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 language | English (US) |
|---|---|
| Pages (from-to) | 1225-1237 |
| Number of pages | 13 |
| Journal | American journal of respiratory and critical care medicine |
| Volume | 199 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2019 |
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Keywords
- Alveolar macrophages
- Bacterial pneumonia
- Host response
- RNA-Seq
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
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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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=85065848104&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065848104&partnerID=8YFLogxK
U2 - 10.1164/rccm.201804-0650OC
DO - 10.1164/rccm.201804-0650OC
M3 - Article
VL - 199
SP - 1225
EP - 1237
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 10
ER -