Mapping acute lung allograft dysfunction of unknown cause after lung transplantation: Insights from clinical and radiological patterns

Background: Acute lung allograft dysfunction (ALAD) is a recently defined post-transplant clinical entity characterized by acute, potentially reversible graft dysfunction. The aim of this study was to describe the clinical and radiological features of ALAD in which no identifiable underlying cause could be recognized, hereafter referred to as idiopathic ALAD (i-ALAD). Methods: Among all bronchoscopies with bronchoalveolar lavage and transbronchial lung biopsy performed in a single-center cohort of lung transplant recipients between 2013 and 2024 (n = 497), we retrospectively identified episodes of i-ALAD. These patients were subsequently evaluated for clinical characteristics and high-resolution computed tomography (HRCT) findings. For exploratory purposes, imaging findings were compared with those of a cohort of lung transplant recipients with biopsy-proven acute cellular rejection (ACR). Results: Among 158 lung transplant recipients, 20 cases of i-ALAD were identified, corresponding to an incidence of 12.4%. ALAD was reversible in most patients, although 2 progressed to chronic lung allograft dysfunction (CLAD). Six patients (30%) met criteria for baseline lung allograft dysfunction (BLAD), and 6 had a history of recurrent ACR. HRCT most frequently demonstrated bronchial wall thickening (85%), smooth interlobular septal thickening, and pulmonary micronodules (80%), with characteristic lobar distribution patterns. Compared with ACR, i-ALAD was associated with a significantly higher prevalence of bronchiectasis/bronchiolectasis, air trapping, and pleural effusion. Conclusions: ALAD is a relatively frequent and potentially reversible complication after lung transplantation but may represent a risk factor for subsequent CLAD development. Distinctive HRCT features may assist in identifying ALAD of unknown cause and stratifying patients according to the risk of disease progression. Prospective, multicenter studies are warranted to validate these findings and further refine the clinical and radiological characterization of i-ALAD.