Persistent alveolar inflammatory response in critically ill patients with COVID-19 is associated with mortality

IntroductionPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We...

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Vydáno v:Thorax Ročník 78; číslo 9; s. 912 - 921
Hlavní autoři: de Brabander, Justin, Boers, Leonoor S, Kullberg, Robert F J, Zhang, Shiqi, Nossent, Esther J, Heunks, Leo M A, Vlaar, Alexander P J, Bonta, Peter I, Schultz, Marcus J, van der Poll, Tom, Duitman, JanWillem, Nossent, E J, Duitman, J W, Saris, A, de Vries, H, Meijboom, L J, Bos, L D J, Reijnders, T D Y, Bontkes, H, Vlaar, A P J, Wiersinga, W J, Lutter, R, van der Poll, T, Bogaard, H J, Heunks, L, Algera, A G, Baarle, F, Beudel, M, Bomers, M, Bonta, P, Bos, L D, Botta, M, de Brabander, J, de Bree, G, de Bruin, S, Bugiani, M, Bulle, E, Buis, D T P, Chouchane, O, Cloherty, A, Dijkstra, M, Dongelmans, D A, Dujardin, R W G, Elbers, P, Fleuren, L, Geerlings, S, Geijtenbeek, T, Girbes, A, Goorhuis, B, Harris, V, Hemke, R, Hermans, S M, Horn, J, de Jong, M D, Koning, R, Lim, E H T, van Mourik, N, Nellen, J, Paulus, F, Peters, E, Pina-Fuentes, D A I, Preckel, B, Prins, J M, Raasveld, J, Reijnders, T, J de Rotte, M C F, Schinkel, M, Schultz, M J, Schrauwen, F A P, Schuurman, A, Schuurmans, J, Sigaloff, K, Slim, M A, Smeele, P, Smit, M, Stijnis, C S, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A M, Tuinman, P R, van der Valk, M, Volleman, C, van Vugt, M, Wouters, D, Zwinderman, A H, Brouwer, M C, van de Beek, D, de Beer, F M, Claushuis, T A, Glas, G J, Hoogendijk, A J, van Hooijdonk, R T, Huson, M A, Juffermans, N P, Scicluna, B, Schouten, L R, van der Sluijs, K F, Wiewel, M A, Witteveen, E
Médium: Journal Article
Jazyk:angličtina
Vydáno: England BMJ Publishing Group Ltd and British Thoracic Society 01.09.2023
BMJ Publishing Group LTD
Témata:
ARDS
Biomarkers
Body mass index
Bronchoscopy
Coronaviruses
COVID-19
critical care
Drug dosages
Hypotheses
innate immunity
Intubation
Laboratories
Mortality
Patients
Plasma
Proteins
Respiratory distress syndrome
Respiratory failure
Respiratory infection
Steroids
Ventilators
United States > US
California
COVID-19
critical care
innate immunity
ARDS
respiratory infection
bronchoscopy
ISSN:0040-6376, 1468-3296, 1468-3296
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Abstract IntroductionPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response.MethodsIn this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar–plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients.Results284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels.ConclusionsPatients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.
AbstractList IntroductionPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response.MethodsIn this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar–plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients.Results284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels.ConclusionsPatients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.
Patients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response.INTRODUCTIONPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response.In this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar-plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients.METHODSIn this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar-plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients.284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels.RESULTS284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels.Patients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.CONCLUSIONSPatients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.
Patients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response. In this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar-plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients. 284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels. Patients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.
Author Pina-Fuentes, D A I
Vlaar, Alexander P J
Bontkes, H
Vught, L A
Nossent, E J
Straat, M
Nellen, J
Lutter, R
de Brabander, J
Bos, L D
Huson, M A
Hamann, J
Claushuis, T A
Elbers, P
Koning, R
Witteveen, E
Schultz, Marcus J
de Jong, M D
Reijnders, T D Y
Heunks, L
Algera, A G
Juffermans, N P
Schouten, L R
Schultz, M J
Schuurman, A
Wouters, D
Reijnders, T
Hoogendijk, A J
de Brabander, Justin
Fleuren, L
de Vries, H
Boers, Leonoor S
Teunissen, C
Dongelmans, D A
Schuurmans, J
Lagrand, W A
Blok, S G
Hugenholtz, F
Cloherty, A
Zhang, Shiqi
Paulus, F
Sigaloff, K
Saris, A
Wieske, L
Tuinman, P R
Preckel, B
Garcia Vallejo, J J
Schuurman, A R
Meijboom, L J
Hollmann, M
Grobusch, M P
Raasveld, J
Bos, L D J
Wiewel, M A
Horn, J
Lim, E H T
Stilma, W
Beudel, M
Bogaard, H J
van Vugt, M
van Hooijdonk, R T
van der Sluijs, K F
Dijkstra, M
van der Poll, T
Peters, E
Buis, D T P
Nossent, Esther J
Prins, J M
Stijnis, C S
Kullberg, Robert F J
Bonta, Peter I
van der Valk, M
Tsonas, A M
van Mourik, N
Duitman, J W
Olie, S
Geijtenbeek, T
Baarle, F
Girbes, A
Smeele, P
Smit, M
Chouchane, O
Appelman, B
Heun
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/37142421$$D View this record in MEDLINE/PubMed
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Issue 9
Keywords COVID-19
critical care
innate immunity
ARDS
respiratory infection
bronchoscopy
Language English
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PublicationDate 2023-09-01
PublicationDateYYYYMMDD 2023-09-01
PublicationDate_xml – month: 09
  year: 2023
  text: 2023-09-01
  day: 01
PublicationDecade 2020
PublicationPlace England
PublicationPlace_xml – name: England
– name: London
PublicationTitle Thorax
PublicationTitleAbbrev Thorax
PublicationTitleAlternate Thorax
PublicationYear 2023
Publisher BMJ Publishing Group Ltd and British Thoracic Society
BMJ Publishing Group LTD
Publisher_xml – name: BMJ Publishing Group Ltd and British Thoracic Society
– name: BMJ Publishing Group LTD
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Snippet IntroductionPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments...
Patients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are...
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SubjectTerms ARDS
Biomarkers
Body mass index
Bronchoscopy
Coronaviruses
COVID-19
critical care
Drug dosages
Hypotheses
innate immunity
Intubation
Laboratories
Mortality
Patients
Plasma
Proteins
Respiratory distress syndrome
Respiratory failure
Respiratory infection
Steroids
Ventilators
Title Persistent alveolar inflammatory response in critically ill patients with COVID-19 is associated with mortality
URI https://thorax.bmj.com/content/early/2023/05/04/thorax-2023-219989.full
https://www.ncbi.nlm.nih.gov/pubmed/37142421
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