PMID- 34293318 OWN - NLM STAT- MEDLINE DCOM- 20220111 LR - 20240205 IS - 1931-3543 (Electronic) IS - 0012-3692 (Linking) VI - 160 IP - 5 DP - 2021 Nov TI - Parapneumonic Effusions Are Characterized by Elevated Levels of Neutrophil Extracellular Traps. PG - 1645-1655 LID - S0012-3692(21)01357-X [pii] LID - 10.1016/j.chest.2021.07.026 [doi] AB - BACKGROUND: Neutrophil extracellular traps (NETs) increasingly are implicated in acute and chronic conditions involving multiple organ systems. RESEARCH QUESTION: Are NET concentrations higher in parapneumonic effusions compared with effusions of other origin and does this reflect the inflammatory nature of these effusions? STUDY DESIGN AND METHODS: Patients (N = 101) seeking hospital treatment for undifferentiated pleural effusion underwent pleural fluid classification based on cytologic analysis results, biochemical findings, microbiological characteristics, and clinical judgement. Concentrations of NET markers (extracellular DNA [eDNA], citrullinated histone H3 [citH3]), neutrophils (alpha-defensins), and inflammation (IL-1beta)-related proteins were quantified by enzyme-linked immunosorbent assay. Differences between groups were analyzed using the Kruskal-Wallis one-way analysis of variance. Correlations used Spearman coefficient. Receiver operating characteristic (ROC) curves were calculated. RESULTS: Effusions were classified into four groups: parapneumonic (n = 18), malignant (n = 35), transudative (n = 22), and unclassifiable (n = 26). Concentrations of NETs markers were significantly higher in the parapneumonic group compared with malignant, transudative, and unclassifiable groups (median eDNA, 12.8 ng/mL vs 0.77 ng/mL, 0.44 ng/mL, and 0.86 ng/mL [P < .001]; and median citH3, 127.1 ng/mL vs 0.44 ng/mL, 0.34 ng/mL, and 0.49 ng/mL [P < .001]). citH3 and eDNA were correlated highly with lactate dehydrogenase (LDH; Spearman r = 0.66 and r = 0.73, respectively; P < .001) and moderately negatively correlated with pH (r = -0.55 and r = -0.62, respectively; P < .001). alpha-Defensins and IL-1beta were higher in the parapneumonic group than in other groups (median alpha-defensins, 124.4 ng/mL vs 4.7 ng/mL,7 ng/mL, and 6.9 ng/mL [P < .001]; and median IL-1beta, 145 pg/mL vs 1.87 pg/mL, 1.39 pg/mL, and 2.6 pg/mL [P < .001]) and moderately correlated with LDH (r = 0.60 and r = 0.57; P < .001). ROC curves showed high sensitivity and specificity for NET markers for prediction of parapneumonic effusion. INTERPRETATION: High levels of some NET-related mediators in parapneumonic effusions correlate with inflammation. Effusions of other causes do not show high levels of NETs. These results may have treatment implications because NETs may be an important contributor to the inflammation and viscosity of parapneumonic effusions and may help us to understand the therapeutic benefit of deoxyribonuclease in empyema. CI - Copyright (c) 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. FAU - Twaddell, Scott H AU - Twaddell SH AD - Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, The University of Newcastle, and Hunter Medical Research Institute, Newcastle, NSW, Australia. Electronic address: scott.twaddell@health.nsw.gov.au. FAU - Gibson, Peter G AU - Gibson PG AD - Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, The University of Newcastle, and Hunter Medical Research Institute, Newcastle, NSW, Australia. FAU - Grainge, Christopher AU - Grainge C AD - Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, The University of Newcastle, and Hunter Medical Research Institute, Newcastle, NSW, Australia. FAU - Baines, Katherine J AU - Baines KJ AD - School of Medicine and Public Health, Faculty of Health and Medicine and Priority Research Centre for Healthy Lungs, The University of Newcastle, and Hunter Medical Research Institute, Newcastle, NSW, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210719 PL - United States TA - Chest JT - Chest JID - 0231335 RN - 0 (Cell-Free Nucleic Acids) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Histones) RN - 0 (IL1B protein, human) RN - 0 (Interleukin-1beta) SB - IM CIN - Chest. 2022 Apr;161(4):e250. PMID: 35396062 CIN - Chest. 2022 Apr;161(4):e251. PMID: 35396063 MH - Aged MH - Analysis of Variance MH - Cell-Free Nucleic Acids/*analysis MH - Correlation of Data MH - Extracellular Matrix Proteins/*analysis MH - Extracellular Traps/*immunology MH - Female MH - Histones/*analysis MH - Humans MH - Inflammation/immunology MH - Interleukin-1beta/*analysis MH - Male MH - Microbiological Techniques/methods MH - Neutrophils/*pathology MH - *Pleural Effusion/classification/diagnosis/immunology/microbiology MH - ROC Curve OTO - NOTNLM OT - empyema OT - infection OT - inflammation OT - neutrophil extracellular traps OT - pleural disease EDAT- 2021/07/23 06:00 MHDA- 2022/01/12 06:00 CRDT- 2021/07/22 20:10 PHST- 2021/01/06 00:00 [received] PHST- 2021/07/05 00:00 [revised] PHST- 2021/07/11 00:00 [accepted] PHST- 2021/07/23 06:00 [pubmed] PHST- 2022/01/12 06:00 [medline] PHST- 2021/07/22 20:10 [entrez] AID - S0012-3692(21)01357-X [pii] AID - 10.1016/j.chest.2021.07.026 [doi] PST - ppublish SO - Chest. 2021 Nov;160(5):1645-1655. doi: 10.1016/j.chest.2021.07.026. Epub 2021 Jul 19.