Survival In Lung Transplant Recipients Research Articles

Impact of Prolonged Cold Ischemia Time on Long-Term Survival in Lung Transplant Recipients

Cold ischemia time (CIT) influences short- and long-term outcomes in lung transplant recipients. Most studies proved that prolonged CIT causes increased mortality. This study aimed to investigate the impact of prolonged CIT on patient survival time after lung transplantation (LTx). The retrospective study group consisted of 139 patients who underwent double LTx in a single center between January 2018 and August 2022. Prolonged ischemic time (PIT) was defined as total ischemic time >6 hours and divided into smaller time intervals according to increasing PIT (6-8, 8-10, 10-12, >12 hours). The assessed outcomes were 1- and 4-year survival. Among the study group, PIT was observed in 98% (n = 137), and its average value was 10.33 hours. The prolonged CIT of 6 to 8 hours occurred in 10% (n = 14), 8 to 10 hours in 34% (n = 47), 10 to 12 hours in 36% (n = 49), and >12 hours in 20% (n = 27). In a comparison of 1-year survival between the PIT 6- to 10-hour group and the >10-hour arm (88% vs 78%), the difference was not statistically significant (P > .05). PIT is a risk factor for reduced long-term survival in LTx recipients. Increasing PIT may be associated with higher mortality at 1 and 4 years. All efforts to reduce the duration of ischemic time can benefit patient survival after LTx.

(1019) - Long-Term Survival of Lung Transplant Recipients with Connective Tissue Disease and Esophageal Dysfunction: An 11-Year Single-Center Experience

(1019) - Long-Term Survival of Lung Transplant Recipients with Connective Tissue Disease and Esophageal Dysfunction: An 11-Year Single-Center Experience

(945) - Outcomes and Risk Factors for Poor Graft Survival in Lung Transplant Recipients with BMI = 35 Kg/m2 - A Single Center Experience

(945) - Outcomes and Risk Factors for Poor Graft Survival in Lung Transplant Recipients with BMI = 35 Kg/m2 - A Single Center Experience

O204: The influence of HLA matching on graft survival in lung transplant recipients is indication specific: An UNOS database analysis

Abstract Background and aims The importance of human leukocyte antigen (HLA) matching in lung transplantation remains unclear, and the influence of indication in HLA compatibility is unknown. This study aimed to determine the relationship between HLA matching and lung graft survival using a large-scale multi-center database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication. Methods This retrospective observational analysis was performed using 26,312 lung transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs 4-6 mismatches) and then subcategorized by indication. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. Results Increased HLA mismatch was associated with reduced allograft survival. Adjusted models found that the total HLA mismatch >3 increased the mortality hazard at 15 years (HR 1·05, p <0·05) and 20 years (HR 1·05, p<0·01). Pulmonary hypertension was the only indication with a statistically significant association between HLA mismatch and graft survival. Allografts in patients with 0-3 mismatches survived for 401 days longer than those with 4-6 mismatches (p=0·02). Conclusion Increased HLA mismatch reduced graft survival. When stratified by indication, this association was preserved exclusively in pulmonary hypertension. This finding is of potential clinical relevance to the management of this subsection of lung transplant recipients, impacting organ allocation, transplant surveillance and use of desensitisation and immunosuppression protocols.

PULM1: Outcomes of Recipients Aged 65 Years and Older Bridged to Lung Transplant with Extracorporeal Membrane Oxygenation (ECMO)

Background: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (BTT) has been used to support critically ill patients on the waitlist with excellent outcomes post-transplant. Some centers cite candidate age ≥65 years as a contraindication despite minimal data to support restricting ECMO BTT among older candidates. We compared outcomes of ECMO BTT, mechanical ventilation (MV)-only BTT, and no BTT in recipients ≥65 years. Methods: For our waitlist analysis, lung transplant candidates ≥65 years with known ECMO cannulation dates 2005-2020 in the United Network for Organ Sharing (UNOS) database were included. Waitlist outcomes within one year of either listing or ECMO cannulation, whichever occurred first, were assessed. For the post-transplant analysis, lung-only recipients ≥65 years were included and stratified into ECMO BTT, MV-only BTT, or no BTT. Cox regression was used to assess 1- and 3-year mortality post-transplant. Multivariable models adjusted for baseline characteristics with p<0.1 on univariate analysis. Results: Of the 171 waitlist candidates ≥65 years with known ECMO implant dates, 96 (56.1%) were transplanted and 72 (42.1%) deteriorated/died within one year of listing or ECMO cannulation. Those who deteriorated/died spent more waitlist days on ECMO support compared to candidates who were transplanted (11 [5-17] vs. 4 [2-12] days, p<0.001). Of recipients ≥65 years, 135 (1.6%) received ECMO BTT, 219 (2.6%) received MV-only BTT, and 8,074 (95.7%) received no BTT. ECMO BTT recipients had higher LAS at transplant (86 [84-88] ECMO vs. 73 [41-88] MV-only vs. 39 [34-49] no BTT, p<0.001), spent fewer days on the waitlist (12 [5-34] ECMO vs. 18 [6-76] MV-only vs. 47 [14-141] no BTT, p<0.001), and were more likely to have restrictive disease pathology (92.6% ECMO vs. 67.1% MV-only vs. 66.3% no BTT, p<0.001; Table 1). At 72 hours post-transplant, ECMO BTT recipients were more likely to remain intubated than those who received no BTT (70.6% ECMO vs. 71.2% MV-only vs. 22.6% no BTT, p<0.001) and more likely to be on ECMO than those who received either MV-only or no BTT (30.4% ECMO vs. 8.2% MV-only vs. 4.3% no BTT, p<0.001). ECMO BTT recipients had lower likelihood of pre-discharge acute rejection (3.0% ECMO vs. 10.5% MV-only vs. 6.9% no BTT, p=0.02). On multivariable analysis, ECMO vs. MV-only BTT was associated with increased mortality risk at 1 year (aHR[95% CI] 2.11[1.33-3.35]) and 3 years (aHR 1.51[1.07-2.12], Figure 1) post-transplant. Conclusion: We found that ECMO BTT in candidates ≥65 years is associated with inferior post-transplant outcomes compared to MV-only or no BTT, even after adjusting for donor and recipient characteristics. However, despite being sicker at transplant, more than half of recipients ≥65 years receiving ECMO BTT were alive at 3 years post-transplant, furthering our understanding of whether ECMO BTT is a reasonable choice in older candidates. Table 1. Baseline characteristics of lung transplant recipients ≥65 years of age from 2005 to 2020 in the United Network for Organ Sharing registry, by bridging strategy.Figure 1. (A) Unadjusted and (B) adjusted 3-year survival of lung transplant recipients ≥65 years of age from 2005 to 2020 in the United Network for Organ Sharing registry, by bridging strategy. Hazard ratios represent extracorporeal membrane oxygenation (ECMO) bridge-to-transplant (BTT) versus mechanical ventilation (MV)-only BTT.

(96) Impact of Donor Age on Survival of Lung Transplant Recipients According to Their Primary Diagnosis

(96) Impact of Donor Age on Survival of Lung Transplant Recipients According to Their Primary Diagnosis

Impact of Culture-Positive Preservation Fluid on Early Morbidity and Mortality After Lung Transplantation.

The prevalence, risk factors and outcomes associated with culture-positive preservation fluid (PF) after lung transplantation (LT) are unknown. From January 2015 to December 2020, the microbiologic analyses of PF used to store the cold ischaemia-placed lung graft(s) of 271 lung transplant patients were retrospectively studied. Culture-positive PF was defined as the growth of any microorganism. Eighty-three (30.6%) patients were transplanted with lung grafts stored in a culture-positive PF. One-third of culture-positive PF were polymicrobial. Staphylococcus aureus and Escherichia coli were the most frequently isolated microorganisms. No risk factors for culture-positive PF based on donor characteristics were identified. Forty (40/83; 48.2%) patients had postoperative pneumonia on Day 0 and 2 (2/83; 2.4%) patients had pleural empyema with at least one identical bacteria isolated in culture-positive PF. The 30-day survival rate was lower for patients with culture-positive PF compared with patients with culture-negative PF (85.5% vs. 94.7%, p = 0.01). Culture-positive PF has a high prevalence and may decrease lung transplant recipient survival. Further studies are required to confirm these results and improve understanding of the pathogenesis of culture-positive PF and their management.

Cross-Regulation of F-Box Protein FBXL2 with T-bet and TNF-α during Acute and Chronic Lung Allograft Rejection.

Chronic lung allograft dysfunction is the major barrier to long-term survival in lung transplant recipients. Evidence supports type 1 alloimmunity as the predominant response in acute/chronic lung rejection, but the immunoregulatory mechanisms remain incompletely understood. We studied the combinatorial F-box E3 ligase system: F-box protein 3 (FBXO3; proinflammatory) and F-box and leucine-rich repeat protein 2 (FBXL2; anti-inflammatory and regulates TNFR-associated factor [TRAF] protein). Using the mouse orthotopic lung transplant model, we evaluated allografts from BALB/c → C57BL/6 (acute rejection; day 10) and found significant induction of FBXO3 and diminished FBXL2 protein along with elevated T-bet, IFN-γ, and TRAF proteins 1-5 compared with isografts. In the acute model, treatment with costimulation blockade (MR1/CTLA4-Ig) resulted in attenuated FBXO3, preserved FBXL2, and substantially reduced T-bet, IFN-γ, and TRAFs 1-5, consistent with a key role for type 1 alloimmunity. Immunohistochemistry revealed significant changes in the FBXO3/FBXL2 balance in airway epithelia and infiltrating mononuclear cells during rejection compared with isografts or costimulation blockade-treated allografts. In the chronic lung rejection model, DBA/2J/C57BL/6F1 > DBA/2J (day 28), we observed persistently elevated FBXO3/FBXL2 balance and T-bet/IFN-γ protein and similar findings from lung transplant recipient lungs with chronic lung allograft dysfunction versus controls. We hypothesized that FBXL2 regulated T-bet and found FBXL2 was sufficient to polyubiquitinate T-bet and coimmunoprecipitated with T-bet on pulldown experiments and vice versa in Jurkat cells. Transfection with FBXL2 diminished T-bet protein in a dose-dependent manner in mouse lung epithelial cells. In testing type 1 cytokines, TNF-α was found to negatively regulate FBXL2 protein and mRNA levels. Together, our findings show the combinatorial E3 ligase FBXO3/FBXL2 system plays a role in the regulation of T-bet through FBXL2, with negative cross-regulation of TNF-α on FBXL2 during lung allograft rejection.

Characterization of B Cells in Lungs of Chronic Lung Allograft Dysfunction Patients by Single-Cell RNA Sequencing

<h3>Purpose</h3> The primary factor limiting long-term survival in lung transplant recipients is chronic lung allograft dysfunction (CLAD), which manifests as fibrosis of the airways and/or lung parenchyma. The high incidence of CLAD despite the use of T cell-targeted immunosuppressive therapies suggests that other immune cells may contribute to its development. While multiple studies point towards a role of B cells in CLAD, knowledge regarding the specific populations of B cells prevalent in lungs of CLAD patients is lacking. We aimed to define the transcriptional signatures of B cell populations in explanted CLAD lungs by single-cell RNA sequencing (scRNAseq). <h3>Methods</h3> Single cell suspensions were made from 4 samples of CLAD lung explants. B cells were isolated by flow sorting and transcriptionally profiled using 10X genomics (10,000 cells, 50,000 reads/cell) within 2 hours. The transcriptional heterogeneity of B cells in CLAD lungs was analyzed using the R package Seurat. <h3>Results</h3> Based on flow cytometry, B cells (CD45+/CD3-/CD19+) were present in the lungs of all four CLAD patients, consistent with previously published reports of B cell-rich tertiary lymphoid organs in CLAD lungs. ScRNAseq analysis of expression levels of immunoglobulins, transcription factors, and surface markers of conventional B cells subsets revealed the presence of both naïve and antigen-experienced B cells in CLAD lungs. We identified populations of transitional B cells, naïve follicular B cells, germinal center cells, plasmablasts, and memory B cells. Notably, we identified a distinct population of class-switched B cells (IgM/IgD low, IgG/IgA high, and CD38+). In addition, our analysis revealed that many B cells expressed markers of antigen presentation including CD74, CIITA, and HLA-DMA, suggesting that B cells in CLAD lungs may function as antigen-presenting cells. <h3>Conclusion</h3> Our scRNAseq results show the prevalence of both naïve and antigen-experienced B cells in the lungs of CLAD patients. Further analyses will aim to identify specific B cell populations that may be associated with allograft dysfunction.

Mechanical Circulatory Support in Lung Transplant Recipients: Early and Long-Term Survival

<h3>Purpose</h3> Lung transplantation can be performed off-pump with sequential one-lung ventilation or with mechanical circulatory support (MCS) either by using a cardiopulmonary bypass or veno-venous / veno-arterial extracorporeal membrane oxygenation. Furthermore, MCS might be necessary throughout postoperative course for improving pulmonary function. Here we aimed to investigate early and long-term survival of lung recipients, who are temporarily in need for mechanical circulatory support during lung transplantation and / or after and additionally who did not receive any mechanical circulatory support. <h3>Methods</h3> We performed a retrospective review of patients who underwent lung transplantation at our center between January 2009 and July 2021. We compared 100 days survival as well as five-year survival of lung transplant recipients, who received mechanical circulatory support intra- and postoperatively (group 1, n=14) vs. no mechanical circulatory support (group 2, n=14) or just intraoperatively (group 3, n=69). Survival depicted as Kaplan-Meier-Curves. <h3>Results</h3> Recipients treated with mechanical circulatory support intra- and postoperatively after lung transplantation (n=14), presented with pulmonary artery hypertension (n=5), pulmonary veno-occlusive disease (n=1), idiopathic fibrosis (n=2), Sarcoidosis (n=1) and chronic obstructive pulmonary disease (n=5). 100 days after initial lung transplantation 4 out of 14 patients were alive. Early survival between group 1 and 2 was 38.5% vs. 85.7% (p=0.0073) and as compared to group 3 38.5% vs 90.9% (p<0.0001). Five-year survival was 33.3% in patient group 1 compared to 67.3% in group 3 (p<0.0001) as well as 33.3% vs 64.3% when compared to patient group 2 (p=0.0262). Survival between group 2 and 3 did not differ significantly. <h3>Conclusion</h3> Here we report clearly that patients after lung transplantation who needed intra- and postoperatively mechanical circulatory support have a significantly reduced early as well as long-term survival compared to recipients without any need of mechanical circulatory support or only intraoperatively. Early and long-term survival of lung recipients treated with circulatory support only intraoperatively did not differ when compared to patients without any use of support.

Myeloid-Derived Suppressor Cells Are Increased in Lung Transplant Recipients and Regulated by Immunosuppressive Therapy

Lung transplantation remains as a primary treatment for end-stage lung diseases. Although remarkable improvement has been achieved due to the immunosuppressive protocols, long-term survival for lung transplant recipients (LTR) is still limited. In the last few decades, an increasing interest has grown in the study of dysregulation of immune mechanisms underlying allograft failure. In this regard, myeloid-derived suppressor cells (MDSCs) could play an important role in the promotion of graft tolerance due to their immune regulatory function. Here, we describe for the first time circulating subsets MDSCs from LTR at several time points and we evaluate the relationship of MDSCs with sort-term lung transplant outcomes. Although no effect of MDSCs subsets on short-term clinical events was observed, our results determine that Mo-MDSCs frequencies are increased after acute cellular rejection (ACR), suggesting a possible role for Mo-MDSCs in the development of chronic lung allograft dysfunction (CLAD). Therefore, whether MDSCs subsets play a role as biomarkers of chronic rejection remains unknown and requires further investigations. Also, the effects of the different immunosuppressive treatments on these subpopulations remain under research and further studies are needed to establish to what extend MDSCs immune modulation could be responsible for allograft acceptance.

Suboptimal Six Minute Walk Distance Does Not Impact Survival in Lung Transplant Recipients Bridged with Extracorporeal Support

<h3>Purpose</h3> Preoperative six-minute walk distance (6MWD) is associated with survival following lung transplantation; however, its predictive value remains unclear for patients on extracorporeal support (ECMO). Our study aimed to assess the impact of ECMO utilization on posttransplant survival among patients with suboptimal 6MWD. <h3>Methods</h3> Using data from the United Network for Organ Sharing, we included adult, first-time lung transplant recipients between May 3, 2005 and March 20, 2020 with suboptimal 6MWD (< 1200 feet). All patients on ECMO at listing who subsequently underwent 6MWD testing within 30 days were included in our ECMO cohort. Mechanically ventilated patients at listing were excluded. We then compared posttransplant survival based on ECMO status via Kaplan-Meier analysis. Descriptive analyses of the cohorts were done via Wilcoxon rank-sum tests for continuous variables and chi-square tests for categorical variables. <h3>Results</h3> Our overall study population included 21,266 patients: 60 in the ECMO cohort and 21,206 in the non-ECMO cohort. Both cohorts were predominantly male (57% in ECMO cohort vs. 58%, p = 0.972). In the ECMO cohort, the median age was lower (49 years, IQR 34-56 vs. 60 years, IQR 53-65; p < 0.0001); a greater percentage of patients underwent bilateral transplant (92% in ECMO cohort vs. 69%; p < 0.0001); and median 6MWD was lower (0, range 0-720 in ECMO cohort vs. 700, range 0-1199; p < 0.0001). Within the ECMO cohort, no difference in 3-year survival was observed between ambulatory (6MWD > 0) and non-ambulatory (6MWD = 0) patients (log rank, p = 0.536). Overall, no survival difference by ECMO status at 3 years was observed (log rank, p=0.718; Figure 1). <h3>Conclusion</h3> Our results suggest that ECMO, in appropriately selected patients, does not significantly impact postoperative survival compared to a population with similar suboptimal pretransplant functional status. Furthermore, no minimum distance was observed that conferred better or worse outcomes.

Should Lungs from Hepatitis C NAT+ Donors Continue to Be Transplanted? A UNOS Registry Analysis

<h3>Purpose</h3> With the advent of a cure for HCV, HCV NAT+ donor lungs are being increasingly utilized for transplantation, but their outcomes are understudied. Our goal was to examine one-year survival of lung transplant recipients from HCV NAT+ donors. <h3>Methods</h3> We conducted retrospective review of all primary adult lung transplant recipients in the UNOS registry between January 1, 2015 and June 12, 2020. Donors were identified as being HCV NAT+ or HCV NAT-. One-year survival was examined with the Kaplan Meier method and a multivariable Cox-proportional hazards model. <h3>Results</h3> Of 11809 lung transplants performed during the study period, 222 (2%) came from HCV NAT+ donors. HCV NAT+ donors tended to be younger (33±8 vs 35±14 yrs, p=0.01) and were more likely to be white (82% vs 61%, p<0.01), blood group O (61% vs 50%, p<0.01), CDC high risk (84% vs 24%, p<0.01), and have drug intoxication as cause of death (61% vs 12%, p<0.01). Recipients of HCV NAT+ donor lungs were less likely to have diabetes (10% vs 20%, p<0.01), cystic fibrosis (5% vs 9%, p<0.01), IPF (28% vs 36%, p<0.01), have chronic steroid use (32% vs 44%) or be treated with IV antibiotics 2 weeks prior transplant (5% vs 12%, p=0.02). They had lower LAS scores (42±15 vs 48 ± 18, p<0.01), oxygen requirements at rest (4.5 vs 5.5 L, p<0.01), and were more likely to receive double lungs (83% vs 74%, p<0.01). One-year survival was not significantly different among recipients of HCV NAT+ and NAT- donor lungs on univariate (HR 1.00, 95% CI 0.62-1.62, p=0.98) or multivariate analysis (aHR 0.94, 95% CI 0.53-1.67, p=0.84). Incidence of treatment for acute rejection at one year was also not significantly different (23% vs 23%, p=0.86). <h3>Conclusion</h3> Despite coming from high-risk donors, HCV NAT+ lungs have similar one-year survival and acute rejection as those coming from HCV NAT- donors. While longer-term studies are necessary, this report supports the use of NAT+ donor lungs among lung transplant candidates.

Factors Associated with Very Long-Term Survival for Lung Transplant Recipients

Purpose While median survival for adult lung transplants recipients is approximately 6 years, there is a subset of patients that experiences much greater longevity. We sought to elucidate the characteristics of very long-term survivors and determine the factors associated with this outcome. Methods Utilizing the United Network for Organ Sharing Standard Transplant Analysis and Research files, we retrospectively identified adult recipients of lung transplants between 1987 and 2004. We defined the very long-term survival (VLT) cohort by those who lived ≥15 years post transplant. The remaining patients served as the control group. Baseline recipient and donor characteristics as well as outcomes were compared using chi-squared analyses for categorical data and t-tests for continuous variables. A multivariate logistic regression model was implemented to determine the influence of these factors on the odds of VLT survival. Results Between 1987 and 2004, 11,669 patients met inclusion criteria, and 1,296 (11%) survived ≥ 15 years. VLT survivors were younger (43±12 vs 49±12 years; p Conclusion Approximately 11% of lung transplant recipients from 1987 to 2004 have lived to become VLT survivors. Factors associated with the odds of VLT survival were related to younger age, race congruence between donor and recipient, and receipt of a double lung transplant. Information gleaned from VLT survivors can inform best practices for allograft selection with the aim of prolonging survival for the lung transplant population at large.

Frailty and aging-associated syndromes in lung transplant candidates and recipients.

Many lung transplant candidates and recipients are older and frailer compared to previous eras. Older patients are at increased risk for pre- and posttransplant mortality, but this risk is not explained by numerical age alone. This manuscript represents the product of the American Society of Transplantation (AST) conference on frailty. Experts in the field reviewed the latest published research on assessment of elderly and frail lung transplant candidates. Physical frailty, often defined as slowness, weakness, low physical activity, shrinking, and exhaustion, and frailty evaluation is an important tool for evaluation of age-associated dysfunction. Another approach is assessment by cumulative deficits, and both types of frailty are common in lung transplant candidates. Frailty is associated with death or delisting before transplant, and may be associated with posttransplant mortality. Sarcopenia, cognitive dysfunction, depression, and nutrition are other important components for patient evaluation. Aging-associated inflammation, telomere dysfunction, and adaptive immune system senescence may also contribute to frailty. Developing tools for frailty assessment and interventions holds promise for improving patient outcomes before and after lung transplantation.

Long-term outcomes of metallic endobronchial stents in lung transplant recipients are not affected by bacterial colonization.

We evaluated associations of endobronchial stenting with airway bacterial colonization, the antimicrobial resistance profile, hospitalizations for pneumonia and survival in lung transplant recipients. This is a retrospective single-centre study of 582 recipients of lung transplant during 2002-2018. We compared outcomes of 57 patients (9.7%) who received endobronchial stents (intervention group) to a control group of 57 patients without stents who were matched one to one for age, sex, year of transplantation, unilateral/bilateral transplantation and underlying disease. For the intervention compared to the control group, airway colonization was more common for Pseudomonas (86% vs 35%, P < 0.001), Acinetobacter (21% vs 7%, P = 0.05), Klebsiella (21% vs 5%, P = 0.02) and Staphylococcus species (11% vs 0%, P = 0.02). The respective proportions of patients with positive bronchoalveolar lavage cultures on the third post-transplantation day, the day of stent insertion and 6-month post-stent insertion were 47.4%, 50.9% and 65.4% for Pseudomonas sp.; 15.8%, 12.3% and 3.8% for Klebsiella sp.; and 8.8%, 5.3% and 5.8% for Acinetobacter sp. The mean number of hospitalizations for pneumonia per patient was higher, without statistical significance, in the intervention than the control group (1.5 ± 1.7 vs 0.9 ± 1.5, P = 0.1). Kaplan-Meier survival curves did not show a statistically significant difference between the intervention group and the entire group without endobronchial stents (n = 525) (P = 0.4). Lung transplant recipients with endobronchial stents were more likely to be colonized with pathologic bacteria and having pneumonia; however, stent placement was not associated with increased long-term mortality with appropriate stent maintenance.

Donor-specific antibody characteristics, including persistence and complement-binding capacity, increase risk for chronic lung allograft dysfunction

Chronic lung allograft dysfunction (CLAD) is the major complication limiting long-term survival in lung transplant recipients (LTRs), with those developing donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) previously found to have increased risk for CLAD. However, as DSA responses vary in timing of development, specificity, breadth, persistence, and complement-binding capacity, we hypothesized that these characteristics would impact CLAD and survival outcomes. We retrospectively analyzed DSA characteristics and outcomes in a single-center cohort of 582 LTRs who had serum samples collected prospectively from 2010 to 2016. Luminex-based single antigen bead assays were performed to assess DSA. DSAs were detected in 247 LTRs (42%), of which 124 (21.3%) were de novo DSAs and 53 (9.1%) were complement-binding (C1q+). CLAD developed in 208 LTRs (35.7%) during the follow-up period, with 67.8% determined as bronchiolitis obliterans syndrome phenotype and 32.2% as restrictive allograft syndrome phenotype. We found a shorter time to CLAD in LTRs with persistent DSAs (p = 0.04) and HLA-DQ-specific DSAs (p = 0.03). LTRs who developed C1q+ DSAs had significantly shorter time to CLAD (p < 0.001), with 100% of C1q+ DSAs being persistent and no differences between CLAD phenotypes. CLAD-free survival was significantly reduced in LTRs who developed C1q+ DSAs (p = 0.001), HLA-DQ-specific DSAs (p = 0.03), and multiple DSAs (p = 0.02). Together, our findings demonstrate that DSA characteristics of persistence, HLA-DQ specificity, and C1q+ DSAs are associated with shorter time to CLAD. Additionally, C1q+, HLA-DQ-specific, and multiple DSAs are associated with decreased CLAD-free survival. These characteristics may improve DSA risk stratification for deleterious outcomes in LTRs.

New Clue: Prediction from Cell-Free DNA

The main challenge for a positive long-term outcome in lung transplantation is the lack of early detection for chronic lung allograft dysfunction (CLAD). With advancements in technology, an increasing number of studies demonstrate that cell-free DNA (cfDNA) in body fluids could be used as a marker for disease diagnosis, prognosis or monitoring response to treatment. A previous report from this journal found the joint assessment of cfDNA and CXCL10 from brochoalveolar lavage (BAL) could determine the subphenotypes of CLAD and predict lung transplant survival. This is an exciting attempt in monitoring the progress for lung transplant recipients. More studies and better understanding of cfDNA are needed to develop an accessible and reliable biomarker to monitor the progress of CLAD to improve the long-term survival for lung transplant recipients.

The Impact of Airway Complications on Survival Among Lung Transplant Recipients

IntroductionLong-term outcomes of airway complications (AC) after lung transplantation are unknown. The incidence of AC varies from 1.6% to 32% with the related mortality rate of 2% to 4%. The management of most AC is based on endobronchial methods, including balloon bronchoplasty, endobronchial stent placement, and ablative techniques. The aim of the study was to assess the connection between airway complications treated by bronchial intervention (BI) and the survival of lung transplant recipients. Materials and MethodsThe single-center retrospective study reviewed the cases of 165 patients (63 women [38.18%], 103 men [61, 82%]; median age at referral for lung transplantations (LTx), 41 years [range, 15-68 years]). The cohort was stratified into 2 groups comprising those whose procedures were complicated by ACs and those without. The primary outcome measured was mortality, with survival endpoints calculated at 6 months. ResultsThe comparison of the survival of recipients regarding underlying disease (cystic fibrosis [CF], chronic obstructive pulmonary disease [COPD], idiopathic pulmonary artery hypertension [IPAH], and others) with the use of the Kaplan-Meier estimator indicated that the only statistically significant (P = .0194) differences between patients who underwent BI and patients without BI performed were observed in CF patients (Fig 1). In any other diagnosis, the results were not statistically significant (P > .05). ConclusionsBronchoscopic intervention because of airway complications after lung transplantation are often-used procedures, but they have no impact on the survival of patients with cystic fibrosis.

Genotype in MUC5B-Promoter Polymorphism and Chronic Lung Allograft Dysfunction (CLAD) in a German Cohort: Preliminary Results

The long-term survival of lung transplant recipients is significantly limited by the occurrence of chronic lung allograft dysfunction (CLAD). A single nucleotide polymorphism (SNP) in the promoter region of the MUC5B-gene (rs35705950) has been identified as an independent risk factor for the development of idiopathic pulmonary fibrosis (IPF). Moreover, MUC5B genotype is associated with survival in IPF patients. Aim of the study was to investigate whether the development of CLAD is associated with genotype in MUC5B-promoter polymorphism. 73 patients, who underwent lung transplantation from 1998 to 2015 for several indications, and 50 healthy controls were retrospectively studied. CLAD was defined as persistent decline of FEV1 to < 80 % of the post-transplant baseline. MUC5B rs35705950 SNP genotype was detected by real time PCR and pyrosequencing. During the follow-up period of 8 ± 4 years, 51 % of patients developed CLAD. MUC5B rs35705950 alleles were in Hardy-Weinberg equilibrium and genotype distribution did not differ between healthy controls and transplant recipients. 53 % of the patients carrying the GG genotype and 40 % of the patients carrying the GT genotype group developed CLAD (p=0.398). No correlation between MUC5B rs35705950 genotype and age, gender, lung function tests and survival was found. In our cohort, genotype in the MUC5B-promoter polymorphism was not associated with the development of CLAD or survival.