When BAL meets CT scan: enhancing noninvasive diagnosis of acute cellular rejection after lung transplantation

Abstract Background Acute cellular rejection (ACR) is a common complication after lung transplantation (LTX) and it is considered a risk factor for chronic lung allograft dysfunction (CLAD). Lung transbronchial biopsy is still the gold standard for a correct diagnosis of ACR. The aim of the present study was to evaluate the predictive role of bronchoalveolar lavage (BAL) cellular composition in combination with CT scan features for the diagnosis of ACR. Method We retrospectively evaluated all LTX recipients who underwent transbronchial biopsies combined with BAL procedures and CT scan at a single Institution between January 2019 and October 2024 (n = 169). ACR histological diagnosis was made according to current guidelines, BAL analysis included percentage of cellular composition, lymphocytes’ typing and microbiology. A qualitative analysis of specific CT was conducted by an expert thoracic radiologist. Results Among the 169 biopsies analyzed, 34% showed acute cellular rejection (ACR), predominantly grade A1 (68%). Patients with ACR exhibited significantly higher lymphocyte percentages in BAL (p = 0.025), and the cutoff of 25% showed 22% sensibility and 92% specificity for the diagnosis of ACR. Combing BAL findings with CT features, patients with lymphocyte ≥ 25% in BAL and concomitant pleural effusion showed 95.7% specificity of ACR. Infections were associated with elevated neutrophil levels in BAL (p = 0.026); eosinophil levels were significantly higher in patients with significant ACR (grade ≥ 2) and concomitant infection than those with infection only (p = 0.0014). Conclusion BAL cellular composition proved to be a strong predictive tool for the diagnosis of ACR. The lymphocyte threshold of 25% was able to distinguish patients with ACR, while the combination of increased BAL lymphocytes with ACR associated CT scan abnormalities especially pleural effusion significantly enhanced diagnostic accuracy. Elevated eosinophil levels were associated to more severe rejection and concomitant infection, highlighting their crucial role in the alloreactive immune response. These findings suggest the role of BAL and CT scan in combination as a valuable diagnostic tool in ACR diagnosis, although histological confirmation remains the gold standard.