Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies

Esther Wittermans; Philip A van der Zee; Hongchao Qi; Ewoudt M W van de Garde; Claudine A Blum; Mirjam Christ-Crain; Diederik Gommers; Jan C Grutters; G Paul Voorn; Willem Jan W Bos; Henrik Endeman

doi:10.1183/23120541.00489-2021

Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies

Esther Wittermans, Philip A van der Zee, Hongchao Qi, Ewoudt M W van de Garde, Claudine A Blum, Mirjam Christ-Crain, Diederik Gommers, Jan C Grutters, G Paul Voorn, Willem Jan W Bos, Henrik Endeman

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Latent class analysis (LCA) has identified subgroups with meaningful treatment implications in acute respiratory distress syndrome. We performed a secondary analysis of three studies to assess whether LCA can identify clinically distinct subgroups in community-acquired pneumonia (CAP) and whether the treatment effect of adjunctive corticosteroids differs between subgroups.

Methods: LCA was performed on baseline clinical and biomarker data from the Ovidius trial (n=304) and the Steroids in Pneumonia (STEP) trial (n=727), both randomised controlled trials investigating adjunctive corticosteroid treatment in CAP, and the observational TripleP cohort (n=201). Analyses were conducted independently in two cohorts (Ovidius-TripleP combined and the STEP trial). In both cohorts, differences in clinical outcomes and response to adjunctive corticosteroid treatment were examined between subgroups identified through LCA.

Results: A two-class model fitted both cohorts best. Class 2 patients had more signs of systemic inflammation compared to class 1. In both cohorts, length of stay was longer and in-hospital mortality rate was higher in class 2. In the Ovidius trial, corticosteroids reduced the median length of stay in class 2 (6.5 versus 9.5 days) but not in class 1 (p-value for interaction=0.02). In the STEP trial, there was no significant interaction for length of stay. We found no significant interaction between class assignment and adjunctive corticosteroid treatment for secondary outcomes.

Conclusions: In two independent cohorts, LCA identified two classes of CAP patients with different clinical characteristics and outcomes. Given the different response to adjunctive corticosteroids in the Ovidius trial, LCA might provide a useful basis to improve patient selection for future trials.

Original language	English
Article number	00489-2021
Pages (from-to)	1-11
Journal	ERJ Open Research
Volume	8
Issue number	1
DOIs	https://doi.org/10.1183/23120541.00489-2021
Publication status	Published - 1 Jan 2022

Bibliographical note

Funding Information:
Conflict of interest: E. Wittermans has nothing to disclose. P.A. van der Zee has nothing to disclose. H. Qi has nothing to disclose. E.M.W. van de Garde has nothing to disclose. C.A. Blum reports grants from the Helmut Horten Foundation, Switzerland, and Novo Nordisk, outside the submitted work. M. Christ-Crain has nothing to disclose. D. Gommers reports speaker fees and travel expenses from Drager and Maquet, personal fees and other support for a medical advisory board from 2009 to 2012 from GE Healthcare, and personal fees and other support for a medical advisory board from 2015 to 2018 from Novalung, outside the submitted work. J.C. Grutters has nothing to disclose. G.P. Voorn has nothing to disclose. W.J.W. Bos has nothing to disclose. H. Endeman has nothing to disclose.

Funding Information:
Support statement: This study was supported by the St Antonius Research Fund. Funding information for this article has been deposited with the Crossref Funder Registry.

Publisher Copyright:
© The authors 2022.

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Wittermans, E., van der Zee, P. A., Qi, H., van de Garde, E. M. W., Blum, C. A., Christ-Crain, M., Gommers, D., Grutters, J. C., Voorn, G. P., Bos, W. J. W., & Endeman, H. (2022). Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies. ERJ Open Research, 8(1), 1-11. Article 00489-2021. https://doi.org/10.1183/23120541.00489-2021

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title = "Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies",

abstract = "Background: Latent class analysis (LCA) has identified subgroups with meaningful treatment implications in acute respiratory distress syndrome. We performed a secondary analysis of three studies to assess whether LCA can identify clinically distinct subgroups in community-acquired pneumonia (CAP) and whether the treatment effect of adjunctive corticosteroids differs between subgroups.Methods: LCA was performed on baseline clinical and biomarker data from the Ovidius trial (n=304) and the Steroids in Pneumonia (STEP) trial (n=727), both randomised controlled trials investigating adjunctive corticosteroid treatment in CAP, and the observational TripleP cohort (n=201). Analyses were conducted independently in two cohorts (Ovidius-TripleP combined and the STEP trial). In both cohorts, differences in clinical outcomes and response to adjunctive corticosteroid treatment were examined between subgroups identified through LCA.Results: A two-class model fitted both cohorts best. Class 2 patients had more signs of systemic inflammation compared to class 1. In both cohorts, length of stay was longer and in-hospital mortality rate was higher in class 2. In the Ovidius trial, corticosteroids reduced the median length of stay in class 2 (6.5 versus 9.5 days) but not in class 1 (p-value for interaction=0.02). In the STEP trial, there was no significant interaction for length of stay. We found no significant interaction between class assignment and adjunctive corticosteroid treatment for secondary outcomes. Conclusions: In two independent cohorts, LCA identified two classes of CAP patients with different clinical characteristics and outcomes. Given the different response to adjunctive corticosteroids in the Ovidius trial, LCA might provide a useful basis to improve patient selection for future trials.",

author = "Esther Wittermans and \{van der Zee\}, \{Philip A\} and Hongchao Qi and \{van de Garde\}, \{Ewoudt M W\} and Blum, \{Claudine A\} and Mirjam Christ-Crain and Diederik Gommers and Grutters, \{Jan C\} and Voorn, \{G Paul\} and Bos, \{Willem Jan W\} and Henrik Endeman",

note = "Funding Information: Conflict of interest: E. Wittermans has nothing to disclose. P.A. van der Zee has nothing to disclose. H. Qi has nothing to disclose. E.M.W. van de Garde has nothing to disclose. C.A. Blum reports grants from the Helmut Horten Foundation, Switzerland, and Novo Nordisk, outside the submitted work. M. Christ-Crain has nothing to disclose. D. Gommers reports speaker fees and travel expenses from Drager and Maquet, personal fees and other support for a medical advisory board from 2009 to 2012 from GE Healthcare, and personal fees and other support for a medical advisory board from 2015 to 2018 from Novalung, outside the submitted work. J.C. Grutters has nothing to disclose. G.P. Voorn has nothing to disclose. W.J.W. Bos has nothing to disclose. H. Endeman has nothing to disclose. Funding Information: Support statement: This study was supported by the St Antonius Research Fund. Funding information for this article has been deposited with the Crossref Funder Registry. Publisher Copyright: {\textcopyright} The authors 2022.",

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doi = "10.1183/23120541.00489-2021",

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Wittermans, E, van der Zee, PA, Qi, H, van de Garde, EMW, Blum, CA, Christ-Crain, M, Gommers, D, Grutters, JC, Voorn, GP, Bos, WJW & Endeman, H 2022, 'Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies', ERJ Open Research, vol. 8, no. 1, 00489-2021, pp. 1-11. https://doi.org/10.1183/23120541.00489-2021

TY - JOUR

T1 - Community-acquired pneumonia subgroups and differential response to corticosteroids

T2 - a secondary analysis of controlled studies

AU - Wittermans, Esther

AU - van der Zee, Philip A

AU - Qi, Hongchao

AU - van de Garde, Ewoudt M W

AU - Blum, Claudine A

AU - Christ-Crain, Mirjam

AU - Gommers, Diederik

AU - Grutters, Jan C

AU - Voorn, G Paul

AU - Bos, Willem Jan W

AU - Endeman, Henrik

N1 - Funding Information: Conflict of interest: E. Wittermans has nothing to disclose. P.A. van der Zee has nothing to disclose. H. Qi has nothing to disclose. E.M.W. van de Garde has nothing to disclose. C.A. Blum reports grants from the Helmut Horten Foundation, Switzerland, and Novo Nordisk, outside the submitted work. M. Christ-Crain has nothing to disclose. D. Gommers reports speaker fees and travel expenses from Drager and Maquet, personal fees and other support for a medical advisory board from 2009 to 2012 from GE Healthcare, and personal fees and other support for a medical advisory board from 2015 to 2018 from Novalung, outside the submitted work. J.C. Grutters has nothing to disclose. G.P. Voorn has nothing to disclose. W.J.W. Bos has nothing to disclose. H. Endeman has nothing to disclose. Funding Information: Support statement: This study was supported by the St Antonius Research Fund. Funding information for this article has been deposited with the Crossref Funder Registry. Publisher Copyright: © The authors 2022.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Background: Latent class analysis (LCA) has identified subgroups with meaningful treatment implications in acute respiratory distress syndrome. We performed a secondary analysis of three studies to assess whether LCA can identify clinically distinct subgroups in community-acquired pneumonia (CAP) and whether the treatment effect of adjunctive corticosteroids differs between subgroups.Methods: LCA was performed on baseline clinical and biomarker data from the Ovidius trial (n=304) and the Steroids in Pneumonia (STEP) trial (n=727), both randomised controlled trials investigating adjunctive corticosteroid treatment in CAP, and the observational TripleP cohort (n=201). Analyses were conducted independently in two cohorts (Ovidius-TripleP combined and the STEP trial). In both cohorts, differences in clinical outcomes and response to adjunctive corticosteroid treatment were examined between subgroups identified through LCA.Results: A two-class model fitted both cohorts best. Class 2 patients had more signs of systemic inflammation compared to class 1. In both cohorts, length of stay was longer and in-hospital mortality rate was higher in class 2. In the Ovidius trial, corticosteroids reduced the median length of stay in class 2 (6.5 versus 9.5 days) but not in class 1 (p-value for interaction=0.02). In the STEP trial, there was no significant interaction for length of stay. We found no significant interaction between class assignment and adjunctive corticosteroid treatment for secondary outcomes. Conclusions: In two independent cohorts, LCA identified two classes of CAP patients with different clinical characteristics and outcomes. Given the different response to adjunctive corticosteroids in the Ovidius trial, LCA might provide a useful basis to improve patient selection for future trials.

AB - Background: Latent class analysis (LCA) has identified subgroups with meaningful treatment implications in acute respiratory distress syndrome. We performed a secondary analysis of three studies to assess whether LCA can identify clinically distinct subgroups in community-acquired pneumonia (CAP) and whether the treatment effect of adjunctive corticosteroids differs between subgroups.Methods: LCA was performed on baseline clinical and biomarker data from the Ovidius trial (n=304) and the Steroids in Pneumonia (STEP) trial (n=727), both randomised controlled trials investigating adjunctive corticosteroid treatment in CAP, and the observational TripleP cohort (n=201). Analyses were conducted independently in two cohorts (Ovidius-TripleP combined and the STEP trial). In both cohorts, differences in clinical outcomes and response to adjunctive corticosteroid treatment were examined between subgroups identified through LCA.Results: A two-class model fitted both cohorts best. Class 2 patients had more signs of systemic inflammation compared to class 1. In both cohorts, length of stay was longer and in-hospital mortality rate was higher in class 2. In the Ovidius trial, corticosteroids reduced the median length of stay in class 2 (6.5 versus 9.5 days) but not in class 1 (p-value for interaction=0.02). In the STEP trial, there was no significant interaction for length of stay. We found no significant interaction between class assignment and adjunctive corticosteroid treatment for secondary outcomes. Conclusions: In two independent cohorts, LCA identified two classes of CAP patients with different clinical characteristics and outcomes. Given the different response to adjunctive corticosteroids in the Ovidius trial, LCA might provide a useful basis to improve patient selection for future trials.

UR - https://www.scopus.com/pages/publications/85127676052

U2 - 10.1183/23120541.00489-2021

DO - 10.1183/23120541.00489-2021

M3 - Article

C2 - 35036417

SN - 2312-0541

VL - 8

SP - 1

EP - 11

JO - ERJ Open Research

JF - ERJ Open Research

IS - 1

M1 - 00489-2021

ER -

Community-acquired pneumonia subgroups and differential response to corticosteroids: a secondary analysis of controlled studies

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