Plasma Cell-free DNA Associated With Risk of Mortality and Chronic Lung Allograft Dysfunction Among Lung Transplant Recipients With Aspergillus.

BACKGROUND

Aspergillus species is a common pathogen in lung transplant patients. However, existing clinical standards rely on a complex constellation of clinical, radiological, and microbiologic criteria with limited sensitivity to differentiate between invasive Aspergillus infection and colonization. We therefore tested whether a molecular measure of allograft injury-donor-derived cell-free DNA (dd-cfDNA)-better identifies invasive aspergillosis compared with current guidelines-based classification.

METHODS

This multicenter prospective cohort study included lung transplant patients. Microbiological isolates of Aspergillus were matched with temporally available dd-cfDNA data. Invasive aspergillosis was defined either by clinical criteria using published guidelines or by molecular criteria (dd-cfDNA >1%).

RESULTS

Among 177 lung transplant recipients, 33 patients had 34 positive Aspergillus results. Of those, 16 met clinical criteria and 19 met molecular criteria of invasive aspergillosis. Eighteen met clinical criteria and 15 met molecular criteria for colonization. Patients who met molecular criteria for invasive disease had significantly reduced chronic lung allograft dysfunction-free survival (hazard ratio, 10.5; 95% confidence interval, 1.34-82.1; P = 0.03) compared with the patients with colonization. In contrast, classification based on clinical criteria was not associated with worse outcomes (hazard ratio, 2.3; 95% confidence interval, 0.7-7.8; P = 0.19).

CONCLUSIONS

Invasive aspergillosis, as defined by molecular criteria (dd-cfDNA >1%), was associated with reduced chronic lung allograft dysfunction-free survival in lung transplant recipients.