Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation

Background: Aspiration of gastroesophageal refluxate may contribute to lung transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in bronchoalveolar lavage fluid (BALF) and studied its role in BOS. Materials and Methods: Surveillance pulmonary function tests and BALF were evaluated in 120 lung recipients. BOS-(0p-3) was diagnosed after 6 months' survival. BOS was defined as early if diagnosed within 12 months after a transplant. BALF was assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile acids were considered elevated if greater than normal serum levels (>= 8 mu mol/L). Results: Elevated BALF bile acids were measured in 20 (17%) of 120 patients. BOS was diagnosed in 36 (34%) of 107 patients and judged early in 21 (57%) of 36. Median BALF bile acid values were 1.6 mu mol/L (range, 0.32 mu mol/L) in BOS patients and 0.3 mu mol/L (range, 0-16 mu mol/L) in non-BOS patients (P = .002); 2.6 mu mol/L (range, 0-32 mu mol/L) in early BOS patients and 0.8 mu mol/L (range, 0-4.6 mu mol/L) in late BOS patients, (P = .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P = .0004, and r = 0.3, P = .004, respectively), but not with IL-15. Freedom from BOS was significantly shortened in patients with elevated BALF bile acids (Cox-Mantel test, P = .0001). Conclusions: Aspiration of duodenogastroesophageal refluxate is prevalent after lung transplantation and is associated with the development of BOS. Elevated BALF bile acids may promote early BOS development via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.