Chronic lung allograft dysfunction after lung transplantation: The moving target

Chronic lung allograft dysfunction is a major challenge in long-term management of lung transplant recipients. Both alloimmune-dependent factors (rejection) and alloimmune-independent factors contribute to the development of chronic lung allograft dysfunction. Thus, use of the term "chronic rejection" tends to be intentionally avoided among specialists in the field, although "chronic rejection" is still an acceptable lay word understood by many patients. Several different phenotypes have been identified in chronic lung allograft dysfunction, including restrictive allograft syndrome, neutrophilic reversible allograft dysfunction, and fibrous bronchiolitis obliterans syndrome. Restrictive allograft syndrome is characterized by restrictive physiology and peripheral foci of inflammation and fibrosis, which contrasts the obstructive physiology and pathological foci in small airways in conventional bronchiolitis obliterans syndrome. Among patients with bronchiolitis obliterans syndrome, there is a subpopulation that responds relatively well to azithromycin. Because these patients show airway neutrophilia, this subtype of chronic lung allograft dysfunction was named neutrophilic reversible allograft dysfunction. Conversely, patients with bronchiolitis obliterans syndrome unresponsive to azithromycin show airway fibrosis with less inflammation (fibrous bronchiolitis obliterans syndrome). In general, restrictive allograft syndrome shows poorer survival than does bronchiolitis obliterans syndrome, and early-onset bronchiolitis obliterans syndrome (within 2 years) shows a worse prognosis than does late-onset bronchiolitis obliterans syndrome. Until preventive and therapeutic options are refined, chronic lung allograft dysfunction will remain a major life-limiting factor. It has significant psychological, physical, social, and economic impacts. Early introduction of palliative care is another important strategy to improve patients' quality of life. © 2012 The Japanese Association for Thoracic Surgery.