Lung Transplantation Research Articles

Creating a Risk Score for Prolonged Length of Stay Following Pediatric Lung Transplants

ABSTRACTBackgroundPediatric lung transplant (LT) outcomes correlate with prolonged length of stay (pLOS), yet a paucity of research exists predicting pLOS in this population. We aim to identify factors associated with pLOS following pediatric LT, and to create a risk score identifying individual patients at increased risk of pLOS.MethodsUsing the OPTN database, we analyzed 733 pediatric patients who received an LT between January 2000‐July 2022. We used LASSO regularization to identify factors predicting pLOS. A risk score was calculated using odds ratios for each variable in the model.ResultsLASSO was run on 51 factors and identified 13 to be included in the model. The variables with the highest negative impact on LOS were recipient ethnicity (Asian, Native American, Pacific Islanders, or Mixed Race) (OR = 3.187), recipient requiring life support (OR = 2.354), and recipient age 2–10 years old (OR = 2.203). In contrast, low cold ischemia time (OR = 0.562), time on waitlist 21–60 days (OR = 0.284), and diagnosis of primary pulmonary hypertension (OR = 0.307) had protective effects on LOS. Using the risk score, we stratified patients into three equal groups: low (mean LOS = 20.60 days), medium (mean LOS = 22.53 days), and high risk (mean LOS = 36.72 days) of pLOS. The c‐statistic for the model was 0.7931 and 0.7757 for the risk score.ConclusionsUsing this model and risk score, physicians and healthcare systems could identify patients at risk of pLOS and could intervene on preventable variables before transplantation.

Diagnostic value and safety of transbronchial cryobiopsy in postoperative complications after lung transplantation

Objective: To compare the diagnostic rate and safety of postoperative complications between transbronchial cryobiopsy (TBCB) and transbronchial lung biopsy (TBLB) in patients with lung transplantation. Methods: A retrospective analysis of patients who underwent TBCB or TBLB in the Department of Lung Transplantation in China-Japan Friendship Hospital from June 2017 to June 2024 was conducted to determine the postoperative complications and analyze clinical characteristics, procedures, diagnostic rates and safety. Results: Thirty-five and 153 patients with lung transplantation received TBCB and TBLB, respectively. Patients who received TBCB had lower preoperative oxygenation index (t'=2.4, P<0.01). Meanwhile, the pathological diagnosis rate (85.7% vs. 45.7%, χ²=18.27, P<0.01) and clinical diagnosis rate (94.2% vs. 69.9%, χ²=8.80, P<0.01) of patients who received TBCB were significantly higher than those who received TBLB. There was no significant difference in the incidence of severe bleeding (2.9% vs. 0.7%, χ²=1.3, P=0.86) and pneumothorax (0 vs. 3.9%, χ²=0.43, P=0.24) between patients receiving TBCB and TBLB. The most common complications after lung transplantation in the group of TBCB were chronic lung allograft dysfunction (45.4%, 15/33), antibody mediated rejection (18.2%, 6/33) and organizing pneumonia (12.2%, 4/33). While antibody mediated rejection (29.9%, 32/107), chronic lung allograft dysfunction (16.8%, 18/107), and pneumonia (16.8%, 18/107) were more frequent in the patients who received TBLB. Conclusions: TBCB has a high diagnostic value for postoperative complications after lung transplantation, with an acceptable complication rate of bleeding and pneumothorax.

Abstract Sa1107: Resuscitation of Lungs after Cardiac Arrest with Ex-Vivo Lung Perfusion: A Bench Study to Minimize Ventilator-Induced Lung Injury through Flow Modulation

Introduction: Lung donation after uncontrolled circulatory death (uDCD) following a witnessed cardiac arrest is feasible after resuscitation and assessment with ex vivo lung perfusion (EVLP). This bench study explores the efficacy of expiratory flow modulation in minimizing damage caused by mechanical power during volume-controlled ventilation within the EVLP procedure. Methods: Donor lungs were simulated using the ASL 5000 lung simulator (IngMar Medical) and ventilated in volume-controlled mode using the ViX-ventilator (KU Leuven), set at 7 breaths per minute with a positive end-expiratory pressure of 5 cmH 2 O. (Figure 1) Baseline measurements were obtained to deliver tidal volumes (VT) of 300, 400, and 500 mL. These measurements were then compared to an intervention where expiratory flow was modulated using an in-house designed device, the flow modulator. Mechanical power (J/min) was calculated using the pressure-volume curve. Differences in power between the baseline and various levels of flow modulation were assessed using a one-sided t-test. Results: No clinically relevant differences were observed in VT delivery between baseline settings and during expiratory flow modulation. (Table 1) However, significant differences in mechanical power were noted between baseline and flow modulation across the three VT settings (p&lt;0.001). The reduction in power varied from 10.9% to 58.5%, depending on the selected VT and the degree of flow modulation applied. Notably, the extent of power reduction increased with the level of flow modulation. Conclusion: Flow modulation in the expiratory circuit during volume-controlled ventilation in a bench set-up does not affect VT delivery and can significantly reduce mechanical power by up to 58.5%. This reduction in mechanical power could potentially reduce iatrogenic damage during EVLP. Consequently, this might extend preservation times and improve the resuscitation outcomes of uncontrolled DCD lungs. Emergency medicine has the opportunity to leverage this vital pool of donor lungs, moving towards a future with minimal transplant waitlists.

A 2‐year Review of the Diagnostic Performance of Serum and Bronchoalveolar Lavage Galactomannan Testing in Lung Transplant Recipients in a National Heart and Lung Transplant Centre

ABSTRACTBackgroundThe 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly.MethodsA single‐center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA.ResultsOver the study period, 394 serum galactomannan samples were received from 144 patients and 420 BAL galactomannan samples from 143 patients. Using a cut‐off of ≥ 1.0 for BAL galactomannan, the sensitivity and specificity were 65.9% and 98.4%, respectively. In total, 30 patients had positive BAL galactomannan. Antifungal therapy was commenced or continued in 29 of these patients either as targeted or pre‐emptive treatment. Using a cut‐off of ≥ 0.5 for serum galactomannan, the sensitivity and specificity were 9.7% and 99.7%, respectively. In total, four patients had a positive serum galactomannan. All four patients were either already on antifungal treatment for IA or were started before the serum galactomannan result was available, supported by laboratory, clinical, and radiological findings. A positive serum galactomannan was used to monitor treatment response in one patient.ConclusionSerum galactomannan is not a valuable test in the diagnosis of IA in our LTx recipients, is costly, and does not remove the need for bronchoscopy and BAL galactomannan. This supports the ISHLT recommendation.

Pathologists Providing Direct Patient Care in Thoracic Transplant: Same Objective, Different Scope

Context.— Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance. Objective.— To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists’ role in their continuing care. Design.— At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our “On My Path” program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience. Results.— One hundred fifty-eight interactions have been documented (2017–2022), including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program. Conclusions.— Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Heart Transplantation Outcomes in Patients With Hypertrophic Cardiomyopathy in the Era of Mechanical Circulatory Support

Mechanical circulatory support has emerged as a vital therapeutic modality for patients awaiting heart transplantation (HT). However, it is unknown how it affected the characteristics and post-HT outcomes of patients with hypertrophic cardiomyopathy (HCM). This retrospective cohort study analyzed adult HT recipients from the International Society for Heart and Lung Transplantation registry (1998–2017). Two equal-duration eras were defined: era 1 1998–2007 and era 2 2008–2017. Patients with HCM were compared across the two eras (n1 = 742 and n2 = 1,211) and within each era, they were contrasted with individuals with nonischemic (NICM) (n1 = 15,964 and n2 = 20,394) and ischemic cardiomyopathy (ICM) (n1 = 14,140 and n2 = 12,986). Across eras, the number of HTs among patients with HCM increased by 63%. The rate of recipients with HCM in the intensive care unit (ICU) supported with intra-aortic balloon pump (IABP) increased, yet their pre-HT functional status improved, and 5 year post-HT survival remained unchanged and favorable. In era 2, at the time of HT, patients with HCM were more frequently than their NICM and ICM counterparts in the ICU and supported with inotropes. In the same era, 1 and 5 year survival were more favorable in HCM compared to ICM and comparable to NICM.

Factors Influencing the Attrition Rate of a 10-Week Multimodal Rehabilitation Program in Patients After Lung Transplant: A Neural Network Analysis

Background/Objectives: Despite the effectiveness of exercise and nutritional interventions to improve aerobic capacity and quality of life in lung transplant (LT) recipients, their compliance is low. Strategies to reduce the high attrition rate (participants lost over time) is a major challenge. Artificial neural networks (ANN) may assist in the early identification of patients with high risk of attrition. The main objective of this study is to evaluate the usefulness of ANNs to identify prognostic factors for high attrition rate of a 10-week rehabilitation program after a LT. Methods: This prospective observational study included first-time LT recipients over 18 years of age. The main outcome for each patient was the attrition rate, which was estimated by the amount of missing data accumulated during the study. Clinical variables including malnutrition, sarcopenia, and their individual components were assessed at baseline. An ANN and regression analysis were used to identify the factors determining a high attrition rate. Results: Of the 41 participants, 17 (41.4%) had a high rate of attrition in the rehabilitation program. Only 23 baseline variables had no missing data and were included in the analysis, from which a low age-dependent body mass index (BMI) was the most important conditioning factor for a high attrition rate (p = 7.08 × 10−5), followed by end-stage respiratory disease requiring PT (p = 0.000111), low health-related quality-of-life (HRQoL) (p = 0.0009078), and low handgrip strength (p = 0.023). Conclusions: The prevalence of high attrition rate in LT recipients is high. The profile of patients with a high probability of attrition includes those with chronic obstructive pulmonary disease, low BMI and handgrip strength, and reduced HRQoL.

Is Screening for GERD Necessary in All Asymptomatic Lung Transplant Candidates?

Background: Gastroesophageal reflux disease (GERD) is a known contributor to allograft dysfunction after lung transplantation. Evaluation for GERD has been advocated for all lung transplant candidates. The aim of this study is to evaluate the outcomes of GERD testing in lung transplant patients without GERD symptoms and determine if a subset can skip/defer these tests. Methods: A retrospective chart review was conducted on lung transplant candidates who had pre- transplant GI evaluation at our institution between 2019 and 2022. Adult patients were included if they reported no GERD symptoms and completed GERD screening with Multichannel intraluminal impedance-pH testing. Demographics and results of prior testing were collected for included patients. Results were analyzed using STATA. Results: 176 patients met inclusion criteria. 88 (50%) tested positive for GERD and 88 (50%) tested negative. 68/88 (77.3%) were positive by pH alone. Only 20/176 (11%) had elevated reflux episodes and were recommended to undergo anti-reflux procedures. There were no statistically significant differences in evaluated variables differentiating GERD+ versus GERD- patients. Conclusion: Lung transplant candidates without symptoms concerning for GERD tested positive for GERD 50% of the time with no reliable pre-test characteristics to stratify patients. The large majority of positive results were from high acid exposure time alone without elevated reflux episodes—a low risk phenotype for allograft dysfunction. Only 11% had increased reflux episodes and thus were recommended for anti-reflux procedures. Thus, deferring GERD screening in asymptomatic low-risk candidates until post-transplant is unlikely to impact clinical management while benefiting patients and health systems.

Ischemia/Reperfusion Upregulates Genes Related to PANoptosis in Human Lung Transplants

Background. Activation of multiple programmed cell death (PCD) pathways has been reported in cellular and animal studies of ischemia/reperfusion injury in lung transplantation. However, the status of these pathways in human lung transplants remains unknown. This study investigates the involvement of PCD pathways and their relationship with inflammation and signaling pathways in human lung transplants. Methods. Transcriptomic analysis was conducted on 54 paired human lung tissue samples at the end of cold preservation time and 2 h after reperfusion, collected between 2008 and 2011. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA were used to examine the activation of genes in 6 PCD pathways. The relationships between PCD pathways and inflammation, as well as signaling pathways, were assessed via single-gene GSEA. Results. GSEA results indicated that apoptosis and necroptosis were significantly upregulated after reperfusion in human lung transplants, whereas the gene sets related to pyroptosis, ferroptosis, autophagy, and cuproptosis were not significantly upregulated. Notably, single-sample GSEA demonstrated an intricate interplay among pyroptosis, apoptosis, and necroptosis, collectively referred to as PANoptosis, which is further supported by enrichment of genes related to PANoptosome, inflammatory response, and nuclear factor-κB and interferon signaling pathways, via single-gene GSEA assays. Conclusions. This study demonstrated the genes of PANoptosis are upregulated in human lung grafts during reperfusion. The discovery of PANoptosis as an underlying mechanism of cell death in human lung grafts implies that effective therapeutics to prevent or reduce PANoptosis may alleviate ischemia/reperfusion injury and improve clinical lung transplant outcomes.

Ceftazidime-avibactam treatment dilemma of blaKPC−2-containing Klebsiella pneumoniae due to the development of co-existence of mixed strains carrying blaKPC−2 or blaKPC−33 in lung transplant recipients

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to immunocompromised populations, including lung transplant recipients. This study investigates mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 following ceftazidime-avibactam (CAZ/AVI) exposure, particularly in the context of lung transplantation. Mixed CRKP strains with shifting resistance phenotypes were frequently identified in patients exposed to CAZ/AVI. We aimed to elucidate the transitional state of blaKPC variants by selecting CAZ/AVI-sensitive and -resistant CRKP strains from a lung transplantation patient.MethodsThe blaKPC-variant-carrying CRKP strains were collected from lung transplant recipients exposed to CAZ/AVI in less than two years. Antibiotic susceptibility testing (AST) was conducted using microbroth dilution, and whole-genome sequencing (WGS) was used to identify genotypes and resistance mechanisms. Limiting dilution, drop-plate, and in vitro induction experiments determined blaKPC-variant changes during CAZ/AVI administration. qPCR primers/probes were designed to identify blaKPC−2 mutations.ResultsAmong 104 lung transplant recipients infected by blaKPC-harboring CRKP strains and receiving CAZ/AVI, 10 (9.6%) experienced changing resistance phenotypes. The limiting dilution method found that Patient 10’s CRKP strains carried either blaKPC−2 or blaKPC−33. The drop-plate experiment showed differing growth patterns on CAZ/AVI mediums. The in vitro induction experiment demonstrated shifting from blaKPC−2 to blaKPC−33.ConclusionsThe study identified a “transitional state” of the mixed CRKP strains carrying either blaKPC−2 or blaKPC−33 in CAZ/AVI-exposed patients. Molecular diagnostics are crucial for identifying mixed strains and the transitional state of blaKPC variants, guiding treatment decisions in this complex landscape.

Prevalence of Trypanosoma cruzi infection in Solid Organ Transplant recipients: a neglected disease in America

Abstract This study investigates the prevalence of Trypanosoma cruzi infection among solid organ transplant recipients in the United States from 2019 to 2023 before transplantation. Utilizing data from a large multicenter network, we identified a rising seroprevalence of 4.8% from 1523 Solid Organ Transplant Recipients at the time of the evaluation for transplantation, particularly among lung and heart transplant recipients. The findings highlight the need for improved screening protocols to address this neglected tropical disease in transplant populations.

Efficacy of a Standardized Regimen of Therapeutic Plasma Exchange and IVIG for Treatment of Antibody-Mediated Rejection in Lung Transplant Recipients.

Antibody-mediated rejection (AMR) in lung transplantation has been associated with poor long-term clinical course and is a risk factor for chronic lung allograft dysfunction and graft loss. Appropriate management of AMR is necessary to improve graft survival in lung transplant recipients. There is currently no standardized approach to the treatment of lung AMR, and practices vary by institution. We sought to examine the efficacy of a standardized protocol of plasma exchange (PLEX) and IVIG in decreasing donor-specific antibodies (DSAs) and improving AMR in lung transplant recipients. A retrospective chart review was conducted on all lung transplant recipients who completed a course of PLEX per UT Southwestern AMR protocol between January 2012 and December 2019 for diagnosis of AMR. Data were collected on the patient clinical course, treatment regimen, pre-PLEX DSA, post-PLEX DSA, follow-up (> 1-month post-PLEX) DSA, and pre-and post-PLEX biopsy, when available. Of 527 patients who underwent lung transplantation during the study period, 56 (11%) received an acute course of PLEX every other day per protocol for AMR of lung transplant. Forty (71%) of 56 patients had one episode of AMR requiring PLEX; 16 patients (29%) had repeat episodes of AMR within 6 weeks to 47 months of the first episode. Most patients showed improvement in AMR on biopsy (69%) and a decline in DSA (68%). Our data suggest that treatment with combined PLEX and IVIG protocol appears effective for treating lung AMR.

Interdisciplinary crosstalk for enduring and future challenges in lung transplantation.

Interdisciplinary crosstalk for enduring and future challenges in lung transplantation.

Prevalence, Clinical Features, and Outcomes of Young Patients with Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) can occur at any age; however, studies on younger IPF patients are scarce because it primarily affects the elderly. This study aimed to investigate the clinical features and outcomes of younger IPF patients. We analyzed the National Korean Health Insurance Review and Assessment Service (HIRA) database from 2015 to 2021. Patients with IPF were identified using the International Classification of Diseases 10th Revision (ICD-10) codes and the Rare Intractable Diseases codes and were categorized into three age groups: <50, ≥50 and <65, and ≥65 years. The risk of acute exacerbation (AE) and mortality was analyzed. Among 4,243 patients with IPF, 91 were under 50. These younger patients, who were predominantly female, exhibited less comorbidities and received more systemic steroids, whereas older group received more pirfenidone. Although AE risk increased with age, it was not statistically significant. Mortality and lung transplantation risks increased notably with age from the <50 group to the ≥50 and <65 group (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 0.93-2.49) and the ≥65 group (HR: 2.44, 95% CI: 1.51-3.93). These risks were influenced by factors such as age, comorbidities, previous AEs, and steroid use. Conversely, pirfenidone treatment reduced the risk. While younger IPF patients had a lower risk of mortality and lung transplantation, with no significant differences in the risk of AEs, they were less likely to receive antifibrotic therapy and more often treated with steroids, which may affect outcomes. Early, targeted treatment strategies, including antifibrotic use, are crucial for improving their prognosis.

Transfusions in Lung Transplantation: Reply

Transfusions in Lung Transplantation: Reply

Have CFTR modulators changed the need for liver and lung transplantation among patients with cystic fibrosis? An analysis of the UNOS database.

Have CFTR modulators changed the need for liver and lung transplantation among patients with cystic fibrosis? An analysis of the UNOS database.

The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient’s overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies.

Association of COVID-19 With Risk of Posttransplant Diabetes Mellitus

Background. Posttransplant diabetes mellitus (PTDM) is an important complication for solid organ transplant recipients (SOTRs). COVID-19 has been associated with an increased risk of incident diabetes in the general population. However, the association between COVID-19 and new-onset PTDM has not been explored. Methods. Using the National COVID Cohort Collaborative Enclave, we conducted a cohort study of adults without diabetes receiving a solid organ transplant (heart, lung, kidney, or liver) in the United States between April 1, 2020, and March 31, 2023, with and without a first diagnosis of COVID-19 (COVID+ versus COVID–) within 180 d of SOT. We propensity score matched a single COVID+ SOTR with a COVID– SOTR who was diabetes free at the same point posttransplant. Within this matched cohort, we used multivariable Cox proportional hazards models to examine the adjusted risk of PTDM associated with COVID+. Results. Among 1342 COVID+ SOTRs matched to 1342 COVID– SOTRs, the crude rate of newly diagnosed PTDM in the 2 y post-COVID was 17% in those with versus 13% in those without COVID-19 (P = 0.007). COVID-19 was significantly associated with new PTDM (adjusted hazard ratio, 1.37; 95% confidence interval, 1.12-1.68 at 2 y). Conclusions. Similar to other viral infections, COVID-19 is associated with an increased risk of PTDM in SOTRs.

GenCOLT: a multicenter European biobank for investigating genome-wide determinants of lung transplant outcomes.

GenCOLT: a multicenter European biobank for investigating genome-wide determinants of lung transplant outcomes.

Time to Rethink Bronchiolitis Obliterans Syndrome Following Lung or Hematopoietic Cell Transplantation in Pediatric Patients

Background: Similar in histological characteristics and clinical manifestations, bronchiolitis obliterans syndrome (BOS) can develop following lung transplantation (LTx) or hematopoietic cell transplantation (HCT). In contrast to lung transplantation, where BOS is restricted to the lung allograft, HCT-related systemic graft-versus-host disease (GVHD) is the root cause of BOS. Because lung function declines following HCT, diagnosis becomes more difficult. Given the lack of proven effective medicines, treatment is based on empirical evidence. Methods: Cross-disciplinary learning is crucial, and novel therapies are under investigation to improve survival and avoid LTx. Recent advances have focused on updating the understanding of the etiology, clinical features, and pathobiology of BOS. It emphasizes the significance of learning from experts in other transplant modalities, promoting cross-disciplinary knowledge. Results: Our treatment algorithms are derived from extensive research and expert clinical input. It is important to ensure that immunosuppression is optimized and that any other conditions or contributing factors are addressed, if possible. Clear treatment algorithms are provided for each condition, drawing from the published literature and consensus clinical opinion. There are several novel therapies currently being investigated, such as aerosolized liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies, and B-cell-directed therapies. Conclusions: We urgently need innovative treatments that can greatly increase survival rates and eliminate the need for LTx or re-transplantation.