Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation

Rationale: Severe and recurrent acute vascular rejection of the pulmonary allograft is an accepted major risk factor for obliterative bronchiolitis. Objectives: We assessed the role of lymphocytic bronchiolitis as a risk factor for bronchiolitis obliterans syndrome (BOS) and death after lung transplantation. Methods: Retrospective analysis of 341 90-day survivors of lung transplant performed in 1995-2005 who underwent 1,770 trans-bronchial lung biopsy procedures. Measurements and Main Results: Transbronchial biopsies showed grade 130 (normal) (n = 501), B1 (minimal) (n = 762), B2 (mild) (n = 176), B3 (moderate) (n = 70), B4 (severe) (n = 4) lymphocytic bronchiolitis, and Bx (no bronchiolar tissue) (n = 75). A total of 182 transbronchial biopsies were ungraded (8 inadequate, 142 cytomegalovirus, 32 other diagnoses). Lung transplant recipients were grouped by highest B grade before diagnosis of BOS: B0 (n = 12), 131 (n = 166), B2 (n = 89), and B3-B4 (n = 51). Twenty-three were un-classifiable. Cumulative incidence of BOS and death were dependent on highest B grade (Kaplan-Meier, P < 0.001, log-rank). Multivariable Cox proportional hazards analysis showed significant risks for BOS were highest B grade (relative risk [RR], 1.62; 95% confidence interval [Cl], 1.31-2.00) (P < 0.001), longer ischemic time (RR, 1.00; Cl, 1.00-1.00) (P < 0.05), and recent year of transplant (RR, 0.93; Cl, 0.87-1.00) (P < 0.05), whereas risks for death were BOS as a time-dependent covariable (RR, 19.10; Cl, 11.07-32.96) (P < 0.001) and highest B grade (RR, 1.36; Cl, 1.07-1.72) (P < 0.05). Acute vascular rejection was not a significant risk factor in either model. Conclusions: Severity of lymphocytic bronchiolitis is associated with increased risk of BOS and death after lung transplantation independent of acute vascular rejection.