Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40-70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.