RISK-FACTORS FOR THE DEVELOPMENT OF OBLITERATIVE BRONCHIOLITIS AFTER LUNG TRANSPLANTATION

Background: Acute rejection has emerged as sin important risk factor f or obliterative bronchiolitis after lung transplantation. We performed a multivariate analysis to assess the impact of additional variables. Methods: Seventy-four recipients (48 heart-lung, 18 single-lung, and 8 bilateral-lung recipients) who survived longer than 90 days and unde rwent transplantation more than 15 months before data analysis were in cluded in this study. Several variables were entered into a Cox regres sion analysis to determine their association with the development of b ronchiolitis obliterans syndrome. Results: Bronchiolitis obliterans sy ndrome developed in 48 (65%) of 74 patients. Significant correlations were detected for acute rejection score, defined as the sum of patholo gic grades of each separate acute rejection episode (p = 0.0004, likel ihood ratio test value = 12.4) and for lymphocytic bronchiolitis (p = 0.03). In a bivariate model, episodes of organizing pneumonia and bact erial or fungal pneumonia significantly increased the likelihood ratio test value of the acute rejection score. The addition of the cytomega lovirus infection score, reflecting the frequency and severity of infe ction, to the combination of the acute rejection score and episodes of bacterial or fungal pneumonia resulted in a further significant incre ase in the likelihood ratio test value. Significant risk factors for m oderate to severe stages of airflow limitation were at least one episo de of acute rejection of grade greater than or equal to 2, younger rec ipient age, and any acute rejection episode 180 days or longer after t ransplantation. Conclusions: Increasing frequency and severity of acut e rejection episodes are strongly associated with the development of b ronchiolitis obliterans syndrome. Lymphocytic bronchiolitis appeared t o be significant by univariate analysis, but in a two-risk factor mode l, it did not augment the influence of acute rejection. Organizing pne umonia, bacterial or fungal pneumonia, and increasing severity and fre quency of cytomegalovirus infections potentiate the effect of acute re jection. Late episodes of acute rejection and younger recipient age in crease the risk for development of advanced disease.