Obliterative bronchiolitis following lung transplantation: from old to new concepts?

Abstract

Summary Lung transplantation has come of age and is now considered a valid treatment for selected patients with end‐stage lung disease. In recent years, survival rates have much improved, although the development of chronic rejection, characterized by a progressive and irreversible decline in FEV1, which is clinically defined as bronchiolitis obliterans syndrome (BOS) remains the major obstacle to long‐term survival. Extensive research efforts with special emphasis on innate immunity have recently led to new insights with the identification of at least two different phenotypes: on the one hand there is an azithromycin‐responsive phenotype (the so‐called neutrophilic reversible allograft/airways dysfunction (NRAD), on the other hand there is an azithromycin‐unresponsive phenotype (the fibroproliferative form of BOS or classical obliterative bronchiolitis). The present review intends to give the scientific evidence for these two subtypes, and to clarify the role of azithromycin in the treatment of BOS.

Heterogeneity of chronic lung allograft dysfunction: Insights from protein expression in broncho alveolar lavage

“…Our group further refined this as only a subset of the BOS patients (NRAD) showed an increased BAL neutrophilia and IL-8, while the fBOS group showed levels comparable to stable patients (8). This study confirmed the involvement of many other proteins in BAL.…”

“…Based on the response to azithromycin, our group identified the existence of at least 2 different phenotypes within BOS (8,9). The first phenotype, characterized by airway neutrophilia, FEV 1 improvement ≥10% after azithromycin treatment, an early onset and a gradual FEV 1 decline is termed Neutrophilic Reversible Allograft Dysfunction (NRAD), the other phenotype demonstrated no airway neutrophilia, no FEV 1 improvement after azithromycin thereapy, a rather late onset (after 2 years) and a rapid FEV 1 decline.…”

Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

“…38,39 This may be of potential clinical interest because the number of neutrophils in the airways has been associated with clinically defined BOS phenotypes following lung transplantation. 40 Increasing interest is rewarded the role of B cells in chronic GvHD. 41 Elevated blood levels of B-cell activating factor, essential for survival and differentiation of B cells, have been demonstrated in cGvHD- 42,43 and BO-patients.…”

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…сятся поражение дыхательных путей за счет ПДТ, ГЭР, различных инфекций, а также ишемия дыха тельных путей, вызванная механическим поврежде нием бронхиальных сосудов во время операции [14][15][16]. Эти неиммунные факторы могут вызывать по вреждение тканей и воспаление, при воздействии ко торых, в свою очередь, провоцируется и усиливается аллоиммунный ответ организма реципиента.…”