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Erschienen in: Intensive Care Medicine 11/2018

05.10.2018 | Original

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

verfasst von: Pratik Sinha, Kevin L. Delucchi, B. Taylor Thompson, Daniel F. McAuley, Michael A. Matthay, Carolyn S. Calfee, for the NHLBI ARDS Network

Erschienen in: Intensive Care Medicine | Ausgabe 11/2018

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Abstract

Purpose

Using latent class analysis (LCA), we have consistently identified two distinct subphenotypes in four randomized controlled trial cohorts of ARDS. One subphenotype has hyper-inflammatory characteristics and is associated with worse clinical outcomes. Further, within three negative clinical trials, we observed differential treatment response by subphenotype to randomly assigned interventions. The main purpose of this study was to identify ARDS subphenotypes in a contemporary NHLBI Network trial of infection-associated ARDS (SAILS) using LCA and to test for differential treatment response to rosuvastatin therapy in the subphenotypes.

Methods

LCA models were constructed using a combination of biomarker and clinical data at baseline in the SAILS study (n = 745). LCA modeling was then repeated using an expanded set of clinical class-defining variables. Subphenotypes were tested for differential treatment response to rosuvastatin.

Results

The two-class LCA model best fit the population. Forty percent of the patients were classified as the “hyper-inflammatory” subphenotype. Including additional clinical variables in the LCA models did not identify new classes. Mortality at day 60 and day 90 was higher in the hyper-inflammatory subphenotype. No differences in outcome were observed between hyper-inflammatory patients randomized to rosuvastatin therapy versus placebo.

Conclusions

LCA using a two-subphenotype model best described the SAILS population. The subphenotypes have features consistent with those previously reported in four other cohorts. Addition of new class-defining variables in the LCA model did not yield additional subphenotypes. No treatment effect was observed with rosuvastatin. These findings further validate the presence of two subphenotypes and demonstrate their utility for patient stratification in ARDS.
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Literatur
1.
Zurück zum Zitat Frank AJ, Thompson BT (2010) Pharmacological treatments for acute respiratory distress syndrome. Curr Opin Crit Care 16:62–68CrossRef Frank AJ, Thompson BT (2010) Pharmacological treatments for acute respiratory distress syndrome. Curr Opin Crit Care 16:62–68CrossRef
2.
Zurück zum Zitat Bosma KJ, Taneja R, Lewis JF (2010) Pharmacotherapy for prevention and treatment of acute respiratory distress syndrome: current and experimental approaches. Drugs 70:1255–1282CrossRef Bosma KJ, Taneja R, Lewis JF (2010) Pharmacotherapy for prevention and treatment of acute respiratory distress syndrome: current and experimental approaches. Drugs 70:1255–1282CrossRef
3.
Zurück zum Zitat Jacobson JR, Barnard JW, Grigoryev DN, Ma SF, Tuder RM, Garcia JG (2005) Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol 288:L1026–L1032CrossRef Jacobson JR, Barnard JW, Grigoryev DN, Ma SF, Tuder RM, Garcia JG (2005) Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol 288:L1026–L1032CrossRef
4.
Zurück zum Zitat Chopra V, Rogers MA, Buist M, Govindan S, Lindenauer PK, Saint S, Flanders SA (2012) Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis. Am J Med 125:1111–1123CrossRef Chopra V, Rogers MA, Buist M, Govindan S, Lindenauer PK, Saint S, Flanders SA (2012) Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis. Am J Med 125:1111–1123CrossRef
5.
Zurück zum Zitat Shyamsundar M, McKeown ST, O’Kane CM, Craig TR, Brown V, Thickett DR, Matthay MA, Taggart CC, Backman JT, Elborn JS, McAuley DF (2009) Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers. Am J Respir Crit Care Med 179:1107–1114CrossRef Shyamsundar M, McKeown ST, O’Kane CM, Craig TR, Brown V, Thickett DR, Matthay MA, Taggart CC, Backman JT, Elborn JS, McAuley DF (2009) Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers. Am J Respir Crit Care Med 179:1107–1114CrossRef
6.
Zurück zum Zitat McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder TJ, Johnston P, Hopkins PA, Johnston AJ, McDowell C, McNally C, HARP-2 Investigators, Irish Critical Care Trials Group (2014) Simvastatin in the acute respiratory distress syndrome. N Engl J Med 371:1695–1703CrossRef McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder TJ, Johnston P, Hopkins PA, Johnston AJ, McDowell C, McNally C, HARP-2 Investigators, Irish Critical Care Trials Group (2014) Simvastatin in the acute respiratory distress syndrome. N Engl J Med 371:1695–1703CrossRef
7.
Zurück zum Zitat National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT (2014) Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 370:2191–2200CrossRef National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT (2014) Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 370:2191–2200CrossRef
8.
Zurück zum Zitat Calfee CS, Delucchi K, Famous KR (2017) Reply: next step to understanding subphenotypes of acute respiratory distress syndrome. Am J Respir Crit Care Med 196:796CrossRef Calfee CS, Delucchi K, Famous KR (2017) Reply: next step to understanding subphenotypes of acute respiratory distress syndrome. Am J Respir Crit Care Med 196:796CrossRef
9.
Zurück zum Zitat Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS, Network A (2017) Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med 195:331–338CrossRef Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS, Network A (2017) Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med 195:331–338CrossRef
10.
Zurück zum Zitat Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O’Kane CM, McAuley DF, Irish Critical Care Trials Group (2018) Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med 6:691–698CrossRef Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O’Kane CM, McAuley DF, Irish Critical Care Trials Group (2018) Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med 6:691–698CrossRef
11.
Zurück zum Zitat Delucchi K, Famous KR, Ware LB, Parsons PE, Thompson BT, Calfee CS, ARDS Network (2018) Stability of ARDS subphenotypes over time in two randomised controlled trials. Thorax 73:439–445CrossRef Delucchi K, Famous KR, Ware LB, Parsons PE, Thompson BT, Calfee CS, ARDS Network (2018) Stability of ARDS subphenotypes over time in two randomised controlled trials. Thorax 73:439–445CrossRef
12.
Zurück zum Zitat Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, NHLBI ARDS Network (2014) Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2:611–620CrossRef Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, NHLBI ARDS Network (2014) Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2:611–620CrossRef
13.
Zurück zum Zitat Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O’Kane CM, McAuley DF (2018) ARDS subphenotypes and differential response to simvastatin: secondary analysis of a randomized controlled trial. Lancet Respir Med 6:691–698CrossRef Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O’Kane CM, McAuley DF (2018) ARDS subphenotypes and differential response to simvastatin: secondary analysis of a randomized controlled trial. Lancet Respir Med 6:691–698CrossRef
14.
Zurück zum Zitat Sinha P, Delucchi K, Thompson BT, McAuley DF, Matthay MA, Calfee CS (2018) Latent class analysis of acute respiratory distress syndrome (ARDS): secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) trial. Am J Respir Crit Care Med 197:A6187 Sinha P, Delucchi K, Thompson BT, McAuley DF, Matthay MA, Calfee CS (2018) Latent class analysis of acute respiratory distress syndrome (ARDS): secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) trial. Am J Respir Crit Care Med 197:A6187
15.
Zurück zum Zitat Muthén LK, Muthén BO (2017) Mplus user’s guide (version 8). Muthen & Muthen, Los Angeles Muthén LK, Muthén BO (2017) Mplus user’s guide (version 8). Muthen & Muthen, Los Angeles
16.
Zurück zum Zitat Pierrakos C, Vincent JL (2012) The changing pattern of acute respiratory distress syndrome over time: a comparison of two periods. Eur Respir J 40:589–595CrossRef Pierrakos C, Vincent JL (2012) The changing pattern of acute respiratory distress syndrome over time: a comparison of two periods. Eur Respir J 40:589–595CrossRef
17.
Zurück zum Zitat Wurpts IC, Geiser C (2014) Is adding more indicators to a latent class analysis beneficial or detrimental? Results of a Monte-Carlo study. Front Psychol 5:920CrossRef Wurpts IC, Geiser C (2014) Is adding more indicators to a latent class analysis beneficial or detrimental? Results of a Monte-Carlo study. Front Psychol 5:920CrossRef
18.
Zurück zum Zitat Maiolo G, Collino F, Vasques F, Rapetti F, Tonetti T, Romitti F, Cressoni M, Chiumello D, Moerer O, Herrmann P, Friede T, Quintel M, Gattinoni L (2018) Reclassifying acute respiratory distress syndrome. Am J Respir Crit Care Med 197:1586–1595CrossRef Maiolo G, Collino F, Vasques F, Rapetti F, Tonetti T, Romitti F, Cressoni M, Chiumello D, Moerer O, Herrmann P, Friede T, Quintel M, Gattinoni L (2018) Reclassifying acute respiratory distress syndrome. Am J Respir Crit Care Med 197:1586–1595CrossRef
19.
Zurück zum Zitat Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, Matthay MA (2002) Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 346:1281–1286CrossRef Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, Matthay MA (2002) Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 346:1281–1286CrossRef
20.
Zurück zum Zitat Warren MA, Zhao Z, Koyama T, Bastarache JA, Shaver CM, Semler MW, Rice TW, Matthay MA, Calfee CS, Ware LB (2018) Severity scoring of lung oedema on the chest radiograph is associated with clinical outcomes in ARDS. Thorax 73:840–846CrossRef Warren MA, Zhao Z, Koyama T, Bastarache JA, Shaver CM, Semler MW, Rice TW, Matthay MA, Calfee CS, Ware LB (2018) Severity scoring of lung oedema on the chest radiograph is associated with clinical outcomes in ARDS. Thorax 73:840–846CrossRef
21.
Zurück zum Zitat Landesberg G, Levin PD, Gilon D, Goodman S, Georgieva M, Weissman C, Jaffe AS, Sprung CL, Barak V (2015) Myocardial dysfunction in severe sepsis and septic shock: no correlation with inflammatory cytokines in real-life clinical setting. Chest 148:93–102CrossRef Landesberg G, Levin PD, Gilon D, Goodman S, Georgieva M, Weissman C, Jaffe AS, Sprung CL, Barak V (2015) Myocardial dysfunction in severe sepsis and septic shock: no correlation with inflammatory cytokines in real-life clinical setting. Chest 148:93–102CrossRef
22.
Zurück zum Zitat Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX (2016) Toward smarter lumping and smarter splitting: rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med 194:147–155CrossRef Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX (2016) Toward smarter lumping and smarter splitting: rethinking strategies for sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med 194:147–155CrossRef
23.
Zurück zum Zitat Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, Rautanen A, Gordon AC, Garrard C, Hill AV, Hinds CJ, Knight JC (2016) Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med 4:259–271CrossRef Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, Rautanen A, Gordon AC, Garrard C, Hill AV, Hinds CJ, Knight JC (2016) Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med 4:259–271CrossRef
24.
Zurück zum Zitat Sweeney TE, Azad TD, Donato M, Haynes WA, Perumal TM, Henao R, Bermejo-Martin JF, Almansa R, Tamayo E, Howrylak JA, Choi A, Parnell GP, Tang B, Nichols M, Woods CW, Ginsburg GS, Kingsmore SF, Omberg L, Mangravite LM, Wong HR, Tsalik EL, Langley RJ, Khatri P (2018) Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters. Crit Care Med 46:915–925CrossRef Sweeney TE, Azad TD, Donato M, Haynes WA, Perumal TM, Henao R, Bermejo-Martin JF, Almansa R, Tamayo E, Howrylak JA, Choi A, Parnell GP, Tang B, Nichols M, Woods CW, Ginsburg GS, Kingsmore SF, Omberg L, Mangravite LM, Wong HR, Tsalik EL, Langley RJ, Khatri P (2018) Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters. Crit Care Med 46:915–925CrossRef
25.
Zurück zum Zitat Scicluna BP, van Vught LA, Zwinderman AH, Wiewel MA, Davenport EE, Burnham KL, Nurnberg P, Schultz MJ, Horn J, Cremer OL, Bonten MJ, Hinds CJ, Wong HR, Knight JC, van der Poll T, MARS consortium (2017) Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med 5:816–826CrossRef Scicluna BP, van Vught LA, Zwinderman AH, Wiewel MA, Davenport EE, Burnham KL, Nurnberg P, Schultz MJ, Horn J, Cremer OL, Bonten MJ, Hinds CJ, Wong HR, Knight JC, van der Poll T, MARS consortium (2017) Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med 5:816–826CrossRef
26.
Zurück zum Zitat Wong HR, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Willson DF, Freishtat RJ, Anas N, Meyer K, Checchia PA, Monaco M, Odom K, Shanley TP (2009) Identification of pediatric septic shock subclasses based on genome-wide expression profiling. BMC Med 7:34CrossRef Wong HR, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Willson DF, Freishtat RJ, Anas N, Meyer K, Checchia PA, Monaco M, Odom K, Shanley TP (2009) Identification of pediatric septic shock subclasses based on genome-wide expression profiling. BMC Med 7:34CrossRef
27.
Zurück zum Zitat Siempos II, Maniatis NA, Kopterides P, Magkou C, Glynos C, Roussos C, Armaganidis A (2010) Pretreatment with atorvastatin attenuates lung injury caused by high-stretch mechanical ventilation in an isolated rabbit lung model. Crit Care Med 38:1321–1328CrossRef Siempos II, Maniatis NA, Kopterides P, Magkou C, Glynos C, Roussos C, Armaganidis A (2010) Pretreatment with atorvastatin attenuates lung injury caused by high-stretch mechanical ventilation in an isolated rabbit lung model. Crit Care Med 38:1321–1328CrossRef
28.
Zurück zum Zitat Craig TR, Duffy MJ, Shyamsundar M, McDowell C, O’Kane CM, Elborn JS, McAuley DF (2011) A randomized clinical trial of hydroxymethylglutaryl-coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med 183:620–626CrossRef Craig TR, Duffy MJ, Shyamsundar M, McDowell C, O’Kane CM, Elborn JS, McAuley DF (2011) A randomized clinical trial of hydroxymethylglutaryl-coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med 183:620–626CrossRef
29.
Zurück zum Zitat Sahebkar A, Rathouska J, Simental-Mendia LE, Nachtigal P (2016) Statin therapy and plasma cortisol concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res 103:17–25CrossRef Sahebkar A, Rathouska J, Simental-Mendia LE, Nachtigal P (2016) Statin therapy and plasma cortisol concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol Res 103:17–25CrossRef
30.
Zurück zum Zitat Sahebkar A, Serban C, Ursoniu S, Mikhailidis DP, Undas A, Lip GY, Bittner V, Ray K, Watts GF, Hovingh GK, Rysz J, Kastelein JJ, Banach M, Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group (2016) The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials. Thromb Haemost 115:520–532CrossRef Sahebkar A, Serban C, Ursoniu S, Mikhailidis DP, Undas A, Lip GY, Bittner V, Ray K, Watts GF, Hovingh GK, Rysz J, Kastelein JJ, Banach M, Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group (2016) The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials. Thromb Haemost 115:520–532CrossRef
31.
Zurück zum Zitat Bonsu KO, Reidpath DD, Kadirvelu A (2015) Effects of statin treatment on inflammation and cardiac function in heart failure: an adjusted indirect comparison meta-analysis of randomized trials. Cardiovasc Ther 33:338–346CrossRef Bonsu KO, Reidpath DD, Kadirvelu A (2015) Effects of statin treatment on inflammation and cardiac function in heart failure: an adjusted indirect comparison meta-analysis of randomized trials. Cardiovasc Ther 33:338–346CrossRef
32.
Zurück zum Zitat Smith MEB, Lee NJ, Haney E, Carson S (2009) Drug class review: HMG-CoA reductase inhibitors (statins) and fixed-dose combination products containing a statin: final report update 5. Oregon Health & Science University, Portland Smith MEB, Lee NJ, Haney E, Carson S (2009) Drug class review: HMG-CoA reductase inhibitors (statins) and fixed-dose combination products containing a statin: final report update 5. Oregon Health & Science University, Portland
33.
Zurück zum Zitat Lee CC, Lee MG, Hsu TC, Porta L, Chang SS, Yo CH, Tsai KC, Lee M (2018) A population-based cohort study on the drug-specific effect of statins on sepsis outcome. Chest 153:805–815CrossRef Lee CC, Lee MG, Hsu TC, Porta L, Chang SS, Yo CH, Tsai KC, Lee M (2018) A population-based cohort study on the drug-specific effect of statins on sepsis outcome. Chest 153:805–815CrossRef
34.
Zurück zum Zitat Mansur A, Steinau M, Popov AF, Ghadimi M, Beissbarth T, Bauer M, Hinz J (2015) Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study. BMC Med 13:128CrossRef Mansur A, Steinau M, Popov AF, Ghadimi M, Beissbarth T, Bauer M, Hinz J (2015) Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study. BMC Med 13:128CrossRef
35.
Zurück zum Zitat Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL (2003) C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 123:2043–2049CrossRef Lobo SM, Lobo FR, Bota DP, Lopes-Ferreira F, Soliman HM, Melot C, Vincent JL (2003) C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 123:2043–2049CrossRef
36.
Zurück zum Zitat Castell JV, Gomez-Lechon MJ, David M, Fabra R, Trullenque R, Heinrich PC (1990) Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 12:1179–1186CrossRef Castell JV, Gomez-Lechon MJ, David M, Fabra R, Trullenque R, Heinrich PC (1990) Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6. Hepatology 12:1179–1186CrossRef
37.
Zurück zum Zitat Bajwa EK, Khan UA, Januzzi JL, Gong MN, Thompson BT, Christiani DC (2009) Plasma C-reactive protein levels are associated with improved outcome in ARDS. Chest 136:471–480CrossRef Bajwa EK, Khan UA, Januzzi JL, Gong MN, Thompson BT, Christiani DC (2009) Plasma C-reactive protein levels are associated with improved outcome in ARDS. Chest 136:471–480CrossRef
38.
Zurück zum Zitat Pierrakos C, Vincent JL (2010) Sepsis biomarkers: a review. Crit Care 14:R15CrossRef Pierrakos C, Vincent JL (2010) Sepsis biomarkers: a review. Crit Care 14:R15CrossRef
39.
Zurück zum Zitat Navarro SL, Kantor ED, Song X, Milne GL, Lampe JW, Kratz M, White E (2016) Factors associated with multiple biomarkers of systemic inflammation. Cancer Epidemiol Biomarkers Prev 25:521–531CrossRef Navarro SL, Kantor ED, Song X, Milne GL, Lampe JW, Kratz M, White E (2016) Factors associated with multiple biomarkers of systemic inflammation. Cancer Epidemiol Biomarkers Prev 25:521–531CrossRef
40.
Zurück zum Zitat Mackenzie I, Woodhouse J (2006) C-reactive protein concentrations during bacteraemia: a comparison between patients with and without liver dysfunction. Intensive Care Med 32:1344–1351CrossRef Mackenzie I, Woodhouse J (2006) C-reactive protein concentrations during bacteraemia: a comparison between patients with and without liver dysfunction. Intensive Care Med 32:1344–1351CrossRef
41.
Zurück zum Zitat Bos LD, Schouten LR, van Vught LA, Wiewel MA, Ong DSY, Cremer O, Artigas A, Martin-Loeches I, Hoogendijk AJ, van der Poll T, Horn J, Juffermans N, Calfee CS, Schultz MJ, Consortium M (2017) Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis. Thorax 72:876–883CrossRef Bos LD, Schouten LR, van Vught LA, Wiewel MA, Ong DSY, Cremer O, Artigas A, Martin-Loeches I, Hoogendijk AJ, van der Poll T, Horn J, Juffermans N, Calfee CS, Schultz MJ, Consortium M (2017) Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis. Thorax 72:876–883CrossRef
Metadaten
Titel
Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study
verfasst von
Pratik Sinha
Kevin L. Delucchi
B. Taylor Thompson
Daniel F. McAuley
Michael A. Matthay
Carolyn S. Calfee
for the NHLBI ARDS Network
Publikationsdatum
05.10.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 11/2018
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-018-5378-3

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