ORIGINAL ARTICLE Bronchiolitis obliterans in patients undergoing allogeneic hematopoietic SCT AG Vieira, VAM Funke, EC Nunes, R Frare and R Pasquini Bronchiolitis obliterans (BO) is a severe pulmonary complication of allo-SCT. This study evaluated the incidence of BO in patients undergoing allo-SCT in Hospital Universitário da Universidade Federal do Paraná, risk factors for developing this complication and prognostic factors for those patients who developed this entity. The study included 1286 patients transplanted between 1979 and 2009 who survived for 100 days or more. We diagnosed 53 cases of BO. The cumulative incidence was 2.9% in 1 year and 3.7% in 3 years. Among patients with chronic GVHD, the cumulative incidence at the same intervals was 8.4% and 9.9%, respectively. The median time between transplantation and diagnosis of BO was 260 days (49–3877 days). In the multivariate analysis the risk factors for BO were female donor, older recipients and acute GVHD. The main prognostic factor was the severity of pulmonary impairment. Patients who developed BO earlier than 260 days had a worse prognosis than those who did so later. At least 80% of deaths were directly related to BO. Bone Marrow Transplantation (2014) 49, 812–817; doi:10.1038/bmt.2014.25; published online 10 March 2014 INTRODUCTION The study of late complications of SCT has acquired increasing importance owing to the increase in survival of patients submitted to this procedure. Among these complications, bronchiolitis obliterans (BO) is outstanding. It is a disease that affects the small airways, and presents high rates of morbidity and mortality. 1–7 Within the context of SCT, BO is closely related to chronic GVHD. 2,6,8–11 The treatment of BO is still largely unsatisfactory, and in the majority of cases, stabilization of the obstructive disturbance has been considered a good result. As in any field related to chronic GVHD, the study of BO has been made difficult for a long time because of the disparity between the definitions used in the various studies. This situation began to change in 2005, when a working group of the National Institutes of Health published a proposal of consensus for the diagnosis and graduation of the severity of patients affected by chronic GVHD. 12 Since then, diverse centers have published their experience on the management of this entity, 10,13,14 generating a mass of data that will certainly be fundamental for the delineation of prospective studies capable of answering the innumerable questions that remain unanswered. In this study, we retrospectively analyzed 1286 allo-SCT performed in a single center to determine risk factors for BO, factors affecting survival and causes of death for patients diagnosed with BO. MATERIALS AND METHODS Patients From October 1979 to December 2009, 1672 patients were submitted to allo-SCT at the Hospital Universitário da Universidade Federal do Paraná, and patients with a survival ⩾ 100 days were included in the study, totalizing 1286 patients. First, we searched the database for patients with diagnosis of BO, BO with organizing pneumonia or lung GVHD. Once these patients had been identified, we proceeded a review of their record charts, seeking to confirm or exclude the diagnosis of BO. Follow-up of the patients In our center, patients are seen every week in the first 100 days and then at least monthly until they complete 6 months of transplantation. Then, they are evaluated at least every 3 months until 2 years after transplantation, every 6 months until 5 years and then annually indefinitely in our center itself. Thus, our loss to follow-up was very small. We proceeded pulmonary function tests (PFTs) 100 days, 6 months and 1 year after the transplant in all patients, irrespective of the symptomatology. Diagnosis of BO The diagnosis of BO was made based on the criteria suggested by the National Institutes of Health study group, adjusted to meet the retro- spective nature of the study, as well as the limitations of the information available in the database. Patients considered to have BO were those who presented signs and symptoms suggestive of this entity, associated with a new obstructive ventilatory disturbance, without response to bronchodi- lator drugs, detected by means of the PFT performed in the absence of active pulmonary infection. We considered a suggestive clinical picture the presence of cough, dyspnea of progressive intensity and wheezing. A diagnosis of obstructive disturbance was established in the presence of both of the following factors: forced expiratory volume in 1 second (FEV1) o80% of the expected value and FEV1/forced vital capacity (FVC) o0.7 (values obtained before bronchodilator). The National Institutes of Health study group suggested the value of FEV1 o75% for diagnosis; however, they considered patients with mild BO, those with FEV1 between 60 and 79%. When it was impossible to perform the PFT, the diagnosis was based on the signs and symptoms together with tomographic findings (computed tomography became available at our center around 1990) suggestive of this entity, which are the following: evidence of air trapping, thickening of small airways and bronchiectasis. Severity criteria The severity of pulmonary impairment by BO was primordially based on the FEV1 measure taken in the absence of active pulmonary infection: Mild BO: FEV1 ⩽ 79 and ⩾ 60% Moderate BO: FEV1 ⩽ 59 and ⩾ 40% Severe BO: FEV1 ⩽ 39% Universidade Federal do Paraná, Curitiba, Brazil. Correspondence: Dr AG Vieira, João Pio Duarte Silva street, 682, apartment B501, 88037000 Florianópolis, Brazil. E-mail: andre.gv@linhalivre.net Received 23 April 2013; revised 4 January 2014; accepted 8 January 2014; published online 10 March 2014 Bone Marrow Transplantation (2014) 49, 812 – 817 © 2014 Macmillan Publishers Limited All rights reserved 0268-3369/14 www.nature.com/bmt