Sepsis is a pressing healthcare problem that presents a very real threat to human health around the world, with some estimates suggesting it kills 5,000,000 people annually.
Sepsis occurs as the result of an extreme immune response generated when the body is fighting an infection. This causes inflammation and, if not treated quickly, eventually leads to organ failure and death. Part of the solution to this challenge is increasing the speed with which patients suspected of entering sepsis can receive treatment in hospital emergency rooms.
Aiming to help physicians do just that, a new diagnostic test developed by a team of researchers — including UBC professor of microbiology and immunology, Bob Hancock — promises to dramatically reduce the speed and increase the accuracy of sepsis diagnoses.
The early stages of sepsis are triggered by an infection, which leads to an aggressive immune response known as a “cytokine storm.” Cytokines are signalling proteins that help to regulate immune function and during a cytokine storm, they cause extreme inflammation in an attempt to attack the infection.
After several days, however, cytokines are released that suppress inflammation — a sign of the immune system beginning to stop functioning to combat the infection. This greatly increases the risk of patient mortality.
It was this transition point from cytokine storm to immune failure that initially interested Hancock and his team, who hypothesized that the unresponsiveness of the immune system was the result of cellular reprogramming.
They found that there were indeed changes occurring in cells called monocytes, which were manifested in a set of gene expressions that became the focus of their study. After conducting a meta-analysis, Hancock and his team found that these gene expressions were actually emerging up to three days before patients would begin to move from cytokine storm to immune shutdown.
Since the gene expression signatures preceded the beginning of the immune system's failure by several days, they were a logical choice for a biomarker to use as a new way to diagnose sepsis.
Current diagnostic techniques involve tracking changes in blood pressure, respiratory rate and level of consciousness to indicate a patient may possibly be septic, and then analyzing blood cultures to confirm whether they actually are or not, at which point an acute intervention can begin.
The primary advantages of screening for gene expressions as a way to diagnose sepsis are speed and predictive power. According to Hancock, this new diagnostic can return a result in a little over 60 minutes, compared to 24 to 48 hours for a blood test. Furthermore, it is not only able to predict which patients will become septic, but also predict which patients will go on to have organ failure.
“So what this would allow is physicians some certainty to allow them to use the most powerful antibiotics that they have available,” said Hancock. “It means [patients] get, if you like, a ticket to enter the most intensive part of the hospital.”
Getting that ticket faster could decrease the mortality rate from sepsis by up to seven per cent, said Hancock.
Hancock and his team are now beginning a round of clinical studies that will eventually involve collecting and analyzing data from a thousand patients across a number of different sites. At the same time, Hancock is pursuing a partner company to produce a platform the test can run on.
According to Hancock, depending on the results of the latest clinical studies, these fully-developed diagnostic platforms could make their way into hospital emergency rooms in as little as three years’ time, bringing with them the promise of the potential for major improvements in patient outcomes.
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