LACK OF ASSOCIATION OF ASPERGILLUS COLONIZATION WITH DEVELOPMENT OF BRONCHIOLITIS OBLITERANS SYNDROME IN LUNG TRANSPLANT RECIPIENTS: AN INTERNATIONAL COHORT STUDY

ABSTRACT Background Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTR's). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of lung transplant recipients, to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS. Methods Consecutive LTR's from January-2005 to December-2008 were evaluated. Rates of BOS and associated risk-factors, were recorded at 4 years. ISHLT criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization, and development of BOS controlling for confounders. Results A total of 747 LTR's were included. The cumulative incidence of BOS at 4 years post-transplant was 33% (250/747). 22% of LTR's experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (HR=0.6, 95%CI=0.3-1.2, p=0.12) or small conidia (HR=0.9, 95%CI=0.6-1.4, p=0.74) was not associated with development of BOS. Factors associated with increased risk of development of BOS were male gender (HR=1.4, 95% CI=1.1-1.8, p=0.02), and episodes of acute rejection (1-2 episodes HR=1.5, 95% CI=1.1-2.1, p=0.014;3-4 episodes HR=1.6, 95% CI=1.0-2.6, p=0.036;>4 episodes HR=2.2, 95% CI=1.1-4.3, p=0.02), while tacrolimus use was associated with reduced risk of BOS (HR=0.6, 95% CI=0.5-0.9, p=0.007). Conclusions We conclude from this large multi-center cohort of lung transplant patients, that Aspergillus colonization with large or small conidia, did not show an association with the development of BOS.