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Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation® Canada
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iCPET Retrospective Study of ME/CFS & Long COVID

STUDY AIM
This retrospective study aims to evaluate exercise pathophysiology in people with ME/CFS and Long COVID via invasive cardiopulmonary exercise tests (iCPETs).

Lead

INVESTIGATORS
  • Wenzhong Xiao, PhD
  • Peng Li, PhD
  • David Systrom, MD
  • Phillip Joseph, MD

UPDATES

AND POTENTIAL
  • An abstract on exercise pathophysiology in ME/CFS and Long COVID, identifying commonalities detected by iCPET, was presented at ATS. A manuscript on this work is in preparation. You can read the abstract here.
  • Preliminary results incorporating autonomic function testing indicates that small fiber neuropathy is more prevalent in ME/CFS (66%) and Long COVID (72%) than the general population.
  • We are investigating patient clinical information in electronic health records to identify patterns of disease phenotypes and mechanisms of ME/CFS.

STUDY HYPOTHESIS AND DESCRIPTION

iCPET on ME/CFS  patients shows a characteristic pattern of “preload failure” (PLF) that could be associated with postural orthostatic tachycardia syndrome (POTS) and/or post-exertional malaise (PEM).

PLF comes in 2 forms: a high flow and a low flow. The low flow form may be caused by a failure to reduce venous compliance with exercise or a pre-existing reduced overall blood volume. However, the latter is less likely because the PLF persists even when one liter of saline is given to increase the blood volume just prior to the iCPET study.  On the other hand, the high flow PLF may be caused by peripheral arterial-venous shunt effects or deficient oxygen delivery or utilization. A final explanation is that blood travels through the peripheral capillary system normally but cellular oxygen uptake and/or utilization by the mitochondria is deficient.

This project will also investigate autonomic dysfunction and the prevalence of small fiber neuropathy (SFN). SFN is a condition in which small nerve fibers are damaged, which can lead to autonomic dysfunction. Therefore, it may be more likely to be present in conditions like ME/CFS and Long COVID.

 

OBJECTIVES

Illustration of cardio vascular system

  • Evaluate ME/CFS patients impaired with PLF, as diagnosed by a single iCPET or by sequential iCPET, to measure large vessel vascular capacitance and blood volume. Conduct additional diagnostic testing (i.e., screening for adrenal insufficiency, tilt-table testing, nerve conduction studies) and the presence of peripheral shunting and oxygen delivery.
  • Combine autonomic function testing reports with iCPET to evaluate autonomic dysfunction in ME/CFS and Long COVID.
  • Study the EHR and characterize patient phenotypes and trajectories. Identify disease subtypes and investigate targeted treatments for patients.

Consent management

Consent Preferences

Data Subject Access Request (DSAR) Form 

Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.