Chronic lung allograft dysfunction: a narrative review of evolving concepts in diagnosis and management

Background and Objective: Chronic lung allograft dysfunction (CLAD) remains the leading cause of late morbidity and mortality after lung transplantation, affecting nearly half of recipients within five years and a major cause of death beyond the first post-transplant year. CLAD reflects epithelial injury, dysregulated immune responses, and maladaptive repair, leading to progressive airway and parenchymal fibrosis. Contemporary classification includes bronchiolitis obliterans syndrome, restrictive allograft syndrome, and mixed forms with distinct prognostic implications. Despite advances in transplant care, CLAD diagnosis and management remain limited by delayed detection, heterogeneous phenotypes, and absence of reliable early biomarkers. Current frameworks rely on spirometric decline, which often reflects established injury, while therapies primarily aim to slow progression rather than reversing dysfunction. This review synthesizes evolving concepts in CLAD pathogenesis, classification, diagnosis, and management, with emphasis on emerging diagnostics, limitations of current approaches, and future directions in risk stratification and therapy.

Methods: A narrative review was conducted using literature from PubMed and Google Scholar. Studies published between January 2000 and January 2026 were included, with the final search performed on January 10, 2026. Search terms included “chronic lung allograft dysfunction”, “bronchiolitis obliterans syndrome”, “restrictive allograft syndrome”, “lung transplantation”, “biomarkers”, “imaging”, and “immunomodulation”. Articles were selected based on relevance. English-language publications were included.

Key Content and Findings: Diagnosis relies on spirometric decline but lacks sensitivity for early disease. Emerging tools, including quantitative computed tomography, magnetic resonance imaging, oscillometry, and molecular biomarkers from blood and bronchoalveolar lavage, offer potential for earlier detection and improved phenotyping. However, no single modality has sufficient reproducibility to replace physiologic surveillance, highlighting the need for multimodal integration. Management is constrained by irreversible injury, with current strategies focused on slowing progression. Therapies such as azithromycin, leukotriene receptor antagonists, extracorporeal photopheresis, and selective immunomodulation provide benefit in selected patients, while retransplantation remains the only definitive option for advanced disease.

Conclusions: CLAD remains the principal barrier to long-term survival after lung transplantation. Future progress will depend on earlier detection, multimodal diagnostic integration, and development of phenotype-specific and personalized therapies. Advancing the field will require improved biomarker validation and prospective studies to guide treatment and risk stratification.