Patients Undergoing Lung Transplantation Research Articles

Risk factors and impact of swallowing impairment and aspiration after lung transplantation.

Oropharyngeal swallowing impairment frequently occurs following lung transplantation, placing patients at risk of aspiration-related complications and mortality. The primary objectives of this study were to characterize swallowing impairment and explore potential risk factors for aspiration after lung transplantation. A retrospective review of lung transplant recipients treated between January 2018 and December 2022 that received an instrumental swallow study was conducted. Clinical characteristics, post-operative outcomes, and results of swallow studies were evaluated. Airway invasion was classified using the Penetration-Aspiration Scale (PAS). Swallowing physiology was characterized using the Modified Barium Swallow Impairment Profile. Chi-squared, Wilcoxon signed-rank, Kaplan-Meier, Student's t-tests, and regression analyses were conducted. One hundred eighteen patients underwent lung transplantation and had an instrumental swallow study. Fifty-nine percent (70/118) demonstrated airway invasion. Delayed swallow initiation occurred in all patients that had videofluoroscopy (39/118). Body mass index (BMI) and body surface area (BSA) were significantly lower in patients with airway invasion (24.7±4.5 vs. 26.8±4.6 kg/m2, P=0.02; 1.8±0.2 vs. 1.9±0.2 m2, P=0.02, respectively), and were associated with airway invasion [odds ratio (OR): 0.91, P=0.02; OR: 0.13, P=0.02]. Intra- and post-operative outcomes and long-term survival did not differ significantly in our cohort. Oropharyngeal swallowing impairment and airway invasion occurred with high frequency, and linkages to low BMI or frailty were found. Although the true prevalence of aspiration after lung transplantation might be underestimated by referral patterns in this cohort, the negative impact of aspiration after lung transplantation may be mitigated by appropriate recognition and intervention.

Risk factors and prognostic modeling in bridging extracorporeal membrane oxygenation patients before lung transplantation.

The increased use of preoperative extracorporeal membrane oxygenation (ECMO) as a life support system before lung transplantation demands a better understanding of the associated prognostic factors. This study aims to discern the critical factors influencing the survival outcomes of ECMO patients and design a prognostic model tailored to this patient group. We retrospectively gathered and analyzed baseline and clinical data of patients who underwent preoperative bridging ECMO before lung transplantation from the United Network for Organ Sharing (UNOS) database. Univariate and multivariate Cox regression analyses were conducted and a prognostic model was generated to identify the independent factors influencing survival outcomes in these patients. The predictive model was cross-validated using the k-fold method where k=5. Our study included 1,202 patients. Both single and multiple analyses showed that age over 51 years, high body mass index (BMI), a history of dialysis before transplantation, donor hypertension, prolonged cold ischemia time, and high serum total bilirubin are adverse prognostic factors for the survival of ECMO-bridged lung transplant patients. Using the multivariate analysis, we created a prognosis model and a nomogram to predict 1-year post-transplant survival, with a receiver operating characteristic (ROC) curve area of 0.760 in internal validation. The 1-year survival rate calibration curve supported the nomogram's accuracy. This study involved the development of a survival prognosis model for patients undergoing lung transplantation with preoperative ECMO bridging, which was validated through extensive data analysis. The prognosis model exhibited high accuracy and predictive capability, effectively predicting the survival outcomes of patients both pre- and post-surgery.

Kidney After Lung Transplants or Combined Kidney-Lung Transplantation: A Single-Center Retrospective Cohort Study.

BACKGROUND End-stage renal disease is a major issue in the management of patients undergoing lung transplantation. Combined kidney-lung transplantation (CKLT) and kidney after lung transplantation (KALT) are the 2 preferred solutions to manage this situation. To evaluate these strategies, we describe kidney and lung graft outcomes and patient survival in patients managed with CKLT and KALT. MATERIAL AND METHODS We conducted a retrospective single-center cohort study. Patients who underwent a CKLT or a KALT were included in this study. Retrospective extraction of data from medical records was performed. RESULTS Seventeen patients underwent CKLT and 9 underwent KALT. Most of the patients had cystic fibrosis and presented renal failure related to anti-calcineurin toxicity. The 30-day and 1-year survival of CKLT recipients were both 75.6%. No patients with KALT died during the follow-up. Kidney graft prognosis was almost exclusively influenced by patient survival in relation to postoperative lung transplant complications. The rate of severe surgical complications was close to 60% for CKLT compared with 30% for KALT. The kidney graft function (estimated kidney graft function) did not differ according to the transplantation strategy. CONCLUSIONS KALT is a safe option, with postoperative morbidity and renal graft function identical to those of kidney transplantation in non-lung-transplanted patients. The results of CKLT depend mainly on the morbidity associated with lung transplantation but remain an attractive option for patients with respiratory failure associated with end-stage renal disease. The choice of transplant strategy must also take into account the most ethical and efficient allocation of kidney grafts.

Model-Informed Dosing Optimization of Tacrolimus for Concomitant Administration with Itraconazole to Japanese Lung Transplant Recipients.

Tacrolimus is an immunosuppressant administered to patients undergoing lung transplantation. Itraconazole is often concomitantly used with tacrolimus to prevent fungal infections and increase tacrolimus concentration. However, the pharmacokinetics of tacrolimus in Japanese lung transplant recipients and the effect of itraconazole on its pharmacokinetics have not been adequately evaluated. Population pharmacokinetic analysis was conducted to develop an optimal dose adjustment method for use upon itraconazole initiation in Japanese lung transplant recipients. This study comprised Japanese lung transplant recipients whose blood tacrolimus and itraconazole concentrations were measured between January 2017 and December 2019. A nonlinear mixed-effects modeling program was used to explore the covariates of tacrolimus pharmacokinetics and effects of concomitant itraconazole use. Using the model, the optimal initial tacrolimus dose was calculated and a dose adjustment method comprising concomitant itraconazole use was developed. A total of 1693 tacrolimus trough blood concentrations and 85 itraconazole trough plasma concentrations were obtained from 43 patients. Postoperative day, albumin level, and administration route were extracted as covariates for tacrolimus pharmacokinetics. The drug-drug interaction between tacrolimus and itraconazole could be predicted more accurately by considering the concentration-dependent inhibition of itraconazole. The optimal initial tacrolimus dose was 2.0 mg twice daily for tube and 1.5 mg twice daily for oral administration. To maintain the target concentration, the tacrolimus dose was reduced by 60% upon itraconazole initiation. This study is the first to use population pharmacokinetic analysis to assess the interaction between tacrolimus and itraconazole in patients who underwent lung transplantation. These results provide useful insights for optimizing the initial tacrolimus dose for concomitant itraconazole use.

Outcomes of extracorporeal membrane oxygenation cannulation strategy in lung transplantation: A retrospective cohort study

ObjectivesExtracorporeal membrane oxygenation (ECMO) with different cannulation strategies is determined according to surgical position and patient condition. However, no cannulation guidelines have been proposed. This retrospective study assessed the outcomes of diverse ECMO cannulation strategies in patients undergoing lung transplantation (LTx). MethodsData of patients undergoing intraoperative veno-arterial ECMO-assisted LTx were retrospectively collected from December 1st, 2015 to October 31st, 2021. Patients were classified into three groups based on the different cannulation strategies: femoral artery-femoral vein (F–F)-ECMO, axillary artery-femoral vein (A-F)-ECMO, and ascending aorta-femoral vein (AAO-F)-ECMO. The F-F-ECMO, A-F-ECMO, and AAO-F-ECMO groups comprised 34, 44, and 30 patients, respectively. Main resultsThe AAO-F-ECMO group exhibited a significantly shorter duration of postoperative ECMO therapy (3 vs. 2 vs. 0 days, P < 0.01).the level of postoperative proBNP was lower on the third and seventh days (P < 0.001). AAO-F-ECMO patients had a significantly lower incidence of postoperative infections, heart failure, and bleeding (P < 0.05). Similar outcomes were observed in postoperative survival rates among the three groups (P > 0.05). ConclusionsAscending aorta-femoral vein ECMO can provide sufficient and effective aerobic blood to perfuse organs with fewer side effects than cannulation in the femoral artery-femoral vein or axillary artery-femoral vein.

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

Uncertainty and Communication Preferences Among Patients Undergoing Lung Transplant Evaluation: A Mixed-Methods Study.

Higher uncertainty is associated with poorer quality of life and may be impacted by clinician communication about the future. We determined how patients undergoing lung transplant evaluation experience uncertainty and communication about the future from clinicians. We performed a convergent parallel mixed-methods study using a cross-sectional survey and semistructured interviews. Patients undergoing lung transplant evaluation at the University of Colorado and the University of Washington answered questions about future communication and completed the Mishel Uncertainty in Illness Scale-Adult (MUIS-A; range 33-165, higher scores indicate more uncertainty). Interviews were analyzed using content analysis. Integration of survey and interview results occurred during data interpretation. A total of 101 patients completed the survey (response rate: 47%). Twelve survey participants completed interviews. In the survey, most patients identified changing family roles as important (76%), which was infrequently discussed with clinicians (31%). Most patients (86%) worried about the quality of their life in the future, and 74% said that not knowing what to expect in the future prevented them from making plans. The mean MUIS-A score was 85.5 (standard deviation 15.3). Interviews revealed three themes: (1) uncertainty of the future distresses participants; (2) participants want practical information from clinicians; and (3) communication preferences vary among participants. Participants experienced distressing uncertainty and wanted information about the future. Communication topics that were important to participants were not always addressed by physicians. Clinicians should address how chronic lung disease and lung transplant can directly impact patients' lives and support patients to cope with uncertainty.

ECMO produces very rapid changes in primary hemostasis detected by PFA-200 during lung transplantation: An observational study

BackgroundThe pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited. AimsThe aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200®, ROTEM® platelet and von Willebrand factor (vWF) analyses. MethodsIn patients undergoing lung transplantation surgery using intra-operative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200®, ROTEM® platelet tests, vWF antigen, ristocetin cofactor (RCo) and collagen binding protein (CB) before, during and after ECMO support. ResultsBlood samples from 32 patients were analyzed. All three PFA-200® tests (COL/EPI, COL/ADP and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p<0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p<0.05) was found with an increase of ristocetin cofactor and collagen binding protein levels, although it was not significant (p>0.05). ConclusionsShort-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200®. Despite there being persistent platelet dysfunction after ECMO cessation as seen with the ROTEM® platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200®.

A cost-free approach to evaluating vertebral body bone density and height loss in lung transplant recipients using routine chest CT

BackgroundTo assess changes in bone density and vertebral body height of patients undergoing lung transplant surgery using computed tomography (CT). MethodsThis institutional review board (IRB) approved retrospective observational study enrolled patients with a history of lung transplant who had at least two chest CT scans. Vertebral body bone density (superior, middle, and inferior sections) and height (anterior, middle, and posterior sections) were measured at T1-T12 at baseline and follow up CT scans. Changes in the mean bone density, mean vertebral height, vertebral compression ratio (VBCR), percentage of anterior height compression (PAHC), and percentage of middle height compression (PMHC) were calculated and analyzed. ResultsA total of 93 participants with mean age of 58 ± 12.3 years were enrolled. The most common underlying disease that led to lung transplants was interstitial lung diseases (57 %). The inter-scan interval was 34.06 ± 24.8 months. There were significant changes (p-value < 0.05) in bone density at all levels from T3 to T12, with the greatest decline at the T10 level from 163.06 HU to 141.84 HU (p-value < 0.05). The average VBCR decreased from 96.91 to 96.15 (p-value < 0.05). ConclusionRoutine chest CT scans demonstrate a gradual decrease in vertebral body bone density over time in lung transplant recipients, along with evident anatomic changes such as vertebral body bone compression. This study shows that utilizing routine chest CT for lung transplant recipients can be regarded as a cost-free tool for assessing the vertebral body bone changes in these patients and potentially aiding in the prevention of complications related to osteoporosis.

Comparison of the Effects of Multiple Frailty and Nutritional Indexes on Postoperative Outcomes in Critically Ill Patients Undergoing Lung Transplantation.

Background and Objective: Lung transplantation is the only life-extending therapy for end-stage pulmonary disease patients, but its risks necessitate an understanding of outcome predictors, with the frailty index and nutritional status being key assessment tools. This study aims to evaluate the relationship between preoperative frailty and nutritional indexes and the postoperative mortality rate in patients receiving lung transplants, and to determine which measure is a more potent predictor of outcomes. Materials and Methods: This study reviewed 185 adults who received lung transplants at a single medical center between January 2013 and May 2023. We primarily focused on postoperative 7-year overall survival. Other outcomes measured were short-term mortalities, acute rejection, kidney complications, infections, and re-transplantation. We compared the predictive abilities of preoperative nutritional and frailty indicators for survival using receiver operating characteristic curve analysis and identified factors affecting survival through regression analyses. Results: There were no significant differences in preoperative nutritional indicators between survivors and non-survivors. However, preoperative frailty indicators did differ significantly between these groups. Multivariate analysis revealed that the American Society of Anesthesiologists Class V, clinical frailty scale, and Charlson Comorbidity Index (CCI) were key predictors of 7-year overall survival. Of these, the CCI had the strongest predictive ability with an area under the curve of 0.755, followed by the modified frailty index at 0.731. Conclusions: Our study indicates that for critically ill patients undergoing lung transplantation, frailty indexes derived from preoperative patient history and functional autonomy are more effective in forecasting postoperative outcomes, including survival, than indexes related to preoperative nutritional status.

Vaccine-Induced Immunity Against Pertussis in Lung Transplant Candidates

Background. Given the high prevalence of Bordetella pertussis, patients with respiratory disorders are at risk of getting infected with this pathogen and developing pertussis. Therefore, they should be considered a target group for vaccination against this infection. Aims — the objective of the study was to assess vaccine-induced immunity against pertussis in lung transplant candidates. Methods. Twenty-four patients with severe bronchopulmonary diseases, aged 18 to 60, were vaccinated against pertussis with Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine. Five patients underwent lung transplantation. Immunoglobulin G (IgG) antibodies (Abs) were measured using the RIDASCREEN® Bordetella IgG test system. Results. In the post-vaccination period, only 8.3% of the patients developed such local reactions as tenderness and induration at the injection site. The proportions of patients who were seropositive for pertussis before vaccination, one month and one year after vaccination were 71, 100 and 100%, respectively (p = 0.02). A significant increase in anti-pertussis IgG Ab levels was identified one month after a single vaccine dose, and was still observed after 12 months. In the group of two-dose vaccination, there was no statistical difference between the levels of IgG Abs one month after the first dose and one month after the second dose. A significant increase in anti-Bordetella pertussis IgG Ab levels was observed in the group of initially seronegative patients compared to seropositive patients (p = 0.03). A year after vaccination, there was no statistically significant difference in IgG Ab levels between the patients with and without a history of lung transplantation. Conclusions. The majority (71%) of patients with severe bronchopulmonary disease was seropositive for B. pertussis. Single-dose vaccination against pertussis was safe; it induced the production of additional specific Abs and an increase in their levels in all patients. Therapy administered after lung transplantation did not significantly affect the levels of vaccine-induced Abs.

A case of successful contribution of therapeutic drug monitoring of valganciclovir as the prophylaxis against cytomegalovirus infection in a lung transplant recipient

BackgroundGanciclovir and its prodrug, valganciclovir, are first-line agents for cytomegalovirus infection prophylaxis after lung transplantation. Although valganciclovir prophylaxis is known to result in severe leukopenia as an adverse effect, dosage adjustment based on therapeutic drug monitoring (TDM) of ganciclovir concentration is not generally implemented in clinical practice.Case presentationIn this report, we describe the case of a female in her fifties after lung transplantation who successfully maintained valganciclovir prophylaxis under TDM with a minimal occurrence of severe leukopenia. Valganciclovir administration was initiated at a conventional dose of 450 mg/day on postoperative day 43 but was reduced to 450 mg/2 days on postoperative day 69 because of a decrease in white blood cell count and an increase in trough ganciclovir concentration. Subsequently, the valganciclovir dose adjustment was switched from label-indicated renal function-guided dosing to TDM-based dosing, targeting a trough level of 300–800 ng/mL. This target range was determined through deliberations with infectious disease specialists and pharmacists based on previously reported data. The TDM-based dose adjustment successfully prevented cytomegalovirus reactivation without causing significant adverse effects. Valganciclovir prophylaxis was completed on postoperative day 256, and the patient was transferred to another hospital for rehabilitation.ConclusionsThe findings of the present case suggest that TDM-based dosing could be helpful for clinicians in optimizing the prophylactic administration of valganciclovir in patients undergoing lung transplantation.

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.

Outcomes of idiopathic pulmonary fibrosis patients with high body mass index undergoing extracorporeal membrane oxygenation support

To evaluate the extracorporeal membrane oxygenation (ECMO) related outcomes during hospitalization during the intensive care unit (ICU) in idiopathic pulmonary fibrosis (IPF) patients with high body mass index (BMI, > 25 kg/m2) undergoing lung transplantation with ECMO support. A retrospective observational study was conducted. IPF patients who received ECMO during lung transplantation admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from 2019 to 2020 were enrolled. Preoperative indicators including, demographics, comorbidities, arterial blood gas, and laboratory indicators; intraoperative indicators, such as lung lobe volume reduction, surgical type, surgical time, cold ischemia time, blood loss and transfusion volume; immediate indicators upon admission to the ICU, such as blood gas analysis and laboratory indicators; ECMO related outcomes, such as ECMO mode, ECMO support time, ECMO related complications (bleeding at the catheterization site, intraductal thrombosis, lower limb ischemia), and the length of ICU stay, duration of mechanical ventilation, and 30-day survival rate were collected. According to BMI, patients were divided into three groups: light weight group (BMI < 18.5 kg/m2), normal weight group (BMI 18.5-24.9 kg/m2), and overweight group (BMI ≥ 25.0 kg/m2). Mainly to compare the relevant outcomes of ECMO among patients during ICU. A total of 114 IPF patients who received ECMO support during lung transplantation were collected, including 23 cases in the light weight group, 63 cases in the normal weight group, and 28 cases in the overweight group. Compared with patients with underweight and normal weight, overweight patients were more likely to have hypertension (46.4% vs. 8.7%, 23.8%, P < 0.01) and coronary heart disease (32.1% vs. 4.3%, 20.6%, P < 0.05) before surgery, which was consistent with international guidelines for obesity. Other clinical data (preoperative, intraoperative, ICU characteristics) showed no statistically significant differences and were comparable. There was no statistically significant difference in terms of ECMO related outcomes, such as ECMO related complications [veno-venous (V-V) mode: 78.3%, 77.8%, 78.6%, veno-arterial (V-A) mode: 21.7%, 22.2%, 21.4%], ECMO support time (hours: 61.70±20.03, 44.57±5.76, 41.77±7.26), ECMO related complications (bleeding at the catheterization site: 4.3%, 7.9%, 14.3%; intraductal thrombosis: 8.7%, 12.7%, 17.9%; lower limb ischemia: 8.7%, 12.7%, 14.3%), and the length of ICU stay (days: 11±3, 7±1, 9±1), duration of mechanical ventilation [days: 2 (2, 11), 2 (2, 6), 3 (2, 8)] among the light weight group, normal weight group, and overweight group (all P > 0.05). Kaplan-Meier survival curve analysis showed that there was no statistically significant difference in the 30-day cumulative survival rate among the three groups (Log-Rank test: χ 2 = 0.919, P = 0.632). High BMI does not worsen ECMO-related outcomes or adversely affect early prognosis in IPF patients undergoing lung transplantation. BMI as a single parameter should not be a contraindication for the use of ECMO in lung transplantation surgery for IPF patients.

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.