Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients

ABSTRACT

Background

Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection.

Research design and methods

A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort.

Results

There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group.

Conclusions

Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.

KEYWORDS:

• Ventilator-associated pneumonia
• VAT
• tracheobronchitis
• sepsis
• critical illness

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conceptualization: I Martin-Loeches; Writing – original draft: I Martin-Loeches, G Sganzerla Martinez, JF Bermejo-Martin; Writing (review and editing): All authors. All authors read and approved the final manuscript.

Ethical approval and patient consent

The Institutional Review Board of all participating hospitals approved the study, and informed consent was obtained from the patient’s relatives.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14787210.2023.2256979.

Additional information

Funding

This work was supported by awards from ISCIII and Provost award TCD 2020-2021(IML) and the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 –170357), Research Nova Scotia (DK), Atlantic Genome/Genome Canada (DK), Li-Ka Shing Foundation (DK), and the Dalhousie Medical Research Foundation (DK).