Silent Hypoxia Mask Induced Pleurisy

When individuals are required to wear masks for prolonged periods of time it creates an inadequate supply of oxygen and increased levels of carbon dioxide result in the lungs creating a "silent hypoxia" induced form of Pleurisy.

Pleurisy, also known as pleuritis, is inflammation of the membranes that surround the lungs and line the chest cavity. This can result in a sharp chest pain while breathing.

Descriptions of the condition date from at least as early as 400 BC by Hippocrates.

The defining symptom of pleurisy is a sudden sharp, stabbing, burning or dull pain in the right or left side of the chest during breathing, especially when one inhales and exhales.

It feels worse with deep breathing, coughing, sneezing, or laughing. The pain may stay in one place, or it may spread to the shoulder or back.

The pleural space can be invaded by fluid, air, and particles from other parts of the body.

The following may be helpful in the management of pleurisy:

  • Lying on the painful side may be more comfortable

  • Breathing deeply and coughing to clear mucus as the pain eases. Otherwise, pneumonia may develop.

  • Getting rest

The Genes & Related Pathways

An important gene associated with Pleurisy is ADA (Adenosine Deaminase), and among its related pathways/superpathways are Innate Immune System and PEDF Induced Signaling.

Adenosine deaminase is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.

Its primary function in humans is the development and maintenance of the immune system.

Adenosine deaminase deficiency leads to pulmonary fibrosis, suggesting that chronic exposure to high levels of adenosine can exacerbate inflammation responses rather than suppressing them. It has also been recognized that adenosine deaminase protein and activity is upregulated in mouse hearts that overexpress HIF-1 alpha.

Adenosine deaminase inhibitors may include:

Cordycepin, kaempferol, quercetin, myricetin, and naringenin [R]

One of the genes involved with the regulation of ADA is Fibroblast Activation Protein Alpha (FAP).

FAP is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, and tissue repair.

Of note, both ADA and FAP communicate with DPP4, a known receptor for COVID-19.

Cyclooxygenase-2 (COX-2) inhibitors help to regulate Fibroblast Activation Protein Alpha (FAP).

  • Rosmarinic acid, found in Prunella Vulgaris (strong) [R]

  • Ursolic acid, found in Prunella Vulgaris [R]

  • Ginger (strong) [R]

  • Resveratrol [R, R, R]

  • Pomegranate extract [R]

  • Glucosamine (NAG) [R, R]

  • Chinese skullcap [R]

  • Zinc [R]

  • Selenium [R]

Dipeptidyl peptidase-4(DPP4) is associated with immune regulation, signal transduction, and apoptosis. DPP-4 also binds the enzyme adenosine deaminase specifically and with high affinity.

Middle East respiratory syndrome coronavirus has been found to bind to DPP4.

Compounds for Dipeptidyl peptidase-4 may include:

Mannose [R]

Proline [R]

Chrysin, found in Bee propolis [R]

Kaempferol [R]

Rutin [R]

Nattokinase (Glycine max) [R]

Salvianolic Acid (Dan shen) [R]


HIF1A is considered as the master transcriptional regulator of cellular and developmental response to hypoxia.

The transcription factor HIF-1 plays an important role in the cellular response to systemic oxygen levels in mammals.

Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level.

In acute or silent hypoxia, a person’s oxygen level in blood cells and tissue can drop without any initial warning. Doctors report cases of silent hypoxia with COVID-19 patients who did not experience shortness of breath or coughing until their oxygen levels had plummeted to such a degree that the patients risked acute respiratory distress (ARDS) and organ failure.

In a New York Times opinion piece (4/20/20), emergency room doctor Richard Levitan reports "a vast majority of Covid pneumonia patients I met had remarkably low oxygen saturations at triage — seemingly incompatible with life — but they were using their cellphones as we put them on monitors."

Carbon monoxide poisoning

Carbon monoxide competes with oxygen for binding sites on hemoglobin molecules. As carbon monoxide binds with hemoglobin hundreds of times tighter than oxygen, it can prevent the carriage of oxygen. In so doing, the hemoglobin is less likely to release its oxygens at the peripheral tissues.

In the lungs, the response to hypoxia is vasoconstriction. This is known as hypoxic pulmonary vasoconstriction, or "HPV".

Research conducted suggests that stabilizing HIF using HIF prolyl-hydroxylase inhibitors enhances the function of Hypoxia-inducible factors which in turn helps to regulate adequate supplies of oxygen.

HIF-Prolyl Hydroxylase 2 (EGLN1 Gene), which is a major player in HIF prolyl-hydroxylase, requires:

  • Vitamin C

  • Succinic acid

  • Oxogluric acid

  • Proline

In addition, HIF-1alpha inhibitors have also been shown in research to help control the supply of oxygen.

  • Vinpocetine [R]

  • Resveratrol [R]

  • Isoflavones (Kudzu, Nattokinase) [R]

As a key regulator of oxygen homeostasis, HIF-1 is tightly regulated by the level of oxygen.

Since the first report of the interaction between HIF-1α protein and the molecular chaperone heat shock protein 90 (hsp90), a number of studies have investigated the significance of this interaction using pharmacological agents that inhibit hsp90. Recent studies suggested that hsp90 binds to the HIF-1α PAS domains and stabilizes HIF-1α protein, and the HIF-1β /ARNT subunit competes with hsp90 for the same binding sites to stabilize HIF-1α protein.

Heat shock protein 90 Inhibitor:

  • Ashwagandha [R]

HIF-1 target gene expression suggested that the mitogen-activated protein kinase (MAPK) pathway also regulates HIF-1 activity.

RAS-MAPK-ERK Inhibitor:

In conclusion, Pleurisy and other disorders of the pleurae can be serious, depending on what caused them. If left untreated it can cause severe complications. For example, a resulting pulmonary heart disease cor pulmonale, which manifests itself with an inflammation of the arms and legs, can lead to heart failure.

"In a sea of possibilities, pattern recognition is the key to unlocking the door to new therapeutic interventions." - Joey Phillips



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