The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation

Levy, Liran; Huszti, Ella; Tikkanen, Jussi; Ghany, R.; Klement, William; Ahmed, M.; Husain, Shahid; Fiset, Pierre; Hwang, David; Keshavjee, S.; Singer, L.G.; Juvet, S.; Martinu, T.

doi:10.1111/ajt.15561

Cited by 31 publications

(12 citation statements)

References 29 publications

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“…In accordance with the literature, 12 acute cellular rejection (A > 0) on conventional histology did not predict graft loss in TBB Set 2 or in the TBBs collected alongside the mucosal biopsies (see Supplementary Figure S2a and b online). Similarly, DSA did not predict future graft loss (see Supplementary Figure S2c and d online).…”

Section: Association With Future Graft Losssupporting

confidence: 90%

Molecular T-cell‒mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss

Halloran

Parkes

Timofte

et al. 2020

The Journal of Heart and Lung Transplantation

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BACKGROUND: We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying Tcell-mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival. METHODS: We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB−TBB, mucosal−mucosal, and TBB−mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies. RESULTS: The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies,

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Section: Association With Future Graft Losssupporting

confidence: 90%

Molecular T-cell‒mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss

Halloran

Parkes

Timofte

et al. 2020

The Journal of Heart and Lung Transplantation

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“…High grade acute rejection episode (≥ A2) were rare. It was demonstrated that low grade A1 rejection was not associated with CLAD[34]. Other groups used the discrepancy between immunosuppressant dosages and prescription refills or data from health insurances for the assessment of adherence[35,36].…”

Section: Discussionmentioning

confidence: 99%

Adherence is associated with a favorable outcome after lung transplantation

et al. 2019

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Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was assessed in 427 patients undergoing lung transplantation from 2010 to 2013. Objective criteria of adherence were judged by health care workers on every visit on a five item Likert scale including trough level monitoring, home spirometry and contact with an overall rating of adherence between 0 and 100%. Cut-off values for good vs. suboptimal adherence were defined retrospectively. Primary outcome was allograft survival, secondary outcomes were patient survival, prevalence of chronic lung allograft dysfunction, hospitalizations, renal function and quality of life. Follow-up ended on 31st December 2018. Median adherence was 86% on 6,623 visits, this cut-off was used as a discriminator between good and suboptimal adherers. Patients with good adherence within the first three years showed better 5-year allograft (74% vs. 60%, p = 0.003) and patient survival (79% vs. 64%, p<0.001) and lower prevalence of chronic allograft dysfunction (33% vs. 45%, p = 0.011) after 5 years compared to patients with suboptimal adherence. A multidimensional adherence score proved to be a simple tool to assess adherence in clinical practice. Suboptimal adherence was associated with impaired outcome in lung transplant patients.

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“…Additional pathologic findings, including the histologic location and pattern of eosinophils, were noted. The concurrent matched FEV 1 immediately preceding the TBBx occasion was compared with the average baseline (average of the two best FEV 1 measured ≥ 3 weeks apart) and the recent baseline (the highest of the 2 previous FEV 1 ) to determine a %‐change [20].…”

Section: Methodsmentioning

confidence: 99%

Eosinophils in transbronchial biopsies: a predictor of chronic lung allograft dysfunction and reduced survival after lung transplantation — a retrospective single‐center cohort study

Darley

Huszti

et al. 2020

Transpl. Int.

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Long‐term outcomes after lung transplantation remain inferior to those of other solid organ groups. The significance of eosinophils detected on transbronchial biopsies (TBBx) after lung transplantation and their relationship to long‐term outcomes remain unknown. A retrospective single‐center cohort study was performed of patients transplanted between January 01, 2001, and July 31, 2018, who had at least 1 TBBx with evaluable parenchymal tissue. Multivariable Cox proportional hazard models were used to assess the associations between eosinophil detection and: all‐cause mortality and Chronic Lung Allograft Dysfunction (CLAD). 8887 TBBx reports from 1440 patients were reviewed for the mention of eosinophils in the pathology report. 112 (7.8%) patients were identified with eosinophils on at least one TBBx. The median (95% CI) survival time for all patients was 8.28 (7.32–9.31) years. Multivariable analysis, adjusted for clinical variables known to affect post‐transplant outcomes, showed that the detection of eosinophils was independently associated with an increased risk of death (HR 1.51, 95% CI 1.24–1.85, p < 0.01) and CLAD (HR 1.35, 95% CI 1.07–1.70, P = 0.01). Eosinophils detected in TBBx are associated with an increased risk of CLAD and death. There may be benefit in specifically reporting the presence of eosinophils in TBBx reports and incorporating their presence in clinical decision‐making.

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The impact of first untreated subclinical minimal acute rejection on risk for chronic lung allograft dysfunction or death after lung transplantation

Cited by 31 publications

References 29 publications

Molecular T-cell‒mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss

Molecular T-cell‒mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss

Adherence is associated with a favorable outcome after lung transplantation

Eosinophils in transbronchial biopsies: a predictor of chronic lung allograft dysfunction and reduced survival after lung transplantation — a retrospective single‐center cohort study

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