Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia

James McCauley Walter*, Ziyou Ren, Tyrone Yacoub, Paul Andrew Reyfman, Raj D. Shah, Hiam Abdala-Valencia, Kiwon Nam, Vince K. Morgan, Kishore R. Anekalla, Nikita Joshi, Alexandra C. McQuattie-Pimentel, Ching I. Chen, Monica Chi, Seung Hye Han, Francisco J. Gonzalez-Gonzalez, Saul Soberanes, Raul P. Aillon, Satoshi Watanabe, Kinola J.N. Williams, Ziyan Lu & 13 others Joseph Paonessa, Peter Hountras, Madonna Breganio, Nicole Borkowski, Helen K. Donnelly, Jonathan P. Allen, Luis A N Amaral, Ankit Bharat, Alexander Misharin, Neda Bagheri, Alan R Hauser, GR Scott Budinger, Richard G Wunderink

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.

Original languageEnglish (US)
Pages (from-to)1225-1237
Number of pages13
JournalAmerican journal of respiratory and critical care medicine
Volume199
Issue number10
DOIs
StatePublished - May 15 2019

Fingerprint

Bacterial Pneumonia
Pneumonia
Macrophages
Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Transcriptome
Critical Illness
Infection
Response Elements
Pseudomonas aeruginosa
Neutrophils
RNA

Keywords

  • Alveolar macrophages
  • Bacterial pneumonia
  • Host response
  • RNA-Seq

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Walter, James McCauley ; Ren, Ziyou ; Yacoub, Tyrone ; Reyfman, Paul Andrew ; Shah, Raj D. ; Abdala-Valencia, Hiam ; Nam, Kiwon ; Morgan, Vince K. ; Anekalla, Kishore R. ; Joshi, Nikita ; McQuattie-Pimentel, Alexandra C. ; Chen, Ching I. ; Chi, Monica ; Han, Seung Hye ; Gonzalez-Gonzalez, Francisco J. ; Soberanes, Saul ; Aillon, Raul P. ; Watanabe, Satoshi ; Williams, Kinola J.N. ; Lu, Ziyan ; Paonessa, Joseph ; Hountras, Peter ; Breganio, Madonna ; Borkowski, Nicole ; Donnelly, Helen K. ; Allen, Jonathan P. ; Amaral, Luis A N ; Bharat, Ankit ; Misharin, Alexander ; Bagheri, Neda ; Hauser, Alan R ; Budinger, GR Scott ; Wunderink, Richard G. / Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia. In: American journal of respiratory and critical care medicine. 2019 ; Vol. 199, No. 10. pp. 1225-1237.
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title = "Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia",
abstract = "Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50{\%} had a negative predictive value of greater than 90{\%} for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.",
keywords = "Alveolar macrophages, Bacterial pneumonia, Host response, RNA-Seq",
author = "Walter, {James McCauley} and Ziyou Ren and Tyrone Yacoub and Reyfman, {Paul Andrew} and Shah, {Raj D.} and Hiam Abdala-Valencia and Kiwon Nam and Morgan, {Vince K.} and Anekalla, {Kishore R.} and Nikita Joshi and McQuattie-Pimentel, {Alexandra C.} and Chen, {Ching I.} and Monica Chi and Han, {Seung Hye} and Gonzalez-Gonzalez, {Francisco J.} and Saul Soberanes and Aillon, {Raul P.} and Satoshi Watanabe and Williams, {Kinola J.N.} and Ziyan Lu and Joseph Paonessa and Peter Hountras and Madonna Breganio and Nicole Borkowski and Donnelly, {Helen K.} and Allen, {Jonathan P.} and Amaral, {Luis A N} and Ankit Bharat and Alexander Misharin and Neda Bagheri and Hauser, {Alan R} and Budinger, {GR Scott} and Wunderink, {Richard G}",
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Walter, JM, Ren, Z, Yacoub, T, Reyfman, PA, Shah, RD, Abdala-Valencia, H, Nam, K, Morgan, VK, Anekalla, KR, Joshi, N, McQuattie-Pimentel, AC, Chen, CI, Chi, M, Han, SH, Gonzalez-Gonzalez, FJ, Soberanes, S, Aillon, RP, Watanabe, S, Williams, KJN, Lu, Z, Paonessa, J, Hountras, P, Breganio, M, Borkowski, N, Donnelly, HK, Allen, JP, Amaral, LAN, Bharat, A, Misharin, A, Bagheri, N, Hauser, AR, Budinger, GRS & Wunderink, RG 2019, 'Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia', American journal of respiratory and critical care medicine, vol. 199, no. 10, pp. 1225-1237. https://doi.org/10.1164/rccm.201804-0650OC

Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia. / Walter, James McCauley; Ren, Ziyou; Yacoub, Tyrone; Reyfman, Paul Andrew; Shah, Raj D.; Abdala-Valencia, Hiam; Nam, Kiwon; Morgan, Vince K.; Anekalla, Kishore R.; Joshi, Nikita; McQuattie-Pimentel, Alexandra C.; Chen, Ching I.; Chi, Monica; Han, Seung Hye; Gonzalez-Gonzalez, Francisco J.; Soberanes, Saul; Aillon, Raul P.; Watanabe, Satoshi; Williams, Kinola J.N.; Lu, Ziyan; Paonessa, Joseph; Hountras, Peter; Breganio, Madonna; Borkowski, Nicole; Donnelly, Helen K.; Allen, Jonathan P.; Amaral, Luis A N; Bharat, Ankit; Misharin, Alexander; Bagheri, Neda; Hauser, Alan R; Budinger, GR Scott; Wunderink, Richard G.

In: American journal of respiratory and critical care medicine, Vol. 199, No. 10, 15.05.2019, p. 1225-1237.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Multidimensional assessment of the host response in mechanically ventilated patients with suspected pneumonia

AU - Walter, James McCauley

AU - Ren, Ziyou

AU - Yacoub, Tyrone

AU - Reyfman, Paul Andrew

AU - Shah, Raj D.

AU - Abdala-Valencia, Hiam

AU - Nam, Kiwon

AU - Morgan, Vince K.

AU - Anekalla, Kishore R.

AU - Joshi, Nikita

AU - McQuattie-Pimentel, Alexandra C.

AU - Chen, Ching I.

AU - Chi, Monica

AU - Han, Seung Hye

AU - Gonzalez-Gonzalez, Francisco J.

AU - Soberanes, Saul

AU - Aillon, Raul P.

AU - Watanabe, Satoshi

AU - Williams, Kinola J.N.

AU - Lu, Ziyan

AU - Paonessa, Joseph

AU - Hountras, Peter

AU - Breganio, Madonna

AU - Borkowski, Nicole

AU - Donnelly, Helen K.

AU - Allen, Jonathan P.

AU - Amaral, Luis A N

AU - Bharat, Ankit

AU - Misharin, Alexander

AU - Bagheri, Neda

AU - Hauser, Alan R

AU - Budinger, GR Scott

AU - Wunderink, Richard G

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.

AB - Rationale: The identification of informative elements of the host response to infection may improve the diagnosis and management of bacterial pneumonia. Objectives: To determine whether the absence of alveolar neutrophilia can exclude bacterial pneumonia in critically ill patients with suspected infection and to test whether signatures of bacterial pneumonia can be identified in the alveolar macrophage transcriptome. Methods: We determined the test characteristics of alveolar neutrophilia for the diagnosis of bacterial pneumonia in three cohorts of mechanically ventilated patients. In one cohort, we also isolated macrophages from alveolar lavage fluid and used the transcriptome to identify signatures of bacterial pneumonia. Finally, we developed a humanized mouse model of Pseudomonas aeruginosa pneumonia to determine if pathogen-specific signatures can be identified in human alveolar macrophages. Measurements and Main Results: An alveolar neutrophil percentage less than 50% had a negative predictive value of greater than 90% for bacterial pneumonia in both the retrospective (n = 851) and validation cohorts (n = 76 and n = 79). A transcriptional signature of bacterial pneumonia was present in both resident and recruited macrophages. Gene signatures from both cell types identified patients with bacterial pneumonia with test characteristics similar to alveolar neutrophilia. Conclusions: The absence of alveolar neutrophilia has a high negative predictive value for bacterial pneumonia in critically ill patients with suspected infection. Macrophages can be isolated from alveolar lavage fluid obtained during routine care and used for RNA-Seq analysis. This novel approach may facilitate a longitudinal and multidimensional assessment of the host response to bacterial pneumonia.

KW - Alveolar macrophages

KW - Bacterial pneumonia

KW - Host response

KW - RNA-Seq

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JF - American Journal of Respiratory and Critical Care Medicine

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