Donor Lungs For Transplantation Research Articles

Evaluation of Donor Lungs for Transplantation: The Efficacy of Screening Bronchoscopy for Detecting Donor Aspiration and Its Relationship to the Resulting Allograft Function in Corresponding Recipients

Potential organ donors often have suffered anoxic and/or traumatic brain injury during which they may have experienced aspiration of gastric material (AGM). Evaluation of such donors typically includes a screening bronchoscopic examination during which determinations of aspiration are made. The efficacy of this visual screening and its relationship to post-transplant allograft function are unknown. Before procurement, bronchoscopy was performed on donors in which both bronchoalveolar lavage fluid (BALF) was collected and a visual inspection made. As a marker of AGM, BALF specimens were analyzed for the presence of bile salts. Data collected on the corresponding recipients included primary graft dysfunction (PGD) score, post-transplant spirometry, acute rejection scores (ARS), and overall survival. Of 31 donors evaluated, bronchoscopies revealed only 2 with visual evidence of AGM, whereas BALF analysis for bile salts indicated AGM in 14. As such, screening bronchoscopy had a sensitivity of only 7.1%. Visual detection of AGM via bronchoscopy was not associated with any resulting grade of PGD (χ2=2.96, P=.23); however, AGM defined by detection of bile salts was associated (χ2=7.56, P=.02). Over the first post-transplant year, the corresponding recipients experienced a similar improvement in allograft function (χ2=1.63, P=.69), ARS (P=.69), and survival (P=.24). Visual inspection during a single bronchoscopic examination of lung donors underestimates the prevalence of AGM. The detection of bile salts in donor BALF is associated with early allograft dysfunction in the corresponding recipients but not with later allograft proficiency, acute rejection responses, or 1-year post-transplant survival.

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.

PO-02-145 SPATIAL TRANSCRIPTOMICS IN THE HUMAN PULMONARY VEIN SLEEVE

AF is often treated by ablation to isolate the pulmonary veins where ectopic pacemaker activity or reentry may initiate AF. The relationship of gene expression and histology in the pulmonary vein is unknown. To identify gene expression in pulmonary vein sections and identify regions where gene expression may be indicative of AF pathogenesis. Human pulmonary vein (PV) sleeve tissues form the ostia of the left atrium were obtained from 8 unused lung or heart transplant donors in a protocol approved by the Cleveland Clinic IRB. After tissue sectioning and staining, spatial RNAseq was performed using the 10x Genomics Visium platform. mRNAs from∼1000 to 2500 genes were sequenced in each spatial area. Seurat clustering yielded 15 different clusters. These split into two segregating populations, with one connecting population. Multiple cells and cell types may reside in each 55 μm diameter spatial area. A clear asymmetry of clusters was observed in the PV sections. Cell-type marker genes derived from published human heart single nuclei RNAseq were used to determine the dominant cell types in the 15 different clusters. One group of segregating clusters was enriched in cardiomyocytes, while the other group of segregating clusters was enriched for other cell types including fibroblasts, vascular smooth muscle cells, endothelial cells, and adipocytes. Spatial transcriptomics clearly resolved the venous, cardiomyocyte, and epicardial regions of the PV (Figure, showing histology and spatial expression UMAP clusters for two PV specimens), as well as fibrotic regions. Spatial expression of the AF-associated genes PITX2, SHOX2, and HCN4 was also mapped, confirming higher expression of the cardiac master transcription factor SHOX2 in the PV vs. left atrial appendage (LAA) tissues. Expression of the hyperpolarization-activated ion channel HCN4 was sporadic in both PV and LAA specimens. Spatial transcriptomics identified gene expression profiles in the PV easily identifying the venous vascular smooth muscle, cardiomyocyte, and epicardial layers. The predominant cell type in each spatial region was identified by leveraging heart single nuclei RNAseq data. Spatial transcriptomics may help to discover gene expression and cell types associated with ectopic pacemaker activity in the PV.

Association of Socioeconomic Position With Racial and Ethnic Disparities in Survival After Lung Transplant

A recent National Academies of Sciences, Engineering, and Medicine study found that transplant outcomes varied greatly based on multiple factors, including race, ethnicity, and geographic location. They proposed a number of recommendations including studying opportunities to improve equity in organ allocation. To evaluate the role of donor and recipient socioeconomic position and region as a mediator of observed racial and ethnic differences in posttransplant survival. This cohort study included lung transplant donors and recipients with race and ethnicity information and a zip code tabulation area-defined area deprivation index (ADI) from September 1, 2011, to September 1, 2021, whose data were in the US transplant registry. Data were analyzed from June to December 2022. Race, neighborhood disadvantage, and region of donors and recipients. Univariable and multivariable Cox proportional hazards regression were used to study the association of donor and recipient race with ADI on posttransplant survival. Kaplan-Meier method estimation was performed by donor and recipient ADI. Generalized linear models by race were fit, and mediation analysis was performed. Bayesian conditional autoregressive Poisson rate models (1, state-level spatial random effects; 2, model 1 with fixed effects for race and ethnicity, 3; model 2 excluding region; and 4: model 1 with fixed effects for US region) were used to characterize variation in posttransplant mortality and compared using ratios of mortality rates to the national average. Overall, 19 504 lung transplant donors (median [IQR] age, 33 [23-46] years; 3117 [16.0%] Hispanic individuals, 3667 [18.8%] non-Hispanic Black individuals, and 11 935 [61.2%] non-Hispanic White individuals) and recipients (median [IQR] age, 60 [51-66] years; 1716 [8.8%] Hispanic individuals, 1861 [9.5%] non-Hispanic Black individuals, and 15 375 [78.8%] non-Hispanic White individuals) were included. ADI did not mediate the difference in posttransplant survival between non-Hispanic Black and non-Hispanic White recipients; it mediated only 4.1% of the survival difference between non-Hispanic Black and Hispanic recipients. Spatial analysis revealed the increased risk of posttransplant death among non-Hispanic Black recipients may be associated with region of residence. In this cohort study of lung transplant donors and recipients, socioeconomic position and region of residence did not explain most of the difference in posttransplant outcomes among racial and ethnic groups, which may be due to the highly selected nature of the pretransplant population. Further research should evaluate other potentially mediating effects contributing to inequity in posttransplant survival.

(911) Older Donors in Lung Transplantation: The Portuguese Experience

(911) Older Donors in Lung Transplantation: The Portuguese Experience

Management of donor partial anomalous pulmonary veins during lung transplantation

Management of donor partial anomalous pulmonary veins during lung transplantation

Transient hyperthermia during ex vivo lung perfusion has no protective effect in rat model

BackgroundAlthough ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation, EVLP itself can lead to inflammation in the lung. Heat shock proteins (HSPs) have anti-inflammatory effects and can reduce ischemic reperfusion injury in the donor's lungs after transplantation. In this study, the effects of transient hyperthermia during EVLP on the expression of HSPs and inflammatory pathways were examined. MethodsFifteen male Sprague–Dawley rats were randomly divided into three groups: sham (n = 5), normothermic EVLP (37 °C, n = 5), and transient hyperthermia during EVLP (42 °C, n = 5). Lung function analyses regarding PaO2/FiO2 ratio, compliance, and pulmonary vascular resistance were conducted. The expression levels of HSPs and inflammatory cytokines were also evaluated. The degree of lung injury was histopathologically evaluated. Transcriptome analysis was performed on lung tissues from the sham (n = 2), normothermic EVLP (n = 2), and heat stress-EVLP (n = 2) groups. ResultsThere were no significant differences in functional or histological parameters between the three groups. The expression of HSPs had significantly increased, especially that of HSPs 40 and 60 in the heat stress EVLP group; this was consistent with the inflammatory response. Inflammatory cytokine levels were significantly higher during EVLP and intensified with transient hyperthermia. ConclusionTransient hyperthermia during EVLP has no protective effect on the donor lung graft or activation of the inflammatory pathway at the gene level.

Comparison of Inflation and Ventilation with Hydrogen Sulfide during the Warm Ischemia Phase on Ischemia-Reperfusion Injury in a Rat Model of Non-Heart-Beating Donor Lung Transplantation.

Donor lung ventilation and inflation during the warm ischemia could attenuate ischemia-reperfusion injury (IRI) after lung transplantation. Hydrogen sulfide (H2S), as a kind of protective gas, has demonstrated the antilung IRI effect. This study is aimed at observing the different methods of administering H2S in the setting of warm ischemia, ventilation, and inflation on the lung graft from a rat non-heart-beating donor. After 1 h of cardiac arrest, donor lungs in situ were inflated with 80 ppm H2S (FS group), ventilated with 80 ppm H2S (VS group), or deflated (control group) for 2 h. Then, the lung transplantation was performed after 3 h cold ischemia. The rats without ischemia and reperfusion were in the sham group. Pulmonary surfactant in the bronchoalveolar lavage fluid was measured in donor lung. The inflammatory response, cell apoptosis, and lung graft function were assessed at 3 h after reperfusion. The lung injury was exacerbated in the control group, which was attenuated significantly after the H2S treatment. Compared with the FS group, the pulmonary surfactant in the donor was deteriorated, the lung oxygenation function was decreased, and the inflammatory response and cell apoptosis were increased in the graft in the VS group (P < 0.05). In conclusion, H2S inflation during the warm ischemia phase improved the function of lung graft via regulating pulmonary surfactant stability and decreased the lung graft IRI via decreasing the inflammatory response and cell apoptosis.

Triaging donor lungs based on a microaspiration signature that predicts adverse recipient outcome

Aspiration is a relative contraindication to accepting donor lungs for transplant and is currently assessed by visual inspection of the airways via bronchoscopy. However, this method is limited as it does not assess for microaspiration. Bile acids measured in large airway bronchial wash (LABW) samples have been shown to be a marker of aspiration in lung transplant recipients. Herein, we investigate the utility of measuring total bile acids (TBA) in donor LABW to predict performance of donor lungs and recipient outcomes. TBA was measured in 605 consecutive lung donors at the Toronto Lung Transplant Program. TBA levels were compared in donor lungs deemed unsuitable for transplant, requiring further assessment on ex vivo lung perfusion (EVLP), and those suitable for direct transplantation using Mann-Whitney-U tests. Relationships between LABW TBA concentrations and recipient outcomes were evaluated using multivariable Cox-PH models and log-rank analysis. Donor TBA was highest in lungs deemed unsuitable for transplant and correlated with clinical assessment of aspiration. LABW TBA concentration correlated with calcium, decreased pH, and increased pro-inflammatory mediators in EVLP perfusate. TBA cut-off of 1245 nM was able to differentiate donor lungs directly declined from those suitable for direct transplantation with a 91% specificity (AUROC: 73%). High donor TBA status was associated with the increased rate of primary graft dysfunction, longer time to extubation, and shorter time to chronic lung allograft dysfunction. In a large retrospective cohort, we observed that donor LABW TBA was associated with suitability of donor lungs for transplant, performance of the organ on EVLP, and adverse recipient outcomes.

Microbiological and Clinical Outcomes of Methicillin-Susceptible Staphylococcus aureus Isolated in Lung Transplant Perioperative Donor and Recipient Respiratory Cultures.

Staphylococcus aureus is one of the most common organisms isolated from respiratory secretions in lung transplant donors and recipients perioperatively. Within the first 90 days after lung transplantation, methicillin-susceptible Staphylococcus aureus (MSSA) infections have been associated with increased mortality and acute and chronic rejection. However, it is unclear whether respiratory cultures positive for MSSA at the time of transplantation can lead to clinically significant infection. The aim of this study was to assess the microbiological and clinical outcomes for lung transplant recipients (LTRs) with positive perioperative donor or/and recipient respiratory cultures for MSSA. A retrospective study was conducted evaluating MSSA-positive respiratory cultures at the time of lung transplantation from donors and/or recipients from January 1, 2008, to December 30, 2019. Patients who did not have a bronchoalveolar lavage at 2 weeks after the lung transplant or died within 2 weeks of lung transplant were excluded. The main outcome was MSSA eradication at 2-week bronchoscopy. Recipients were evaluated for MSSA infections at the 12-week period after the transplant. Of the 1,678 individuals who underwent lung transplantation, 218 LTRs had S. aureus isolated in perioperative donor or recipient respiratory cultures, and 29 were subsequently excluded. Of the remaining 189 LTRs, MSSA eradication at the 2-week bronchoscopy was achieved in 186 (98.4%) recipients. During the 12-week follow-up, 15 (7.9%) recipients were diagnosed with MSSA pneumonia; concurrent MSSA bacteremia was noted in one recipient. No anastomotic infection, empyema, or lung abscess related to MSSA was diagnosed during the follow-up period.In LTRs, the rate of MSSA eradication at 2-week post-transplant recipients is high, and it is associated with a low rate of infectious complication within the first 12 weeks after transplant. Most of the recipients received a combination therapy with at least one agent active against MSSA. More studies to evaluate the optimal antimicrobial stewardship policies regarding the regimen and duration of antibiotic therapy for these patients are needed.

A Randomized, Multicenter, Blinded Pilot Study Assessing the Effects of Gaseous Nitric Oxide in an Ex Vivo System of Human Lungs.

Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health. A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2). Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group. The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.

Donor substance use and lung transplantation: A single center experience

BackgroundLung transplantation (LT) demand outpaces supply. Consequently, extended criteria for donor selection are used, resulting in LT from donors with a history of substance use (SU). The aim of this study is to assess the association between donor SU and short-term LT outcomes. MethodsWe obtained recipient and donor data for LTs performed between January 2014 to January 2019 from electronic health records and the United Network for Organ Sharing (UNOS) database. We defined SU as cigarette/e-cigarette smoking, illicit SU (cannabis, cocaine, opioids, amphetamines), or heavy alcohol use (2+ alcoholic drinks per day). Our primary outcome was late high-grade primary graft dysfunction (PGD), which we defined as grade 2-3 PGD between 48-72 hours post-LT. Secondary outcomes included mechanical ventilation (MV) hours, intensive care unit (ICU) length of stay (LOS), hospital LOS, number of bronchoscopies, cumulative acute rejection (CAR) score in the first year after LT, and overall survival (OS). ResultsA total of 352 LTs were included in this study. On multivariable regression, we found that any donor cigarette smoking was associated with increased odds of late high grade PGD (p=0.021), while any donor cannabis use was associated with reduced odds of late high grade PGD (p=0.002). There was no association between any donor SU and secondary outcomes. ConclusionsDonor cigarette use was associated with higher risk for PGD. Our findings may suggest a history of donor cannabis use and other illicit SU are not associated with PGD or worse OS.

Survival Outcomes of Lung Transplant Recipients From Donors With Abnormal Kidney Function

BackgroundRecovering lungs with pulmonary edema due to abnormal kidney function is considered one of the expanded selection criteria for lung transplant. The aim of this study is to assess lung transplant recipients’ survival from donors with abnormal kidney function and to determine differences in lung recovery rates from donors with and donors without abnormal kidney function. MethodsWe reviewed the United Network for Organ Sharing registry for first-time adult lung transplant donors and recipients from June 2005 to March 2017. Donor kidney function was categorized into three groups based on estimated glomerular filtration rate: group I, greater than 60 mL/min; group II, 15 to 59 mL/min; and group III, less than 15 mL/min. Recipient survival was stratified based on estimated glomerular filtration rate using Kaplan-Meier. A multivariate Cox Regression model with known risk factors that affect survival was used to compare survival among groups. Comparison of lung recovery among the three groups was also performed. ResultsLung recovery rates were 29.7% (15,670 of 52,747), 19.4% (3879 of 20,040), and 18.1% (704 of 3898) for groups I, II, and III, respectively. The 1-, 3-, and 5-year recipient survival rates were 86.2%, 69.2%, and 55.7% for group I; 84.9%, 66.9%, and 53.8% for group II; and 85.5%, 65.3%, and 50.3% for group III, respectively (adjusted P = .25; multivariate Cox regression method). When group I was used as reference, the adjusted hazard ratio for group II was 1.04 (95% CI, 0.98-1.10) and for group III, it was 1.08 (95% CI, 0.96-1.23), after adjusting with the multivariate Cox regression model. ConclusionsThere was no significant difference in lung recipient survival. The lung recovery rate from donors with abnormal kidney function was lower compared with that of donors with normal kidney function.

Trends in use and three-year outcomes of hepatitis C virus–viremic donor lung transplants for hepatitis C virus–seronegative recipients

ObjectiveThe feasibility and 6-month outcome safety of lung transplants (LTs) from hepatitis C virus (HCV)-viremic donors for HCV-seronegative recipients (R–) were established in 2019, but longer-term safety and uptake of this practice nationally remain unknown. MethodsWe identified HCV-seronegative LT recipients (R–) 2015-2020 using the Scientific Registry of Transplant Recipients. We classified donors as seronegative (D–) or viremic (D+). We used χ2 testing, rank-sum testing, and Cox regression to compare posttransplant outcomes between HCV D+/R– and D–/R– LT recipients. ResultsHCV D+/R– LT increased from 2 to 97/year; centers performing HCV D+/R– LT increased from 1 to 25. HCV D+/R– versus HCV D–/R– LT recipients had more obstructive disease (35.7% vs 23.3%, P < .001), lower lung allocation score (36.5 vs 41.1, P < .001), and longer waitlist time (P = .002). HCV D+/R– LT had similar risk of acute rejection (adjusted odds ratio [aOR], 0.87; P = .58), extracorporeal membranous oxygenation (aOR, 1.94; P = .10), and tracheostomy (aOR, 0.42; P = .16); similar median hospital stay (P = .07); and lower risk of ventilator > 48 hours (aOR, 0.68; P = .006). Adjusting for donor, recipient, and transplant characteristics, risk of all-cause graft failure and mortality were similar at 30 days, 1 year, and 3 years for HCV D+/R– versus HCV D–/R– LT (all P > .1), as well as for high- (≥20/year) versus low-volume LT centers and high- (≥5/year) versus low-volume HCV D+/R– LT centers (all P > .5). ConclusionsHCV D+/R– and HCV D–/R– LT have similar outcomes at 3 years posttransplant. These results underscore the safety of HCV D+/R– LT and the potential benefit of expanding this practice further.

Long-Term Persisting Donor-Derived Human Leukocyte Antigen Antibody as a Possible Passenger Lymphocyte Syndrome Following Lung Transplantation: A Case Report

Herein, we reported the transfer of donor-derived antihuman leukocyte antigen (HLA) antibodies in 2 recipients after lung transplantation. Case 1: A 39-year-old woman with pleuroparenchymal fibroelastosis underwent a single brain-dead donor lung transplantation. Antibody screening 36 days after transplantation demonstrated high levels of de novo nondonor HLA class I-specific antibodies. The antibody screening in the donor serum revealed that the donor demonstrated a largely overlapping antibody profile. Importantly, the donor serum also included high-level HLA-specific antibodies against the recipient HLA-specific antigens, which were not detected in the recipient sera after transplantation. Donor-derived anti-HLA antibodies were still detected in the recipient 39 months after transplantation, without causing any complications such as graft-vs-host disease. Case 2: A 47-year-old woman underwent living-donor lobar lung transplantation for pulmonary complications after bone marrow transplantation with a right lower lobe from her husband and the left lower lobe from her sister. On postoperative day 39, the recipient's anti-HLA-class I antibody profile was found to be similar to that of the highly sensitized left lung donor. These donor-derived anti-HLA antibodies remained to be produced in the recipient 66 months after transplantation, without the development of complications.

Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation

Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model. Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses. Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model. Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.

Hyperammonemia syndrome in immunosuppressed individuals.

Hyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients. Growing evidence suggests hyperammonemia syndrome is associated with systemic infections caused by urease-producing organisms, namely Ureaplasma spp., an organism unable to grow with routine culturing techniques. This review will summarize the epidemiology and clinical manifestations of hyperammonemia syndrome, as well as diagnostic and management strategies once hyperammonemia syndrome is suspected. Hyperammonemia syndrome is being described in increasing frequency in the solid organ transplant population. Morbidity and mortality, even with treatment, is high once hyperammonemia syndrome occurs. Surveillance studies indicate the prevalence of lung donor colonization with Ureaplasma spp. is high, suggesting screening and treatment may be of benefit. Antibiotic resistance is common, and rapid diagnostics can facilitate appropriate antimicrobial therapy in the peri-transplant period. Hyperammonemia syndrome is most commonly seen in lung transplant recipients and has a high mortality rate once it occurs. Screening for Ureaplasma spp. should be considered in all lung transplant donors.

Clinical significance of donor lung weight at procurement and during ex vivo lung perfusion.

Elevated donor lung weight may adversely affect donor lung transplant suitability and post-transplant outcomes. The objective of this study is to investigate the impact of lung weight after procurement and ex vivo lung perfusion (EVLP) on transplant suitability, post-transplant graft dysfunction, and clinical outcomes and define the donor lung weight range most relevant to clinical outcomes. From February 2016 to August 2020, 365 human lung donors to a single transplant center were retrospectively reviewed. 239 were transplanted without EVLP, 74 treated with EVLP (50 went on to transplant), and 52 declined for transplant without EVLP consideration. Donor lung weights were measured immediately after procurement and, when performed, after EVLP. Lung weights were adjusted by donor height and divided into 4 quartiles. Donor lungs in the highest weight quartile at donor hospital had a significantly lower transplant suitability rate after EVLP, higher rates of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay. For lungs treated with lung perfusion, the highest lung weight quartile at the end of lung perfusion was associated with a significantly lower transplant suitability rate, higher incidence of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay, compared to the other categories. Donor lung weight stratified by quartile categories can assist decision-making regarding need for EVLP at the donor hospital as well as during EVLP evaluation. Caution should be used when considering donor lungs in the highest weight quartile for transplantation.

Impact of ex vivo lung perfusion on brain-dead donor lung utilization: The French experience

Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50years, smoking history, PaO2 /FiO2 ratio ≤300mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO2 /FiO2 ratio ≤300mmHg, and abnormal chest imaging.

Emerging Paradigms in Bioengineering the Lungs.

In end-stage lung diseases, the shortage of donor lungs for transplantation and long waiting lists are the main culprits in the significantly increasing number of patient deaths. New strategies to curb this issue are being developed with the help of recent advancements in bioengineering technology, with the generation of lung scaffolds as a steppingstone. There are various types of lung scaffolds, namely, acellular scaffolds that are developed via decellularization and recellularization techniques, artificial scaffolds that are synthesized using synthetic, biodegradable, and low immunogenic materials, and hybrid scaffolds which combine the advantageous properties of materials in the development of a desirable lung scaffold. There have also been advances in the design of bioreactors in terms of providing an optimal regenerative environment for the maturation of functional lung tissue over time. In this review, the emerging paradigms in the field of lung tissue bioengineering will be discussed.