Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome

Abstract

Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between January 2000 and June 2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87-520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS.

Figure 1

The timing and incidence of Aspergillus infections in our cohort. All initial Aspergillus infections after lung transplantation are plotted over time. The dark shaded bars represent those initial Aspergillus infections occurring before a diagnosis of BOS (n=54). All cases of Pre-BOS Aspergillus infections initially met criteria for Aspergillus colonization. The light shaded bars represent infections where the initial isolation occurred after the diagnosis of BOS (n=9).

Figure 2

Kaplan-Meier representation of Freedom from BOS. Freedom from BOS after lung transplantation is reduced in the pre-BOS Aspergillus colonization group compared to the group without pre-BOS Aspergillus.

Figure 3

Kaplan-Meier representation of freedom from progression to end-stage allograft dysfunction in patients with BOS stage 1. End-stage allograft dysfunction is defined as progression to BOS stage 3 or death due to BOS. Patients with Aspergillus infections after the diagnosis of BOS (new or recurrent isolations), have an increased likelihood of progression to end-stage allograft dysfunction as compared to those without Aspergillus infections.