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Severity of Lymphocytic Bronchiolitis Predicts Long-Term Outcome after Lung Transplantation

¹ The Lung Transplant Unit, and ² Department of Anatomical Pathology, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia

Correspondence and requests for reprints should be addressed to Allan R. Glanville, M.D., F.R.A.C.P., The Lung Transplant Unit, Xavier 4, St. Vincent's Hospital, Victoria Street, Darlinghurst NSW, Australia 2010. E-mail: aglanville{at}stvincents.com.au

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 transbronchial lung biopsy procedures.

Measurements and Main Results: Transbronchial biopsies showed grade B0 (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), B1 (n = 166), B2 (n = 89), and B3–B4 (n = 51). Twenty-three were unclassifiable. 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 [CI], 1.31–2.00) (P < 0.001), longer ischemic time (RR, 1.00; CI, 1.00–1.00) (P < 0.05), and recent year of transplant (RR, 0.93; CI, 0.87–1.00) (P < 0.05), whereas risks for death were BOS as a time-dependent covariable (RR, 19.10; CI, 11.07–32.96) (P < 0.001) and highest B grade (RR, 1.36; CI, 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.

Key Words: lung transplantation • graft rejection • bronchiolitis obliterans

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Obliterative small airway disease is the major cause of death after lung transplantation and has been associated with severe and recurrent acute vascular rejection in the absence of a direct pathogenic link. What This Study Adds to the Field This study establishes the importance of severity of lymphocytic bronchiolitis as a risk factor for bronchiolitis obliterans syndrome and death after lung transplantation independent of acute vascular rejection.

 

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