Wesley H Self1, Richard G Wunderink2, Mark J DiNubile3, Thomas P Stossel3, Susan L Levinson3, Derek J Williams4, Evan J Anderson5, Anna M Bramley6, Seema Jain6, Kathryn M Edwards4, Carlos G Grijalva7. 1. Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 2. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 3. BioAegis Therapeutics, North Brunswick, New Jersey. 4. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. 5. Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. 6. Centers for Disease Control and Prevention, Atlanta, Georgia. 7. Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee.
Abstract
BACKGROUND: Plasma gelsolin (pGSN) is an abundant circulating protein that neutralizes actin exposed by damaged cells, modulates inflammatory responses, and enhances alveolar macrophage antimicrobial activity. We investigated whether adults with low pGSN at hospital admission for community-acquired pneumonia (CAP) were at high risk for severe outcomes. METHODS: Admission pGSN concentrations in 455 adults hospitalized with CAP were measured using enzyme-linked immunosorbent assay. Patients were grouped into the following 4 hierarchical, mutually exclusive categories based on maximum clinical severity experienced during their hospitalization: general floor care without intensive care unit (ICU) admission, invasive respiratory or vasopressor support (IRVS), or death; ICU care without IRVS or death; IRVS without death; or death. Admission pGSN concentrations were compared across these discrete outcome categories. Additionally, outcomes among patients in the lowest quartile of pGSN concentration were compared to those in the upper 3 quartiles. RESULTS: Overall, median (interquartile range) pGSN concentration was 38.1 (32.1, 45.7) μg/mL. Patients with more severe outcomes had lower pGSN concentrations (P = .0001); median values were 40.3 μg/mL for floor patients, 36.7 μg/mL for ICU patients, 36.5 μg/mL for patients receiving IRVS, and 25.7 μg/mL for patients who died. Compared to patients with higher pGSN concentrations, patients in the lowest quartile (pGSN ≤ 32.1 μg/mL) more often required IRVS (21.2% vs 11.7%, P = .0114) and died (8.8% vs 0.9%, P < .0001). CONCLUSIONS: Among adults hospitalized with CAP, lower pGSN concentrations were associated with more severe clinical outcomes. Future studies are planned to investigate possible therapeutic benefits of recombinant human pGSN in this population.
BACKGROUND: Plasma gelsolin (pGSN) is an abundant circulating protein that neutralizes actin exposed by damaged cells, modulates inflammatory responses, and enhances alveolar macrophage antimicrobial activity. We investigated whether adults with low pGSN at hospital admission for community-acquired pneumonia (CAP) were at high risk for severe outcomes. METHODS: Admission pGSN concentrations in 455 adults hospitalized with CAP were measured using enzyme-linked immunosorbent assay. Patients were grouped into the following 4 hierarchical, mutually exclusive categories based on maximum clinical severity experienced during their hospitalization: general floor care without intensive care unit (ICU) admission, invasive respiratory or vasopressor support (IRVS), or death; ICU care without IRVS or death; IRVS without death; or death. Admission pGSN concentrations were compared across these discrete outcome categories. Additionally, outcomes among patients in the lowest quartile of pGSN concentration were compared to those in the upper 3 quartiles. RESULTS: Overall, median (interquartile range) pGSN concentration was 38.1 (32.1, 45.7) μg/mL. Patients with more severe outcomes had lower pGSN concentrations (P = .0001); median values were 40.3 μg/mL for floor patients, 36.7 μg/mL for ICU patients, 36.5 μg/mL for patients receiving IRVS, and 25.7 μg/mL for patients who died. Compared to patients with higher pGSN concentrations, patients in the lowest quartile (pGSN ≤ 32.1 μg/mL) more often required IRVS (21.2% vs 11.7%, P = .0114) and died (8.8% vs 0.9%, P < .0001). CONCLUSIONS: Among adults hospitalized with CAP, lower pGSN concentrations were associated with more severe clinical outcomes. Future studies are planned to investigate possible therapeutic benefits of recombinant human pGSN in this population.
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