Hospital-Acquired Pneumonia After Lung Resection Surgery Is Associated With Characteristic Cytokine Gene Expression

White, Mary; Martín‐Loeches, Ignacio; Lawless, Matthew W.; O'Dwyer, Michael J; Doherty, Derek G.; Young, Vincent; Kelleher, Dermot; McManus, Ross; Ryan, Thomas M.

doi:10.1378/chest.10-0016

Cited by 34 publications

(24 citation statements)

References 31 publications

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“…Again this is unsurprising as the maintenance of adequate Major Histocompatibility Complex (MHC) class ΙΙ molecules such as HLA-DR on the surface of antigen presenting cells is crucial to maintain immune competence. Others have proposed genomic signatures where higher ratios of antiinflammatory to pro-inflammatory cytokines correlate with postoperative infection [14]. What remains elusive is the mechanism whereby alarmin release and the subsequent enzymatic cascades lead to an immunosuppressed phenotype and the survival advantage, if any, of this trait.…”

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confidence: 99%

The perioperative immune response

O’Dwyer

Owen

Torrance

2015

Current Opinion in Critical Care

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Purpose of ReviewA host of immune modulators are now available in clinical practice. The perioperative period is characterised by profound alterations in host immunity, which can result in poor outcomes, which include infection, cancer recurrence and organ failure. Manipulation of the peri-operative immune response has the potential to improve outcomes. A complete understanding of the mechanisms and clinical consequences of altered immune function in this setting is therefore imperative. Recent findingsRecent in vivo data has emerged which furthers our understanding of the interaction between tissue damage, immune modulation and clinical outcomes by utilising novel laboratory techniques capable of monitoring single cell immune signatures. Traditional gene expression assays have continued to demonstrate their utility and have been instrumental in defining the host response to perioperative allogeneic blood transfusion. These mechanistic studies are complemented by large clinical studies describing associations between anaesthetic modalities and immune-related outcomes. SummaryLaboratory techniques are now available that can monitor the perioperative immune response and could be further developed to introduce personalised care pathways. Consideration must also be given to anaesthesia techniques and perioperative treatments that, whilst not immediately harmful, may be associated with poor outcomes temporally distant from the treatment, secondary to induced immunosuppression.3

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confidence: 99%

The perioperative immune response

O’Dwyer

Owen

Torrance

2015

Current Opinion in Critical Care

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“…The genes selected as candidates in this study are well described as surrogate measures of the specific immune pathways outlined in Table 1 [10,11,16]. Furthermore, the construction of a ratio of gene expression that incorporates the prototypical proinflammatory cytokine, TNFα, and the archetypal anti-inflammatory cytokine, IL-10, permits the concurrent assessment of both major facets of the immune response and has previously been utilised to predict postoperative outcome [17].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the packed red cells transfused in the study reported here were universally leukodepleted. Furthermore, the use of qRT-PCR in this study to assay gene expression allows for a validated ultrasensitive technique to assess immune pathways in the in vivo state [8][9][10][11]. The results we present suggest that the immunosuppression observed following perioperative transfusion may not be solely dependent on the presence of allogeneic leukocytes in the transfused blood.…”

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confidence: 81%

“…It has been repeatedly demonstrated that messenger RNA (mRNA), assayed using real-time polymerase chain reaction (RT-PCR), can be used to accurately quantify patterns of gene expression [8][9][10]. Furthermore, careful selection of key regulatory and effector cytokines in conjunction with transcription factors specific to T cell subtypes allow inferences to be made as to the activity of specific inflammatory pathways related to T-helper (T h ) cell development [11].…”

Section: Introductionmentioning

confidence: 99%

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Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study

et al. 2014

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Introduction: Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications. Methods: Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria.

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“…There are several factors which may or may not be preventable. Whilst some non-modifiable factors that are present are related to the host, and therefore the immune response may be important in generating an initial predisposition for the occurrence and subsequent outcome of infection [4], some other factors can by modified by medical intervention [5]. Bronchial bacterial colonization has been widely investigated in patients with chronic lung disease and, following this hypothesis, Ioanas et al [6] performed bilateral protected specimen brush and lung tissue biopsy during surgical procedures on patients with resectable lung cancer and found that almost half of them presented with bronchial colonization with at least one potential pathogenic micro-organism.…”

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confidence: 99%