Confocal laser endomicroscopy in patients with acute respiratory failure

BACKGROUND: Survivors of the early exudative phase of acute respiratory distress syndrome (ARDS) may develop a fibroproliferative repair response and persistent microstructural remodeling associated with adverse outcomes. Conventional imaging, including chest computed tomography (CT), has limited biological specificity for early microscopic remodeling. Confocal laser endomicroscopy (CLE) enables real-time bronchoscopic imaging of the alveolar compartment with near-histologic resolution. We evaluated the feasibility and safety of bedside bronchoscopic CLE in invasively ventilated ICU patients with acute respiratory failure and explored whether in vivo CLE provides microscopic alveolar information complementary to chest CT. METHODS: In this single-center observational pilot study, mechanically ventilated adult ICU patients with a clinical indication for bronchoalveolar lavage (BAL) underwent additional bedside bronchoscopic CLE. Primary endpoints were feasibility (≥ 1 interpretable alveolar video with visible septal architecture per procedure) and safety (CLE-related adverse events within 24 h). Secondary exploratory endpoints were dominant in vivo CLE patterns of alveolar filling (air, fluid, cells) and architecture (thin elastin fibers with hexagonal architecture; increased elastin with preserved architecture; increased elastin with distortion) and qualitative comparison with CT abnormalities in the imaged segments. As an exploratory additional analysis, ex vivo CLE was performed in a single autopsy case and compared with histopathology. RESULTS: A total of 33 patients were included (median age 64 years; 61% male); 31/33 met Berlin ARDS criteria. Forty-one CLE procedures were performed, all yielding high-resolution alveolar imaging (procedural feasibility 100%). A total of 150 videos were acquired (mean acquisition time 46 s per video), with a mean of three bronchial segments imaged per procedure. No CLE-related adverse events occurred. Patterns that were recognized by CLE were: alveolar filling with air (n = 94, 63%), fluid (n = 18, 12%), cells (n = 38, 25%); alveolar architecture was described as thin elastin fibers with hexagonal architecture (n = 37; 25%), increased elastin fibers with preserved architecture (n = 80; 53%) or distorted architecture (n = 29; 19%). Architecture was undeterminable in 4 (3%) videos. CLE detected abnormalities in 6/7 CT-normal appearing segments and demonstrated architectural changes in 60/78 segments with ground-glass opacities. In the autopsy case, ex vivo CLE was concordant with histopathology: regions with increased and distorted CLE signal corresponded to thickened alveolar septa and fibrotic remodeling. CONCLUSION: Bedside bronchoscopic CLE is feasible and safe in mechanically ventilated ICU patients with ARDS. CLE provides complementary microscopic information on alveolar filling and architecture beyond chest CT, including features compatible with early structural remodeling.