Alveolo-Capillary Protein Permeability and Lung Function in Patients with Late Pulmonary Complications after Allogeneic Bone Marrow Transplantation

Abstract.

A prospective study was performed to identify markers predictive for the development of pulmonary complications in the early (<50 days) and late (>50 days) phase after bone marrow transplantation (BMT). The characterization of BMT patients with early or late pulmonary complications revealed clear-cut differences. Early and long term increase of alveolo-capillary protein permeability was associated with smoking and was found in 20 patients developing pulmonary complications within 50 days after BMT (group 1). The 22 patients who developed such complications thereafter (group 2) had more acute graft vs host disease than 66 patients who remained free of these complications for a minimum of 1 year. Concentrations of bronchoalveolar lavage (BAL) fluid albumin (alb) and serum β₂-microglobulin (S-β₂m) were determined 10 days before BMT, on days 1, 30, and 40 after BMT, whereas lung function tests were performed before BMT, after discharge from the hospital, and 6 months as well 1 year after BMT. Using cut-off values for BAL fluid alb (>2.3 mg/dl) and S-β₂m (>0.8 mg/liter) we could significantly discriminate 12 patients out of 19 group 1 patients (early pulmonary complications) as well as 9 out of 21 group 2 patients (late pulmonary complications) from 12 out of 64 group 3 patients (without such complications) 1 day after BMT. Our results demonstrate that early increased alveolo-capillary protein permeability defines a patient population at risk to develop pulmonary complications later than 50 days after BMT with up to 1 year significantly decreased lung volumes (FEV1, 73% predicted, VC, 85% predicted).