Mortality In Lung Transplant Recipients Research Articles

Low Mortality Associated with COVID-19 Infection in Lung Transplant Recipients at a Single Center

Lung Transplant Recipients (LTR) are particularly vulnerable to severe infection, hospitalization, and death due to community acquired respiratory viruses. As a result, the global SARS-Cov-2 pandemic poses a higher risk to this population. We aim to study the lung function, severity of infection and mortality among LTR at a single center. A retrospective chart review was performed on all LTR at the University of San Diego, California Medical Center between June 2020 and September 2022. Spirometry was performed at 1-2 months and then again 3 months after infection. Patients were closely monitored for the development of acute cellular rejection (ACR). 72 LTR were infected with COVID-19. 37.5% required hospital admission, of which 25.9% required management in the intensive care unit (ICU). 73.6% LTR had received at least one vaccination dose prior to infection. Post-infection, the median drop in FEV1 was 140 mL and FVC was 25 mL within 1-2 months. At 3 months post-infection the median reduction in FVC was slightly larger at 75 ml, while median decline in FEV1 decreased to 55 ml. Overall, the rates of ACR and mortality in this population were both 4.2%. Additionally, monoclonal antibody (mAb) therapy reduced hospitalization (20.9% vs 62%) and mortality (0% vs 10.3%), Our study found low rates of ACR and mortality in LTR with confirmed COVID-19, despite the statistically significant decline in FEV1, and trends with FVC. The use of vaccinations and mAb therapy decreased rates of hospitalizations, with mAb therapy reducing mortality as well.

Real-time, random-access organ screening for carbapenem-resistant organisms (CRO) reduces CRO-associated, donor-derived infection mortality in lung transplant recipients.

Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. Multivariate analysis showed that CRO-related death due to DDI within 60days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.

Oesophageal stasis is a risk factor for chronic lung allograft dysfunction and allograft failure in lung transplant recipients.

Morbidity and mortality in lung transplant recipients are often triggered by recurrent aspiration events, potentiated by oesophageal and gastric disorders. Previous small studies have shown conflicting associations between oesophageal function and the development of chronic lung allograft dysfunction (CLAD). Herein, we sought to investigate the relationship between oesophageal motility disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. All lung transplant recipients at the Toronto Lung Transplant Program from 2012 to 2018 with available oesophageal manometry testing within the first 7 months post-transplant were included in this study. Patients were categorised according to the Chicago Classification of oesophageal disorders (v3.0). Associations between oesophageal motility disorders with the development of CLAD and allograft failure (defined as death or re-transplantation) were assessed. Of 487 patients, 57 (12%) had oesophagogastric junction outflow obstruction (OGJOO) and 47 (10%) had a disorder of peristalsis (eight major, 39 minor). In a multivariable analysis, OGJOO was associated with an increased risk of CLAD (HR 1.71, 95% CI 1.15-2.55, p=0.008) and allograft failure (HR 1.69, 95% CI 1.13-2.53, p=0.01). Major disorders of peristalsis were associated with an increased risk of CLAD (HR 1.55, 95% CI 1.01-2.37, p=0.04) and allograft failure (HR 3.33, 95% CI 1.53-7.25, p=0.002). Minor disorders of peristalsis were not significantly associated with CLAD or allograft failure. Lung transplant recipients with oesophageal stasis characterised by OGJOO or major disorders of peristalsis were at an increased risk of adverse long-term outcomes. These findings will help with risk stratification of lung transplant recipients and personalisation of treatment for aspiration prevention.

Association Between Severe SARS-CoV-2 Infection and De Novo HLA Donor Specific Antibody Production in Lung Transplant Recipients: Single-center study

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR. We performed a retrospective chart review of 80 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 liters of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 liters of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. A total of 23, 47, and 10 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSAwere detected in 0/23 (0%), 3/47 (6.3%), and 4/10 (40%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.0007) within 6 months post-COVID-19 diagnosis. Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.

Invasive fungal infections after respiratory viral infections in lung transplant recipients are associated with lung allograft failure and chronic lung allograft dysfunction within 1 year

Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction (CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not been investigated. We performed a single center retrospective study including LTRs diagnosed with 5 different respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression. The impact of IFIs on CLAD stage progression/death was examined by Cox regression. A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2, 30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients was included for analysis. Thirty-one episodes (15%) were associated with secondary IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from 96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85 (2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI) of 2.45 (1.29-4.64). This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly, secondary IFIs were associated with CLAD stage progression/death, underscoring the importance of screening for fungal infections in this setting.

Immunity After Vaccination Against SARS-CoV-2 in Lung Transplant?

Introduction: SARS-CoV2 infection causes high morbidity and mortality in lung transplant recipients (LT). Vaccination with mRNA vaccines has been shown to play a key role in controlling the severity of infection in the general population. The aim of our study is to analyze whether vaccination with 2 doses of SARS-Cov2 provides immunity in LT.Material and Methods: Retrospective descriptive and analytical study of LTs vaccinated with 2 doses of SARS-CoV2. We analyzed the vaccine received, if they had COVID-19, antibody levels (anti-spike and anti-nucleoprotein), anticalcineurin levels, infections in the last year and the presence of neoplasias.Results: The most commonly administered vaccine was from the Moderna laboratory, with 27% of patients showing immunity with a median antibody levels of 4.81 BAU/ml far from the values considered protective (>34 BAU/ml). Thirteen patients were infected with SARS-CoV2, seven post-vaccination (five of them were anti-spike positive). No relationship was demonstrated between generation of immunity and age and level of immunosuppression.Conclusion: Vaccination against SARS-CoV2 in LT generates limited and ineffective immunity with only 2 doses.

Impact of Tacrolimus Trough Variability on Acute Rejection Following Lung Transplantation

Acute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation. We retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included. The mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P=.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P=.55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P=.62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated. High tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability.

P16.07: Association Between SARS-CoV-2 Infection and de Novo HLA Donor Specific Antibody Production in Lung Transplant Recipients: Single-Center Study

Introduction: COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients. Respiratory viral infections may be associated with de-novo HLA donor-specific antibody production and impacting lung transplant outcome. Methods: Since one of the immunomodulation strategies post-SARS-CoV-2 infection in lung transplant recipients include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo HLA donor specific antibody production in lung transplant recipients. We performed a retrospective chart review of 24 consecutive lung transplant recipients diagnosed with COVID-19 to investigate this concern. Results: We observed no significant association between SARS-CoV-2 infection and immunomodulation on pre-existing or de novo HLA donor specific antibodies. Conclusion: SARS-CoV-2 infection was not associated with a significant increase in de-novo HLA DSA production or MFI levels of pre-existing HLA DSA compared to pre-COVID-19 diagnosis in lung transplant recipients. These results provide a valuable insight on the effects of SARS-CoV-2 infection on immunogenicity in lung transplant recipients.

Association between SARS-CoV-2 infection and de novo HLA donor specific antibody production in lung transplant recipients: Single-center study

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients. Respiratory viral infections may be associated with de-novo HLA donor-specific antibody production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in lung transplant recipients include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo HLA donor specific antibody production in lung transplant recipients. We performed a retrospective chart review of 24 consecutive lung transplant recipients diagnosed with COVID-19 to investigate this concern. We observed no significant differences in the CPRA or MFI levels of HLA class I and II antibodies pre- COVID-19 compared to 1 and 6 months post-COVID-19 diagnosis in 11/24 (45.8 %) LTR (p = 0.98 and p = 0.63 respectively). HLA class I and II DSA were detected in 5/24 LTR pre-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.89). De-novo HLA class I and II DSA were detected in 1/24 (4.2 %) LTR at one month post-COVID-19 diagnosis and persisted with no significant differences in the median MFI levels at 1 and 6 months post-COVID-19 diagnosis (p = 0.54). Our results suggest that there was no significant association between SARS-CoV-2 infection and immunomodulation on pre-existing or de novo HLA donor specific antibodies.

CD11b suppresses TLR activation of nonclassical monocytes to reduce primary graft dysfunction after lung transplantation.

Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and the most important risk factor for development of chronic lung allograft dysfunction. The mechanistic basis for the variability in the incidence and severity of PGD between lung transplant recipients is not known. Using a murine orthotopic vascularized lung transplant model, we found that redundant activation of Toll-like receptors 2 and 4 (TLR2 and -4) on nonclassical monocytes activates MyD88, inducing the release of the neutrophil attractant chemokine CXCL2. Deletion of Itgam (encodes CD11b) in nonclassical monocytes enhanced their production of CXCL2 and worsened PGD, while a CD11b agonist, leukadherin-1, administered only to the donor lung prior to lung transplantation, abrogated CXCL2 production and PGD. The damage-associated molecular pattern molecule HMGB1 was increased in peripheral blood samples from patients undergoing lung transplantation after reperfusion and induced CXCL2 production in nonclassical monocytes via TLR4/MyD88. An inhibitor of HMGB1 administered to the donor and recipient prior to lung transplantation attenuated PGD. Our findings suggest that CD11b acts as a molecular brake to prevent neutrophil recruitment by nonclassical monocytes following lung transplantation, revealing an attractive therapeutic target in the donor lung to prevent PGD in lung transplant recipients.

Impact of Lung Function Decline on Mortality in Lung Transplant Recipients: Long-Term Results From the L-CsA-i Study for the Prevention of Bronchiolitis Obliterans Syndrome.

BackgroundChronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx).Methods10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis.ResultsA total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality (p < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk.ConclusionBased on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions.

Influence of Fluid Therapy on Kidney Function in the Early Postoperative Period After Lung Transplantation

Perioperative fluid therapy among patients undergoing lung transplantation (LT) has a significant clinical importance, including developing of acute kidney injury (AKI). The presence of AKI in the early postoperative period is associated with increased mortality in lung transplant recipients. Analysis includes the relationship between the volume of infused fluids, the balances of crystalloids and colloids during LT procedure and in the first 24 hours and the estimated glomerular filtration rate (eGFR) values in the following days of the postoperative period. Retrospective study of 73 consecutive patients undergoing LT between 2015 and 2018 in our institution. Deterioration of renal function was defined as the change in eGFR that occurred between baseline eGFR and the first and 7 first postoperative days following transplantation. The Chronic Kidney Disease Epidemiology Collaboration formula was used to calculate the eGFR value. The greatest decline of eGFR in the early postoperative period was demonstrated on day 7 (ΔeGFR=75.76 ± 40.08). Increased negative crystalloid balances during the LT procedure were strongly associated to less decrease in eGFR value on the seventh day post-LT (r=-0.997, P < .05). Increased volumes of transfused colloids during LT were correlated to less decline of eGFR value on day 7 (r=-0.3981, P < .05). Negative crystalloid balance in the early postoperative period post-LT has a potentially protective effect on kidney function, although fluid balances management should be individually considered for potential clinical benefits. The impact of the fluid administration after LT on the occurrence and recovery of AKI among lung transplant recipients requires further investigation.

Esophageal Disorders in Lung Transplant Recipients: Association with Chronic Lung Allograft Dysfunction and Survival

<h3>Purpose</h3> Chronic lung allograft dysfunction (CLAD) is a major cause of morbidity and mortality in lung transplant recipients and is often triggered by aspiration events, potentiated by esophageal and gastric disorders. The two major classes of esophageal disorders include: 1) disorders of peristalsis and 2) esophagogastric junction outflow obstruction (EGJOO). Previous small studies have shown conflicting relationships between esophageal function and the development of CLAD. Herein, we sought to investigate the relationship between esophageal disorders and long-term outcomes in a large retrospective cohort of lung transplant recipients. <h3>Methods</h3> All lung transplant recipients from 2000-2018 with available esophageal manometry testing within first 7 months post-transplant were included in this study. Subjects were categorized into three groups: 1) no esophageal disorders, 2) disorder of peristalsis, and 3) EGJOO (defined by the 2007 Chicago Classification System). Disorders of peristalsis were further divided into major disorder (absent contractions) and minor disorder (irregular contractions). Univariable Cox proportional hazards models were used to determine the relationship between esophageal disorders and the development of CLAD and allograft failure (death/retransplant). <h3>Results</h3> Of 487 subjects, 47 (10%) had a disorder of peristalsis (8 major, 39 minor) and 57 (12%) had EGJOO. Older subjects were more likely to have an esophageal disorder (p=0.001). A major disorder of peristalsis was associated with an increased risk of CLAD [HR 2.78 (95% CI 1.23-6.28); p=0.01] and allograft failure [HR 3.17 (95% CI 1.49-6.77); p=0.003]. A minor disorder of peristalsis was not significantly associated with CLAD or allograft failure. EGJOO was associated with an increased risk of CLAD [HR 1.63 (95% CI 1.11-2.40); p=0.01] and allograft failure [HR 1.73 (1.18-2.54); p=0.005]. <h3>Conclusion</h3> In a large retrospective cohort we observed that lung transplant recipients with major disorders of peristalsis and EGJOO were at an increased risk of CLAD and death/retransplant. In contrast, people with minor disorders of peristalsis were not at an increased risk of these outcomes. These findings will help with risk-stratification of lung transplant recipients and personalization of treatment for aspiration prevention.

Secondary Bacterial and Fungal Pneumonia Complicating SARS-CoV-2 and Influenza Infections in Lung Transplant Recipients

PurposeSelect bacterial and mold infections are known risk factors for chronic allograft dysfunction (CLAD) in a subset of lung transplant recipients (LTR). Secondary bacterial (SBI) and fungal infections (SFI) have been described among people with severe influenza infection and COVID-19 requiring mechanical ventilation, but the incidence and clinical outcomes of LTR who develop secondary infections following respiratory viral infections (RVI) are not well described.MethodsWe conducted a retrospective study of LTR who were diagnosed with either influenza or COVID-19 from January 2011-May 2021. Infection definitions and CLAD stage were defined according the International Society of Heart and Lung Transplantation guidelines.ResultsFifty-seven LTR with influenza and 33 with COVID-19 were identified. Eleven (19%) of the LTR with influenza developed SBI and seven (21%) with COVID-19 developed SBI (p=0.83). Among patients who developed SBI, Pseudomonas aeruginosa was the most common isolated pathogen (44%). Five (9%) and 7 (21%) LTR developed SFI within 90 days post Influenza and COVID-19 infection, respectively (p = 0.09). Among patients with fungal infection, Aspergillus species were the most common pathogen (75%). At 180 days post RVI, all-cause mortality was higher in LTR with SBI (17%) compared to those without (3%), p=0.02. Mortality was similarly higher in LTR with SFI (33%), compared to those without (1.3%), p<0.0001. At 180 days post RVI, LTR with SBI had progression of CLAD stage 43% vs 11%, p=0.004. Based on univariable logistic regression, LTR who had augmented corticosteroids at time of RVI, and lower respiratory tract infection (LRTI) had higher risk of SFI (odds ratio (OR) of 6.57 (1.8, 23.9), p=0.002 and 12.5 (2.53, 61.7), p=0.004, respectively). There were trends of increased OR of SBI among LTR with LRTI and LTR requiring ICU admission due to RVI with the ORs of 2.78 (0.98, 8.01), p=0.06 and 3.77 (0.90, 15.84), p=0.07, respectively.ConclusionSecondary bacterial and fungal infections are associated with increased all-cause mortality in LTR with influenza and COVID-19, and in the case of SBI, also associated with CLAD stage progression. LTR with LRTI and augmented steroids may be at increased risk of secondary fungal infections. Strategies to mitigate and improve diagnosis may warrant further examination.

Worsening in the Lung Transplant-Valued Life Activities Scale is Associated with Mortality in Lung Transplant Recipients

<h3>Purpose</h3> The Lung Transplant-Valued Life Activities (LT-VLA) scale is a patient-reported outcome measure of physical functioning and disability, validated in lung recipients. We hypothesized that worsening LT-VLA disability would predict reduced survival after lung transplant (LT). <h3>Methods</h3> We analyzed data from participants in Breathe Again, a single-center prospective cohort of adults undergoing lung transplantation from 2010 to 2017. Participants completed the LT-VLA assessment before and at 6-month intervals up to 3 years after transplant. The 15-item LT-VLA can be completed in ≤3 minutes and measures patient-reported ability to complete a spectrum of physical activities that the respondent deems important. Participants rate the level of difficulty in performing each activity on a 4-point scale (0 = no difficulty, 1 = some, 2 = a great deal, 3 = unable to perform). In the LT-VLA score (0-3) higher value represents greater disability, with a 0.3-point change being a clinically important difference. We tested the association between LT-VLA scores over time and mortality by Cox proportional hazard models, modeling LT-VLA as a time-varying predictor adjusted for pre-operative age, gender, race, and diagnosis, as well as allograft function modeled as a time-varying covariate. <h3>Results</h3> Among 238 participants, 45% were female and 72% white, with mean age of 56 (± 12) years, 72% transplanted for pulmonary fibrosis. Mean Lung Allocation Score was 58 ± 22, and 93% of subjects received bilateral LT. A 0.3-point worsening in LT-VLA during any 6-month period up to 3 years after LT was associated with a 10% increased risk of mortality (HR 1.1, 95% confidence interval 1.04 to 1.2, p = 0.001). <h3>Conclusion</h3> Worsening patient-reported disability after transplant was associated with death, independent of lung allograft function. Longitudinal assessment of patient-reported disability, feasible by the brief LT-VLA scale applied remotely, may allow identification of lung recipients who may benefit from interventions to prevent poor outcomes.

Effect of antifibrotic therapy in patients with idiopathic pulmonary fibrosis undergoing lung transplant in the peri and post-operative period

BackgroundIdiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease with high mortality. Lung transplant remains a cornerstone of treatment despite the advent of antifibrotic therapy. In light of the increasing number of patients on antifibrotic therapy prior to lung transplantation it is paramount to demonstrate these medications do not augment postoperative complications following transplant. Research questionDoes antifibrotic therapy increase perioperative complications and mortality in lung transplant recipients? Study design and methodsWe conducted a retrospective chart review of all patients actively listed for lung transplant at Temple University Hospital from June 2014 to April 2017 with a listing diagnosis of IPF. Subjects who received treatment with antifibrotic therapy (either pirfenidone or nintedanib) up until the time of lung transplantation were compared to subjects not on therapy. Data was collected regarding baseline demographics, pulmonary function tests, IPF exacerbations, perioperative bleeding and cardiac events, and outcomes in the postoperative period. ResultsA total of 94 subjects were included in the study: 42 subjects on antifibrotic therapy (28 pirfenidone, 14 nintedanib) and 52 subjects not on therapy in the pre-transplant period. Baseline characteristics were similar between study groups. Subjects treated with antifibrotic therapy pre-transplant were noted to have less FVC decline, fewer hospitalizations, and greater weight loss while on the transplant waiting list. No difference in post-transplant airway anastomosis complications, bleeding or mortality was observed between study groups. InterpretationSubjects with IPF on antifibrotic therapy prior to lung transplantation had better preservation of lung function in the pre-transplant period, and similar outcomes in the postoperative period compared to those not on antifibrotic therapy before lung transplant.

Lung Transplant Recipients With Prior Coronary Artery Bypass Grafting Are at Increased Risk of Death and Early Perioperative Hemorrhage

Prior coronary artery bypass grafting (CABG) has been considered a relative contraindication to lung transplantation due to the atherosclerotic disease burden and technical challenges. We hypothesized that lung transplant recipients with prior CABG have increased mortality compared to recipients without prior CABG. Further, the causes of death are different for lung transplant recipients with prior CABG vs without CABG. The Scientific Registry of Transplant Recipients database was queried to define the survival and causes of death of lung transplant recipients with or without CABG during the Lung Allocation Score era from May 5, 2005 to December 31, 2015. The primary end-points were all-cause mortality at 1 year and 5 years, as well as mortality due to major causes of death. This retrospective study cohort included a total of 13,064 lung transplant recipients, of whom 319 patients had previously undergone CABG, representing 2.4% of all transplants. Patients without prior CABG were more likely to have undergone bilateral lung transplantation compared to those with prior CABG (61.2 % vs 15.7%, P < 0.001). Among patients with prior CABG, single right lung transplant was most common. Overall patient survival at 1 year was 76.8% for lung transplant recipients with prior CABG and 85.4% for patients without prior CABG. Freedom from death due to graft failure at 1 and 5 years in patients with a prior CABG was 93.1% and 76.2% respectively, cardiac and/or cerebrovascular disease 96.2% and 88.5% respectively, and hemorrhage 97.9% and 97.5% respectively. In a multivariate Cox regression model utilizing time-dependent coefficients for recipient age, prior CABG, among several other risk factors, was associated with increased mortality within 1 year. Prior CABG is associated with short- and long-term mortality in lung transplant recipients with history of CABG despite the majority of these patients undergoing single lung transplantation vs bilateral lung transplantation. Graft failure and/or pulmonary causes are the most common cause of death regardless of whether or not the lung transplant recipient had prior CABG, but patients with prior CABG are at increased risk of death due to graft failure, cardiac or cerebrovascular disease, and hemorrhage.

Nebulized Micafungin Treatment for Scopulariopsis/Microascus Tracheobronchitis in Lung Transplant Recipients.

Scopulariopsis/Microascus isolates cause infections with high mortality in lung transplant recipients. Treatment is challenging due to antimicrobial resistance. We describe two cases of Scopulariopsis/Microascus tracheobronchitis in lung transplant recipients successfully treated with nebulized micafungin. This antifungal was well tolerated and achieved high concentrations in epithelial lining fluid up to 14 h after nebulization without significant plasma concentrations. Nebulized micafungin may be a safe and effective option for the treatment of fungal tracheobronchitis.

Atelectasis in primary graft dysfunction survivors after lung transplantation.

Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not been characterized. We studied adult double lung transplant recipients from 2010 to 2016 for whom protocol 3-month post-transplant CT scans were available. We assessed CTs for changes including pleural effusions, ground glass opacification, atelectasis, centrilobular nodularity, consolidation, interlobular septal thickening, air trapping and fibrosis, and their relationship to prior post-transplant PGD, future lung function, post-transplant baseline lung allograft dysfunction (BLAD), and chronic lung allograft dysfunction (CLAD). Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72h. PGD3 was associated with increased interlobular septal thickening (p=.0389) and atelectasis (p=.0001) at 3months, but only atelectasis remained associated after correction for multiple testing. Atelectasis severity was associated with lower peak forced expiratory volume in 1s (FEV1) and increased risk of BLAD (p=.0014) but not with future CLAD onset (p=.7789). Severe PGD was associated with atelectasis on 3-month post-transplant CT in our cohort. Atelectasis on routine CT may be an intermediary identifiable stage between PGD and future poor lung function.

Are Psychopharmacological Treatments Risk Factors for Mortality in Lung Transplant Recipients? - Retrospective Study

Purpose Despite clinical advance, long-term survival after lung transplantation (LT) remains poor. Thus, the recognition of risk factors associated with poorer survival is a key goal of LT research. Few studies have examined the psychiatric risk factors for mortality in LT recipients. The aim of this research was to study psychopharmacological treatment during lung transplant hospitalization (LTH) as predictor of mortality. Methods We conducted a retrospective cohort analysis of clinical records of lung transplant recipients, transplanted at Favaloro Foundation University Hospital between 2007 and 2019 (n = 238). Psychopharmacological treatment was measured as the number of days of treatment during LTH with: antidepressants (AD), antipsychotics (AP), hypnotics (HYP), and benzodiazepines (BZD). In addition, the number of psychology and psychiatry consultations during LTH and the prescription of psychotropic drugs at medical discharge were measured. Mortality was measured as survival at two years from LT. A multiple logistic regression model was used for data analysis. Results 12.2% of patients were treated with hypnotics. Greater number of days of treatment with HYP in LTH is associated with a higher mortality at two years after LT (β = -0.49; 95% CI, -0.92, -0.06; p=.02). Prescription of psychotropic drugs at medical discharge is associated with an increase survival at two years after LT (β = 0.36; 95% CI, 0.05, 0.66; p=.02). However, the number of days of treatment with AD, AP, BZD, and the number of psychology and psychiatry consultations during the LTH didn´t report significant results. Conclusion In this study, prescription of psychotropic drugs at medical discharge was significantly associated with increased survival; showing a significant association between HYP treatment in LTH and mortality. Future research is needed to study more specifically post-LT psychiatric interventions.