{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:06:02Z","timestamp":1768565162029,"version":"3.49.0"},"posted":{"date-parts":[[2023,5,16]]},"group-title":"Intensive Care and Critical Care Medicine","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rationale<\/jats:title>\n                  <jats:p>Disruption of respiratory bacterial communities predicts poor clinical outcomes in critical illness; however, the role of respiratory fungal communities (mycobiome) is poorly understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We investigated whether mycobiota variation in the respiratory tract is associated with host-response and clinical outcomes in critically ill patients.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To characterize the upper and lower respiratory tract mycobiota, we performed rRNA gene sequencing (internal transcribed spacer) of oral swabs and endotracheal aspirates (ETA) from 316 mechanically-ventilated patients. We examined associations of mycobiome profiles (diversity and composition) with clinical variables, host-response biomarkers, and outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Measurements and Main Results<\/jats:title>\n                  <jats:p>\n                    ETA samples with &gt;50% relative abundance for\n                    <jats:italic>C. albicans<\/jats:italic>\n                    (51%) were associated with elevated plasma IL-8 and pentraxin-3 (p=0.05), longer time-to-liberation from mechanical ventilation (p=0.04) and worse 30-day survival (adjusted hazards ratio (adjHR): 1.96 [1.04-3.81], p=0.05). Using unsupervised clustering, we derived two clusters in ETA samples, with Cluster 2 (39%) showing lower alpha diversity (p&lt;0.001) and higher abundance of\n                    <jats:italic>C. albicans<\/jats:italic>\n                    (p&lt;0.001). Cluster 2 was significantly associated with the prognostically adverse hyperinflammatory subphenotype (odds ratio 2.07 [1.03-4.18], p=0.04) and predicted worse survival (adjHR: 1.81 [1.03-3.19], p=0.03).\n                    <jats:italic>C. albicans<\/jats:italic>\n                    abundance in oral swabs was also associated with the hyper-inflammatory subphenotype and mortality.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Variation in respiratory mycobiota was significantly associated with systemic inflammation and clinical outcomes.\n                    <jats:italic>C. albicans<\/jats:italic>\n                    abundance emerged as a negative predictor in both the upper and lower respiratory tract. The lung mycobiome may play an important role in the biological and clinical heterogeneity among critically ill patients and represent a potential therapeutic target for lung injury in critical illness.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.05.11.23289861","type":"posted-content","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T16:55:19Z","timestamp":1684256119000},"source":"Crossref","is-referenced-by-count":4,"title":["Respiratory Fungal Communities are Associated with Systemic Inflammation and Predict Survival in Patients with Acute Respiratory 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