Severe influenza tied to increased invasive pulmonary aspergillosis risk
Patients admitted to the intensive care unit (ICU) with severe influenza have an elevated risk of developing invasive pulmonary aspergillosis, particularly if they are immunocompromised at time of admission, a recent study has shown.
Participants in this retrospective study were 432 adult patients (mean age 59 years, 56 percent male) with severe influenza admitted to seven ICUs in Belgium and the Netherlands for acute respiratory failure over seven influenza seasons (2009–2016). A majority (82 percent) of patients were diagnosed with influenza A. Twenty-five percent of patients died in the ICU.
Nineteen percent of patients with influenza were diagnosed with invasive pulmonary aspergillosis at a median 3 days post-ICU admission with comparable incidence among patients diagnosed with influenza A and B (20 and 16 percent, respectively). The prevalence of invasive pulmonary aspergillosis consistently exceeded 10 percent despite influenza-caused ICU admission fluctuating over the study period. [Lancet Respir Med 2018;doi:10.1016/S2213-2600(18)30274-1]
“[The results show that] once a patient with influenza needs intensive care support, the risk for invasive pulmonary aspergillosis does not depend on the influenza season and influenza subtype,” said the researchers. “[T]he severity of illness rather than influenza subtype is more important,” they said.
The incidence of invasive pulmonary aspergillosis was even higher among patients with influenza who were immunocompromised (as per EORTC/MSG* criteria) at admission (32 percent) compared with those who were non-immunocompromised (14 percent), whereas the incidence was lower among non-immunocompromised patients without influenza but with severe community-acquired pneumonia (5 percent).
Patients with invasive pulmonary aspergillosis had a longer stay in the ICU than those without (19 vs 9 days; p<0.0001) as well as a higher mortality rate, be it in the ICU (45 percent vs 20 percent; p<0.0001) or 90 days postadmission (51 percent vs 28 percent; p=0.0001). They were also more likely to require mechanical ventilation (90 percent vs 72 percent; p=0.0004) and for lengthier periods (additional 5 days; p=0.001).
Factors independently associated with a higher risk for invasive pulmonary aspergillosis were corticosteroid therapy 4 weeks pre-ICU admission (adjusted odds ratio [adjOR], 1.59, 95 percent confidence interval [CI], 1.30–1.99; p<0.0001 per 0.1 mg/kg/day prednisone equivalent), male sex (adjOR, 1.84, 95 percent CI, 1.05–3.22; p=0.034), and higher APACHE** II score at admission (adjOR, 1.05, 95 percent CI, 1.01–1.09; p=0.007 per 1 point increase).
A subgroup analysis comparing the 315 non-immunocompromised influenza-positive patients (influenza group) with 315 non-immunocompromised influenza-negative patients with severe community-acquired pneumonia (control group) also demonstrated an independent association between influenza and invasive pulmonary aspergillosis (adjOR, 5.19, 95 percent CI, 2.63–10.26; p<0.0001).
“Given the results of the present study … it seems reasonable to add invasive pulmonary aspergillosis to the list of influenza complications,” said Dr Frederic Lamoth and Professor Thierry Calandra from Lausanne University Hospital in Lausanne, Switzerland, in an accompanying editorial. [Lancet Respir Med 2018;doi:10.1016/S2213-2600(18)30332-1]
“Why patients with influenza are at risk for invasive pulmonary aspergillosis is not yet clear. Respiratory epithelium damage and mucociliary clearance dysfunction might facilitate the invasion of Aspergillus. Moreover, influenza-induced [acute respiratory distress syndrome] and hypoxia might cause immune paralysis,” said the researchers.
They highlighted the potential role of antifungal prophylaxis in reducing the incidence of invasive pulmonary aspergillosis but questioned whether prophylaxis would be a better option compared with standardized diagnosis and prompt antifungal treatment upon diagnosis of invasive pulmonary aspergillosis.
“The independent association between influenza and invasive pulmonary aspergillosis and the high mortality, calls for increased awareness and a more aggressive diagnostic approach,” they said.