Severe influenza is an independent risk factor for invasive pulmonary aspergillosis with an accompanying increased mortality in the ICU, according to a multicenter retrospective cohort study at seven tertiary centers in Belgium and the Netherlands.

Aspergillosis histology shows the presence of conidial heads. Wikimedia Commons
The research study was reported by Alexander F.A.D. Schauwvlieghe, MD, of Erasmus MC University Medical Center, Rotterdam, the Netherlands, and his colleagues.

Data was collected from criteria-meeting adult patients admitted to the ICU for more than 24 hours with acute respiratory failure during the 2009-2016 influenza seasons. The included cohort of 432 patients was composed of 56% men and had a median age of 59 years; all participants were diagnosed as having severe type A or type B influenza infection according to positive airway RT-PCR results.

The full cohort was subcategorized into 117 immunocompromised and 315 as nonimmunocompromised individuals using criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study group (EORTC/MSG) . To assess influenza as an independent variable in the development of invasive pulmonary aspergillosis, the 315 nonimmunocompromised influenza positive individuals were compared to an influenza-negative control group of 315 nonimmunocompromised patients admitted to the ICU that presented similar respiratory insufficiency symptoms with community-acquired pneumonia.

Determination of other independent risk factors for incidence of invasive pulmonary aspergillosis was achieved by multivariate analysis of factors such as sex, diabetes status, prednisone use, age, and acute physiology and chronic health evaluation (APACHE) II score. The mean APACHE II score was 22, with the majority of patients requiring intubation for mechanical ventilation for a median duration of 11 days.

Influenza is not considered a host factor for invasive pulmonary aspergillosis and will often miss being diagnosed when using strict interpretation of the current EORTC/MSG or AspICU algorithm criteria, according to the researchers. Consequently for patients with influenza and the noninfluenza control group with community-acquired pneumonia, the definition of invasive pulmonary aspergillosis was modified from the AspICU algorithm. Stringent mycological criteria, including bronchoaveolar lavage (BAL) culture, a positive Aspergillus culture, positive galactomannan test, and/or positive serum galactomannan tests, provided supporting diagnostics for an invasive pulmonary aspergillosis determination.

At a median of 3 days following admission to the ICU, a diagnosis of invasive pulmonary aspergillosis was determined for 19% of the 432 influenza patients. Similar incident percentages of invasive pulmonary aspergillosis occurring for type A and type B, 71/355 (20%) and 12/77 (16%) patients respectively, showed that there was no clear association of the disease development with influenza subtypes that occurred during different annual seasons.

AspICU or EORTC/MSG criteria characterized only 43% and 58% of cases as proven or possible aspergillosis, respectively. On the other hand, stringent mycological tests yielded better invasive pulmonary aspergillosis classification, with 63% of BAL cultures being positive for Aspergillus, 88% of BAL galactomannan tests being positive, and 65% of serum galactomannan tests being positive in the 81/83 patients tested.

The study found that, for influenza patients, being immunocompromised more than doubled the incidence of invasive pulmonary aspergillosis, at 32% versus the 14% of those patients who were nonimmunocompromised. In contrast only 5% in the control group developed invasive pulmonary aspergillosis.

Influenza patients who developed invasive pulmonary aspergillosis in the ICU tended to have their stays significantly lengthened from 9 days (interquartile range, 5-20 days) for those without it to 19 days (IQR, 12-38 days) for those infected (P less than .0001). Likewise, 90-day mortality significantly rose from 28% for those influenza patients without invasive pulmonary aspergillosis to 51% for those with it (P = .0001).

The authors concluded that influenza was “independently associated with invasive pulmonary aspergillosis (adjusted odds ratio, 5.19; P less than.0001) along with a higher APACHE II score, male sex, and use of corticosteroids.”

Furthermore, as influenza appears to be an independent risk factor for invasive pulmonary aspergillosis and its associated high mortality, the authors suggested that “future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.”

The authors reported that they had no conflicts of interest.

SOURCE: Schauwvlieghe AFAD et al. Lancet Respir Med. 2018 Jul 31. doi: 10.1016/S2213-2600(18)30274-1