Diversity of the lung mycobiome is associated with severity of disease in acute respiratory distress syndrome

Abstract

Background: Research into the lung microbiome has focused on bacteria. Research into the fungal communities (mycobiome) has been limited, in part due to technical limitations. Given that the lung mycobiome may represent a potential source of infection as well as driver of immune and inflammatory pathway activation, we sought to describe the diversity of the lung mycobiome in patients with acute respiratory distress syndrome (ARDS).

Methods: We enrolled mechanically-ventilated patients with and at risk for ARDS and collected endotracheal aspirates (ETA) within 48hrs of intubation. We used extracted DNA from ETAs to perform fungal (internal transcribed spacer) rRNA gene sequencing on the Illumina MiSeq platform.

Results: Of the 202 patients enrolled, 21% had a diagnosis of ARDS (mean age 50.2 years; 61% females). Fungal alpha diversity was lower in ARDS compared to airway controls (p <0.001) but not patients at risk for ARDS (p=0.26). In ARDS, shock (p=0.03), sepsis (p=0.03) and a sequential organ failure assessment (SOFA) score 5 (p=0.02) were associated with lower diversity. Decreased diversity was associated with higher lung injury prediction scores (LIPS) (p=0.05), lower plateau pressures (p=0.03) and vasopressor use (p=0.01) in ARDS. Elevated plasma pentraxin-3, a biomarker of inflammatory response and disease severity, was correlated with lower diversity (p=0.01).

Conclusion: Next-generation sequencing analysis identifies differences in the diversity of the mycobiome of patients with ARDS. Lower fungal alpha diversity in ARDS and increased severity of disease suggests a relationship between the lung mycobiome and the inflammatory cascade associated with ARDS.