Background: Bronchiolitis obliterans syndrome (BOS), defined as an irreversible, staged decline in forced expiratory volume in 1 second (FEV(1)), is an established marker of obliterative bronchiolitis. Potential causes of BOS include sub-clinical chronic rejection and/or exaggerated healing response following acute injury. BOS may thus result from two or more distinct processes, both acute and chronic.
Methods: A total of 5,916 measurements of FEV(1) from 204 lung transplant recipients surviving at least 6 months after transplantation were analyzed. Follow-up ranged from 6 months to 13 years. By adjusting for the acute effects of rejection, pulmonary infection and measurement variation on FEV(1) trace, patients either had a linear decline characterized by a single acute drop in FEV(1) of >15% at BOS onset, or a chronic linear decline in FEV(1). The fraction having acute onset was estimated. Acute events occurring within the first 6 months were assessed as risk factors for acute onset BOS.
Results: Of the 204 patients, 8% died before BOS onset and 18% were BOS-free at analysis. For 18% of patients, BOS onset followed a chronic linear decline in FEV(1) of 3.7% per year, with a median time of BOS onset >99 months. For 56% of patients, BOS onset followed an acute drop in FEV(1) of median 33.8% (95% CI 19.1% to 39.7%), with median onset time of 52 months. During the first 6 months, acute rejection was significantly and independently associated with acute onset of BOS (relative risk = 1.15 per episode, 95% CI [1.03 to 1.29], p = 0.01), whereas pulmonary infection and cytomegalovirus (CMV) infection were not. Acute BOS onset followed a documented acute event in the previous 6 months in 38 of 114 (33%) of cases.
Conclusions: BOS likely reflects more than one process. Compared with those who had a slow linear decline in lung function, acute BOS onset was associated with acute rejection in the first 6 months, was often triggered by an acute event and had poor prognosis, with obliterative bronchiolitis (OB) the main cause of death.