Diagnosis of Acute Cellular Rejection Using Probe-Based Confocal Laser Endomicroscopy in Lung Transplant Recipients: a Prospective, Multicenter Trial

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 to 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<.01 the number of blood vessels identified with pvc on pcle was significantly correlated histopathologic activity grading acr agreement among investigators improved after consensus meeting conclusions when found is a feasible and reproducible criterion for assessment in vivo but there learning curve image interpretation. reprints: cesar a. keller md lung transplant program mayo clinic san pablo rd jacksonville fl phone: fax: presented at american thoracic society international conference may washington dc. portions this manuscript have been published abstract form: c arenberg da smith m islam s. probe-based confocal laser endomicroscopy diagnosis acute rejection: results prospective multicenter trial. am j respir crit care med. authorship author contributions: dr. contributed to conception design experiments collection analysis interpretation data generation figures tables writing critical revision article. khoor images disclosures: none authors disclosures pertaining study. unrelated study serves as vats lobectomy course instructor ethicon endosurgery which they contribute norton institute. funding: mauna kea technologies paris france copyright wolters kluwer health inc. all rights reserved.>

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