Patients Undergoing Lung Transplantation Research Articles

Pulmonary pathological changes in the patient undergoing lung transplantation after chronic graft-versus-host disease complicated by pulmonary infection post-hematopoietic stem cell transplantation: report of a case

Pulmonary pathological changes in the patient undergoing lung transplantation after chronic graft-versus-host disease complicated by pulmonary infection post-hematopoietic stem cell transplantation: report of a case

Early extracorporeal photopheresis treatment is associated with better survival in patients with chronic or recurrent acute lung allograft dysfunction.

Due to development of chronic lung allograft dysfunction (CLAD), prognosis for patients undergoing lung transplantation (LTx) is still worse compared to other solid organ transplant recipients. Treatment options for slowing down CLAD progression are scarce with extracorporeal photopheresis (ECP) as an established rescue therapy. The aim of the study was to identify characteristics of responders and non-responders to ECP treatment, assess their survival, lung function development and by that define the subset of patients who should receive early ECP treatment. We performed a retrospective study of all LTx patients receiving ECP treatment at the University Hospital Zurich between January 2010 and March 2020. Patients were followed-up for a maximum period of 5 years. Mortality and lung function development were assessed by CLAD stage and by CLAD subtype before initiation of ECP treatment. Overall, 105 patients received at least one ECP following LTx. A total of 57 patients (61.3%) died within the study period with a median survival of 15 months. Mortality was 57% for patients who started ECP at CLAD1, 39% for CLAD2, 93% for CLAD3, and 90% for CLAD4 (p < 0.001). Survival and lung function development was best in young patients at early CLAD stages 1 and 2. Response to ECP treatment was worst in patients with CLAD-RAS/mixed subtype (14.3%) and patients with ECP initiation in CLAD stages 3 (7.1%) and 4 (11.1%). Survival was significantly better in a subset of patients with recurrent acute allograft dysfunction and earlier start of ECP treatment (105 vs 15 months). In this retrospective analysis of a large group of CLAD patients treated with ECP after LTx, early initiation of ECP was associated with better long-term survival. Besides a subset of patients suffering of recurrent allograft dysfunction, especially a subset of patients defined as responders showed an improved response rate and survival, suggesting that ECP should be initiated in early CLAD stages and young patients. ECP might therefore prevent long-term disease progression even in patients with CLAD refractory to other treatment options and thus prevent or delay re-transplantation.

Influence of acute kidney injury and its recovery subtypes on patient-centered outcomes after lung transplantation

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation.

Prognostic factors in lung transplantation after extracorporeal membrane oxygenation bridging therapy: a systematic review and meta-analysis.

Extracorporeal membrane oxygenation (ECMO) has recently emerged as a critical support system for lung function in patients awaiting lung transplantation. This meta-analysis investigates the prognostic factors of lung transplantation following ECMO bridging therapy. A comprehensive search was conducted in PubMed, Cochrane Library, Embase, CINAHL, Web of Science, Scopus, and ProQuest databases from inception to August 11, 2023. Included were cohort or case-control studies focusing on prognostic factors of lung transplantation with ECMO bridging therapy. Data extraction was performed independently, and study quality was assessed. A meta-analysis was carried out using RevMan 5.4 and Stata17.0 software to aggregate mortality rates and pertinent prognostic factors of ECMO as a bridge to lung transplantation. The search identified eight trials encompassing 1,086 participants. The prognosis of patients undergoing lung transplantation with ECMO bridging was significantly associated with several factors: prolonged ECMO support [odds ratio 1.07, 95% confidence interval (CI): 1.02-1.12, I2=77%], deterioration in liver and kidney function (odds ratio 3.62, 95% CI: 2.37-5.54, I2=0%), and complications during ECMO (odds ratio 2.24, 95% CI: 1.45-3.44, I2=5%). Prolonged ECMO support, declining liver and kidney functions, and complications during ECMO are vital prognostic factors in lung transplantation following ECMO bridging therapy.

Defining Optimal Settings for Lung Cryobiopsy in End-Stage Pulmonary Disease. A Human, Ex Vivo, Diseased Lung Clinical Trial.

To evaluate optimal settings of probe size, freezing time, and distance to the pleura that influence the size and quality of biopsy specimens during transbronchial lung cryobiopsies in ESPD. We prospectively recruited 17 patients undergoing lung transplantation. We created a nonperfused ex vivo bronchoscopy setting to perform multiple cryobiopsies with different probe sizes (1.7, 1.9, and 2.4mm), freezing times (3, 5, 7, 10, 20, 30 seconds), and probe distance from pleura (5, 10, and 20mm). Alveolated pulmonary parenchyma area≥50% in histology was considered a good quality biopsy, with a minimum procedural artifact. We used logistic regression to identify independent parameters as risk factors for histologic adequacy. A total of 545 cryobiopsies were obtained from 34 explanted lungs after pneumonectomy for lung transplantation. The mean maximum diameter of the specimen achieved with the 1.7 probe was larger (13.5mm) than those obtained with 1.9 and 2.4mm probes (11.3 and 10.7mm, P= 0.07). More pleural macroscopic damage and pleural tissue in histology occurred with the 2.4mm probe ( P <0.001). There was no difference in the quality of specimens between the different freezing times and the distance from the pleura. Freezing time and distance from the pleura did not affect the histologic quality for diagnosing ESPD in severely damaged lungs. Smaller cryoprobe size did not negatively affect sample adequacy.

Elucidating immune cell dynamics in chronic lung allograft dysfunction: A comprehensive single-cell transcriptomic study

Chronic Lung Allograft Dysfunction (CLAD) is a critical post-transplant complication that predominantly determines the long-term survival rates and quality of life of patients undergoing lung transplantation. The limited efficacy of current immunosuppressive strategies underscores our incomplete understanding of the immunological aspects of CLAD. Hence, there is an urgent need for more comprehensive and targeted research to unravel the complex interplay of immune cells in the development and progression of CLAD. This study conducts an in-depth analysis of the immune environment in CLAD. By examining the gene expression profiles of T cells, natural killer cells, B cells, macrophages, and monocytes, we have elucidated a unique immunological landscape in CLAD compared to healthy controls. We highlight the heterogeneity within the immune populations and provide a comprehensive understanding of the immune mechanisms driving CLAD. Enrichment analysis identified specific pathways that are either overactive or suppressed in CLAD, revealing potential molecular targets for therapeutic intervention. Our findings emphasize the crucial role of T cells in the pathophysiology of CLAD, coordinating the immune response and revealing an amplified immune cell network, potentially leading to maladaptive tissue responses. By integrating a comprehensive cellular and molecular portrait of the immune environment, our research not only deepens our understanding of the pathogenesis of CLAD but also lays a foundational approach for the development of targeted therapies.

Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multi-organ transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over six months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

Intracellular Pseudomonas aeruginosa within the Airway Epithelium of Cystic Fibrosis Lung Tissues.

Rationale: Pseudomonas aeruginosa is the major bacterial pathogen colonizing the airways of adult patients with cystic fibrosis (CF) and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evade the immune system and antibiotic therapy. Although the ability of P. aeruginosa to invade and survive within epithelial cells has been described invitro in different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking. Objectives: To detect and characterize intracellular P. aeruginosa in CF airway epithelium from human lung explant tissues. Methods: We sampled lung explant tissues from patients with CF undergoing lung transplantation and non-CF lung donor control tissue. We analyzed lung tissue sections for the presence of intracellular P. aeruginosa using quantitative culture and microscopy, in parallel to histopathology and airway morphometry. Measurements and Main Results: P. aeruginosa was isolated from the lungs of seven patients with CF undergoing lung transplantation. Microscopic assessment revealed the presence of intracellular P. aeruginosa within airway epithelial cells in three of the seven patients analyzed at a varying but low frequency. We observed those events occurring in lung regions with high bacterial burden. Conclusions: This is the first study describing the presence of intracellular P. aeruginosa in CF lung tissues. Although intracellular P. aeruginosa in airway epithelial cells is likely relatively rare, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.

Interest in the new thromboelastometry device, Clot Pro®, for predicting thrombocytopenia and hypofibrinogenemia during lung transplantation

IntroductionLung transplantation is associated with high proportion of transfusion. Monitoring of coagulopathy using viscoelastic tests could aid in the perioperative management of bleeding. The aim of the study was to assess the predictive cut-off values for thrombocytopenia and hypofibrinogenemia using the new thromboelastography analyzer, ClotPro. MethodsWe retrospectively enrolled 65 patients who underwent lung transplantation and were sampled for both viscoelastic assays and conventional coagulation assays simultaneously during the procedure. We characterized the correlation between the EX-test (extrinsic pathway) and platelet count as well as between the FIB-test (extrinsic pathway after platelet inhibition) and fibrinogen concentration. Then, we used ROC curve analysis to determine the optimal EX-test and FIB-test values for predicting thrombocytopenia and hypofibrinogenemia. ResultsAll the amplitude values of the EX-test (A5, A10, A20, MCF) showed correlation with platelets count (Spearman's rank correlation coefficient ranging from 0.75 to 0.77, all p < 0.0001). We also observed a strong correlation between the amplitude values of the FIB-test (A5, A10, A20 and MCF) and the fibrinogen concentration (Spearman's rank correlation coefficient ranging from 0.68 to 0.71, all p < 0.0001). The AUCs of the EX-test values for thrombocytopenia <100 G/L and <80 G/L ranged from 0.80 to 0.93. Similarly, the AUCs of the FIB-test values for hypofibrinogenemia <1.5 g/L and <2 g/L ranged from 0.74 to 0.83. These results indicate that only the five-minute parameter of thromboelastometry is sufficient for detecting thrombocytopenia and hypofibrinogenemia in patients undergoing lung transplantation. The proposed cut off values for the EX-test to predict thrombocytopenia <80 G/L showed high sensitivity (>86 %), high specificity (>89 %) and high negative predictive value (>95 %). FIB-test cut off values predictive of fibrinogen below 1.5 g/L showed sensitivity (>78 %), specificity (>55 %) and negative predictive value (>88 %). ConclusionsOur study provided preliminary results that are useful for developing a ClotPro-based algorithm to guide transfusion in lung transplantation. Future interventional studies will be necessary to validate these cut-off values of ClotPro for guiding transfusion.

2714. Invasive Fungal Disease in Lung Transplant Recipients: Incidence, Risk Factors, and Outcomes

Abstract Background Invasive fungal disease (IFD) is common after lung transplant and is associated with increased morbidity and mortality. Antifungal prophylaxis is a common preventative strategy against IFD in lung transplant recipients (LTRs). We assessed the incidence of IFD in the first 3-years post-transplant, diagnosed by EORTC/MSG criteria, risk factors for developing IFD, and outcomes of LTRs stratified by development of IFD at a single center that does not use universal antifungal prophylaxis post-lung transplant. Table 1 Preoperative and perioperative characteristics and clinical outcomes of lung transplant recipients stratified by invasive fungal disease (IFD) status Methods A single-center, retrospective study of lung transplant recipients between January 2017 and December 2019 was performed with 3-year follow-up. Donor and recipient preoperative characteristics, microbiologic and radiographic data, perioperative characteristics, and 1- and 3-year outcomes were adjudicated and analyzed. Results In this 3-year study period, 168 patients underwent lung transplant. 26 (15%) developed IFD; 23 (14%) were proven or probable, and 3 (1%) were possible [Table 1]. 21 (81%) had evidence of pulmonary infection and 17 (65%) were mold infections with Aspergillus being the predominant pathogen. 4 (15%) were Candida. 81% (21/26) of patients who developed IFD were recipients of bilateral lung transplants compared to 95% (135/142) of patients who did not develop IFD (p = 0.022). Other donor/recipient characteristics and 12-month outcomes between patients who did vs did not develop IFD were similar. 21% of patients (4/19) who developed IFD had developed antibody-mediated rejection (AMR) by three years post-transplant compared to only 4% of patients without IFD (5/112) (p = 0.025). The incidence of acute cellular rejection, chronic allograft rejection, and overall survival at three years were similar. Conclusion Despite the lack of universal antifungal prophylaxis in the first 90 days post-transplant, we observed a low incidence of IFD in LTRs at our center in this 3-year cohort. Other than receipt of a single vs bilateral lung transplant, there were no significant differences in preoperative or perioperative recipient characteristics. Other than an increased proportion of patients who had AMR, patients who developed IFD had similar overall outcomes to those who did not have IFD, including overall survival at 1, 2, and 3 years. Disclosures Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Astellas: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Fujifilm: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support

Donor and recipient age matching in lung transplantation: A retrospective study

PurposeThis study aimed to clarify the effect of donor and recipient age combinations on the short-term survival rates of patients undergoing lung transplantation. Patients and methodsWe retrospectively reviewed the 2017–2020 data of the Affiliated Wuxi People’s Hospital of Nanjing Medical University database for all adults (≥18 years), lung transplant recipients, and their associated donors. The impact of donor and recipient ages on survival was analyzed using a multivariable Cox proportional hazards regression model. Subgroup analysis was also performed based on recipient and donor ages. ResultsDifferent donor and recipient age combinations affected the short-term postoperative survival rates. When recipients were ≤55 years, the survival rates of the younger donor age group were significantly higher than the older donor age group at 30 days after surgery (P = 0.040); when the donors were ≤40 years, the postoperative survival rates of the younger recipient age group were significantly higher than the older recipient age group (P = 0.031, P = 0.026, P = 0.034, and P = 0.018 for 30 days, 90 days, 180 days, and 1 year after surgery, respectively). ConclusionYounger recipients had a higher survival rate after transplantation than older recipients, and this benefit could be compromised by older donors. Furthermore, the influence of donor age on patient survival rate was limited and more pronounced in younger recipients and shortly after surgery.

Echocardiography and pulmonary hypertension in patients with chronic obstructive pulmonary disease undergoing lung transplantation evaluation

BackgroundThe use of echocardiography in pulmonary hypertension (PH) in advanced chronic obstructive pulmonary disease (COPD) is understudied. We aimed to compare the performance of echocardiography with right heart catheterization (RHC) in the diagnosis of PH in COPD patients undergoing lung transplant evaluation. MethodsWe included 111 patients with severe COPD who underwent RHC in a single center as part of lung transplantation evaluation. COPD-PH and severe COPD-PH were defined based on RHC per the 6th world symposium on pulmonary hypertension. Echocardiographic probability of PH was described according to the European Society of Cardiology guidelines. Summary and univariate analyses were performed. ResultsThe mean age (±SD) was 62 (8) and 47% (n=52) were men. A total of 82 patients (74 %) had COPD-PH. The sensitivity, specificity, positive predictive, and negative predictive values of echocardiography in diagnosing COPD-PH were 43 %, 83 %, 88 %, and 34 % respectively and for severe COPD-PH were 67 %, 75 %, 50 %, and 86 % respectively. Echocardiography was consistent with RHC in ruling in/out PH in 53% (n=59) of patients. After controlling for age, sex. BMI, pack year, echocardiography-RHC time difference, GOLD class, FVC, and CT finding of emphysema, higher TLC decreased consistency (parameter estimate=-0.031; odds ratio: 0.97, 95%CI 0.94-0.99; p=0.037) and higher DLCO increased consistency (parameter estimate=0.070; odds ratio: 1.07, 95%CI 0.94-0.99; p=0.026). ConclusionsEchocardiography has high specificity but low sensitivity for the diagnosis of PH in advanced COPD. Its performance improves when ruling out severe COPD-PH. This performance correlates inversely with lung hyperinflation.

Implementation of a prospective screening strategy to identify adults with a telomere biology disorder among those undergoing lung transplant evaluation for interstitial lung disease

IntroductionPatients with interstitial lung disease (ILD) secondary to telomere biology disorders (TBD) experience increased morbidity after lung transplantation. Identifying patients with TBD may allow for personalized management to facilitate better outcomes. However, establishing a TBD diagnosis in adults is challenging. MethodsA TBD screening questionnaire was introduced prospectively into the lung transplant evaluation. Patients with ILD screening positive were referred for comprehensive TBD phenotyping and concurrent telomere length measurement and germline genetic testing. ResultsOf 98 patients, 32 (33%) screened positive. Eight patients (8% of total; 25% of patients with a positive screen) met strict TBD diagnostic criteria, requiring either critically short lymphocyte telomeres (<1st percentile) (n = 4), a pathogenic variant in a TBD-associated gene (n = 1), or both (n = 3) along with a TBD clinical phenotype. Additional patients not meeting strict diagnostic criteria had histories consistent with TBD along with telomere lengths <10th percentile and/or rare variants in TBD-associated genes, highlighting a critical need to refine TBD diagnostic criteria for this patient population. ConclusionA TBD phenotype screening questionnaire in patients with ILD undergoing lung transplant evaluation has a diagnostic yield of 25%. Additional gene discovery, rare variant functional testing, and refined TBD diagnostic criteria are needed to realize the maximum benefit of testing for TBD in patients undergoing lung transplantation.

The impact of pulmonary hypertension on early postoperative period after lung transplantation with particular emphasis on kidney function

Abstract Background A special group of lung transplantation (LTx) recipients are patients diagnosed with pulmonary hypertension (PH) in the form of idiopathic pulmonary arterial hypertension (IPAH) or chronic lung diseases associated PH (CLD-PH). Acute left heart failure is a major complication observed in the early post-transplant period of patients with PH. To avoid post-transplant cardiac failure, the following measures may be implemented: use of intraoperative veno-arterial extracorporeal membrane oxygenation, administration of inotropic agents, a restrictive fluid management or use of continuous renal replacement therapy. Although, it remains unclear whether such a therapy affects long-term kidney function and patient survival. Purpose To analyze the influence of pulmonary hypertension diagnosis on early postoperative outcome including deterioration of renal function defined as the change in eGFR that occurred between baseline eGFR and the first and seventh day of observation post-LTx. Methods Retrospective data analysis of 79 patients undergoing lung transplantation in 2015-2018 in our institution with diagnosis of PH. Exclusion criterium was absence of 7 days observation post LTx or lack of PH diagnosis. The comparison of pre- and postoperative data was performed between IPAH (N=7) and CLD-PH (N=43) patients. Results We found differences in preoperative serum creatinine levels between IPAH and CLD-PH group (109,5 umol/l (70-126) vs 62,3 umol/l (49,3-73,4), respectively), p&amp;lt;0.05. The greatest decline of eGFR in the early postoperative period was demonstrated on day 7 in both groups (ΔeGFR=42,2±6,7 for CLD-PH group and 56,5±9,8 for IPAH group). Patients did not differ according to age, sex and BMI values. In IPAH group operation tend to last longer (657,9±78,2 min vs 539,6±111,6 min, p&amp;lt;0.05), all of them were performed with the use of cardiopulmonary bypass. All patients from IPAH group and 95,6% from CLD-PH group received inotropic support during LT procedure and early postoperative days. Duration of mechanical ventilation was statistically shorter among CLD-PH patients (2,9 days (0,8-1,4) vs 6,1 days (3,3-39), p&amp;lt;0.001). Conclusion It seems to be probable that pulmonary hypertension could be significant risk factor of kidney deterioration after lung transplantation. Identification of factors modifying renal insufficiency development in lung transplant recipients needs further investigations.

Abstract 18422: Long-Term Changes in Tricuspid Regurgitation and Right Ventricular Function in Patients Undergoing Lung Transplantation: A 5-Year Study

Introduction: The presence and severity of tricuspid regurgitation (TR) has been associated with cardiovascular morbidity and mortality in a number of disease states. The impact of TR on future outcomes in patients selected for lung transplantation has not been adequately evaluated. Methods: We retrospectively evaluated patients who underwent lung transplant at Cleveland Clinic between 2000 and 2022. Patients undergoing multi-organ transplant, CABG, surgery or valve repair were excluded. The presence of baseline TR and its severity was assessed on the closest echo antecedent to transplantation utilizing an IRB approved Echocardiography registry. We used survival analyses to assess our primary outcome of all-cause mortality. We also assessed distribution of TR severity over short and long-term follow up. Results: We evaluated pre-transplant echocardiograms in 1490 individuals who had a mean age of 55 years; 60% being female. The proportion of 0, 1+, 2+, 3+ and 4+ TR was 56%, 25%,12%, 4% and 3% respectively. During a 5-year post-transplant follow-up period, the presence of severe TR pre-operatively was associated with an increased risk for all-cause mortality [aHR 2.1, 95% CI (1.09, 5.1); p = 0.029]. The distribution of TR severity did not appear to be significantly modified by the procedure at 6, 12, 24, 36, 48 and greater than 48-month follow up [OR 1.32, 95% CI (1.76), p = 0.062). Conclusions: Pre-operative TR severity as measured by echocardiography was associated with an increase in all-cause mortality in patients undergoing lung transplant, but the distribution of TR severity did not significantly differ on long-term post-transplant follow up.

Lung Transplantation from hepatitis C+ donor lungs: Reassuring midterm outcomes

The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and mid-term outcomes of lung transplant recipients of HCV NAT+ donor allografts. All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity-score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by one year, early (30-day and in-hospital) mortality and both 1- and 3-year survival were compared between matched groups. A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%), and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, P<0.001), more often female (44% vs 39%, P<0.01) and more commonly died due to drug intoxication (56% vs 15%, P<0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, P=0.69) and female gender (43% vs 39%, P=0.15) but had lower lung allocation scores (38 vs 41, P<0.001) compared to others. Rates of acute rejection (13% vs 17%, P=0.09), early mortality (30-day: 2% vs 1%, P=0.59, in-hospital: 3% vs 4%, P=0.38) as well as 1- (90% vs 92%, P=0.29) and 3-year survival (69% vs 75%, P=0.13) were not significantly different between matched groups. Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

Predicting outcomes, describing complications and optimising rehabilitation in patients undergoing lung transplantation

Massimiliano Polastri and Gian Maria Paganelli discuss the clinical tools used to predict the clinical progress of patients undergoing lung transplantation.

Intraoperative partial pressure of arterial carbon dioxide levels and adverse outcomes in patients undergoing lung transplantation

ObjectivePatients undergoing lung transplantation (LTx) often experience abnormal hypercapnia or hypocapnia. This study aimed to investigate the association between intraoperative PaCO2 and postoperative adverse outcomes in patients undergoing LTx. MethodsWe retrospectively reviewed the medical records of 151 patients undergoing LTx. Patients’ demographics, perioperative clinical factors, and pre- and intraoperative PaCO2 data after reperfusion were collected and analyzed. Based on the PaCO2 levels, patients were classified into three groups: hypocapnia (≤35 mmHg), normocapnia (35.1–55 mmHg), and hypercapnia (>55 mmHg). Univariate and multivariable logistic regressions were used to identify independent risk factors for postoperative composite adverse events and in-hospital mortality. ResultsIntraoperative hypercapnia occurred in 69 (45.7%) patients, and hypocapnia in 17 (11.2%). Patients with intraoperative PaCO2 of 35.1–45 mmHg showed a lower incidence of composite adverse events (53.3%) and mortality (6.2%) (P < 0.001). There was no significant difference in composite adverse events and mortality among preoperative PaCO2 groups (P > 0.05). Compared with intraoperative PaCO2 at 35.1–45 mmHg, the risk of composite adverse events in hypercapnia group increased: the adjusted OR was 3.07 (95% confidence interval [CI]: 1.36–6.94; P = 0.007). The risk of death was significantly higher in hypocapnia group than normocapnia group, the adjusted OR was 7.69 (95% CI: 1.68–35.24; P = 0.009). Over ascending ranges of PaCO2, PaCO2 at 55.1–65 mmHg had the strongest association with composite adverse events, the adjusted OR was 6.40 (95% CI: 1.18–34.65; P = 0.031). ConclusionThese results demonstrate that intraoperative hypercapnia independently predicts postoperative adverse outcomes in patients undergoing LTx. Intraoperative hypocapnia shows predictive value for postoperative in-hospital mortality in LTx.

Outcomes Following Lung Transplant for COVID-19–Related Complications in the US

The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Overall survival and graft failure rates. Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.

Donors in lung transplantation: does age matter?

A best-evidence topic was written according to a structured protocol. The question addressed was the following: in patient undergoing lung transplantation, are lungs from donors of age >60 years old (yo) associated with equivalent outcomes-including primary graft dysfunction, respiratory function and survival-than lungs from donors ≤60yo? Altogether, >200 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journals, dates, country of publication, patients group studied, study type, relevant outcomes, and results of these papers were tabulated. Amongst the 12 papers reviewed, survival results were different depending on whether donor age was analysed raw or adjusted for recipients' age and initial diagnosis. Indeed, recipients with interstitial lung disease (ILD), pulmonary hypertension or cystic fibrosis (CF) had significantly inferior overall survival when receiving grafts from older donors. When older grafts are allocated to younger donors, a significant decrease in survival has been noticed in the case of single lung transplantation. In addition, 3 papers showed worse results regarding peak forced expiratory volume in 1 second (FEV1) in patients receiving older organs, and 4 showed comparable primary graft dysfunction incidence rates. We conclude that when carefully assessed and allocated to the recipient who could benefit most from the transplant (e.g., a patient with a diagnosis of chronic obstructive pulmonary disease (COPD), who would not require a prolonged cardiopulmonary bypass (CPB)), lung grafts from donors of >60yo offer comparable results to younger donors.