Longitudinal mycological profiling of influenza-associated and COVID-19-associated pulmonary aspergillosis.
Influenza- and COVID-19-associated pulmonary aspergillosis (IAPA and CAPA respectively) are associated with increased mortality in critically ill patients. We evaluated whether longitudinal bronchoalveolar lavage (BAL) galactomannan (GM) dynamics predict clinical outcomes in these patients.
In a retrospective cohort (2009-2024) at a tertiary care ICU in Belgium, 180 adult patients with probable/proven IAPA (n = 68) or CAPA (n = 112) requiring mechanical ventilation were included. A total of 698 BAL samples were analysed. GM optical density values were modelled using linear mixed-effects models (10- and 30-day follow-up windows), with outcome measures at 30 and 90 days. Bayesian joint models linked longitudinal GM trends with time-to-death, adjusting for age, Charlson Comorbidity Index (CCI) and immunosuppression. Associations between Aspergillus culture results dynamics and mortality were also assessed.
In general, BAL GM values declined significantly over days after diagnosis of aspergillosis, with steeper reductions in survivors (interaction p < 0.05). Joint models revealed each unit increase in GM over time corresponded to a 19% higher hazard of death at both 30 (aHR 1.19, p = 0.02) and 90 days (aHR 1.19, p = 0.007) after ICU admission. Persistent BAL culture positivity also correlated with worse outcomes.
In this large virus-associated pulmonary aspergillosis cohort, BAL GM kinetics emerged as a potential prognostic biomarker. Early and sustained increases in BAL GM values identify patients at increased risk of mortality.
In a retrospective cohort (2009-2024) at a tertiary care ICU in Belgium, 180 adult patients with probable/proven IAPA (n = 68) or CAPA (n = 112) requiring mechanical ventilation were included. A total of 698 BAL samples were analysed. GM optical density values were modelled using linear mixed-effects models (10- and 30-day follow-up windows), with outcome measures at 30 and 90 days. Bayesian joint models linked longitudinal GM trends with time-to-death, adjusting for age, Charlson Comorbidity Index (CCI) and immunosuppression. Associations between Aspergillus culture results dynamics and mortality were also assessed.
In general, BAL GM values declined significantly over days after diagnosis of aspergillosis, with steeper reductions in survivors (interaction p < 0.05). Joint models revealed each unit increase in GM over time corresponded to a 19% higher hazard of death at both 30 (aHR 1.19, p = 0.02) and 90 days (aHR 1.19, p = 0.007) after ICU admission. Persistent BAL culture positivity also correlated with worse outcomes.
In this large virus-associated pulmonary aspergillosis cohort, BAL GM kinetics emerged as a potential prognostic biomarker. Early and sustained increases in BAL GM values identify patients at increased risk of mortality.
Authors
Delanote Delanote, Heylen Heylen, Lauwers Lauwers, Jacobs Jacobs, Maessen Maessen, Debaveye Debaveye, Frederiks Frederiks, Hermans Hermans, Maertens Maertens, Meersseman Meersseman, Peetermans Peetermans, Vanderbeke Vanderbeke, Van Wijngaerden Van Wijngaerden, Wilmer Wilmer, Lagrou Lagrou, Wauters Wauters, Feys Feys
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