Depression, Immunosuppressant Levels, and Clinical Outcomes in Postlung Transplant Recipients

2020 ◽  
Vol 55 (6) ◽  
pp. 421-436 ◽  
Author(s):  
Michael C Chu ◽  
Patrick J Smith ◽  
John M Reynolds ◽  
Scott M Palmer ◽  
Laurie D Snyder ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Lung Transplant ◽  
Epidemiological Studies ◽  
Hazard Ratio ◽  
Adverse Outcomes ◽  
Consecutive Series ◽  
Transplant Recipients ◽  
Increased Risk ◽  
Coefficient Of Variability ◽  
Lung Transplant Recipients

Objective Posttransplant depression has been linked to increased risk for adverse outcomes in lung transplant patients. Maintaining target serum immunosuppressant levels is also essential for optimal lung transplant clinical outcome and may be a crucial predictor of outcomes. Because depression could affect medication nonadherence, resulting in out-of-range immunosuppressant levels, we examined the relationship between posttransplant depression, immunosuppressant medication trough level variability, indexed by out-of-range values on clinical outcomes and coefficient of variability, and clinical outcomes. Method A consecutive series of 236 lung transplant recipients completed the Center for Epidemiological Studies-Depression two-month posttransplant. Immunosuppressant trough levels (i.e., tacrolimus or cyclosporine) within the range of individualized immunosuppressant targets were obtained at three-, six-, nine-month follow-up clinic visits. Clinical outcomes including hospitalizations and mortality were obtained from medical records. Results Fourteen percent of patients were classified as depressed (Center for Epidemiological Studies-Depression ≥16), 144 (61%) of patients had at least 25% out-of-range immunosuppressant values, and the average coefficient of variability was 36%. Over a median of 2.6 years (interquartile range = 1.2), 32 participants died (14%) and 144 (61%) had at least one unplanned, transplant-related hospitalization. Both depression (hazard ratio = 1.45 (1.19, 1.76), p < . 01) and immunosuppressant variation (immunosuppressant out-of-range: hazard ratio = 1.41 (1.10, 1.81), p < .01) independently predicted more frequent hospitalizations and higher mortality. Conclusions Early posttransplant depression was associated with significantly worse clinical outcomes. While immunosuppressant level variability is also related to adverse outcomes, such variability does not account for increased risk observed with depression.

scholarly journals 2640. Aerosol vs. Oral Ribavirin for the Treatment of Community-Acquired Respiratory Virus Infections in Lung Transplant Recipients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S923-S923
Author(s):  
Emily Mui ◽  
Marisa Holubar ◽  
Roy Lee ◽  
Danielle Pham ◽  
Lina Meng ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Lung Transplant ◽  
Respiratory Virus ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Organ Rejection ◽  
Increased Risk ◽  
Significant Difference ◽  
Lung Transplant Recipients ◽  
Overall Mortality

Abstract Background Community-acquired respiratory virus (CARV) infections are associated with an increased risk of chronic lung allograft dysfunction (CLAD) and graft loss in lung transplant recipients (LTR). Administration of ribavirin by aerosol was the standard of care at Stanford Health Care in the management of CARV infections. Given the sparse evidence of benefit with aerosol ribavirin (AR) and its increasing cost and teratogenic risk for exposed healthcare personnel, AR was restricted to the treatment of respiratory syncytial virus (RSV) in 2016 and was ultimately removed from formulary in 2017. Oral (PO) ribavirin was used at the discretion of the transplant team. The objective of this study was to evaluate the clinical outcomes of AR compared with PO ribavirin in lung transplant recipients. Methods We performed a retrospective cohort analysis of adult lung transplant recipients diagnosed with CARV (metapneumovirus, parainfluenza virus, and RSV) infections treated with either AR or PO ribavirin. The analysis included the first treatment course of ribavirin by either route and patients were excluded if they received ribavirin in the prior 12 months. The primary outcome was the development/progression of CLAD, acute organ rejection, and overall mortality. Results Of 85 patients, 41 received AR and 44 received PO ribavirin. There was no significant difference in the following clinical outcomes with AR and oral ribavirin, respectively: development or progression of CLAD (30 days: 9.7% vs. 4.5%, P = 0.4227; 90 days: 14.6% vs. 6.8%, P = 0.303; 6 months: 17% vs. 9%, P = 0.3413; 12 months: 24% vs. 15.9%, P = 0.4188), acute organ rejection (90 days: 7.3% vs. 4.5%, P = 0.6689; 6 months: 12.1% vs. 9%, P = 0.7329; 12 months: 19.5% vs. 13.6%, P = 0.5635), and overall mortality (30 days: 0% vs. 4.5%, P = 0.4947; 90 days: 7.3% vs. 4.5%, P = 0.6689; 6 months: 7.3% vs. 9%, P = 1.0; 12 months: 7.3% vs. 13.6%, P = 0.4858). There was no observable difference in reported adverse effects between AR and PO ribavirin. Conclusion Lung transplant recipients with CARV infections had similar outcomes when treated with AR or PO ribavirin. Oral ribavirin is a less costly treatment than AR, but the efficacy of ribavirin by any route remains questionable. Disclosures All authors: No reported disclosures.

Pre-transplant cytomegalovirus-specific cellular immunity and risk of viral reactivation following lung transplantation: a prospective cohort study

2020 ◽  
Author(s):  
Mohammed Altaf ◽  
Katie Lineburg ◽  
Pauline Crooks ◽  
Sweera Rehan ◽  
Katherine K Matthews ◽  
...  
Keyword(s):  
Lung Transplant ◽  
Viral Reactivation ◽  
Transplant Recipients ◽  
Post Transplant ◽  
Transplant Patients ◽  
Cell Immunity ◽  
Increased Risk ◽  
Significant Burden ◽  
Lung Transplant Recipients ◽  
Cmv Reactivation

Abstract Cytomegalovirus (CMV) remains a significant burden in lung transplant recipients. Deficiencies in T-cell immunity post-transplant increase the risk of CMV-associated complications. However, it is not clear if underlying poor pre-transplant immunity increases risk. To assess this, we recruited 39 prospective lung transplant patients and performed QuantiFERON-CMV on their peripheral blood. More than a third of prospective CMV-seropositive transplant recipients were CMV non-immune-reactive (CMV-NIR) pre-transplant. CMV-NIR status was associated with a significantly higher incidence of CMV reactivation post-transplant, demonstrating that dysfunctional CMV immunity in prospective lung transplant recipients is associated with an increased risk of viral reactivation post-transplant.

Dementia-Like Symptoms Associated With Posaconazole

2020 ◽  
pp. 089719002095823
Author(s):  
Carmela E. Corallo ◽  
Steven P. Ivulich ◽  
Dr Sakhee Kotecha ◽  
Orla Morrissey
Keyword(s):  
Lung Transplant ◽  
Fungal Infections ◽  
Transplant Recipients ◽  
First Case ◽  
Increased Risk ◽  
Post Marketing ◽  
Scedosporium Prolificans ◽  
Lung Transplant Recipients ◽  
Dose Dependent

Posaconazole is widely used in lung transplant recipients as pre-emptive therapy or universal fungal prophylaxis. In this patient group, posaconazole is increasingly used instead of voriconazole due to the concerns of an increased risk of squamous cell carcinoma (SCC) with voriconazole, particularly with its long-term use. Dose dependent toxicity has not been identified for posaconazole in the registration trials of intravenous (IV) and modified-release tablet formulations. This is supported by post-marketing experience. We describe a lung transplant recipient who experienced dementia-like symptoms almost 3 years after commencing posaconazole for treatment of Aspergillus fumigatus complex and Lomentospora prolificans (formerly Scedosporium prolificans) fungal infections. Symptoms resolved upon discontinuation of posaconazole, but recurred when re-challenged at a lower dose more than a year later. To the best of our knowledge, this is the first case reporting a dementia-like state with posaconazole.

scholarly journals Assessment of Drug Resistance during Phase 2b Clinical Trials of Presatovir in Adults Naturally Infected with Respiratory Syncytial Virus

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Danielle P. Porter ◽  
Ying Guo ◽  
Jason Perry ◽  
David L. Gossage ◽  
Timothy R. Watkins ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Respiratory Syncytial Virus ◽  
Clinical Outcomes ◽  
Lung Transplant ◽  
Fusion Inhibitor ◽  
Transplant Recipients ◽  
Genotypic Resistance ◽  
Resistance Development ◽  
Syncytial Virus ◽  
Lung Transplant Recipients

ABSTRACT This study summarizes drug resistance analyses in 4 recent phase 2b trials of the respiratory syncytial virus (RSV) fusion inhibitor presatovir in naturally infected adults. Adult hematopoietic cell transplant (HCT) recipients, lung transplant recipients, or hospitalized patients with naturally acquired, laboratory-confirmed RSV infection were enrolled in 4 randomized, double-blind, placebo-controlled studies with study-specific presatovir dosing. Full-length RSV F sequences amplified from nasal swabs obtained at baseline and postbaseline were analyzed by population sequencing. Substitutions at RSV fusion inhibitor resistance-associated positions are reported. Genotypic analyses were performed on 233 presatovir-treated and 149 placebo-treated subjects. RSV F variant V127A was present in 8 subjects at baseline. Population sequencing detected treatment-emergent substitutions in 10/89 (11.2%) HCT recipients with upper and 6/29 (20.7%) with lower respiratory tract infection, 1/35 (2.9%) lung transplant recipients, and 1/80 (1.3%) hospitalized patients treated with presatovir; placebo-treated subjects had no emergent resistance-associated substitutions. Subjects with substitutions at resistance-associated positions had smaller decreases in viral load during treatment relative to those without, but they had similar clinical outcomes. Subject population type and dosing regimen may have influenced RSV resistance development during presatovir treatment. Subjects with genotypic resistance development had decreased virologic responses compared to those without genotypic resistance but had comparable clinical outcomes.

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