DECREASED DONOR-SPECIFIC CYTOTOXIC T CELL PRECURSOR FREQUENCIES ONE YEAR AFTER CLINICAL LUNG TRANSPLANTATION DO NOT REFLECT TRANSPLANTATION TOLERANCE: A COMPARISON OF LUNG TRANSPLANT RECIPIENTS WITH OR WITHOUT BRONCHIOLITIS OBLITERANS SYNDROME1

2000 ◽  
Vol 69 (7) ◽  
pp. 1434-1439 ◽  
Author(s):  
Aalzen de Haan ◽  
Ieneke van der Gun ◽  
Bouke G. Hepkema ◽  
Wim J. de Boer ◽  
Wim van der Bij ◽  
...  
Lung ◽  
2019 ◽  
Vol 198 (1) ◽  
pp. 157-161
Author(s):  
Don Hayes ◽  
Michael O. Harhay ◽  
Kathleen K. Nicol ◽  
Namal P. M. Liyanage ◽  
Brian C. Keller ◽  
...  

2019 ◽  
Vol 5 (4) ◽  
pp. 00164-2019 ◽  
Author(s):  
Madeleine Driskel ◽  
Alex Horsley ◽  
Laurice Fretwell ◽  
Nigel Clayton ◽  
Mohamed Al-Aloul

BackgroundLong-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade.Methods51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded.ResultsLCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p<0.001). 27 patients had HRCT within 12 months. LCI in those with HRCT evidence of OB was higher than those without OB (11.1 versus 8.2, p=0.006). 47% patients displayed abnormal LCI (>7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline).ConclusionsLCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS.


2003 ◽  
Vol 22 (1) ◽  
pp. S193-S194
Author(s):  
V.G Valentine ◽  
M.T Knower ◽  
C Eitmann ◽  
D.M Fuchs ◽  
G.S Dhillon ◽  
...  

2018 ◽  
Vol 29 (1) ◽  
pp. 18-25
Author(s):  
Alicia B. Lichvar ◽  
Christopher R. Ensor ◽  
Adriana Zeevi ◽  
Matthew R. Morrell ◽  
Joseph M. Pilewski ◽  
...  

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.


2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  

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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