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Supplemental digital contentAlveolar neutrophil extracellular traps in patients with pneumonia-related acute respiratory distress syndromeMaterial and MethodsPatients and data collectionAll patients with severe or moderate pneumonia-related ARDS (Berlin definition ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"l00wkG8Z","properties":{"formattedCitation":"{\\rtf \\super 1\\nosupersub{}}","plainCitation":"1"},"citationItems":[{"id":1808,"uris":[""],"uri":[""],"itemData":{"id":1808,"type":"article-journal","title":"Acute Respiratory Distress Syndrome: The Berlin Definition","container-title":"JAMA","volume":"307","issue":"23","source":"CrossRef","URL":"","DOI":"10.1001/jama.2012.5669","ISSN":"0098-7484","shortTitle":"Acute Respiratory Distress Syndrome","language":"en","issued":{"date-parts":[["2012",6,20]]},"accessed":{"date-parts":[["2017",8,22]]}}}],"schema":""} 1) were included consecutively with the following inclusion criteria: tracheal intubation and mechanical ventilation since less than 72 hours; pulmonary infection diagnosed less than 7 days before; bilateral pulmonary infiltrates on chest x-ray consistent with pulmonary edema; a PaO2/FiO2 ratio ≤ 200 mm Hg with a positive end-expiratory pressure (PEEP) ≥ 5 cm H2O. Non-inclusion criteria were as follows: age <18 years; pregnancy; chronic respiratory failure requiring long-term oxygen therapy; Child-Pugh C liver cirrhosis; lung fibrosis; immunosuppression (i.e., HIV infection, active hematological malignancy or solid cancer receiving chemotherapy, corticosteroids therapy for more than 0.5 mg/kg/day since more than 4 weeks, organ transplant patients), SAPS II (Simplified Acute Physiology II score) > 90, irreversible neurological disorders, patients with withholding/withdrawing of life-sustaining therapies and profound hypoxaemia (PaO2/FiO2 <75 mm Hg). Control patients, (i.e., patients free of ARDS, any active infection, diffuse interstitial pneumonia or immunosuppression; n=4) undergoing a bronchoscopy with broncho-alveolar lavage and blood sampling as part of routine care, were also included (see eTable 1 for further more details on control patients). ARDS patients received mechanical ventilation using a standardized protective ventilation strategy ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ItiH7CKi","properties":{"formattedCitation":"{\\rtf \\super 2,3\\nosupersub{}}","plainCitation":"2,3"},"citationItems":[{"id":1807,"uris":[""],"uri":[""],"itemData":{"id":1807,"type":"article-journal","title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.","container-title":"New England Journal of Medicine","page":"1301–1308","volume":"342","issue":"18","source":"Google Scholar","author":[{"family":"Brower","given":"Roy G."},{"family":"Matthay","given":"M. A."},{"family":"Morris","given":"A."},{"family":"Schoenfeld","given":"D."},{"family":"Thompson","given":"B. Taylor"},{"family":"Wheeler","given":"A."},{"family":"Wiedemann","given":"H. P."},{"family":"Arroliga","given":"A. C."},{"family":"Fisher","given":"C. J."},{"family":"Komara","given":"J. J."},{"literal":"others"}],"issued":{"date-parts":[["2000"]]}},"label":"page"},{"id":2295,"uris":[""],"uri":[""],"itemData":{"id":2295,"type":"article-journal","title":"Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome: A Randomized Controlled Trial","container-title":"JAMA","page":"646-655","volume":"299","issue":"6","source":"jamanetwork-com.gate2.inist.fr","abstract":"<h3>Context</h3>The need for lung protection is universally accepted, but the optimal level of positive end-expiratory pressure (PEEP) in patients with acute lung injury (ALI) or acute respiratory distress syndrome remains debated.<h3>Objective</h3>To compare the effect on outcome of a strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation to one aimed at minimizing alveolar distension in patients with ALI.<h3>Design, Setting, and Patients</h3>A multicenter randomized controlled trial of 767 adults (mean [SD] age, 59.9 [15.4] years) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005.<h3>Intervention</h3>Tidal volume was set at 6 mL/kg of predicted body weight in both strategies. Patients were randomly assigned to a moderate PEEP strategy (5-9 cm H₂O) (minimal distension strategy; n = 382) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H₂O (increased recruitment strategy; n = 385).<h3>Main Outcome Measures</h3>The primary end point was mortality at 28 days. Secondary end points were hospital mortality at 60 days, ventilator-free days, and organ failure–free days at 28 days.<h3>Results</h3>The 28-day mortality rate in the minimal distension group was 31.2% (n = 119) vs 27.8% (n = 107) in the increased recruitment group (relative risk, 1.12 [95% confidence interval, 0.90-1.40]; P = .31). The hospital mortality rate in the minimal distension group was 39.0% (n = 149) vs 35.4% (n = 136) in the increased recruitment group (relative risk, 1.10 [95% confidence interval, 0.92-1.32]; P = .30). The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days (7 [interquartile range {IQR}, 0-19] vs 3 [IQR, 0-17]; P = .04) and organ failure–free days (6 [IQR, 0-18] vs 2 [IQR, 0-16]; P = .04). This strategy also was associated with higher compliance values, better oxygenation, less use of adjunctive therapies, and larger fluid requirements.<h3>Conclusions</h3>A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality. However, it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure.<h3>Trial Registration</h3> Identifier: NCT00188058","URL":"","DOI":"10.1001/jama.299.6.646","ISSN":"0098-7484","shortTitle":"Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome","journalAbbreviation":"JAMA","language":"en","author":[{"family":"Mercat","given":"Alain"},{"family":"Richard","given":"Jean-Christophe M."},{"family":"Vielle","given":"Bruno"},{"family":"Jaber","given":"Samir"},{"family":"Osman","given":"David"},{"family":"Diehl","given":"Jean-Luc"},{"family":"Lefrant","given":"Jean-Yves"},{"family":"Prat","given":"Gwena?l"},{"family":"Richecoeur","given":"Jack"},{"family":"Nieszkowska","given":"Ania"},{"family":"Gervais","given":"Claude"},{"family":"Baudot","given":"Jér?me"},{"family":"Bouadma","given":"Lila"},{"family":"Brochard","given":"Laurent"},{"family":"Group","given":"for the Expiratory Pressure (Express) Study"}],"issued":{"date-parts":[["2008",2,13]]},"accessed":{"date-parts":[["2018",1,16]]}},"label":"page"}],"schema":""} 2,3. Other treatments, including neuromuscular blocking agents ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"A9lz0J49","properties":{"formattedCitation":"{\\rtf \\super 4\\nosupersub{}}","plainCitation":"4"},"citationItems":[{"id":2257,"uris":[""],"uri":[""],"itemData":{"id":2257,"type":"article-journal","title":"Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome","container-title":"New England Journal of Medicine","page":"1107-1116","volume":"363","issue":"12","source":"Taylor and Francis+NEJM","abstract":"The investigators induced muscle paralysis in patients with the acute respiratory distress syndrome (ARDS) by administering a neuromuscular blocking agent, cisatracurium besylate. As compared with placebo, cisatracurium resulted in a lower adjusted 90-day mortality without more severe sequelae of neuromuscular blockade.","URL":"","DOI":"10.1056/NEJMoa1005372","ISSN":"0028-4793","note":"PMID: 20843245","author":[{"family":"Papazian","given":"Laurent"},{"family":"Forel","given":"Jean-Marie"},{"family":"Gacouin","given":"Arnaud"},{"family":"Penot-Ragon","given":"Christine"},{"family":"Perrin","given":"Gilles"},{"family":"Loundou","given":"Anderson"},{"family":"Jaber","given":"Samir"},{"family":"Arnal","given":"Jean-Michel"},{"family":"Perez","given":"Didier"},{"family":"Seghboyan","given":"Jean-Marie"},{"family":"Constantin","given":"Jean-Michel"},{"family":"Courant","given":"Pierre"},{"family":"Lefrant","given":"Jean-Yves"},{"family":"Guérin","given":"Claude"},{"family":"Prat","given":"Gwena?l"},{"family":"Morange","given":"Sophie"},{"family":"Roch","given":"Antoine"}],"issued":{"date-parts":[["2010",9,16]]}}}],"schema":""} 4, nitric oxide inhalation ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qTUYAJ4E","properties":{"formattedCitation":"{\\rtf \\super 5\\nosupersub{}}","plainCitation":"5"},"citationItems":[{"id":1862,"uris":[""],"uri":[""],"itemData":{"id":1862,"type":"article-journal","title":"Inhaled nitric oxide therapy in adults","container-title":"New England Journal of Medicine","page":"2683–2695","volume":"353","issue":"25","source":"Google Scholar","URL":"","author":[{"family":"Griffiths","given":"Mark JD"},{"family":"Evans","given":"Timothy W."}],"issued":{"date-parts":[["2005"]]},"accessed":{"date-parts":[["2017",8,22]]}}}],"schema":""} 5, prone positioning ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"MotbDebd","properties":{"formattedCitation":"{\\rtf \\super 6\\nosupersub{}}","plainCitation":"6"},"citationItems":[{"id":2256,"uris":[""],"uri":[""],"itemData":{"id":2256,"type":"article-journal","title":"Prone Positioning in Severe Acute Respiratory Distress Syndrome","container-title":"New England Journal of Medicine","page":"2159-2168","volume":"368","issue":"23","source":"CrossRef","URL":"","DOI":"10.1056/NEJMoa1214103","ISSN":"0028-4793, 1533-4406","language":"en","author":[{"family":"Guérin","given":"Claude"},{"family":"Reignier","given":"Jean"},{"family":"Richard","given":"Jean-Christophe"},{"family":"Beuret","given":"Pascal"},{"family":"Gacouin","given":"Arnaud"},{"family":"Boulain","given":"Thierry"},{"family":"Mercier","given":"Emmanuelle"},{"family":"Badet","given":"Michel"},{"family":"Mercat","given":"Alain"},{"family":"Baudin","given":"Olivier"},{"family":"Clavel","given":"Marc"},{"family":"Chatellier","given":"Delphine"},{"family":"Jaber","given":"Samir"},{"family":"Rosselli","given":"Sylvène"},{"family":"Mancebo","given":"Jordi"},{"family":"Sirodot","given":"Michel"},{"family":"Hilbert","given":"Gilles"},{"family":"Bengler","given":"Christian"},{"family":"Richecoeur","given":"Jack"},{"family":"Gainnier","given":"Marc"},{"family":"Bayle","given":"Frédérique"},{"family":"Bourdin","given":"Gael"},{"family":"Leray","given":"Véronique"},{"family":"Girard","given":"Raphaele"},{"family":"Baboi","given":"Loredana"},{"family":"Ayzac","given":"Louis"}],"issued":{"date-parts":[["2013",6,6]]},"accessed":{"date-parts":[["2017",11,30]]}}}],"schema":""} 6 and venovenous extra-corporeal membrane oxygenation were administered depending on the severity of ARDS ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ml4DzNMh","properties":{"formattedCitation":"{\\rtf \\super 7\\nosupersub{}}","plainCitation":"7"},"citationItems":[{"id":1804,"uris":[""],"uri":[""],"itemData":{"id":1804,"type":"article-journal","title":"The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material","container-title":"Intensive Care Medicine","page":"1573-1582","volume":"38","issue":"10","source":"CrossRef","URL":"","DOI":"10.1007/s00134-012-2682-1","ISSN":"0342-4642, 1432-1238","shortTitle":"The Berlin definition of ARDS","language":"en","author":[{"family":"Ferguson","given":"Niall D."},{"family":"Fan","given":"Eddy"},{"family":"Camporota","given":"Luigi"},{"family":"Antonelli","given":"Massimo"},{"family":"Anzueto","given":"Antonio"},{"family":"Beale","given":"Richard"},{"family":"Brochard","given":"Laurent"},{"family":"Brower","given":"Roy"},{"family":"Esteban","given":"Andrés"},{"family":"Gattinoni","given":"Luciano"},{"family":"Rhodes","given":"Andrew"},{"family":"Slutsky","given":"Arthur S."},{"family":"Vincent","given":"Jean-Louis"},{"family":"Rubenfeld","given":"Gordon D."},{"family":"Thompson","given":"B. Taylor"},{"family":"Ranieri","given":"V. Marco"}],"issued":{"date-parts":[["2012",10]]},"accessed":{"date-parts":[["2017",8,22]]}}}],"schema":""} 7. The prevention of ventilator-associated pneumonias followed a multifaceted program ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"y4kTEp0l","properties":{"formattedCitation":"{\\rtf \\super 8\\nosupersub{}}","plainCitation":"8"},"citationItems":[{"id":758,"uris":[""],"uri":[""],"itemData":{"id":758,"type":"article-journal","title":"A multifaceted program to prevent ventilator-associated pneumonia: impact on compliance with preventive measures","container-title":"Critical Care Medicine","page":"789-796","volume":"38","issue":"3","source":"NCBI PubMed","abstract":"OBJECTIVE: To determine the effect of a 2-yr multifaceted program aimed at preventing ventilator-acquired pneumonia on compliance with eight targeted preventive measures.\nDESIGN: Pre- and postintervention observational study.\nSETTING: A 20-bed medical intensive care unit in a teaching hospital.\nPATIENTS: A total of 1649 ventilator-days were observed.\nINTERVENTIONS: The program involved all healthcare workers and included a multidisciplinary task force, an educational session, direct observations with performance feedback, technical improvements, and reminders. It focused on eight targeted measures based on well-recognized published guidelines, easily and precisely defined acts, and directly concerned healthcare workers' bedside behavior. Compliance assessment consisted of five 4-wk periods (before the intervention and 1 month, 6 months, 12 months, and 24 months thereafter).\nMEASUREMENTS AND MAIN RESULTS: Hand-hygiene and glove-and-gown use compliances were initially high (68% and 80%) and remained stable over time. Compliance with all other preventive measures was initially low and increased steadily over time (before 2-yr level, p < .0001): backrest elevation (5% to 58%) and tracheal cuff pressure maintenance (40% to 89%), which improved after simple technical equipment implementation; orogastric tube use (52% to 96%); gastric overdistension avoidance (20% to 68%); good oral hygiene (47% to 90%); and nonessential tracheal suction elimination (41% to 92%). To assess overall performance of the last six preventive measures, using ventilator-days as the unit of analysis, a composite score for preventive measures applied (range, 0-6) was developed. The median (interquartile range) composite scores for the five successive assessments were 2 (1-3), 4 (3-5), 4 (4-5), 5 (4-6), and 5 (4-6) points; they increased significantly over time (p < .0001). Ventilator-acquired pneumonia prevalence rate decreased by 51% after intervention (p < .0001).\nCONCLUSIONS: Our active, long-lasting program for preventing ventilator-acquired pneumonia successfully increased compliance with preventive measures directly dependent on healthcare workers' bedside performance. The multidimensional framework was critical for this marked, progressive, and sustained change.","DOI":"10.1097/CCM.0b013e3181ce21af","ISSN":"1530-0293","note":"PMID: 20068461","shortTitle":"A multifaceted program to prevent ventilator-associated pneumonia","journalAbbreviation":"Crit. Care Med.","language":"eng","author":[{"family":"Bouadma","given":"Lila"},{"family":"Mourvillier","given":"Bruno"},{"family":"Deiler","given":"Véronique"},{"family":"Le Corre","given":"Bertrand"},{"family":"Lolom","given":"Isabelle"},{"family":"Régnier","given":"Bernard"},{"family":"Wolff","given":"Michel"},{"family":"Lucet","given":"Jean-Christophe"}],"issued":{"date-parts":[["2010",3]]}}}],"schema":""} 8; Sedation and mechanical ventilation weaning followed standardized protocols ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"5TKDIyfX","properties":{"formattedCitation":"{\\rtf \\super 9\\nosupersub{}}","plainCitation":"9"},"citationItems":[{"id":2315,"uris":[""],"uri":[""],"itemData":{"id":2315,"type":"article-journal","title":"Ventilator-associated pneumonia during weaning from mechanical ventilation: role of fluid management","container-title":"Chest","page":"58-65","volume":"146","issue":"1","source":"PubMed","abstract":"BACKGROUND: Pulmonary edema may alter alveolar bacterial clearance and infectivity. Manipulation of fluid balance aimed at reducing fluid overload may, therefore, influence ventilator-associated pneumonia (VAP) occurrence in intubated patients. The objective of the present study was to assess the impact of a depletive fluid-management strategy on ventilator-associated complication (VAC) and VAP occurrence during weaning from mechanical ventilation.\nMETHODS: We used data from the B-type Natriuretic Peptide for the Fluid Management of Weaning (BMW) randomized controlled trial performed in nine ICUs across Europe and America. We compared the cumulative incidence of VAC and VAP between the biomarker-driven, depletive fluid-management group and the usual-care group during the 14 days following randomization, using specific competing-risk methods (the Fine and Gray model).\nRESULTS: Among the 304 patients analyzed, 41 experienced VAP, including 27 (17.8%) in the usual-care group vs 14 (9.2%) in the interventional group (P = .03). From the Fine and Gray model, the probabilities of VAC and VAP occurrence were both significantly reduced with the interventional strategy while adjusting for weaning outcome as a competing event (subhazard ratios [25th-75th percentiles], 0.44 [0.22-0.87], P = .02 and 0.50 [0.25-0.96], P = .03, respectively).\nCONCLUSIONS: Using proper competing risk analyses, we found that a depletive fluid-management strategy, when initiating the weaning process, has the potential for lowering VAP risk in patients who are mechanically ventilated.\nTRIAL REGISTRY: ; No.: NCT00473148; URL: .","DOI":"10.1378/chest.13-2564","ISSN":"1931-3543","note":"PMID: 24652410","shortTitle":"Ventilator-associated pneumonia during weaning from mechanical ventilation","journalAbbreviation":"Chest","language":"eng","author":[{"family":"Mekontso Dessap","given":"Armand"},{"family":"Katsahian","given":"Sandrine"},{"family":"Roche-Campo","given":"Ferran"},{"family":"Varet","given":"Hugo"},{"family":"Kouatchet","given":"Achille"},{"family":"Tomicic","given":"Vinko"},{"family":"Beduneau","given":"Gaetan"},{"family":"Sonneville","given":"Romain"},{"family":"Jaber","given":"Samir"},{"family":"Darmon","given":"Michael"},{"family":"Castanares-Zapatero","given":"Diego"},{"family":"Brochard","given":"Laurent"},{"family":"Brun-Buisson","given":"Christian"}],"issued":{"date-parts":[["2014",7]]}}}],"schema":""} 9.Demographics, clinical and laboratory variables were recorded upon ICU admission, at samples collection time points (see below) and during ICU stay. Patients’ severity of illness was assessed using SAPS II ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qoJM3n7S","properties":{"formattedCitation":"{\\rtf \\super 10\\nosupersub{}}","plainCitation":"10"},"citationItems":[{"id":2069,"uris":[""],"uri":[""],"itemData":{"id":2069,"type":"article-journal","title":"A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study","container-title":"JAMA","page":"2957-2963","volume":"270","issue":"24","source":".gate2.inist.fr","abstract":"<h3>Objective.</h3><p>—To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality.</p><h3>Design and Setting.</h3><p>—The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries.</p><h3>Patients.</h3><p>—The 13 152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded.</p><h3>Outcome Measure.</h3><p>—Vital status at hospital discharge.</p><h3>Results.</h3><p>—The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (<i>P</i>=.883 and<i>P</i>=.104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample.</p><h3>Conclusion.</h3><p>—The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units.</p><p>(<i>JAMA</i>. 1993;270:2957-2963)</p>","URL":"","DOI":"10.1001/jama.1993.03510240069035","ISSN":"0098-7484","journalAbbreviation":"JAMA","author":[{"family":"Gall","given":"Jean-Roger Le"},{"family":"Lemeshow","given":"Stanley"},{"family":"Saulnier","given":"Fabienne"}],"issued":{"date-parts":[["1993",12,22]]},"accessed":{"date-parts":[["2017",10,3]]}}}],"schema":""} 10 and sequential organ failure assessment (SOFA) scores ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NFOmIPbT","properties":{"formattedCitation":"{\\rtf \\super 11\\nosupersub{}}","plainCitation":"11"},"citationItems":[{"id":2317,"uris":[""],"uri":[""],"itemData":{"id":2317,"type":"article-journal","title":"Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on \"sepsis-related problems\" of the European Society of Intensive Care Medicine","container-title":"Critical Care Medicine","page":"1793-1800","volume":"26","issue":"11","source":"PubMed","abstract":"OBJECTIVE: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients.\nDESIGN: Prospective, multicenter study.\nSETTING: Forty intensive care units (ICUs) in 16 countries.\nPATIENTS: Patients admitted to the ICU in May 1995 (n = 1,449), excluding patients who underwent uncomplicated elective surgery with an ICU length of stay <48 hrs.\nINTERVENTIONS: None.\nMEASUREMENTS AND MAIN RESULTS: The main outcome measures included incidence of dysfunction/failure of different organs and the relationship of this dysfunction with outcome. In this cohort of patients, the median length of ICU stay was 5 days, and the ICU mortality rate was 22%. Multiple organ dysfunction and high SOFA scores for any individual organ were associated with increased mortality. The presence of infection on admission (28.7% of patients) was associated with higher SOFA scores for each organ. The evaluation of a subgroup of 544 patients who stayed in the ICU for at least 1 wk showed that survivors and nonsurvivors followed a different course. This subgroup had greater respiratory, cardiovascular, and neurologic scores than the other patients. In this subgroup, the total SOFA score increased in 44% of the nonsurvivors but in only 20% of the survivors (p < .001). Conversely, the total SOFA score decreased in 33% of the survivors compared with 21% of the nonsurvivors (p < .001).\nCONCLUSIONS: The SOFA score is a simple, but effective method to describe organ dysfunction/failure in critically ill patients. Regular, repeated scoring enables patient condition and disease development to be monitored and better understood. The SOFA score may enable comparison between patients that would benefit clinical trials.","ISSN":"0090-3493","note":"PMID: 9824069","shortTitle":"Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units","journalAbbreviation":"Crit. Care Med.","language":"eng","author":[{"family":"Vincent","given":"J. L."},{"family":"Mendon?a","given":"A.","non-dropping-particle":"de"},{"family":"Cantraine","given":"F."},{"family":"Moreno","given":"R."},{"family":"Takala","given":"J."},{"family":"Suter","given":"P. M."},{"family":"Sprung","given":"C. L."},{"family":"Colardyn","given":"F."},{"family":"Blecher","given":"S."}],"issued":{"date-parts":[["1998",11]]}}}],"schema":""} 11. Other recorded variables included the use of adjuvant therapies for ARDS (i.e., neuromuscular blocking agents, nitric oxide inhalation, prone positioning, extracorporeal membrane oxygenation), the need for hemodialysis or vasopressors, corticosteroids administration, the number of ventilator- and organ failure-free days at day 28, the duration of mechanical ventilation and of intensive care unit stay in all patients and in survivors only and intensive care unit mortality.BAL fluid processingDuring a standard flexible bronchoscopy, the bronchoscope was wedged within a bronchopulmonary segment. Four aliquots of normal saline (50 mL each) were instilled through the bronchoscope within the selected bronchopulmonary segment. After each aliquot was instilled, saline was retrieved using a negative suction pressure. Broncho-alveolar lavage fluid cytology was performed by direct microscopy after centrifuging broncho-alveolar lavage fluid samples (12?000 revolutions for 10 min) and dying under the May-Grünwald-Giemsa staining. Total (quantified in cells/mL) and differential (i.e., percent of neutrophils, macrophages and lymphocytes) cell counts were measured as recommended ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"bNL79Dz8","properties":{"formattedCitation":"{\\rtf \\super 12\\nosupersub{}}","plainCitation":"12"},"citationItems":[{"id":2378,"uris":[""],"uri":[""],"itemData":{"id":2378,"type":"article-journal","title":"An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of Bronchoalveolar Lavage Cellular Analysis in Interstitial Lung Disease","container-title":"American Journal of Respiratory and Critical Care Medicine","page":"1004-1014","volume":"185","issue":"9","source":"CrossRef","URL":"","DOI":"10.1164/rccm.201202-0320ST","ISSN":"1073-449X, 1535-4970","shortTitle":"An Official American Thoracic Society Clinical Practice Guideline","language":"en","author":[{"family":"Meyer","given":"Keith C."},{"family":"Raghu","given":"Ganesh"},{"family":"Baughman","given":"Robert P."},{"family":"Brown","given":"Kevin K."},{"family":"Costabel","given":"Ulrich"},{"family":"Bois","given":"Roland M.","non-dropping-particle":"du"},{"family":"Drent","given":"Marjolein"},{"family":"Haslam","given":"Patricia L."},{"family":"Kim","given":"Dong Soon"},{"family":"Nagai","given":"Sonoko"},{"family":"Rottoli","given":"Paola"},{"family":"Saltini","given":"Cesare"},{"family":"Selman","given":"Moisés"},{"family":"Strange","given":"Charlie"},{"family":"Wood","given":"Brent"}],"issued":{"date-parts":[["2012",5]]},"accessed":{"date-parts":[["2018",2,13]]}}}],"schema":""} 12.Measurements of BAL fluid and blood NETs and cytokines levels Broncho-alveolar lavage fluid was collected from all ARDS patients during a bronchoscopy within 48 hours of ARDS onset (day 1-2 sample) and, for patients who were alive and still had ARDS criteria five days thereafter (day 4-5 sample). Broncho-alveolar lavage fluid samples were also collected from controls during bronchoscopy. A blood sample (4 ml) for measurement of serum neutrophil extracellular traps and serum cytokines concentrations was obtained in the same time as part of routine care (see online supplementary data for further details).NETs quantificationNeutrophil extracellular traps were specifically quantified by measuring myeloperoxidase (MPO)-DNA complexes in serum and broncho-alveolar lavage samples using a previously described capture ELISA ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"UzCKgYBl","properties":{"formattedCitation":"{\\rtf \\super 13\\nosupersub{}}","plainCitation":"13"},"citationItems":[{"id":2114,"uris":[""],"uri":[""],"itemData":{"id":2114,"type":"article-journal","title":"Human blood monocytes are able to form extracellular traps","container-title":"Journal of Leukocyte Biology","page":"775-781","volume":"102","issue":"3","source":".gate2.inist.fr","abstract":"Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase. Monocyte ET release depends on oxidative burst but not on MPO activity, in contrast to neutrophils. Moreover, we demonstrate procoagulant activity for monocyte ETs, a feature that could be relevant to monocyte thrombogenic properties. This new cellular mechanism is likely to have implications in the multiple pathologic contexts where monocytes are implicated, such as inflammatory disorders, infection, or thrombosis.","URL":"","DOI":"10.1189/jlb.3MA0916-411R","ISSN":"0741-5400, 1938-3673","note":"PMID: 28465447","journalAbbreviation":"J Leukoc Biol","language":"en","author":[{"family":"Granger","given":"Vanessa"},{"family":"Faille","given":"Dorothée"},{"family":"Marani","given":"Vanessa"},{"family":"No?l","given":"Beno?t"},{"family":"Gallais","given":"Yann"},{"family":"Szely","given":"Natacha"},{"family":"Flament","given":"Hélo?se"},{"family":"Pallardy","given":"Marc"},{"family":"Chollet-Martin","given":"Sylvie"},{"family":"Chaisemartin","given":"Luc","dropping-particle":"de"}],"issued":{"date-parts":[["2017",9,1]]},"accessed":{"date-parts":[["2017",9,28]]}}}],"schema":""} 13 considered to be the best way to monitor NETosis in vivo 14. Briefly, 20 μg/ml of rabbit anti-human MPO antibody (Millipore, AB 1224) was coated overnight to 96-well microtiter plates. After blocking with 2% BSA, samples were added together with a peroxidase-labeled anti-DNA monoclonal antibody (component 2 of the Cell Death ELISA kit, Roche). After incubation, the peroxidase substrate was added for 40 min at 37 °C. Optical density was measured at 405 nm. A standard curve was obtained by dilution of a strongly positive serum. Samples were interpolated from the standard curve using the sigmoidal dose-response (variable slope) equation and results were expressed in arbitrary units (a.u.). The detection range was 4-1000 a.u..Quantification of cytokines and biomarkers of alveolar epithelial injury Serum and Broncho-alveolar lavage fluid concentrations of the main pro- and anti-inflammatory cytokines involved in neutrophil chemotaxis and activation (IL-6, IL-8, IL10, TNF-α ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"T0NS2H1E","properties":{"formattedCitation":"{\\rtf \\super 14\\nosupersub{}}","plainCitation":"14"},"citationItems":[{"id":2111,"uris":[""],"uri":[""],"itemData":{"id":2111,"type":"article-journal","title":"Neutrophils in development of multiple organ failure in sepsis","container-title":"The Lancet","page":"157-169","volume":"368","issue":"9530","source":"ScienceDirect","abstract":"Summary\nMultiple organ failure is a major threat to the survival of patients with sepsis and systemic inflammation. In the UK and in the USA, mortality rates are currently comparable with and projected to exceed those from myocardial infarction. The immune system combats microbial infections but, in severe sepsis, its untoward activity seems to contribute to organ dysfunction. In this Review we propose that an inappropriate activation and positioning of neutrophils within the microvasculature contributes to the pathological manifestations of multiple organ failure. We further suggest that targeting neutrophils and their interactions with blood vessel walls could be a worthwhile therapeutic strategy for sepsis.","URL":"","DOI":"10.1016/S0140-6736(06)69005-3","ISSN":"0140-6736","journalAbbreviation":"The Lancet","author":[{"family":"Brown","given":"KA"},{"family":"Brain","given":"SD"},{"family":"Pearson","given":"JD"},{"family":"Edgeworth","given":"JD"},{"family":"Lewis","given":"SM"},{"family":"Treacher","given":"DF"}],"issued":{"date-parts":[["2006",7,8]]},"accessed":{"date-parts":[["2017",10,4]]}}}],"schema":""} 15), as well as lung epithelium injury markers (surfactant protein D, RAGE ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"NKHCihR7","properties":{"formattedCitation":"{\\rtf (Garc\\uc0\\u237{}a-Laorden et al. 2017)}","plainCitation":"(García-Laorden et al. 2017)","dontUpdate":true},"citationItems":[{"id":2284,"uris":[""],"uri":[""],"itemData":{"id":2284,"type":"article-journal","title":"Biomarkers for the acute respiratory distress syndrome: how to make the diagnosis more precise","container-title":"Annals of Translational Medicine","volume":"5","issue":"14","source":"PubMed Central","abstract":"The acute respiratory distress syndrome (ARDS) is an acute inflammatory process of the lung caused by a direct or indirect insult to the alveolar-capillary membrane. Currently, ARDS is diagnosed based on a combination of clinical and physiological variables. The lack of a specific biomarker for ARDS is arguably one of the most important obstacles to progress in developing novel treatments for ARDS. In this article, we will review the current understanding of some appealing biomarkers that have been measured in human blood, bronchoalveolar lavage fluid (BALF) or exhaled gas that could be used for identifying patients with ARDS, for enrolling ARDS patients into clinical trials, or for better monitoring of patient’s management. After a literature search, we identified several biomarkers that are associated with the highest sensitivity and specificity for the diagnosis or outcome prediction of ARDS: receptor for advanced glycation end-products (RAGE), angiopoietin-2 (Ang-2), surfactant protein D (SP-D), inteleukin-8, Fas and Fas ligand, procollagen peptide (PCP) I and III, octane, acetaldehyde, and 3-methylheptane. In general, these are cell-specific for epithelial or endothelial injury or involved in the inflammatory or infectious response. No biomarker or biomarkers have yet been confirmed for the diagnosis of ARDS or prediction of its prognosis. However, it is anticipated that in the near future, using biomarkers for defining ARDS, or for determining those patients who are more likely to benefit from a given therapy will have a major effect on clinical practice.","URL":"","DOI":"10.21037/atm.2017.06.49","ISSN":"2305-5839","note":"PMID: 28828358\nPMCID: PMC5537109","shortTitle":"Biomarkers for the acute respiratory distress syndrome","journalAbbreviation":"Ann Transl Med","author":[{"family":"García-Laorden","given":"M. Isabel"},{"family":"Lorente","given":"José A."},{"family":"Flores","given":"Carlos"},{"family":"Slutsky","given":"Arthur S."},{"family":"Villar","given":"Jesús"}],"issued":{"date-parts":[["2017",7]]}}}],"schema":""} 16) were measured by a single operator (MS) blinded to the clinical data using a Human Magnetic Luminex Assay (Biotechne – R&D Systems, Abingdon, UK) and expressed in ng/mL. Statistical analysisContinuous variables are reported as median [25–75th percentiles] or mean (±standard deviation, SD), as appropriate, and compared using Student t test or the Mann-Whitney test. Categorical variables are reported as number and percentages (95 % confidence interval) and compared using the chi2 or Fischer test, as appropriate. Because no clinically relevant neutrophil extracellular traps concentration threshold value was previously reported in Broncho-alveolar lavage fluid of ARDS patients, we categorized patients according to median broncho-alveolar lavage neutrophil extracellular traps (DNA-myeloperoxidase) levels (i.e., patients with “higher” versus patients with “lower” broncho-alveolar lavage neutrophil extracellular traps levels). A p value <0.05 was considered significant. Analyses were conducted using the SPSS Base 21.0 statistical software package (SPSS Inc., Chicago, IL).REFERENCES ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1. Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA 2012; 3072.Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A, Wiedemann HP, Arroliga AC, Fisher CJ, Komara JJ, others: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. 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N Engl J Med 2005; 353:2683–26956.Guérin C, Reignier J, Richard J-C, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L: Prone Positioning in Severe Acute Respiratory Distress Syndrome. N Engl J Med 2013; 368:2159–687.Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A, Slutsky AS, Vincent J-L, Rubenfeld GD, Thompson BT, Ranieri VM: The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 2012; 38:1573–828.Bouadma L, Mourvillier B, Deiler V, Le Corre B, Lolom I, Régnier B, Wolff M, Lucet J-C: A multifaceted program to prevent ventilator-associated pneumonia: impact on compliance with preventive measures. Crit Care Med 2010; 38:789–969.Mekontso Dessap A, Katsahian S, Roche-Campo F, Varet H, Kouatchet A, Tomicic V, Beduneau G, Sonneville R, Jaber S, Darmon M, Castanares-Zapatero D, Brochard L, Brun-Buisson C: Ventilator-associated pneumonia during weaning from mechanical ventilation: role of fluid management. Chest 2014; 146:58–6510.Gall J-RL, Lemeshow S, Saulnier F: A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study. JAMA 1993; 270:2957–6311.Vincent JL, Mendon?a A de, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 1998; 26:1793–80012.Meyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, Bois RM du, Drent M, Haslam PL, Kim DS, Nagai S, Rottoli P, Saltini C, Selman M, Strange C, Wood B: An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of Bronchoalveolar Lavage Cellular Analysis in Interstitial Lung Disease. Am J Respir Crit Care Med 2012; 185:1004–1413.Granger V, Faille D, Marani V, No?l B, Gallais Y, Szely N, Flament H, Pallardy M, Chollet-Martin S, Chaisemartin L de: Human blood monocytes are able to form extracellular traps. J Leukoc Biol 2017; 102:775–8114.Masuda S, Nakazawa D, Shida H, Miyoshi A, Kusunoki Y, Tomaru U, Ishizu A. NETosis markers: Quest for specific, objective, and quantitative markers. Clin Chim Acta 2016;459:89-93.15. Brown K, Brain S, Pearson J, Edgeworth J, Lewis S, Treacher D: Neutrophils in development of multiple organ failure in sepsis. The Lancet 2006; 368:157–6916.García-Laorden MI, Lorente JA, Flores C, Slutsky AS, Villar J: Biomarkers for the acute respiratory distress syndrome: how to make the diagnosis more precise. Ann Transl Med 2017; 5SUPPLEMENTAL TABLESeTable 1. Characteristics of control patients (n=4) included in the studyVariablesControl patientsa Age40723025GenderMaleMaleMaleMaleImmunosuppressionNoNoNoNoComorbiditiesNoneProstate cancer (2005, in remission)NoneNoneSmokerNoYesYesNoClinical indication for bronchoscopyMicronodules in right upper lobeGround glass lesions in right upper lobe + nodular lesionSuspicion of tuberculosisHilar adenopathyCharacteristics upon BAL samplingWhite blood cell counts, 103/mm3NeutrophilsLymphocytesMonocytes6.43.52.40.417.414.42.20.35.02.41.50.66.03.71.30.8BAL cytologyTotal cell counts, 103/mLMacrophages, %Neutrophils, %Lymphocytes, %778711270841511976613013066133aAll control patients were free of ARDS, active pulmonary infection, infiltrative lung disease, and immunosuppressioneTable 2. Microbiological documentation of patients (n=35) with pneumonia-related ARDSN (%)Bacteria18 (51.4)Enterobacteriaceae6Streptococcus pneumoniae5Staphylococcus aureus2Legionella pneumophila2Mycoplasma pneumoniae2Group A streptococcus1Virus11 (31.4)Influenza H1N17Rhinovirus2Respiratory syncytial virus1Metapneumovirus1No documentation6 (17.1)eTable 3. Baseline characteristics of ARDS patients (n=35) having lower (n=18) or higher (n=17) broncho-alveolar lavage fluid neutrophil extracellular traps concentrations within 72 hours of intubationVariables*Lower BAL NETs(n=18)Higher BAL NETs(n=17)P valueAge, years52.5±16.955.3±17.20.631Gender, male13 (72)11 (65)0.604ICU admission to intubation, days0 [0-1]0 [0-1]0.742Comorbidities (%)Diabetes mellitus3 (17)5 (29)0.443COPD1 (5)3 (18)0.338Chronic heart failure2 (11)2 (12)>0.99Obesity4 (22)2 (12)0.658Liver cirrhosis1(5)2 (12)0.603Sickle cell disease2 (11)2 (12)>0.99Smoker9 (50)3 (18)0.075BMI, kg/cm230.0±8.927.8±4.70.369Within 24 hours of study inclusion** (moderate/severe ARDS criteria)SAPS II39±1442±180.657SOFA8±38±40.991Temperature, Celsius degree38.6 [37.9-39.3]38.7 [38.0-40.0]0.518Shock4 (22)3 (18)>0.99ARDS severity (Berlin classification)moderatesevere9 (50.0)9 (50.0)9 (52.9)8 (47.1)>0.99Lung injury score2.9±0.72.6±0.30.081CRS, mL/cmH2O24 [19-26]25 [21-28]0.389Driving pressure, mmHg17.8±6.016.1±4.00.311PaO2/FiO2 ratio, mmHg99 [81-160]130 [69-186]0.654Tidal volume, mL/kg PBW6.1 [5.5-6.3]6.2 [5.9-7.1]0.131Plateau pressure, cmH2O28±625±30.152PEEP, cmH2O10 [8-15]10 [6-12]0.248Neuromuscular blocking agents17 (94)11 (65)0.041Prone position6 (33)6 (35)>0.99Arterial lactate levels, mmol/L1.0 [0.8-2.9]1.5 [1.0-2.1]0.226Arterial pH7.35±0.107.36±0.120.943Arterial PCO2, mmHg47±943±90.195Serum creatinine, ?mol/L84 [67-156]82 [68-142]0.961White blood cells, 103/mm313.2±8.814.7±7.50.592Blood neutrophils, 103/mm312.3±7.311.1±6.00.603Blood platelets, 103/mm3207±94257±1380.212Blood hemoglobin level, g/dL11.6±2.710.3±1.50.106Upon BAL 1 samplingIntubation to 1st BAL, days1 [1-1]1 [0-2]0.902SOFA8±48±30.952Temperature, Celsius degree38.5 [37.5-39.0]38.3 [37.9-39.7]0.831Shock4 (22)2 (12)>0.99Microbiological documentationBacteriaVirusBacteria + virusNone9 (50.0)6 (33.3)1 (5.5)2 (11.1)8 (47.0)5 (29.4)0 (0.0)4 (23.5)0.621Lung injury score2.7±0.52.4±0.50.076CRS, mL/cmH2O28 [24-37]32 [24-43]0.262Driving pressure, mmHg13.7±2.711.9±3.10.073PaO2/FiO2 ratio, mmHg142 [103-193]242 [149-350]0.006Tidal volume, mL/kg PBW5.8 [5.0-6.2]6.2 [5.9-6.7]0.021Plateau pressure, cmH2O24±323±40.434PEEP, cmH2O10 [8-14]12 [9-14]0.849Neuromuscular blocking agents13 (72.2)11 (64.7)0.725Prone position6 (33)8 (47)0.500Arterial lactate levels, mmol/L1.1 [0.8-2.3]1.4 [1.0-1.7]0.987Arterial pH7.37±0.117.38±0.080.796Arterial PCO2, mmHg49±1342±70.132Serum creatinine, ?mol/L105 [62-155]81 [62-225]0.902White blood cells, 103/mm311.7±7.815.6±8.20.150Blood neutrophils, 103/mm39.3±6.613.6±7.40.091Blood platelets, 103/mm3193±104240±1130.116Shock dose steroids3 (17)1 (6)>0.99Continuous variables are presented as mean ± standard deviation when normally distributed and median [1st-3rd quartiles] otherwise; P values come from the unpaired t-test or the Mann-Whitney test, as appropriate; Categorical variables are shown as n (%); P values come from the chi2 or the Fisher exact test, as appropriate; * None of the data pertaining to this table was missing; ** Worst values recorded; ARDS, acute respiratory distress syndrome; BAL: bronchoalveolar lavage fluid; NETs, neutrophil extracellular traps; ICU, intensive care unit; COPD, chronic obstructive pulmonary disease; BMI, body mass index; SAPS II, Simplified Acute Physiology Score II; SOFA, Sequential Assessment of Organ Failures; PEEP, positive end-expiratory pressure; PBW, predicted body weight; eTable 4. Measurement of neutrophil extracellular traps concentrationsin the alveolar and blood compartments in ARDS patients (n=35) having lower (n=18) or higher (n=17) broncho-alveolar lavage fluid neutrophil extracellular traps concentrations within 72 hours of intubationLower BAL NETs(n=18)Higher BAL NETs(n=17)P valueAlveolar compartmentBAL Fluid NETs levels, AU74 [52-104]1000 [533-1000]<0.0001Blood compartmentSerum NETs levels*, AU25 [4-58]30 [8-93]0.39AU: arbitrary units, BAL: bronchoalveolar lavage fluid; NETs, neutrophil extracellular traps; * Serum NETs levels value was missing for one patient; P values come from the Mann-Whitney test. eTable 5. Correlation matrix exploring the relationship between serum neutrophil extracellular traps concentrations, serum cytokines, and serum alveolar epithelium injury biomarkers levels. BAL biomarkers NETs (o.d.)IL-6IL-8IL-10TNF-αSP-DRAGENETs (o.d.)Rho1.0000.151-0.126-0.135-0.0010.1670.005P value-0.4020.4860.4520.9960.3520.980N34333333333333IL-6Rho1.0000.7220.4950.485-0.4720.239P value-<0.00010.0030.0040.0050.173N343434343434IL-8Rho1.0000.3640.405-0.2120.425P value-0.0340.0170.2290.012N3434343434IL-10Rho1.0000.658-0.5270.349P value-<0.00010.0010.043N34343434TNF-αRho1.000-0.4560.511P value-0.0070.002N343434SP-DRho1.000-0.099P value-0.577N3434RAGERho1.000P value-N34P values and correlation coefficients (rho) were computed using the Spearman’s test; NETs, neutrophil extracellular traps; NETs concentrations were expressed in optical densities (o.d.); N indicates the number of samples available for each biomarker.eTable 6. Exploratory uni- and multiple regression analysis using live ventilator-free days at day 28 as the dependent variable.Univariable analysisMultivariable analysisIndependent variableβ coefficient95% CI of the β coefficientP valueβ coefficient95% CI of the β coefficientP valueNET BAL levels (o.d.)3.70-0.87 ; 8.300.0842.40-2.13 ; 6.920.288PaO2/FiO2 ratio * 0.03-0.01 ; 0.060.0970.01-0.33 ; 0.360.934Tidal volume * 3.661.24 ; 6.090.0043.310.48 ; 6.130.023* Upon BAL 1 collection; CI, confidence interval; p values come from uni- and multiple linear regressionSUPPLEMENTAL FIGURESeFigure 1. Flow chart of patients with pneumonia-related moderate/severe acute respiratory distress syndrome (ARDS) included in the study. * Withholding/Withdrawal of life-sustaining therapies; BAL, broncho-alveolar lavage; NETs, neutrophil extracellular traps; ** Reasons for not performing the second BAL included deceased patients (n=5), extubated patients (n=10) or patient mechanically ventilated but not meeting ARDS criteria at day 5-7 (n=2).eFigure 2. Linear regression of BAL fluid neutrophil extracellular traps (NETs, DNA-MPO) levels on alveolar macrophages. There was a significant invert relationship between BAL fluid NETs, expressed as optical density (o.d.) values and alveolar macrophages, as a percentage of total BAL cell numbers (y=-0.016x + 2.027; r2=0.26; p<0.0001), from ARDS patients sampled at days 1-2 (n=35; red circles) and days 5-7 (n=18; blue circles) and controls (n=4; black circles). The grayed area comprised between the dashed curves depicts the 95% confidence interval of the regression line. ................
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