A Multi-Center Validation Of Pulmonary Aspergillus Fumigatus Colonization As A Risk Factor For Bronchiolitis Obliterans Syndrome After Lung Transplantation

S. Weigt , C. A. Finlen Copeland , A. Derhovanessian , W. A. Davis , L. D. Snyder , D. Ross , A. Ardehali , R. E. Elashoff , S. M. Palmer , J. A. Belperio

Author address: 

David Geffen School of Medicine at UCLA, Los Angeles, CA, Duke University Medical Center, Durham, NC, David Geffen School of Medicine at UCLA, Los Angeles, David Geffen School of Medicine, Los Angeles, UCLA School of Public Health, Los Angeles, C

Abstract: 

Introduction: Pulmonary Aspergillus fumigatus colonization (AFC) is common after lung transplantation. In addition to the risk of invasive fungal disease, we have reported that Aspergillus colonization increases the risk for bronchiolitis obliterans syndrome (BOS) in a single center study performed at UCLA. In the present study, we sought to confirm an association between AFC and BOS in an expanded UCLA cohort. We also sought to validate our findings in an independent external cohort of lung transplant recipients from Duke University Medical Center (DUMC). Methods: The primary study cohort consisted of all adult first lung recipients transplanted at UCLA between 2000 and 2008 with sufficient pulmonary function test (PFT) data to assess for BOS. The validation cohort consisted of all adult first lung recipients transplanted at DUMC between 1998 and 2008 with sufficient PFT data to assess for BOS. Time to AFC onset (first positive Aspergillus fumigatus culture detected in bronchoalveolar lavage or sputum) and time to BOS were recorded. Proportional hazard models were used to assess AFC as a time-dependent predictor of BOS, ensuring only colonization events occurring prior to BOS were considered. Results: In the UCLA cohort (median f/u 2.7 years, IQR 1.5-5.1), 23% (63/281) of patients developed AFCb prior to BOS, within a median of 103 days posttransplant (IQR 74-202). One, three, and five year Kaplan Meier BOS estimates were 8%, 43%, and 58%, respectively (median 4.0 years, IQR 1.9-9.1). Time to first AFC significantly increased the risk for BOS (p=0.02, HR 1.7, 95% CI 1.1-2.7). In the DUMC cohort (median f/u 5.5 years, IQR 2.412), 25% (119/482) of patients developed AFC prior to BOS, within a median of 199 days posttransplant (IQR 103-424). One, three, and five year Kaplan Meier BOS estimates were 6%, 26%, and 45%, respectively (median 5.8 years, IQR 3.0-8.9). Time to first AFC significantly increased the risk for BOS (p=0.004, HR 1.6, 95% CI 1.1-2.1). In each cohort, the effect of AFC on BOS remained unchanged in multivariable analysis adjusted for acute rejection and cytomegalovirus pneumonitis (UCLA: p=0.02, adjusted HR 1.7, 95% CI 1.1-2.7; DUMC: p=0.004, adjusted HR 1.6, 95% CI 1.2-2.1) Conclusions: We have demonstrated for the first time that pulmonary AFC is a significant risk factor for BOS in two large independent cohorts of lung transplant recipients. A strategy of sustained antifungal prophylaxis should be tested as an approach to decrease the burden of BOS after lung transplantation.
2011

abstract No: 

C14

Full conference title: 

American Thoracic Society
    • ATS 2011