Atrial Arrhythmias Following Lung Transplantation: Incidence and Risk Factors in 658 Lung Transplant Recipients

Abstract Background Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. Methods A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Results Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). Conclusions Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

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Fundoplication after lung transplantation in patients with systemic sclerosis–related end-stage lung disease

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211016210 ◽

2021 ◽

pp. 239719832110162

Author(s):

Miguel M Leiva-Juárez ◽

Andreacarola Urso ◽

Joseph Costa ◽

Bryan P Stanifer ◽

Joshua R Sonett ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Systemic Sclerosis ◽

Lung Transplantation ◽

Lung Transplant ◽

Transplant Recipients ◽

Chronic Lung Allograft Dysfunction ◽

Allograft Dysfunction ◽

Increased Risk ◽

Lung Transplant Recipients

Introduction: Gastroesophageal reflux and aspiration are risk factors for chronic lung allograft dysfunction in lung transplant recipients. Patients with systemic sclerosis are at an increased risk of aspiration due to esophageal dysmotility and an ineffective lower esophageal sphincter. The aim of this study is to understand the effect of fundoplication on outcomes in systemic sclerosis recipients. Methods: Between 2001 and 2019, 168 systemic sclerosis patients were referred for lung transplantation—51 (30.3%) were listed and 36 (21.4%) were transplanted. Recipients were stratified whether they underwent a fundoplication (n = 10, 27.8%) or not (n = 26, 72.2%). Freedom from chronic lung allograft dysfunction and survival were analyzed using log-rank test. Multivariable analysis for known risk factors was performed using a Cox-proportional hazards model. Results: Median time to fundoplication after transplantation was 16.4 months (interquartile range: 9.6–25.1) and all were laparoscopic (Dor 50%, Nissen 40%, Toupet 10%). There were no differences in acute rejection ⩾ A1 (26.9% vs 30%), or primary graft dysfunction grades 2–3 at 72 h (42.3% vs 40%) between groups. Recipients with fundoplication had an increased freedom from chronic lung allograft dysfunction (p = 0.035) and overall survival (p = 0.01). Fundoplication was associated with a reduced risk of mortality adjusting for other comorbidities (hazard ratio = 0.13; 95% confidence interval = 0.02–0.65; p = 0.014). Double and single lung transplant did not have different post-transplant survival. Conclusion: Fundoplication in systemic sclerosis lung transplant recipients is associated with greater freedom from chronic lung allograft dysfunction and overall survival. Screening for reflux and aspiration followed by early fundoplication may delay graft deterioration in this population.

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Abstract 11065: Paradoxical Impact of Overweightness on Mortality in Lung Transplantation

Circulation ◽

10.1161/circ.130.suppl_2.11065 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Kongkiat Chaikriangkrai ◽

Hye Yeon Jhun ◽

Soma Jyothula

Keyword(s):

Risk Factors ◽

Lung Transplantation ◽

Lung Transplant ◽

Metabolic Risk Factors ◽

Smoking History ◽

Metabolic Risk ◽

Transplant Recipients ◽

Isolated Lung ◽

Overweight Group ◽

Lung Transplant Recipients

Background: Prognostic value of body mass index (BMI) and cardiorespiratory fitness (CRF) has been described extensively in various populations. The objective of this study was to examine impact of BMI and CRF on all-cause mortality in isolated lung transplant recipients. Methods: Consecutive isolated lung transplant recipients from 2008 to 2013 were identified. Pre-transplant cardio-metabolic risk factors were collected. The cohort was categorized using BMI into normal (BMI 18.5-24.9 kg/m 2 ), underweight (BMI < 18.5 kg/m 2 ), overweight (BMI 25.0-29.9 kg/m 2 ) and obese (BMI ≥ 30 kg/m 2 ). Fit patient was defined as those who had pre-transplant six-minute-walk distance > 300 m. Results: The study comprised of 324 patients with mean age of 57 ± 13 years. Fifty eight percent were male. Primary lung pathologies were 26.9% obstructive, 2.5% vascular, 6.5% cystic fibrosis and 64.2% restrictive lung diseases. Pertinent cardio-metabolic risk factors included 36.7% normal weight, 9.9% underweight, 33.6% overweight, 19.8% obese, 21.9% unfit, 13.9% coronary artery disease, 55.6% hypertension, 29.6% diabetes mellitus, 42.3% hyperlipidemia, 42.9% smoking history. Annualized mortality rate stratified by BMI exhibited J-shaped distribution with lowest mortality in overweight group (p 0.005). Kaplan Meier analysis correspondingly showed highest survival in overweight strata (p 0.006). In subgroup analysis by CRF, paradoxical impact of overweightness on mortality was diminished in fit patients (p>0.05) but not in those who were unfit (p<0.05) as shown in figure 1. Conclusion: In our lung transplant cohort, BMI and mortality had J-shaped relationship with highest survival in overweight group. This paradoxical impact was diminished in patients who were fit. Our findings extend the paradigm of obesity paradox into lung transplantation arena.

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Risk Factors for Bronchiolitis Obliterans Syndrome in Pediatric Lung Transplant Recipients

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2021.01.993 ◽

2021 ◽

Vol 40 (4) ◽

pp. S352

Author(s):

K. Thangappan ◽

D.L. Morales ◽

D. Winlaw ◽

D. Hayes ◽

C. Towe ◽

...

Keyword(s):

Risk Factors ◽

Bronchiolitis Obliterans ◽

Lung Transplant ◽

Bronchiolitis Obliterans Syndrome ◽

Transplant Recipients ◽

Lung Transplant Recipients

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Identification of Epstein-Barr Virus Related Risk Factors for the Occurrence of Post-Transplant Lymphoproliferative Disorder in Lung Transplant Recipients

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2021.01.1904 ◽

2021 ◽

Vol 40 (4) ◽

pp. S67

Author(s):

B.J. Pierce ◽

E. Allen ◽

C. Pham ◽

D.T. Nguyen ◽

E.A. Graviss ◽

...

Keyword(s):

Risk Factors ◽

Lymphoproliferative Disorder ◽

Lung Transplant ◽

Epstein Barr Virus ◽

Transplant Recipients ◽

Post Transplant ◽

Barr Virus ◽

Related Risk ◽

Epstein Barr ◽

Lung Transplant Recipients

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Detrimental Association of Hypogammaglobulinemia With Chronic Lung Allograft Dysfunction and Death Is Not Mitigated by On-Demand Immunoglobulin G Replacement After Lung Transplantation

Progress in Transplantation ◽

10.1177/1526924818817028 ◽

2018 ◽

Vol 29 (1) ◽

pp. 18-25

Author(s):

Alicia B. Lichvar ◽

Christopher R. Ensor ◽

Adriana Zeevi ◽

Matthew R. Morrell ◽

Joseph M. Pilewski ◽

...

Keyword(s):

Lung Transplantation ◽

Immunoglobulin G ◽

Lung Transplant ◽

Primary Outcome ◽

Transplant Recipients ◽

Chronic Lung Allograft Dysfunction ◽

On Demand ◽

Allograft Dysfunction ◽

Group 2 ◽

Lung Transplant Recipients

Background: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. Materials and Methods: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. Results: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). Conclusions: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.

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Community-acquired Respiratory Viruses Are a Risk Factor for Chronic Lung Allograft Dysfunction

Clinical Infectious Diseases ◽

10.1093/cid/ciy1047 ◽

2018 ◽

Vol 69 (7) ◽

pp. 1192-1197 ◽

Cited By ~ 14

Author(s):

Maddalena Peghin ◽

Ibai Los-Arcos ◽

Hans H Hirsch ◽

Gemma Codina ◽

Víctor Monforte ◽

...

Keyword(s):

Infectious Disease ◽

Risk Factors ◽

Acute Rejection ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Lung Transplant ◽

Respiratory Viruses ◽

Transplant Recipients ◽

Independent Risk Factors ◽

Lung Transplant Recipients

Abstract Background The relationship between community-acquired respiratory viruses (CARVs) and chronic lung allograft dysfunction (CLAD) in lung transplant recipients is still controversial. Methods We performed a prospective cohort study (2009–2014) in all consecutive adult patients (≥18 years) undergoing lung transplantation in the Hospital Universitari Vall d’Hebron (Barcelona, Spain). We systematically collected nasopharyngeal swabs from asymptomatic patients during seasonal changes, from patients with upper respiratory tract infectious disease, lower respiratory tract infectious disease (LRTID), or acute rejection. Nasopharyngeal swabs were analyzed by multiplex polymerase chain reaction. Primary outcome was to evaluate the potential association of CARVs and development of CLAD. Time-dependent Cox regression models were performed to identify the independent risk factors for CLAD. Results Overall, 98 patients (67 bilateral lung transplant recipients; 63.3% male; mean age, 49.9 years) were included. Mean postoperative follow-up was 3.4 years (interquartile range [IQR], 2.5–4.0 years). Thirty-eight lung transplant recipients (38.8%) developed CLAD, in a median time of 20.4 months (IQR, 12–30.4 months). In time-controlled multivariate analysis, CARV-LRTID (hazard ratio [HR], 3.00 [95% confidence interval {CI}, 1.52–5.91]; P = .002), acute rejection (HR, 2.97 [95% CI, 1.51–5.83]; P = .002), and cytomegalovirus pneumonitis (HR, 3.76 [95% CI, 1.23–11.49]; P = .02) were independent risk factors associated with developing CLAD. Conclusions Lung transplant recipients with CARVs in the lower respiratory tract are at increased risk to develop CLAD.

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Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

10.21203/rs.3.rs-38454/v1 ◽

2020 ◽

Author(s):

Jens Gottlieb ◽

Alexander Reuss ◽

Konstantin Mayer ◽

Karin Weide ◽

Carmen Schade-Brittinger ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Lung Transplantation ◽

Drug Monitoring ◽

Lung Transplant ◽

Controlled Trial ◽

Therapeutic Drug ◽

Transplant Recipients ◽

Randomized Controlled ◽

Lung Transplant Recipients ◽

Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

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Postoperative Management of Lung Transplant Recipients in the Intensive Care Unit

Anesthesiology ◽

10.1097/aln.0000000000004054 ◽

2021 ◽

Author(s):

Matteo Di Nardo ◽

Jussi Tikkanen ◽

Shahid Husain ◽

Lianne G. Singer ◽

Marcelo Cypel ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Lung Transplantation ◽

Lung Transplant ◽

Postoperative Management ◽

Transplant Recipients ◽

Complex Interplay ◽

Hemodynamic Management ◽

Lung Transplant Recipients ◽

Evidence Based Guidelines

The number of lung transplantations is progressively increasing worldwide, providing new challenges to interprofessional teams and the intensive care units. The outcome of lung transplantation recipients is critically affected by a complex interplay of particular pathophysiologic conditions and risk factors, knowledge of which is fundamental to appropriately manage these patients during the early postoperative course. As high-grade evidence-based guidelines are not available, the authors aimed to provide an updated review of the postoperative management of lung transplantation recipients in the intensive care unit, which addresses six main areas: (1) management of mechanical ventilation, (2) fluid and hemodynamic management, (3) immunosuppressive therapies, (4) prevention and management of neurologic complications, (5) antimicrobial therapy, and (6) management of nutritional support and abdominal complications. The integrated care provided by a dedicated multidisciplinary team is key to optimize the complex postoperative management of lung transplantation recipients in the intensive care unit.

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