Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2021

01-12-2021 | Pneumonia | Research

Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS

Authors: Inès Bendib, Asma Beldi-Ferchiou, Frédéric Schlemmer, Mathieu Surenaud, Bernard Maitre, Anne Plonquet, Guillaume Carteaux, Keyvan Razazi, Veronique Godot, Sophie Hüe, Armand Mekontso Dessap, Nicolas de Prost

Published in: Critical Care | Issue 1/2021

Login to get access

Abstract

Background

Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes.

Methods

Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls.

Results

Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality.

Conclusions

IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.
Appendix
Available only for authorised users
Literature
1.
Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788.PubMed
2.
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. 2006;354:1671–84.
3.
Perkins GD, McAuley DF, Thickett DR, Gao F. The β-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial. Am J Respir Crit Care Med. 2006;173:281–7.PubMed
4.
McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder TJ, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371:1695–703.PubMed
5.
Ware LB, Koyama T, Billheimer DD, Wu W, Bernard GR, Thompson BT, et al. Prognostic and pathogenetic value of combining clinical and biochemical indices in patients with acute lung injury. Chest. 2010;137:288–96.PubMed
6.
Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014;2:611–20.PubMedPubMedCentral
7.
Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, et al. Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med. 2017;195:331–8.PubMedPubMedCentral
8.
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;5:283.PubMedPubMedCentral
9.
Donnelly SC, Strieter RM, Kunkel SL, Walz A, Robertson CR, Carter DC, et al. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet Lond Engl. 1993;341:643–7.
10.
van der Zee P, Rietdijk W, Somhorst P, Endeman H, Gommers D. A systematic review of biomarkers multivariately associated with acute respiratory distress syndrome development and mortality. Crit Care Lond Engl. 2020;24:243.
11.
12.
Monneret G, Lepape A, Venet F. A dynamic view of mHLA-DR expression in management of severe septic patients. Crit Care. 2011;15:198.PubMedPubMedCentral
13.
Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis. 2013;13:260–8.PubMedPubMedCentral
14.
Landelle C, Lepape A, Voirin N, Tognet E, Venet F, Bohé J, et al. Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock. Intensive Care Med. 2010;36:1859–66.PubMed
15.
Monneret G, Lepape A, Voirin N, Bohé J, Venet F, Debard A-L, et al. Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock. Intensive Care Med. 2006;32:1175–83.PubMed
16.
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13:862–74.PubMedPubMedCentral
17.
18.
Monaghan SF, Thakkar RK, Heffernan DS, Huang X, Chung C-S, Lomas-Neira J, et al. Mechanisms of indirect acute lung injury: a novel role for the co-inhibitory receptor, programmed death-1 (PD-1). Ann Surg. 2012;255:158.PubMedPubMedCentral
19.
Brahmamdam P, Inoue S, Unsinger J, Chang KC, McDunn JE, Hotchkiss RS. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol. 2010;88:233–40.PubMedPubMedCentral
20.
Guignant C, Lepape A, Huang X, Kherouf H, Denis L, Poitevin F, et al. Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients. Crit Care. 2011;15:R99.PubMedPubMedCentral
21.
Huang X, Venet F, Wang YL, Lepape A, Yuan Z, Chen Y, et al. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci. 2009;106:6303–8.PubMed
22.
Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306:2594–605.PubMedPubMedCentral
23.
Nierhaus A, Montag B, Timmler N, Frings DP, Gutensohn K, Jung R, et al. Reversal of immunoparalysis by recombinant human granulocyte-macrophage colony-stimulating factor in patients with severe sepsis. Intensive Care Med. 2003;29:646–51.PubMed
24.
Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, et al. GM-CSF to reverse sepsis-associated immunosuppression: a double-blind randomized placebo-controlled multicenter trial. Am J Respir Crit Care Med. 2009;180:640–8.PubMed
25.
Payen D, Faivre V, Miatello J, Leentjens J, Brumpt C, Tissières P, et al. Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression. A case series. BMC Infect Dis. 2019;19:931.PubMedPubMedCentral
26.
27.
Venet F, Lukaszewicz A-C, Payen D, Hotchkiss R, Monneret G. Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies. Curr Opin Immunol. 2013;25:477–83.PubMedPubMedCentral
28.
Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14:121–37.PubMed
29.
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;270:2957–63.PubMed
30.
Mercat A, Richard J-CM, Vielle B, Jaber S, Osman D, Diehl J-L, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA. 2008;299:646–55.PubMed
31.
Papazian L, Forel J-M, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107–16.PubMed
32.
Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. 2005;353:2683–95.PubMed
33.
Guérin C, Reignier J, Richard J-C, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368:2159–68.PubMed
34.
Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38:1573–82.PubMed
35.
Bouadma L, Mourvillier B, Deiler V, Le Corre B, Lolom I, Régnier B, et al. A multifaceted program to prevent ventilator-associated pneumonia: impact on compliance with preventive measures. Crit Care Med. 2010;38:789–96.PubMed
36.
Mekontso Dessap A, Katsahian S, Roche-Campo F, Varet H, Kouatchet A, Tomicic V, et al. Ventilator-associated pneumonia during weaning from mechanical ventilation: role of fluid management. Chest. 2014;146:58–65.PubMed
37.
Meyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, du Bois RM, et al. 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;185:1004–14.PubMed
38.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.PubMed
39.
Amato MBP, Meade MO, Slutsky AS, Brochard L, Costa ELV, Schoenfeld DA, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372:747–55.PubMed
40.
Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest. 1997;99:944–52.PubMedPubMedCentral
41.
Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, et al. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005;33:1–6 (discussion 230–2).PubMed
42.
Herold S, Hoegner K, Vadász I, Gessler T, Wilhelm J, Mayer K, et al. Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014;189:609–11.PubMed
43.
44.
Goto Y, Hogg JC, Whalen B, Shih C-H, Ishii H, van Eeden SF. Monocyte recruitment into the lungs in pneumococcal pneumonia. Am J Respir Cell Mol Biol. 2004;30:620–6.PubMed
45.
Zhang Y, Li J, Lou J, Zhou Y, Bo L, Zhu J, et al. Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients. Crit Care. 2011;15:R70.PubMedPubMedCentral
46.
47.
Erickson JJ, Gilchuk P, Hastings AK, Tollefson SJ, Johnson M, Downing MB, et al. Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest. 2012;122:2967–82.PubMedPubMedCentral
48.
Yu Y-RA, Hotten DF, Malakhau Y, Volker E, Ghio AJ, Noble PW, et al. Flow cytometric analysis of myeloid cells in human blood, bronchoalveolar lavage, and lung tissues. Am J Respir Cell Mol Biol. 2016;54:13–24.PubMedPubMedCentral
49.
Brittan M, Barr L, Morris AC, Duffin R, Rossi F, Johnston S, et al. A novel subpopulation of monocyte-like cells in the human lung after lipopolysaccharide inhalation. Eur Respir J. 2012;40:206–14.PubMed
50.
Dargaville PA, South M, Vervaart P, McDougall PN. Validity of markers of dilution in small volume lung lavage. Am J Respir Crit Care Med. 1999;160:778–84.PubMed
51.
Marcy TW, Merrill WW, Rankin JA, Reynolds HY. Limitations of using urea to quantify epithelial lining fluid recovered by bronchoalveolar lavage. Am Rev Respir Dis. 1987;135:1276–80.PubMed
Metadata
Title
Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS
Authors
Inès Bendib
Asma Beldi-Ferchiou
Frédéric Schlemmer
Mathieu Surenaud
Bernard Maitre
Anne Plonquet
Guillaume Carteaux
Keyvan Razazi
Veronique Godot
Sophie Hüe
Armand Mekontso Dessap
Nicolas de Prost
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2021
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-03427-y

Other articles of this Issue 1/2021

Critical Care 1/2021 Go to the issue

Research

Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

Research

Restricted visitation policies in acute care settings during the COVID-19 pandemic: a scoping review

Research

Helmet CPAP to treat hypoxic pneumonia outside the ICU: an observational study during the COVID-19 outbreak

Research

Patient discharge from intensive care: an updated scoping review to identify tools and practices to inform high-quality care

Research Letter

Psychological evaluation and support in COVID-19 critically ill patients: a feasibility study

Research

A systematic review and meta-analysis of enrollment into ARDS and sepsis trials published between 2009 and 2019 in major journals