Airway remodelling in the transplanted lung

Area of Science:

• Immunology
• Transplantation Medicine
• Pulmonary Medicine

Background:

• Fibrotic airway remodeling is a primary cause of chronic lung allograft failure, leading to poor long-term survival.
• Pulmonary allografts have the highest attrition rate among solid organ transplants, with a 5-year survival rate of 58%.
• Chronic lung allograft dysfunction (CLAD) is now understood as a manifestation of various alloimmune and non-alloimmune injuries, presenting diverse clinical phenotypes.

Purpose of the Study:

• To review the current literature on chronic lung allograft dysfunction (CLAD).
• To discuss classification systems, clinical and morphological changes, and cellular/molecular mechanisms of CLAD.
• To highlight emerging diagnostic and therapeutic strategies for CLAD.

Main Methods:

• Literature review and synthesis of current research on chronic lung allograft dysfunction.
• Analysis of classification systems, clinical phenotypes, and histomorphological changes associated with CLAD.
• Discussion of cellular players, molecular pathways, and diagnostic/therapeutic advancements.

Main Results:

• Fibrotic airway remodeling is the main correlate of chronic graft failure and obstacle to long-term survival post-lung transplantation.
• Chronic lung allograft dysfunction manifests in distinct clinical phenotypes and morphological subentities.
• Advances have been made in categorizing CLAD subgroups based on clinical, functional, and histomorphological changes.

Conclusions:

• The pathophysiological mechanisms of airway remodeling in CLAD remain poorly understood, posing diagnostic and therapeutic challenges.
• Accurate diagnosis and effective therapy for CLAD require a multidisciplinary approach involving clinicians, radiologists, and pathologists.
• Further research into underlying mechanisms and novel approaches is essential for improving outcomes in lung transplant recipients.