Toward a Blood-Borne Biomarker of Chronic Hypoxemia: Red Cell Distribution Width and Respiratory Disease.

Hypoxemia (systemic oxygen desaturation) marks the presence, risk, and progression of many diseases. Episodic or nocturnal hypoxemia can be challenging to detect and quantify. A sensitive, specific, and convenient marker of recent oxygen desaturation represents an unmet medical need. Observations of acclimatization to high altitude in humans and animals reveals several proteosomic, ventilatory, and hematological responses to low oxygen tension. Of these, increased red cell distribution width (RDW) appears to have the longest persistence. Literature review and analyses of a 2M patient database across the full disease pathome revealed that increased RDW is predictive of poor outcome for certain diseases including many if not all hypoxigenic conditions. Comprehensive review of diseases impacting the respiratory axis show many are associated with increased RDW and no apparent counterexamples. The mechanism linking RDW to outcome is unknown. Conjectural roles for iron deficiency, inflammation, and oxidative stress have not been born out experimentally. Sports-doping studies show that erythropoietin (EPO) injection can induce formation of unusually large red blood cells (RBC) in sufficient numbers to increase RDW. Because endogenous EPO responds strongly to hypoxemia, this molecule could potentially mediate a long-lived RDW response to low oxygenation. RDW may be a guidepost signaling that unexploited information is embedded in subtle RBC variation. Applying modern techniques of measurement and analysis to certain RBC characteristics may yield a more specific and sensitive marker of chronic pulmonary and circulatory diseases, sleep apnea, and opioid inhibition of breathing.