Diagnosis of Acute Cellular Rejection Using Probe-based Confocal Laser Endomicroscopy in Lung Transplant Recipients

A Prospective, Multicenter Trial

Cesar A. Keller, Andras Khoor, Douglas A. Arenberg, Michael A. Smith, Shaheen U. Islam

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Acute cellular rejection (ACR) in lung transplant recipients requires demonstration of perivascular lymphocytic infiltration in alveolar tissue samples from transbronchial biopsies (TBBs). Probe-based confocal laser endomicroscopy (pCLE) allows in vivo observation of alveolar, vascular, and cellular microstructures in the lung with potential to identify ACR. The objective of our prospective, blinded, multicenter observational study was to identify pCLE findings in patients with ACR diagnosed histopathologically by TBB. Methods Lung transplant recipients undergoing diagnostic bronchoscopies within 1 year posttransplant for suspected ACR had pCLE video imaging obtained immediately prior to tissue sampling via TBB. Findings of 2 pCLE criteria, abundant alveolar cellularity and perivascular cellularity (PVC), were assessed by 4 investigators familiar with pCLE and compared with histopathologic criteria of ACR to derive sensitivity, specificity, area under the receiver operating characteristic curve, and accuracy. Interobserver agreement was assessed by calculating intraclass coefficient and Fleiss κ. Findings were analyzed before and after a consensus meeting of investigators on interpreting images. Results Thirty pCLE procedures were performed on 24 patients, 8 showing ACR in TBB. Diagnostic performance and interobserver agreement using pCLE to identify PVC were significantly higher than those of abundant alveolar cellularity (P < 0.01). The number of blood vessels identified with PVC on pCLE was significantly correlated with histopathologic activity grading of ACR (P < 0.01). Perivascular cellularity agreement among investigators significantly improved after consensus meeting (P < 0.01). Conclusions When found on pCLE, PVC is a feasible and reproducible criterion for assessment of ACR in vivo, but there is a learning curve for image interpretation.

Original languageEnglish (US)
Pages (from-to)428-434
Number of pages7
JournalTransplantation
Volume103
Issue number2
DOIs
StatePublished - Feb 1 2019

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Multicenter Studies
Lasers
Lung
Biopsy
Research Personnel
Blood Vessels
Consensus
Transplant Recipients
Rejection (Psychology)
Learning Curve
Bronchoscopy
ROC Curve
Observational Studies
Observation
Sensitivity and Specificity

ASJC Scopus subject areas

  • Transplantation

Cite this

Diagnosis of Acute Cellular Rejection Using Probe-based Confocal Laser Endomicroscopy in Lung Transplant Recipients : A Prospective, Multicenter Trial. / Keller, Cesar A.; Khoor, Andras; Arenberg, Douglas A.; Smith, Michael A.; Islam, Shaheen U.

In: Transplantation, Vol. 103, No. 2, 01.02.2019, p. 428-434.

Research output: Contribution to journalArticle

Keller, Cesar A. ; Khoor, Andras ; Arenberg, Douglas A. ; Smith, Michael A. ; Islam, Shaheen U. / Diagnosis of Acute Cellular Rejection Using Probe-based Confocal Laser Endomicroscopy in Lung Transplant Recipients : A Prospective, Multicenter Trial. In: Transplantation. 2019 ; Vol. 103, No. 2. pp. 428-434.
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abstract = "Background Acute cellular rejection (ACR) in lung transplant recipients requires demonstration of perivascular lymphocytic infiltration in alveolar tissue samples from transbronchial biopsies (TBBs). Probe-based confocal laser endomicroscopy (pCLE) allows in vivo observation of alveolar, vascular, and cellular microstructures in the lung with potential to identify ACR. The objective of our prospective, blinded, multicenter observational study was to identify pCLE findings in patients with ACR diagnosed histopathologically by TBB. Methods Lung transplant recipients undergoing diagnostic bronchoscopies within 1 year posttransplant for suspected ACR had pCLE video imaging obtained immediately prior to tissue sampling via TBB. Findings of 2 pCLE criteria, abundant alveolar cellularity and perivascular cellularity (PVC), were assessed by 4 investigators familiar with pCLE and compared with histopathologic criteria of ACR to derive sensitivity, specificity, area under the receiver operating characteristic curve, and accuracy. Interobserver agreement was assessed by calculating intraclass coefficient and Fleiss κ. Findings were analyzed before and after a consensus meeting of investigators on interpreting images. Results Thirty pCLE procedures were performed on 24 patients, 8 showing ACR in TBB. Diagnostic performance and interobserver agreement using pCLE to identify PVC were significantly higher than those of abundant alveolar cellularity (P < 0.01). The number of blood vessels identified with PVC on pCLE was significantly correlated with histopathologic activity grading of ACR (P < 0.01). Perivascular cellularity agreement among investigators significantly improved after consensus meeting (P < 0.01). Conclusions When found on pCLE, PVC is a feasible and reproducible criterion for assessment of ACR in vivo, but there is a learning curve for image interpretation.",
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