Influenza-Associated Aspergillosis: Nationwide Trends, Predictors and Outcomes From 2005 to 2014

Abstract

Background: Influenza-associated aspergillosis (IAA) has been increasingly reported in the literature in recent years, but contemporary large-scale data on the morbidity and mortality burden of IAA are lacking.

Research question: The goal of this study was to estimate the predictors, associations, and outcomes of IAA in the United States.

Study design and methods: This retrospective cohort study was performed by using the National (Nationwide) Inpatient Sample database from 2005 to 2014 to identify influenza and IAA hospitalizations. Baseline variables and outcomes were compared between influenza hospitalizations without IAA and those with IAA. These variables were then used to perform an adjusted analysis for obtaining predictors and associations of the diagnosis and in-hospital mortality of IAA.

Results: Of the 477,556 hospitalizations identified with the principal diagnosis of influenza, IAA was identified in 823 (0.17%) hospitalizations. The IAA cohort consisted more commonly of 45- to 65-year-olds in urban teaching hospitals with substance abuse. Yearly trends revealed that both influenza and IAA hospitalizations have increased over time, with a peak observed in 2009, the year of the influenza A(H1N1) pandemic. Mortality was higher (20.58% vs 1.36%), average length of stay was longer (17.94 vs 4.05 days), and mean cost per hospitalization was higher ($194,932 vs $24,286) in the IAA cohort compared with the influenza cohort without IAA (P < .005). Solid-organ transplantation, hematologic malignancies, and use of invasive mechanical ventilation were associated with higher odds of IAA, among other factors. Use of invasive mechanical ventilation (adjusted OR, 13.43; P < .005), longer length of stay (adjusted OR, 5.47; P < .005), utilization of extracorporeal membrane oxygenation (adjusted OR, 4.99; P = .014), and the group aged 45 to 64 years (adjusted OR, 3.03; P = .012) were associated with higher in-hospital mortality in the IAA cohort.

Interpretation: Although IAA is a rare complication of influenza hospitalizations, it is associated with increased all-cause mortality, more extended hospital stays, and higher hospital charges compared with influenza without IAA.

Keywords: aspergillus; infection; influenza.