Intraoperative Support for Primary Bilateral Lung Transplantation: A Propensity-Matched Analysis.

BACKGROUND: Single-center studies support benefits of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a method of intraoperative support. Propensity-matched data from a large cohort, however, are currently lacking. Therefore, our goal was to compare outcomes of intraoperative VA-ECMO and cardiopulmonary bypass (CPB) during bilateral lung transplantation (LTx) with a propensity analysis. METHODS: We performed a retrospective analysis of 795 consecutive primary adult LTx patients (June 1, 2011-December 26, 2020) using no intraoperative support (n = 210), VA-ECMO (n = 150), or CPB (n = 197). Exclusion criteria included LTx on venovenous-ECMO, single/redo LTx, ex vivo lung perfusion, and concomitant solid-organ transplantation or cardiac procedure. Propensity analysis was performed comparing patients who underwent intraoperative CPB or VA-ECMO. RESULTS: The propensity CPB group required more blood products at 72 hours (P = .02) and longer intensive care unit length of stay (P < .001) and ventilator dependence days (P < .001). There were no differences in cerebrovascular accident (P = 1), reintubation (P = .4), dialysis (P = .068), in-hospital mortality (P = .33), and 1-year (P = .67) and 3-year (P = .32) survival. The CPB group had a higher incidence of grade 3 primary graft dysfunction at 72 hours (P < .001). Neither support strategy was a predictor of 1- and 3-year mortality in our multivariable model (VA-ECMO, P = .72 and P = .57; CPB, P = .45 and P = .91, respectively). CONCLUSIONS: Intraoperative VA-ECMO during lung transplantation was associated with fewer postoperative blood transfusions, shorter length of mechanical ventilation, and lower incidence of a grade 3 primary graft dysfunction at 72 hours. Although there were some differences in the postoperative course between the VA-ECMO and CPB groups, support type was not associated with differences in survival.

Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS).

BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.

Risk factors of bronchial dehiscence after primary lung transplantation.

BACKGROUND: Although the incidence of bronchial dehiscence following lung transplantation has decreased significantly due to improvements in perioperative managements and surgical techniques, it remains a devastating postoperative complication associated with high morbidity and mortality. METHODS: We retrospectively reviewed 811 lung transplantation performed at our institution between January 2011 and December 2020. Bronchial dehiscence was confirmed with flexible bronchoscopy, computed tomography (CT) scan, or clinical findings grade using International Society for Heart and Lung Transplantation recommendations. RESULTS: Bronchial dehiscence was diagnosed in 38 patients (4.7%). The overall survival rates of the patients with bronchial dehiscence were significantly worse than those of the patients without bronchial dehiscence (p = .003). Multivariate analysis identified use of our basiliximab induction protocol (odds ratio = 3.03, p = .008) as an independent predictive factor of postoperative airway dehiscence in our multivariable model, along with total ventilator duration (odds ratio = 1.02, p = .002). CONCLUSIONS: Based on our analysis, patients that underwent our basiliximab induction protocol for lung transplantation experienced a higher rate of postoperative bronchial dehiscence when compared with patients who receive alemtuzumab induction. We believe this may be associated with a higher steroid exposure in this population. Additional studies are necessary to further characterize the relationship between different induction protocols and bronchial dehiscence following transplantation.

Rate of recipient-derived alveolar macrophage development and major histocompatibility complex cross-decoration after lung transplantation in humans.

Alveolar macrophages (AM) play critical roles in lung tissue homeostasis, host defense, and modulating lung injury. The rate of AM turnover (donor AM replacement by circulating monocytes) after transplantation has been incompletely characterized. Furthermore, the anatomic pattern of recipient-derived lung macrophages repopulation has not been reported, nor has their ability to accumulate and present donor major histocompatibility complex (a process we refer to as MHC cross-decoration). We longitudinally characterized the myeloid content of bronchoalveolar lavage (BAL) and biopsy specimens of lung transplant recipients and found a biphasic rate in AM turnover in the allograft, with a rapid turnover perioperatively, accelerated by both the type of induction immunosuppression and the presence of primary graft dysfunction. We found that recipient myeloid cells with cell surface AM phenotype repopulated the lung in a disorganized pattern, comprised mainly of large clusters of cells. Finally, we show that recipient AM take up and present donor peptide-MHC complexes yet are not able to independently induce an in vitro alloreactive response by circulating recipient T cells.

Lung transplantation for idiopathic pulmonary fibrosis enriches for individuals with telomere-mediated disease.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common indication for lung transplantation in North America and variants in telomere-maintenance genes are the most common identifiable cause of IPF. We reasoned that younger IPF patients are more likely to undergo lung transplantation and we hypothesized that lung transplant recipients would be enriched for individuals with telomere-mediated disease due to the earlier onset and more severe disease in these patients. METHODS: Individuals with IPF who underwent lung transplantation or were evaluated in an interstitial lung disease specialty clinic who did not undergo lung transplantation were examined. Genetic evaluation was completed via whole genome sequencing (WGS) of 426 individuals and targeted sequencing for 5 individuals. Rare variants in genes previously associated with IPF were classified using the American College of Medical Genetics guidelines. Telomere length from WGS data was measured using TelSeq software. Patient characteristics were collected via medical record review. RESULTS: Of 431 individuals, 149 underwent lung transplantation for IPF. The median age of diagnosis of transplanted vs non-transplanted individuals was significantly younger (60 years vs 70 years, respectively, p<0.0001). IPF lung transplant recipients (IPF-LTRs) were twice as likely to have telomere-related rare variants compared to non-transplanted individuals (24% vs 12%, respectively, p=0.0013). IPF-LTRs had shorter telomeres than non-transplanted IPF patients (p=0.0028) and >85% had telomeres below the age-adjusted mean. Post-transplant survival and CLAD were similar amongst IPF-LTRs with rare variants in telomere-maintenance genes compared to those without, as well as in those with short telomeres versus longer telomeres. CONCLUSIONS: There is an enrichment for telomere-maintenance gene variants and short telomeres among IPF-LTRs. However, transplant outcomes of survival and CLAD do not differ by gene variants or telomere length within IPF-LTRs. Our findings support individual with telomere-mediated disease should not be excluded from lung transplantation and focusing research efforts on therapies directed toward individuals with short-telomere mediated disease.

Outcomes following lung re-transplantation in patients with cystic fibrosis.

PURPOSE: We examined cystic fibrosis (CF) patients and compared their clinical status at the time of primary versus double lung re-transplantation (re-DLTx) in order to better understand lung retransplant practice patterns. METHODS: We performed a retrospective analysis of the UNOS Database identifying CF patients ≥18 years old undergoing re-DLTx (5/4/2005 and 12/4/2020). Baseline and clinical variables at the primary and re-DLTx were compared utilizing the paired student t-test. Graft survival was defined as time from surgery to retransplant and analyzed using Kaplan-Meier estimates. RESULTS: 277 CF patients who underwent re-DLTx experienced a significantly worse 5-year survival when compared to the primary DLTx cohort (47.9% vs 58.8%, p = 0.00012). The following differences were observed comparing CF re-DLTx group to their primary DLTx: higher LAS score at the time of listing (50.66 vs 42.15, p < 0.001) and transplant (62.19 vs 48.20, p < 0.001), and increase LAS from the time of listing to transplant (+12.22 vs +7.23, p = 0.002). While serum albumin and total bilirubin were similar, CF patients had a higher creatinine (1.05 vs 0.74, p < 0.001), dialysis (4.4% vs 0.6%, p < 0.001), ECMO bridge to transplant rates (7.6% vs 4.0%, p < 0.001), and higher oxygen requirements (5.95 vs 3.93, p < 0.001) at the time of listing for a re-DLTx. CONCLUSION: Compared to their initial transplant, CF patients experience significant clinical decline in renal, cardiac, and pulmonary function at the time of lung retransplantation. This may indicate that an earlier evaluation and rehabilitation process may be necessary to identify patients earlier for lung retransplantation prior significant clinical decline.

Type-1 immunity and endogenous immune regulators predominate in the airway transcriptome during chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) remains the major complication limiting long-term survival among lung transplant recipients (LTRs). Limited understanding of CLAD immunopathogenesis and a paucity of biomarkers remain substantial barriers for earlier detection and therapeutic interventions for CLAD. We hypothesized the airway transcriptome would reflect key immunologic changes in disease. We compared airway brush-derived transcriptomic signatures in CLAD (n = 24) versus non-CLAD (n = 21) LTRs. A targeted assessment of the proteome using concomitant bronchoalveolar lavage (BAL) fluid for 24 cytokines/chemokines and alloimmune T cell responses was performed to validate the airway transcriptome. We observed an airway transcriptomic signature of differential genes expressed (DGEs) in CLAD marked by Type-1 immunity and striking upregulation of two endogenous immune regulators: indoleamine 2, 3 dioxygenase 1 (IDO-1) and tumor necrosis factor receptor superfamily 6B (TNFRSF6B). Advanced CLAD staging was associated with a more intense airway transcriptome signature. In a validation cohort using the identified signature, we found an area under the curve (AUC) of 0.77 for CLAD LTRs. Targeted proteomic analyses revealed a predominant Type-1 profile with detection of IFN-γ, TNF-α, and IL-1ß as dominant CLAD cytokines, correlating with the airway transcriptome. The airway transcriptome provides novel insights into CLAD immunopathogenesis and biomarkers that may impact diagnosis of CLAD.

Dabigatran reversal with idarucizumab prior to lung transplantation.

BACKGROUND: When the transplant candidates are receiving oral anticoagulation therapy before transplantation, it is crucial to have an urgent reversal strategy to prevent hemorrhagic complications perioperatively. The aim of this study was to present the experience with idarucizumab to reverse the anticoagulant activity of dabigatran prior to lung transplantation. METHODS: A single-center retrospective study was performed to analyze the clinical outcomes of idarucizumab use before lung transplantation. RESULTS: Between July 2016 and June 2019, six patients were on dabigatran at the time of transplantation. Out of the six patients, four patients received idarucizumab. These four recipients received a median of 3 units (range 0-4 units) of packed red blood cells (pRBCs) and 450 ml (range 250-1500 ml) of intraoperative salvage of shed blood (cell saver blood) during the lung transplant. The two patients who were not administered idarucizumab received 5 units and 13 units of pRBCs and 900 ml and 3600 ml of cell saver blood, respectively. There was no grade 3 primary graft dysfunction (PGD) at 72 hours after transplantation or in-hospital mortality in idarucizumab group. In the group without idarucizumab, there was one case of grade 3 PGD without any in-hospital mortality. CONCLUSION: Dabigatran reversal with idarucizumab provides reasonable hemostasis during lung transplantation.

Extracorporeal Membrane Oxygenation to Overcome Graft-Cavity Disparity of Lung Transplantation.

The waitlist mortality rate is higher in patients with severe restrictive pulmonary disease because of the rapid clinical progression of the disease and the challenges of finding lung allografts that fit their small chest cavities in a timely manner. This report describes a case of urgent lung transplantation in which venovenous extracorporeal membrane oxygenation was used after open chest management and volume reduction to allow the lung allograft to accommodate to a smaller chest cavity. The use of venovenous extracorporeal membrane oxygenation in this case facilitated early chest closure in a patient with graft-cavity disparity while lowering the risk of infection without hemodynamic or respiratory compromise.

Concomitant surgical aortic valve replacement with bilateral orthotopic lung transplantation.

Concomitant cardiac surgery at the time of lung transplantation while uncommon has been shown to have acceptable morbidity and mortality. We present a case of a 66-year-old man with a history of interstitial pulmonary fibrosis with end-stage lung disease who presented with moderate aortic stenosis and severe aortic regurgitation. He underwent a bioprosthetic surgical aortic valve replacement at the time of bilateral orthotopic lung transplant and recovered without any major complications.

Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival.

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorder (EBV-PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single-center retrospective study to evaluate the risks for PTLD in LTRs over a 7-year period. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan-Meier analysis showed a decreased freedom from PTLD in idiopathic pulmonary fibrosis (IPF)-LTRs (P < .02). Using a multivariable Cox proportional hazards model, we found IPF (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.33-8.21, P = .01) and alemtuzumab induction therapy (HR 2.73, 95% CI 1.10-6.74, P = .03) as risk factors for PTLD, compared to EBV mismatch (HR: 34.43, 95% CI 15.57-76.09, P < .0001). Early PTLD (first year) was associated with alemtuzumab use (P = .04), whereas IPF was a predictor for late PTLD (after first year) (P = .002), after controlling for age and sex. Kaplan-Meier analysis revealed a shorter time to death from PTLD in IPF LTRs compared to other patients (P = .04). The use of alemtuzumab in EBV mismatch was found to particularly increase PTLD risk. Together, our findings identify IPF LTRs as a susceptible population for PTLD. Further studies are required to understand the mechanisms driving PTLD in IPF LTRs and develop strategies to mitigate risk.

Organ Transplantation for Cystic Fibrosis.

Cystic fibrosis (CF) remains the most common indication for lung transplantation in children and the third most common in adults and has the highest median survival posttransplant for all pretransplant diagnoses. Criteria for transplant in patients with CF vary widely among transplant centers and early referral to multiple centers may be needed to maximize opportunities for lung transplantation. Comorbidities unique to CF such as resistant and atypical pathogens like Burkholderia and Mycobacterium abscessus, and cirrhosis require special consideration for lung transplantation but should not be considered as absolute contraindications. For those patients who are listed for lung transplantation, mechanical support with extracorporeal membrane oxygenation and mechanical ventilation can be efficacious as bridges to lung transplantation in experienced centers with adequate resources. Liver and pancreas transplantations are also acceptable options for end-organ disease related to CF and can provide improvements in both quantity and quality of life.

Aerosolization of Second-generation Triazoles: In Vitro Evaluation and Application in Therapy of Invasive Airway Aspergillosis.

BACKGROUND: A lung transplant patient with invasive aspergillosis (IA) manifested symptoms of voriconazole-induced transaminitis with systemic voriconazole and progression of IA after switching to oral posaconazole. With limited options for standard triazole therapy, aerosolized delivery with one of the second-generation triazoles was considered. METHODS: Feasibility for aerosolized delivery was evaluated using cascade impactor and analysis of physicochemical characteristics of voriconazole (10 mg/mL) and posaconazole (6, 12 mg/mL) solutions. RESULTS: Both triazoles showed favorable characteristics for aerosol delivery with mass median aerodynamic diameter, geometric standard deviation, respirable fraction (<5.4 µm) of 2.8 µm, 2.0, 86%; 3.4 µm, 2.4, 78%; and 3.0 µm, 2.3, 79% for voriconazole and 6, 12 mg/mL of posaconazole, respectively. Aspergillus fumigatus isolate from the patient was more susceptible to voriconazole, and hence aerosolized voriconazole was introduced around the third month posttransplant at 40 mg TID for 1 week, 40 mg BID for 1 week, followed by 40 mg daily thereafter, along with IV caspofungin (50 mg/d) and liposomal amphotericin B (300 mg/d). The aerosol regimen was well tolerated by the patient with undetectable trough plasma levels of voriconazole. Bronchoscopy at the fourth month revealed improvement in anastomotic plaques with reduction in bronchoalveolar lavage galactomannan values (7.48-2.15 ng/mL). This consolidated aerosolized and intravenous regimen was maintained until 2.97 years posttransplant. CONCLUSIONS: The intravenous solutions of both second-generation triazoles showed characteristics that were suitable for aerosol delivery. Our report further adds to the therapeutic experience with the use of aerosolized voriconazole for IA in a lung transplant patient.

Characteristics, Trends, and Predictors of Specialty Palliative Care Utilization after Lung Transplantation.

Background: Lung transplant recipients who experience serious illness could benefit from specialty palliative care (SPC), but evidence suggests that referral has been rare. Objective: Examine the characteristics of post-transplant SPC encounters, utilization trends, and patient characteristics associated with SPC at a center with established SPC services. Design: Retrospective cohort study of SPC utilization by 597 lung transplant recipients transplanted between 2010 and 2015. We collected data on pretransplant demographics and post-transplant SPC encounters, including timing, location, and referral reasons. Cumulative incidence of SPC and patient characteristics associated with SPC were examined by competing risks methods. Utilization in the first two post-transplant years was compared between subcohorts defined by year of transplantation. Results: SPC cumulative incidence was 27% and 43% at one and five years. More than 60% of encounters occurred in the first post-transplant year including 34% during the index transplant hospitalization. Over 90% of encounters occurred in the inpatient setting. The majority of consults were for symptom management. From 2010 to 2015 inpatient utilization in the first two post-transplant years increased from 23% to 42%, and outpatient utilization increased from 2% to 16%. Accounting for increasing utilization, pretransplant SPC and double-lung transplantation were associated with greater incidence of post-transplant SPC. Conclusions: Lung transplant recipients may have palliative care needs early after transplantation. Increasing utilization suggests greater awareness of or changing attitudes about the utility of SPC for lung transplant recipients. Understanding transplant recipients' palliative care needs and transplant physicians' views of SPC is critical to improving the provision of SPC in lung transplantation.

Impaired Cytomegalovirus Immunity in Idiopathic Pulmonary Fibrosis Lung Transplant Recipients with Short Telomeres.

RATIONALE: Cytomegalovirus (CMV)-related morbidities remain one of the most common complications after lung transplantation and have been linked to allograft dysfunction, but the factors that predict high risk for CMV complications and effective immunity are incompletely understood. OBJECTIVES: To determine if short telomeres in idiopathic pulmonary fibrosis (IPF) lung transplant recipients (LTRs) predict the risk for CMV-specific T-cell immunity and viral control. METHODS: We studied IPF-LTRs (n = 42) and age-matched non-IPF-LTRs (n = 42) and assessed CMV outcomes. We measured lymphocyte telomere length and DNA sequencing, and assessed CMV-specific T-cell immunity in LTRs at high risk for CMV events, using flow cytometry and fluorescence in situ hybridization. MEASUREMENTS AND MAIN RESULTS: We identified a high prevalence of relapsing CMV viremia in IPF-LTRs compared with non-IPF-LTRs (69% vs. 31%; odds ratio, 4.98; 95% confidence interval, 1.95-12.50; P < 0.001). Within this subset, IPF-LTRs who had short telomeres had the highest risk of CMV complications (P < 0.01) including relapsing-viremia episodes, end-organ disease, and CMV resistance to therapy, as well as shorter time to viremia versus age-matched non-IPF control subjects (P < 0.001). The short telomere defect in IPF-LTRs was associated with significantly impaired CMV-specific proliferative responses, T-cell effector functions, and induction of the major type-1 transcription factor T-bet (T-box 21;TBX21). CONCLUSIONS: Because the short telomere defect has been linked to the pathogenesis of IPF in some cases, our data indicate that impaired CMV immunity may be a systemic manifestation of telomere-mediated disease in these patients. Identifying this high-risk subset of LTRs has implications for risk assessment, management, and potential strategies for averting post-transplant CMV morbidities.

Systematic review and meta-analysis of post-transplant lymphoproliferative disorder in lung transplant recipients.

A systematic review of papers in English on post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random-effects model, and heterogeneity among studies was quantitated using I2 values. Fourteen studies published from 2005 to 2015 were included in the meta-analysis. One hundred and sixty-four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67-fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98-29.70; P = .003). pOR of death for early onset PTLD (<1 year post-LT) vs late onset (>1 year post-LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20-1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI -0.48-0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08-2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31-3.52, P = .94). This meta-analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.

ECMO Support in Lung Transplantation: A Contemporary Analysis of Hospital Charges in the United States.

BACKGROUND: There is little in the literature pertaining to cost associated with the use of extracorporeal membrane oxygenation (ECMO) in lung transplantation. We sought to evaluate charges associated with the index hospitalization among recipients of a lung transplant who required ECMO to identify factors that increase hospital charges in these patients. METHODS: With the use of the Nationwide Inpatient Sample, we reviewed data pertaining to patients who received a lung transplant between 2000 and 2011 and stratified them into ECMO and non-ECMO groups based on use of ECMO. Regression modeling was used to identify differences in charges. RESULTS: Data pertaining to 15,596 recipients of a lung transplant were evaluated, 658 (4.2%) of whom required ECMO. ECMO recipients were more likely to have a diagnosis of idiopathic pulmonary fibrosis (3.5% versus 1.3%, p = 0.007) or pulmonary hypertension (PH) (9.1% versus 3.0%, p < 0.001). Patients who received a bilateral lung transplant had 32.1% (95% confidence interval [CI]: 26.2% to 37.9%, p < 0.001) higher charges. Recipients with PH had 28.7% (95% CI: 14.9% to 42.4%, p = 0.001) higher charges. Median charges for recipients of a lung transplant who required ECMO were $780,391.50 versus $324,279.80 for non-ECMO recipients of a lung transplant and were 50.3% (95% CI: 33.0% to 67.5%, p < 0.001) higher. Hospital charges among Medicare enrollees were 6.6% (95% CI: 0.7% to 12.5%, p = 0.028) higher than privately insured recipients of a lung transplant. Black recipients had approximately 34.2% (95% CI: 3.2% to 65.0%, p = 0.030) higher charges. The ECMO group had longer median length of stay (LOS) (25 versus 15 days, p < 0.001). CONCLUSIONS: Recipients of a lung transplant who required ECMO support had longer LOS and higher hospital charges, specifically among black recipients, recipients with PH, and Medicare enrollees.

Effect of aerosolized antipseudomonals on Pseudomonas positivity and bronchiolitis obliterans syndrome after lung transplantation.

PURPOSE: To describe the effects of aerosolized antipseudomonals (AAPs) on Pseudomonas (PS) culture positivity, bronchiolitis obliterans syndrome (BOS), and acute cellular rejection (ACR) in lung transplant recipients (LTRs). METHODS: Single-center, retrospective cohort study was performed of adult LTRs treated with either AAP for ≥28 days vs no AAP therapy or AAP therapy <28 days, indexed to a matched median date post lung transplantation (LT). Primary outcome was freedom from PS positivity by positive bronchoalveolar lavage or bronchial wash at 1 year. Secondary outcomes were freedom from BOS or BOS progression and ACR burden (defined by the novel composite rejection standardized score. Normality was assessed, and univariate and multivariate parametric and non-parametric statistical tests were used to assess baseline characteristics and outcomes, where appropriate. Freedom from events was compared using the Kaplan-Meier method with log-rank conversion and risk was assigned using multivariable Cox proportional hazards (PH) modeling. RESULTS: In total, 293 LTRs (105 with AAP, 188 with no AAP) were included. Median ages in AAP and control cohorts were 51 (30-63) and 62 (54-67) years (P<.01). Median AAP duration was 198 (interquartile range 94-395) days. Time to median positive PS culture was similar between AAP (median 1.02 [95% confidence interval {CI} 0.74-1.22] years) and control (median 0.96 [95% CI 0.72-1.21] years). Log-rank test for time-to-PS positivity was similar for both groups (log-rank P=.26). Incidence of PS culture positivity at 1 year was similar in APP vs controls (59.0% vs 54.8%, P=.48). In the non-cystic fibrosis (CF) subgroup, AAP use was protective against PS recurrence on univariate Cox PH model (hazard ratio [HR] 0.55, 95% CI 0.38-0.83) and on multivariate Cox PH adjusting for age and induction (HR 0.56, 95% CI 0.38-0.83). Incidence of new-onset BOS or BOS progression in APP vs control at 1 (17.1% vs 14.9%, P=.61) and 3 (38.1% vs 37.8%, P=.96) years was similar. CRSS was similar in APP vs control group at 1 year (0.42 vs 0.33, P=.41). CONCLUSION: AAP use was not associated with less PS positivity, BOS, or ACR in all LTRs. In the non-CF subgroup analysis, treatment with AAPS was associated with protection against recurrent PS. Limitations include retrospective design, heterogeneous AAP therapy among LTRs, and potential convenience sampling of LTRs receiving AAPs for >28 days at our center. Larger assessments and better controlled analyses are required to further define efficacy of AAPs after LT.

Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation.

Refractory acute cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post-lung transplantation. We report the largest cohort of lung transplant recipients (LTRs) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30 days before and 180 days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0-6) and freedom from ≥A2 ACR. BOS outcomes included freedom from BOS progression and FEV1 decline >10%. Univariate parametric and nonparametric statistical approaches were used to assess treatment response. Kaplan-Meier method with log rank conversion was used to assess freedom from events. Fifty-seven alemtuzumab doses (ACR 40 and BOS 17) given to 51 patients were included. Median time to rescue was 722 (IQR 42-1403) days. CRSS declined significantly (3 vs 0.67, P<0.001) after rescue. Freedom from ≥A2 was 62.5% in rACR. Freedom from BOS progression was 52.9% at 180 days in the BOS cohort. Freedom from FEV1 decline >10% was 70% in BOS grade 1 and 14.3% in advanced BOS grades 2-3. Infections developed in 72.5% and 76.5% of rACR and BOS groups. Rescue alemtuzumab appears useful for rACR. Patients with BOS 1 may have transient benefit, and patients with advanced BOS seem not to respond to alemtuzumab.