Real-time and non-invasive acute lung rejection diagnosis using confocal LASER Endomicroscopy in lung transplant recipients: Results from the CELTICS study

Traditionally, the diagnosis of acute rejection (AR) relies on invasive transbronchial biopsies (TBBs) to obtain histopathological samples. We aimed to evaluate the diagnostic yield of probe-based confocal laser endomicroscopy (pCLE) as a complementary and non-invasive tool for ACR screening, comparing its results with those obtained from TBBs. Between January 2015 and April 2022, we conducted a retrospective study of all lung transplant recipients aged over 18 years at Toulouse University Hospital (France). All patients who underwent bronchoscopies with both TBBs and pCLE imaging were included. Two experienced interpreters (TV and MS) reviewed the pCLE images independently, blinded to all clinical information and pathology results. From 120 procedures in 85 patients, 34 abnormal histological samples were identified. Probe-based confocal laser endomicroscopy revealed significant associations between both alveolar (ALC) and perivascular (PVC) cellularities and abnormal histological samples (p<0.0001 and 0.003 respectively). Alveolar cellularity demonstrated a sensitivity (Se) of 85.3 %, specificity (Spe) of 43 %, positive predictive value (PPV) of 37.2 % and negative predictive value (NPV) of 88.1 %. For PVC, Se was 70.6 %, Spe 80.2 %, PPV 58.5 % and NPV 87.3 %. Intra-interpreter correlation (TV) was 88.3 % for the number of vessels (+/-1), 98.3 % for ALC and 90 % for PVC. Inter-interpreter correlation (TV and MS) was 80 % for vessels (+/-1), 97.5 % for ALC and 83.3 % for PVC. Our study demonstrates the feasibility of incorporating pCLE into clinical practice, demonstrating good diagnostic yield and reproducible outcomes in the screening of AR in lung transplant recipients.