A 2-day cardiopulmonary exercise test in chronic fatigue syndrome patients who were exposed to humidifier disinfectants, 2023, Leem et al

Abstract

Some survivors of humidifier disinfectants (HDs) complain of chronic, inexplicable fatigue, and post-exertional malaise (PEM). Two-day cardiopulmonary exercise tests (CPETs) performed 24 hours apart (2-day CPET protocol) are increasingly employed to evaluate PEM and related disabilities among individuals with chronic fatigue syndrome (CFS). The purpose of this study was to assess the reproducibility of CPET variables in individuals who had been exposed to HD and to show that 2-day CPET is an objective means of differentiating between fatigue conditions in people with CFS symptoms who have been exposed to HDs.

Twenty-nine HD survivors with CFS symptoms were enrolled in this study. To document and assess PEM in CFS, a 2-day CPET was conducted to measure baseline functional capacity (CPET1) and provoke PEM. Twenty-four hours later, a second CPET assessed changes in related variables, focusing on PEM effects on functional capacity. This CPET also measured changes in energy production and physiological function, objectively documenting PEM effects.

In the 2-day CPET, the peak oxygen consumption (VO2peak), VO2 at ventilatory threshold (VO2@VT), time to reach VO2peak, and time to reach VO2@VT were significantly decreased (p<0.001). The peak O2 pulse and O2 pulse at VT also decreased significantly (p<0.001). A 6-minute walk test revealed significantly decreased distance (p<0.01). This is the first study to conduct a 2-day consecutive CPET in previously exposed HD participants with CFS symptoms. Our results confirm previous work that demonstrated abnormal responses to PEM in CFS patients. Therefore, a 2-day CPET is an objective measure to differentiate fatigue conditions in people with CFS symptoms who have been exposed to HDs.

Open access, https://www.eaht.org/journal/view.php?doi=10.5620/eaht.2022033

 

Interesting that this seems to involve a well documented group of ME/CFS cases not triggered by a viral infection.

 

None of the sources about HDs in the intro where they discuss a potential link even mention CFS or PEM. (Edit: Seems to be based on a survey mentioned in reference 25.)

They didn’t recruit based on if the CFS symptoms came after HD exposure, as far as I can tell:

They make it clear they are testing in people who had CFS symptoms and also have been exposed to HDs, and don't say one preceded or caused the other:

Edit: Though reference 25 says this:

They're basing it on this survey:

But I can't find that online.

 

Also the WASF3 study and findings came about due to investigation of a patient with a germline TP53 mutation causing Li-Fraumeni syndrome. Although WASF3 protein over-expression was thought to be unrelated.

Some other recent p53 papers on the to-read list —

p53 enables phospholipid headgroup scavenging (2024)
Jossie Yashinskie; Xianbing Zhu; Grace McGregor; Katrina Paras; Benjamin Jackson; Abigail Xie; Richard Koche; Christian Metallo; Lydia Finley

Changes in cell state are often accompanied by altered metabolic demands, and homeostasis depends on cells adapting to their changing needs. One major cell state change is senescence, which is associated with dramatic changes in cell metabolism, including increases in lipid metabolism, but how cells accommodate such alterations is poorly understood.

Here, we show that the transcription factor p53 enables recycling of the lipid headgroups required to meet the increased demand for membrane phospholipids during senescence. p53 activation increases supply of phosphoethanolamine (PEtn), an intermediate in the Kennedy pathway for de novo synthesis of phosphatidylethanolamine (PE), by transactivating genes involved in autophagy and lysosomal catabolism that enable membrane turnover.

Disruption of PEtn conversion to PE is well-tolerated in the absence of p53 but results in dramatic organelle remodeling and perturbs growth and gene expression following p53 activation. Consistently, CRISPR-Cas9-based genetic screens reveal that p53-activated cells preferentially depend on genes involved in lipid metabolism.

Together, these results reveal lipid headgroup recycling to be a homeostatic function of p53 that confers a cell-state specific metabolic vulnerability.


Link | PDF (Preprint: BioRxiv) [Open Access]


p53: A tale of complexity and context (2024)
Moshe Oren; Carol Prives

The story of p53 is illuminating. Despite widespread attention, the tumor-suppressive functions of wild-type p53 or the oncogenic activities of its cancer-associated mutants are still not fully understood, and our discoveries have not yet led to major therapeutic breakthroughs. There is still much to learn about this fascinating protein.


Link | PDF (Cell)