival and HFD.

Purpose Chronic lung allograft dysfunction (CLAD) is the primary cause of long-term mortality after lung transplantation. Aspiration of bile acids has been associated with CLAD and lipidomic dysregulation. This study evaluates the role of large airway bronchial wash (LABW) lipidomics and diagnosis of CLAD. Methods LABW (n=611) samples were obtained from 305 lung transplant recipients at different timepoints. Concentrations of 26 specific lipid subfamilies were obtained using liquid chromatography mass spectrometry. Lipid percentages where stratified by highest tertiles. The primary outcome of interest was development of CLAD from sampling time. Time-to-event analysis was done using Kaplan-Meier functions and a multivariable Cox proportional hazards model adjusting for baseline comorbidities. Results Samples with CLAD at the time of collection showed higher percentages of hexosylceramides (HEXCER), CE, sphingomyelin (SM) and lactosylceramide (LACCER). A high percentage of bismethyl-phosphatidic acid (BMP), CE, phosphatidylethanolamine (PEP), dehydrosphingosine (DHSM), lysophosphatidylethanolamine (LPE), ganglioside (GM3), phosphatidyl-serine (PS) were associated with an increased hazards of CLAD by univariable analysis. A high percentage of CE (HR: 1.48, 95% CI: 1.09-2.03, P=0.013) were independent predictors of CLAD by multivariable analysis. High percentages of CER (HR: 0.49, 95% CI: 0.36-0.66, P<0.001) and a high LACCER:CER ratio (HR: 0.45, 95% CI: 0.34-0.62, P<0.001) were independently associated with decreased hazards of CLAD. Conclusion Airway lipidomic qualititative changes show a distinct phenotype that associate with the presence and risk of development of CLAD. Percentages of CE, CER and LACCER:CER ratios correlate independently with increased risk of development of CLAD. Changes in LABW lipids may serve as biomarkers for CLAD and elucidate pathophysiologic changes after transplant.

Purpose The lung transplant recipient population has become older over the last 10 years. The impact of an aging population on post-operative outcomes, post-transplant survival, and frequency of cancer is not well described. Methods We conducted a single center retrospective cohort study of transplant patients between January 2010 and March 2019. We collected baseline characteristics, early post-operative outcomes, post-transplant survival, and time to malignancy. We divided our cohort by age < 65 and age ≥ 65. Differences in baseline variables were compared with chi-square analysis. Cancer was sub-divided into solid organ, skin, PTLD and other hematologic malignancies. Competing risk regression was used to compare time to malignancy and multivariable Cox proportional hazards model was used compare post-transplant survival. Results 603 patients underwent transplant from 2010- 2019, of whom 470 were less than 65 years of age. Patients ≥ 65 had lower LAS at transplant (47.6 vs 50.9) and decreased post-transplant survival (HR 1.45, 95%CI: 1.06-1.97, p=0.019). One-year survival was similar, 92.4% vs 89.3% for age ≥ 65 and < 65 respectively, while 5-year survival was decreased among patients ≥ 65, 56.0% vs 70.0%. There was no difference in post-transplant length of stay, ICU length of stay, duration of mechanical ventilation, or discharge destination. There may be an increased risk of all cancer in adults ≥ 65, though this was not significant (sHR: 1.42, 95%CI: 0.98 - 2.05). Patients ≥ 65 had increased risk of skin cancer (sHR: 2.02, 95% CI 1.29-3.18, p=0.002), with an incidence of 21.1% after median of 992 days from transplant (IQR 473 - 1509) compared with 12.1% after median of 1171 days (IQR 596 - 2141) in patients < 65. Conclusion Lung transplantation is a viable treatment for patients over 65 with similar early post-transplantation outcomes and a modest reduction in five-year survival. There was an increased risk of skin cancer in adults over 65, and may be an increased risk of all cancers in adults over 65.

PurposeThe role of single vs double lung transplantation for ILD remains controversial due to heterogeneity within this population. This study elucidates the role of explant histology on outcomes among patients undergoing a single vs double lung transplant.MethodsA total of 412 patients with ILD transplanted from 2001-2019 at our institution were retrospectively reviewed. Patients were stratified by those who underwent a single (n=239, 58%) or double (n=173, 42%) lung transplant. Explant pathology reports were analyzed to understand the effect of histologic phenotypes and post-transplant outcomes. Primary outcomes of interest included overall and CLAD free survival. Treatment effects were obtained using a multivariable Cox-proportional hazards function.ResultsOf the total population, 41.7% had UIP, 26.5% NSIP, 5.8% mixed NSIP+UIP, 14.8% hypersensitivity pneumonitis (HP), and 11.2% sarcoid on explant pathology. Overall survival was similar between histologic phenotypes. HP and NSIP had earlier development of CLAD compared to sarcoidosis and UIP. A single lung transplant was an independent predictor of mortality among recipients with HP at explant pathology on multivariable analysis. Single lung transplant was also an independent predictor for CLAD among patients with NSIP and HP. The rest of the histologic phenotypes UIP, mixed NSIP+UIP ad sarcoid failed to show a significant difference in any of the outcomes by the use of single vs double lung transplant.ConclusionPatients with ILD have distinct pathologic characteristics and related post lung transplant outcomes. Recipients with UIP, mixed NSIP+UIP and sarcoid treated with a single lung transplant had no adverse overall and CLAD-free survival. Recipients with conditions at risk for earlier CLAD, such as HP and NSIP, may benefit from double lung transplantation. Lung biopsies prior to transplantation may aid in donor lung allocation among patients with ILD and optimize organ utilization. The role of single vs double lung transplantation for ILD remains controversial due to heterogeneity within this population. This study elucidates the role of explant histology on outcomes among patients undergoing a single vs double lung transplant. A total of 412 patients with ILD transplanted from 2001-2019 at our institution were retrospectively reviewed. Patients were stratified by those who underwent a single (n=239, 58%) or double (n=173, 42%) lung transplant. Explant pathology reports were analyzed to understand the effect of histologic phenotypes and post-transplant outcomes. Primary outcomes of interest included overall and CLAD free survival. Treatment effects were obtained using a multivariable Cox-proportional hazards function. Of the total population, 41.7% had UIP, 26.5% NSIP, 5.8% mixed NSIP+UIP, 14.8% hypersensitivity pneumonitis (HP), and 11.2% sarcoid on explant pathology. Overall survival was similar between histologic phenotypes. HP and NSIP had earlier development of CLAD compared to sarcoidosis and UIP. A single lung transplant was an independent predictor of mortality among recipients with HP at explant pathology on multivariable analysis. Single lung transplant was also an independent predictor for CLAD among patients with NSIP and HP. The rest of the histologic phenotypes UIP, mixed NSIP+UIP ad sarcoid failed to show a significant difference in any of the outcomes by the use of single vs double lung transplant. Patients with ILD have distinct pathologic characteristics and related post lung transplant outcomes. Recipients with UIP, mixed NSIP+UIP and sarcoid treated with a single lung transplant had no adverse overall and CLAD-free survival. Recipients with conditions at risk for earlier CLAD, such as HP and NSIP, may benefit from double lung transplantation. Lung biopsies prior to transplantation may aid in donor lung allocation among patients with ILD and optimize organ utilization.

Purpose: Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the surfactant protein (SP)-A gene of the donor lung allograft and recipient post-transplant outcome. Methods: Lung-transplant patients (n=192) were prospectively followed-up with pulmonary function tests, bronchoscopies with bronchoalveolar lavage and biopsies. Donor lungs were assayed for SP-A1 (6A(n)) and SP-A2 (1A(n)) gene polymorphism using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. Results: SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A(0) (n=102) versus 1A(1) variant (n=68) or SP-A2 genotype 1A(0)1A(0) (n=54) versus 1A0A1 (n=38) had greater survival at 1 year (log-rank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for 1-year survival and diagnosis showed a reduced survival for 1A(1) variant and the 1A(0)1A(1) genotype. Furthermore, when survival was conditional on 1-year survival no significance was observed, indicating that the survival difference was due to the first year's outcome associated with the 1A(1) variant. Conclusion: Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A(1) had a reduced survival at 1 year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.

Prior to November 2017, low local lung availability was associated with longer waitlist times and higher LAS at transplant that were much more pronounced for double lung recipients. Since expanding allocation to 250 miles, meaningful differences in LAS at transplant have not yet been observed.