Cohort Of Lung Transplant Recipients Research Articles

Association between Respiratory Virus Infection and Development of De Novo Donor-Specific Antibody in Lung Transplant Recipients.

Chronic lung allograft dysfunction (CLAD) is the most common cause of long-term lung allograft failure. Several factors, including respiratory virus infection (RVI), have been associated with CLAD development, but the underlying mechanisms of these associations are not well understood. We hypothesize that RVI in lung transplant recipients elicits the development of donor-specific antibodies (DSAs), thus providing a mechanistic link between RVI and CLAD development. To test this hypothesis, we retrospectively evaluated for the presence of HLA antibodies in a cohort of lung transplant recipients with symptomatic RVI within the first four months post-transplant using sera at two time points (at/directly after the transplant and following RVI) and time-matched controls without RVI (post-transplant). We found a trend toward the development of de novo DSAs in those with symptomatic RVI versus controls [6/21 (29%) vs. 1/21 (5%), respectively, p = 0.09]. No cases or controls had DSA at baseline. We also found increased rates of CLAD and death among those who developed class II DSA versus those who did not (CLAD: 5/7 (71.4%) vs. 19/34 (54.3%), death: 5/7 (71.4%) vs. 17/35 (48.6%)). Prospective studies evaluating the temporal development of DSA after RVI in lung transplant patients and the subsequent outcomes are warranted.

COVID-19 infection is mild and has minimal impact on lung function in well vaccinated and widely treated lung transplant recipients

BackgroundCOVID-19 has become a common infection affecting lung transplant recipients (LTR), who are at high risk for poor outcomes. Outcomes early in the pandemic were poor, but since the rollout of vaccination and novel COVID-19 treatments, outcomes of LTR have not been well described. Our aim was to evaluate the effect of COVID-19 on the clinical course and lung function trajectory in an Australian cohort of LTR. MethodsData was retrospectively collected from LTR with confirmed COVID-19 managed at Alfred Health, between August 2020 and December 2022. Baseline demographics, COVID-19 disease details (including severity) and spirometry pre and post infection have been analysed. ResultsA total of 279 LTR were included. The cohort was comorbid, but well vaccinated, with 275/279 (98.6%) having >2 COVID-19 vaccines at symptom onset. Severe disease occurred in only 17 cases (6%) and overall mortality was very low (4%). Prompt treatment with antivirals, particularly remdesevir (OR 0.18, 95% CI 0.04-0.81, p=0.02] and vaccination (OR 0.24, CI 0.08-0.81, p=0.01] were protective. There was not a clinically significant drop in lung function post COVID-19 with the median absolute decline in forced expiratory volume (FEV1) being 40mL (IQR 5-120mL, p<0.001), with a decline of >10% occurring in only 42 patients (17%). After multivariate adjustment, only rejection prior to COVID-19 was significantly associated with FEV1 decline afterwards (OR 3.74, 1.12-11.86, p=0.03). ConclusionsIn our highly COVID-19 vaccinated, promptly treated LTR, the majority of COVID-19 infections were mild and did not result in a clinically significant decline in lung function.

The Association of Post-Lung Transplant Pulmonary Embolism With the Development of Chronic Lung Allograft Dysfunction.

Pulmonary embolism (PE) is a rare yet serious postoperative complication for lung transplant recipients (LTRs). The association between timing and severity of PE and the development of chronic allograft lung dysfunction (CLAD) has not been described. A single-center, retrospective cohort analysis of first LTRs included bilateral or single lung transplants and excluded multiorgan transplants and retransplants. PEs were confirmed by computed tomography angiography or ventilation/perfusion (VQ) scans. Infarctions were confirmed on computed tomography angiography by a trained physician. The PE severity was defined by the Pulmonary Embolism Severity Index (PESI) score, a 30-d post-PE mortality risk calculator, and stratified by low I and II (0-85), intermediate III and IV (85-125), and high V (>125). PE and PESI were analyzed in the outcomes of overall survival, graft failure, and chronic lung allograft dysfunction (CLAD). We identified 57 of 928 patients (6.14%) who had at least 1 PE in the LTR cohort with a median follow-up of 1623 d. In the subset with PE, the median PESI score was 85 (75.8-96.5). Most of the PESI scores (32/56 available) were in the low-risk category. In the CLAD analysis, there were 49 LTRs who had a PE and 16 LTRs (33%) had infarction. When treating PE as time-dependent and adjusting for covariates, PE was significantly associated with death (hazard ratio [HR] 1.8; 95% confidence interval [CI], 1.3-2.5), as well as increased risk of graft failure, defined as retransplant, CLAD, or death (HR 1.8; 95% CI, 1.3-2.5), and CLAD (HR 1.7; 95% CI, 1.2-2.4). Infarction was not associated with CLAD or death. The PESI risk category was not a significant predictor of death or CLAD. PE is associated with decreased survival and increased hazard of developing CLAD. PESI score was not a reliable predictor of CLAD or death in this lung transplant cohort.

Airway pepsinogen A4 identifies lung transplant recipients with microaspiration and predicts chronic lung allograft dysfunction

BackgroundAspiration is a known risk-factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration – however they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs while others, like pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. MethodsExpression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to pre-existing markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after anti-reflux surgery was assessed in a third cohort of LTRs. ResultsPGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Anti-reflux surgery was associated with reduced airway PGA4. ConclusionsAirway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.

Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study

Whether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.

Oesophageal stasis is a risk factor for chronic lung allograft dysfunction and allograft failure in lung transplant recipients.

Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed. Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure. Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.

The effect of allograft ischemic time on outcomes following bilateral, single, and reoperative lung transplantation

ObjectiveTo determine whether allograft ischemic times affect outcomes following bilateral, single, and redo lung transplantation. MethodsA nationwide cohort of lung transplant recipients from 2005 through 2020 was examined using the Organ Procurement and Transplantation Network registry. The effects of standard (<6 hours) and extended (≥6 hours) ischemic times on outcomes following primary bilateral (n = 19,624), primary single (n = 688), redo bilateral (n = 8461), and redo single (n = 449) lung transplantation were analyzed. A priori subgroup analysis was performed in the primary and redo bilateral-lung transplant cohorts by further stratifying the extended ischemic time group into mild (≥6 and <8 hours), moderate (≥8 and <10 hours), and long (≥10 hours) subgroups. Primary outcomes included 30-day mortality, 1-year mortality, intubation at 72 hours' posttransplant, extracorporeal membrane oxygenation (ECMO) support at 72 hours' posttransplant, and a composite variable of intubation or ECMO at 72 hours' posttransplant. Secondary outcomes included acute rejection, postoperative dialysis, and hospital length of stay. ResultsRecipients of allografts with ischemic times ≥6 hours experienced increased 30-day and 1-year mortality following primary bilateral-lung transplantation, but increased mortality was not observed following primary single, redo bilateral, or redo single-lung transplants. Extended ischemic times correlated with prolonged intubation or increased postoperative ECMO support in the primary bilateral, primary single, and redo bilateral-lung transplant cohorts but did not affect these outcomes following redo single-lung transplantation. ConclusionsSince prolonged allograft ischemia correlates with worse transplant outcomes, the decision to use donor lungs with extended ischemic times must consider the specific benefits and risks associated with individual recipient factors and institutional expertise.

(694) Preservation of Lung Function Despite Covid-19 Infection in a Cohort of Lung Transplant Recipients

(694) Preservation of Lung Function Despite Covid-19 Infection in a Cohort of Lung Transplant Recipients

(692) Safety and Immunogenicity of the AntiCOVID19 Vaccines in a Cohort of Lung Transplant Recipients

(692) Safety and Immunogenicity of the AntiCOVID19 Vaccines in a Cohort of Lung Transplant Recipients

Impact of Cytomegalovirus DNAemia Below the Lower Limit of Quantification: Multistate Model in Lung Transplant Recipients

Background Cytomegalovirus (CMV) infections following transplantation lead to significant morbidity. Identification of CMV DNAemia continually improves and now viral loads below the lower limit of quantification (LLOQ) are detectable. However, the clinical course of positive CMV qPCR &lt;LLOQ is unknown. Methods This retrospective study included lung transplant recipients experiencing their first episode of positive CMV qPCR &lt;LLOQ with all qPCR assays conducted using COBAS® AmpliPrep/COBAS® TaqMan®. A Markov-like multistate model was utilized to describe the course of CMV DNAemia &lt;LLOQ. A multivariable model was employed to identify predictors of transitioning to a positive, quantifiable state. Results 100 patients with a CMV &lt;LLOQ result were included, encompassing 1,248 transitions in the six months following first episode of CMV qPCR &lt;LLOQ. There was an 97.8% probability of remaining &lt;LLOQ or undetectable and a 2.2% probability of transitioning to a positive, quantifiable qPCR state. The multivariable regression model identified treatment for rejection, increasing body mass index, valganciclovir therapy, and increasing CMV qPCR viral load as being predictive of transitioning from CMV qPCR undetectable or &lt;LLOQ into a positive, quantifiable CMV qPCR state. Conclusions Most patients did not transition into a positive, quantifiable CMV qPCR state following a first episode of positive CMV qPCR &lt;LLOQ in this cohort of lung transplant recipients.

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series.

Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug-drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.

Outcomes of COVID-19 in a Large Cohort of Lung Transplant Recipients: A Retrospective Study

Background: Early reports of COVID-19 in lung transplant recipients (LTRs) showed high hospitalization and mortality rates. However, the outcomes of COVID-19 in LTRs since the advent of newer therapies and vaccines have been poorly defined. Methods: We evaluated the risks for SARS-CoV-2-related hospitalization and mortality in a cohort of LTRs at the Henry Ford Lung Transplant Program in Detroit, Michigan during the study period March 2020–March 2022. Univariate logistic regression, followed by multivariable modeling were performed to estimate the odds ratio (OR) with 95% confident intervals (CI). Results: Sixty-four laboratory-confirmed SARS-CoV-2 infections were identified in 59 patients. For the primary analysis of the hospitalization and mortality risks, we included these 59 patients with symptomatic COVID-19. SARS-CoV-2 infections were confirmed with real-time polymerase chain reaction (RT-PCR) from a nasopharynx swab. The mean age (±STD) was 61 (±12), 63% were males, 27% were African Americans, and the time from lung transplant to COVID-19 was 5.5 (±4.8) years. Thirty-four (57.6%) patients were hospitalized, and the inpatient mortality rate was 24% (8/34). A multivariable analysis showed that patients with a higher baseline forced expiratory volume (FEV1) were less likely to be hospitalized (OR = 0.91 and 95% CI 0.87–0.98, p = 0.02). Seventy-five percent (75%; 6/8) of patients on invasive mechanical ventilation died, compared with only 8% mortality rate in those without mechanical ventilation (OR = 36.0 and 95% CI 4.2–310.4, p &lt; 0.01). Although a trend toward a higher risk of death was observed in those infected during the Alpha (p = 0.17) and Delta (p = 0.22) waves, no significant risk was detected after adjusting for other covariates. Five LTRs were diagnosed with COVID-19 twice. Thirty of the sixty-four COVID-19 cases (46.8%) occurred in LTRs that had received at least two doses of any of the available mRNA vaccines at a median of 123 days (IQR 98–164 days) after vaccination. Twelve of the thirty (40%) were hospitalized, and four patients (33%) died during their hospitalizations. Conclusions: In our LTR population, the hospitalization and mortality rates associated with COVID-19 were high despite the increased use of new therapies. Vaccine-breakthrough infections were common and were associated with poor outcomes. Studies are needed to determine optimal prevention and therapeutic strategies to improve COVID-19 outcomes in LTRs.

Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA Vaccination.

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0–491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0–159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.

Outcomes of SARS-CoV-2 Infection in Lung Transplant Recipients: A Single Center Experience

PurposeOutcomes of Covid-19 in lung transplant recipients (LTr) were reported in the beginning of the pandemic. Only few centers reported on their experience since December 2020 when vaccines received emergency use authorization. We aim to investigate the outcome of SARS-CoV-2 infection in a cohort of LTr at our center in Detroit, Michigan.MethodsRetrospective chart review study of adult LTr with confirmed SARS-CoV-2 infection from March 2020 to August 2021.ResultsThirty LTr were diagnosed with SARS-CoV-2 infection confirmed by RT PCR of nasopharynx. Median age at diagnosis was 63; 53% were males; 57% Caucasians and 40% of African descendance. Most patients underwent bilateral LT for interstitial lung disease (46%) and for pulmonary sarcoidosis (23%). The median time post LT was 3.1 years. Most patients needed hospitalization for respiratory failure secondary to Covid-19 (73%). Eleven patients were initially managed as outpatient. Five patients received outpatient combination of monoclonal antibodies with three of them later requiring hospitalization for development of hypoxia. None of the patients with initial out of the hospital management died. Amongst 21 hospitalized LTr, six patients were diagnosed with severe pneumonia and ARDS requiring heated high flow and invasive mechanical ventilation (IMV) in 4 patients. 28-day mortality was 10% and ICU mortality was 25% (50% mortality in those on IMV). Twelve hospitalized patients (57%) were treated with remdesivir. Augmented systemic corticosteroids was used in 85% of cases. Cycle cell inhibitor was held in 71% of the cases. Bilateral ground glass opacities of the allografts were common. None of the patients that received at least one dose of mRNA vaccine died.ConclusionOutcomes in LTr infected with SARS-CoV-2 varies. Early reports showed high mortality rate in severe and critical Covid-19 in LTr. Although hospitalization rate in this cohort was high, only four patients in our cohort required IMV during acute Covid-19. Two of them died; both were unvaccinated. Another unvaccinated patient died due to allograft rejection two months after testing positive to SARS-CoV-2. Most cases were mild to moderate despite frequent radiographic findings of pneumonia. Underreporting and exclusion of mild cases as well as likely protective effect of vaccination and use of monoclonal antibodies may explain our different outcomes.

Esophageal Disorders in Lung Transplant Recipients: Association with Chronic Lung Allograft Dysfunction and Survival

<h3>Purpose</h3> Chronic lung allograft dysfunction (CLAD) is a major cause of morbidity and mortality in lung transplant recipients and is often triggered by aspiration events, potentiated by esophageal and gastric disorders. The two major classes of esophageal disorders include: 1) disorders of peristalsis and 2) esophagogastric junction outflow obstruction (EGJOO). Previous small studies have shown conflicting relationships between esophageal function and the development of CLAD. Herein, we sought to investigate the relationship between esophageal disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. <h3>Methods</h3> All lung transplant recipients from 2000-2018 with available esophageal manometry testing within first 7 months post-transplant were included in this study. Subjects were categorized into three groups: 1) no esophageal disorders, 2) disorder of peristalsis, and 3) EGJOO (defined by the 2007 Chicago Classification System). Disorders of peristalsis were further divided into major disorder (absent contractions) and minor disorder (irregular contractions). Univariable Cox proportional hazards models were used to determine the relationship between esophageal disorders and the development of CLAD and allograft failure (death/retransplant). <h3>Results</h3> Of 487 subjects, 47 (10%) had a disorder of peristalsis (8 major, 39 minor) and 57 (12%) had EGJOO. Older subjects were more likely to have an esophageal disorder (p=0.001). A major disorder of peristalsis was associated with an increased risk of CLAD [HR 2.78 (95% CI 1.23-6.28); p=0.01] and allograft failure [HR 3.17 (95% CI 1.49-6.77); p=0.003]. A minor disorder of peristalsis was not significantly associated with CLAD or allograft failure. EGJOO was associated with an increased risk of CLAD [HR 1.63 (95% CI 1.11-2.40); p=0.01] and allograft failure [HR 1.73 (1.18-2.54); p=0.005]. <h3>Conclusion</h3> In a large retrospective cohort we observed that lung transplant recipients with major disorders of peristalsis and EGJOO were at an increased risk of CLAD and death/retransplant. In contrast, people with minor disorders of peristalsis were not at an increased risk of these outcomes. These findings will help with risk-stratification of lung transplant recipients and personalization of treatment for aspiration prevention.

Comparative Influence of Primary Healthcare Payer Types on Patient Outcomes After Lung Transplantation

<h3>Purpose</h3> Optimal outcomes in patients undergoing lung transplantation requires significant utilization of resources. We, therefore, evaluated the association of primary payer type with outcomes after lung transplantation. <h3>Methods</h3> Using the UNOS (United Network for Organ Sharing) registry we studied 15129 first-time lung transplant recipients from January 2000 to December 2017 and compared all-cause mortality at 1 year. Single lung (N=4524) and double lung (N=10605) recipients were subgrouped by payer type: Medicaid (32% and 27% respectively), Medicare (26% and 18%), and commercial insurance (42% and 54%). <h3>Results</h3> Primary payer type was not significantly associated with inferior outcomes at 1 year following both single-lung (P=0.447) and double lung transplant (P=0.531). Insurance was also not a predictor of worse outcomes following single lung transplant after 3 years (P=0.107). However, insurance type was associated with different outcomes in double lung recipients at 3 years (P=0.028) and remained significant predictors of early mortality after adjustment for covariates in multivariate Cox proportional hazard ratio analyses (P<0.05). <h3>Conclusion</h3> These data are among the first to provide insight into the impact of insurance status on patient outcomes for a modern cohort of lung transplant recipients. All-cause mortality after single-lung and double-lung transplantation did not differ significantly by payer type after 1 year. However, primary payer type was associated with 3-year outcomes following double lung transplant. More research is needed to confirm and define the reasons for insurance type playing a role in outcomes after double lung transplant as compared to single lung transplant.

Characterization of Letermovir Use and Pharmacokinetic Interaction with Immunosuppression in Lung Transplant Recipients

<h3>Purpose</h3> Cytomegalovirus (CMV) is a common complication in lung transplant recipients (LTRs). Traditional agents to treat and prevent CMV carry significant toxicities. Prior studies of the CMV-active antiviral letermovir have described pharmacokinetic interactions with immunosuppressive medications, but the LTR population has not routinely been included in these studies and clinical relevance remains unclear. <h3>Methods</h3> This single-center retrospective study included 16 LTRs transplanted between 12/1/2016-7/31/2020 initiated on letermovir while on calcineurin inhibitor and/or mTOR inhibitor-based immunosuppression. Dose-adjusted immunosuppression troughs (concentration/dose or C/D ratios) were collected at baseline and for 14 days after letermovir initiation. Descriptive statistics were used for baseline characteristics and select outcomes. Wilcoxon Sign Rank test was utilized for the primary outcome comparing C/D pre- and post- letermovir initiation. <h3>Results</h3> Patient characteristics are described in Table 1. The median C/D of all immunosuppressive agents were not significantly different after letermovir initiation (Table 2). Median time to resolution of leukopenia/neutropenia was 6 days and time to CMV viremia clearance in those treated was 45 days. <h3>Conclusion</h3> In this cohort of LTRs switched to letermovir for CMV prophylaxis or treatment, immunosuppression C/D ratios were not significantly different after conversion. Empiric dose adjustment is likely unnecessary for all LTRs; future studies should clarify the optimal use of letermovir in the SOT population.

One Year Into the Pandemic: Evolving COVID-19 Outcomes in Lung Transplant Recipients, a Single-center Experience.

Background.In the early months of the coronavirus disease 2019 (COVID-19) pandemic, our center reported a mortality rate of 34% in a cohort of 32 lung transplant recipients with COVID-19 between March and May 2020. Since then, there has been evolving knowledge in prevention and treatments of COVID-19. To evaluate the impact of these changes, we describe the clinical presentation, management, and outcomes of a more recent cohort of lung transplant recipients during the second surge and provide a comparison with our first cohort.Methods.We conducted a retrospective cohort study that included all consecutive lung transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. We compared baseline demographics and major outcomes between the first- and second-surge cohorts.Results.We identified 47 lung transplant recipients (median age, 60; 51% female) who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. The current cohort had a higher proportion of patients with mild disease (34% versus 16%) and fewer patients with a history of obesity (4% versus 25%). Sixty-six percent (n = 31) required hospitalization and were treated with remdesivir (90%) and dexamethasone (84%). Among those hospitalized, 77% (n = 24) required supplemental oxygen, and 22% (n = 7) required invasive mechanical ventilation. The overall 90-d mortality decreased from 34% to 17% from the first cohort to the second (adjusted odds ratio, 0.26; 95% confidence interval, 0.08-0.85; P = 0.026).Conclusions.Although COVID-19–associated mortality rate in lung transplant recipients at our center has decreased over time, COVID-19 continues to be associated with significant morbidity and mortality.

Venoarterial Versus Venovenous Extracorporeal Membrane Oxygenation As Bridge to Lung Transplantation

BackgroundVenovenous (VV) extracorporeal membrane oxygenation (ECMO) has been used as a bridge to lung transplantation with acceptable outcomes. We hypothesized that venoarterial (VA) ECMO, as part of a multidisciplinary ECMO program, yields similar outcomes as VV ECMO as a bridge in lung transplantation. MethodsRecords of all patients who had undergone ECMO with the intention to bridge to lung transplantation at University of California, Los Angeles, from January 1, 2012, to March 31, 2020, were reviewed. Baseline characteristics, in-hospital outcomes, long-term survival, and freedom from bronchiolitis obliterans syndrome were assessed. ResultsDuring this interval, 58 patients were placed on ECMO with the intention to bridge to lung transplantation: 27 on VV ECMO, and 31 on VA ECMO, with a median duration of 7 and 17 days of support, respectively (P = .01). Successful bridge to lung transplantation occurred in 21 VV patients (78%) and in 26 VA patients (84%). Incidence of primary graft dysfunction III at 72 hours in the VV and the VA cohorts was 0% and 4%, respectively (P = .99). In-hospital and 90-day survival of the VV and VA groups was 100% and 96%, respectively (P = .99). Survival of the 2 groups at 3 years was not significantly different from a contemporary cohort of lung transplant recipients not bridged with ECMO. ConclusionsVA and VV ECMO can both be used as a bridge to lung transplantation with high success, with short and medium-term survival similar to non-bridged lung transplant recipients. Both modes should be considered effective at bridging select candidates to lung transplantation.

Outcomes with alemtuzumab induction therapy in lung transplantation: a comprehensive large-scale single-center analysis.

Alemtuzumab is a monoclonal antibody targeting CD52, increasingly used as induction therapy after transplantation. The aim of this study was to analyze the outcomes of alemtuzumab induction therapy followed by a low-dose maintenance immunosuppression in a large single-center cohort of lung transplant recipients. All patients, who received alemtuzumab induction followed by a low-dose maintenance immunosuppression were included in the analysis. Short- and long-term outcomes were analyzed. 721 lung transplant recipients, transplanted between January 2008 and June 2019, were included in this retrospective study. Freedom from higher-grade ACR at 1, 5, and 10years was 98%, 96%, and 96%, respectively. Thirty-nine patients (5%) developed clinical AMR. Twenty-one percent of patients developed high-grade CKD. A total of 1488 infections were recorded. Sixteen percent were diagnosed within the first 3months. Sixty-two patients (9%) developed a malignancy during follow-up. Freedom from CLAD at 1, 5, and 10years was 94%, 72%, and 53%, respectively. Overall survival rates at 1, 5, and 10years were 85%, 71%, and 61%, respectively. Alemtuzumab induction combined with a low-dose tacrolimus protocol is safe and associated with low rates of acute and chronic rejection, as well as an excellent long-term survival.