Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients. A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

Abstract

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.