Biomarkers in Infection

The body's immune system and a subsequent inflammatory response are triggered during
infection. The detection of an activated immune system, and an indication of the degree of
the host response, is helpful to the clinician both in assessing the severity of infection
and in patient treatment and management. Currently, the white blood cell count and the
differential are the most common laboratory parameters for measuring host response. The
sedimentation rate and CRP are also used to detect inflammation. However, these tests are all
imperfect predictors, and a test providing a better assessment of immune response would be
helpful to the clinician in patient care. Additionally, understanding host response to
infection may be helpful in understanding the biology and pathophysiology of sepsis. There
are other biomarkers and inflammatory markers that may be found early in the initial
presentation of infection such as cytokines (VEGF IL-1,IL-4,IL-6, IL-10, PAF, TNF, lectins
iNoS,etc.) and clotting factors (protein C, d-dimer, complements involved in the clotting
cascade, CRP, etc) that may provide a means of early detection of systemic inflammation, cell
dysfunction, and related conditions. Early identification of patients at risk for systemic
inflammatory syndromes, sepsis and septic shock may help direct patients to earlier
antibiotic administration and early intervention with goal directed therapy. It may also
serve as a tool for risk stratification when components such as age, comorbid illness and
infection type are included.

The endothelium and endothelial cell markers are important in sepsis, yet a somewhat
under-studied field of research. Additionally, the endothelium is a key regulator of the
microcirculation, a place where oxygen diffusion occurs. One focus of this study is to
measure endothelial markers (ie VEGF) and other cytokines with the goal of correlating these
markers with severity of sepsis. Another focus is to study the response of various components
in the blood, including the leukocytes, red cells, the endothelium, as well as cellular
components such as the mitochondria. We will specifically look at alterations in thiamine,
Vitamin D, CoQ10,l-carnitine and other nutrients as part of (and as related to) the body's
response. Recently, a non-invasive method of assessing microvascular circulation by
orthogonal polarization spectral (OPS) imagery has become available using a non-invasive
technology known as orthogonal polarization spectroscopy. This technique enables direct
visualization and quantification of microcirculatory blood flow, and represents an important
surrogate outcome to which endothelial cell marker may be correlated. This will involve
placing the microscopy probe gently against the sublingual mucosa and collecting a videotape
of the circulation lasting about twenty seconds. This process involves minimal (or no) risk -
it is akin to taking a temperature and uses no radiation. This videotape will be examined
later by a novel software program that quantifies the circulation and used as an important
surrogate outcome measure. Additionally, we are going to perform echocardiography to better
understand the heart's response to sepsis, and correlated the molecular responses that we
find with the changes in the responses by the heart.

This is a multicenter, observational pilot study which aims to evaluate how early biomarkers
of infection an inflammation perform in identifying patients at risk for poor outcomes in
sepsis and septic shock. The study will utilize a cohort of patients presenting to the ED
with suspected infection as well as non-infected control population.

These patients will be compared with a non-infected population.

Enrolled subjects in the infected group will have blood samples and chart review obtained at
enrollment, 24, 48 and 72 hours. For the control group, only a single blood draw will be
collected at enrollment.

Enrolled subjects will also undergo physiologic assessments using echocardiography,
Microscan, Non-invasive cardiac output monitor (NICOM), extremity temperature as well as
End-Tidal C02 measurements if a trained researcher is present.

Inclusion Criteria for Infected subjects:

- Age 18 years of age or older

- Confirmed or suspected infection

Inclusion Criteria for Control Subjects:

- Age 18 years of age or older

- A non-infectious clinical presentation to include

- Normal white blood cell count ( > 4,000 and/or < 12,000)

- Normothermia ( > 96.5 and/or less 100.4)

- Absence of the following clinical complaints: productive cough, fever, pyuria, rash

- No evidence of acute coronary syndrome

Exclusion Criteria for Control Subjects:

- Suspected infection