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Observational Study
. 2021 Jun 1;49(6):934-942.
doi: 10.1097/CCM.0000000000004861.

The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study

Anne Coste  1   2 , Aurélien Frérou  3 , Anaïs Raute  4 , Francis Couturaud  5 , Jean Morin  6 , Pierre-Yves Egreteau  4 , François-Xavier Blanc  6 , Jean Reignier  7 , Jean-Marc Tadié  3 , Adissa Tran  8 , Charlotte Pronier  9 , Marianne Coste-Burel  10 , Gilles Nevez  8 , Jean-Pierre Gangneux  11 , Patrice Le Pape  12 , Séverine Ansart  2 , Jean-Marie Tonnelier  1 , Cédric Bretonnière  6 , Cécile Aubron  1
Affiliations
Observational Study

The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study

Anne Coste et al. Crit Care Med. .

Abstract

Objectives: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia.

Design: Retrospective multicenter cohort study.

Setting: Five French ICUs.

Patients: Patients with influenza admitted to ICU between 2009 and 2018.

Measurements and main results: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09).

Conclusions: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.

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Conflict of interest statement

Dr. Blanc received funding from Novartis. Dr. Gangneux received funding from Pfizer, Gilead, and MSD. The remaining authors have disclosed they have no potential conflicts of interest.

Comment in

  • Influenza-Associated Pulmonary Aspergillosis: Seek, and You Shall Find!
    Feys SRL, Shoham S, Rijnders BJA, Wauters J. Feys SRL, et al. Crit Care Med. 2021 Dec 1;49(12):e1265-e1266. doi: 10.1097/CCM.0000000000005238. Crit Care Med. 2021. PMID: 34793394 No abstract available.
  • The authors reply.
    Coste A, Aubron C. Coste A, et al. Crit Care Med. 2021 Dec 1;49(12):e1267-e1268. doi: 10.1097/CCM.0000000000005340. Crit Care Med. 2021. PMID: 34793395 No abstract available.

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