Long-term survival after lung transplantation (LT) is primarily limited by the development of chronic lung allograft dysfunction (CLAD), the clinical manifestation of chronic rejection of the transplanted lung. CLAD occurs more frequently than chronic rejection following other solid organ transplantations and affects up to 50% of lung transplant recipients within five years after transplantation. Its annual incidence is estimated at approximately 5–10% during the post-transplant period.

CLAD is characterized by progressive deterioration of lung structure and function resulting from chronic inflammatory and fibrotic processes involving the small airways and/or the lung interstitium. Rather than representing a single disease entity, CLAD is a heterogeneous syndrome that arises from a complex interplay of alloimmune and non-alloimmune injuries acting on an individual's genetic and immunological background. Its marked phenotypic heterogeneity reflects the diversity of its underlying pathophysiological mechanisms and contributes to the limited standardization of diagnostic criteria and therapeutic approaches.

This thesis provides a critical and comprehensive narrative review of the current understanding of CLAD. It examines its clinical presentation, diagnostic criteria, and current phenotypic classification system; reviews recent advances in the understanding of its pathophysiology; and explores established and emerging approaches for early diagnosis. Finally, it discusses current and evolving therapeutic strategies, with the ultimate aim of supporting earlier recognition, more precise phenotypic stratification, and improved clinical outcomes for lung transplant recipients.