TY - JOUR
T1 - Plasma protein biomarkers reflective of the host response in patients developing Intensive Care Unit-acquired pneumonia
AU - van Engelen, Tjitske S R
AU - Reijnders, Tom D Y
AU - Paling, Fleur P
AU - Bonten, Marc J M
AU - Timbermont, Leen
AU - Malhotra-Kumar, Surbhi
AU - Kluytmans, Jan A J W
AU - Peters-Sengers, Hessel
AU - van der Poll, Tom
AU - Cremer, OL
N1 - Funding Information:
The authors acknowledge all member of the ASPIRE-ICU Study Team (Additional file 1) for the participation in data collection and especially acknowledge Rene Lutter, Tamara Dekker, and Barbara Dierdorp (Department of Experimental Immunology and Respiratory Medicine, Amsterdam University Medical Centers, University of Amsterdam), and Christine Lammers (University of Antwerp). The ASPIRE-ICU study team includes Martin Wolkewitz, PhD (Institute of Medical Biometry and Statistics, University Medical Center Freiburg, Freiburg, Germany), Omar Ali, PhD (Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, Maryland), Alexey Ruzin, PhD (Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, Maryland), Leen Timbermont, PhD (University of Antwerp, Antwerp, Belgium), Christine Lammens, BSc (University of Antwerp, Antwerp, Belgium), Sebastiaan Hullegie, MD, PhD (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands), Darren Troeman, MD (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands), Denise van Hout, MD (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands), Daniël Prins, MSc (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands), Rubana Kalyani, MSc (Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, Maryland), Mark Eickhoff, MSc (Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, Maryland), Kathryn Shoemaker, MSc (Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, Maryland), Tuba Vilken, PhD (University of Antwerp, Antwerp, Belgium), Jelle Vlaeminck, MSc (University of Antwerp, Antwerp, Belgium), Jasmine Coppens, PhD (University of Antwerp, Antwerp, Belgium), Thomas van der Schalk, MSc (University of Antwerp, Antwerp, Belgium), Basil Britto Xavier, PhD (University of Antwerp, Antwerp, Belgium), Evelina Odisseeva, PhD (Military Medical Academy, Sofia, Bulgaria), Rossitza Vatcheva, PhD (University Hospital Queen Joanna, Sofia, Bulgaria), Michal Drab, MD, PhD (Hospital Kyjov, Kyjov, Czech Republic), Jaromir Vajter,MD, PhD (Motol University Hospital), Kadri Tamme, MD, PhD (Tartu University Hospital, Tartu, Estonia), Muriel Fartoukh, MD, PhD (Hospital Tenon Ap-Hp, Paris, France), Alain LePape,MD, PhD (Lyon Sud Hospital Center, Lyon, France), Mickael Landais, MD, PhD (Centre Hospitalier du Mans, Le Mans, France), Gaetan Plantefève, MD, PhD (Centre Hospitalier Victor Dupouy, Argenteuil, France), Evelina Tacconelli,MD, PhD (Universitätsklinikum Tübingen, Tübingen, Germany), Achim Kaasch,MD, PhD (Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Dusseldorf, Germany), Róbert Jurkinya, MD, PhD (Josa Andras Hospital, Ny.regyh.za, Hungary), Iványi Zsolt, MD, PhD (Semmelweis University, Budapest, Hungary), Miranda van Rijen, MD, PhD (Amphia Hospital, Breda, the Netherlands), Olaf Cremer, MD, PhD (University Medical Center Utrecht, Utrecht, the Netherlands), Biljana Carevic, MD (Clinical Center of Serbia, Belgrade, Serbia), Jasna Jevdjić, MD, PhD (Clinical Center Kragujevac, Kragujevac, Serbia), Dolores Escudero, MD, PhD (Hospital Universitario Central de Asturias, Oviedo, Spain), Miguel Sanchez Garcia, MD, PhD (Hospital Clínico San Carlos, Madrid, Spain), Cristina Prat-Aymerich, MD, PhD (Hospital Universitario Germans Trias i Pujol, Badalona, Spain), Borja Suberviola-Cañas, MD, PhD (Hospital Universitario Marqués de Valdecilla, Santander, Spain), Angel Arenzana-Seisdedos MD, (Hospital Universitario Virgen Macarena, Sevilla, Spain), Hürrem Bodur, MD, PhD (Ankara Numune Training and Research Hospital, Ankara, Turkey), Cenk Kirakli, MD, PhD (Dr Suat Seren Chest Diseases Hospital, Izmir, Turkey), Ilkay Bozkurt, MD, PhD (University Hospital Ondokuz Mayis, Samsun, Turkey), and Sandra Long, MD, PhD (Royal Blackburn Hospital, Blackburn, United Kingdom).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/7/6
Y1 - 2023/7/6
N2 - Background: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls). Methods: We performed a nested case–control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 h enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and—in cases—on the day of pneumonia diagnosis. Results: Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n = 632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrollment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly (< 5 days, n = 105) or late (> 10 days, n = 68) after ICU admission. Conclusions: Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses. Trial registration: ClinicalTrials.gov Identifier: NCT02413242, posted April 9th, 2015. Graphical abstract: [Figure not available: see fulltext.]
AB - Background: Immune suppression has been implicated in the occurrence of pneumonia in critically ill patients. We tested the hypothesis that Intensive Care Unit (ICU)-acquired pneumonia is associated with broad host immune aberrations in the trajectory to pneumonia, encompassing inflammatory, endothelial and coagulation responses. We compared plasma protein biomarkers reflecting the systemic host response in critically ill patients who acquire a new pneumonia (cases) with those who do not (controls). Methods: We performed a nested case–control study in patients undergoing mechanical ventilation at ICU admission with an expected stay of at least 48 h enrolled in 30 hospitals in 11 European countries. Nineteen host response biomarkers reflective of key pathophysiological domains were measured in plasma obtained on study inclusion and day 7, and—in cases—on the day of pneumonia diagnosis. Results: Of 1997 patients, 316 developed pneumonia (15.8%) and 1681 did not (84.2%). Plasma protein biomarker analyses, performed in cases and a randomly selected subgroup of controls (1:2 ratio to cases, n = 632), demonstrated considerable variation across time points and patient groups. Yet, cases showed biomarker concentrations suggestive of enhanced inflammation and a more disturbed endothelial barrier function, both at study enrollment (median 2 days after ICU admission) and in the path to pneumonia diagnosis (median 5 days after ICU admission). Baseline host response biomarker aberrations were most profound in patients who developed pneumonia either shortly (< 5 days, n = 105) or late (> 10 days, n = 68) after ICU admission. Conclusions: Critically ill patients who develop an ICU-acquired pneumonia, compared with those who do not, display alterations in plasma protein biomarker concentrations indicative of stronger proinflammatory, procoagulant and (injurious) endothelial cell responses. Trial registration: ClinicalTrials.gov Identifier: NCT02413242, posted April 9th, 2015. Graphical abstract: [Figure not available: see fulltext.]
KW - Biomarkers
KW - Critical care
KW - Respiratory tract infections
UR - http://www.scopus.com/inward/record.url?scp=85164255296&partnerID=8YFLogxK
U2 - 10.1186/s13054-023-04536-0
DO - 10.1186/s13054-023-04536-0
M3 - Article
C2 - 37415223
SN - 1466-609X
VL - 27
JO - Critical care (London, England)
JF - Critical care (London, England)
IS - 1
M1 - 269
ER -