Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers

Abstract

IntroductionA previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR.MethodsA re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST.ResultsHVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, p<0.001 (55.4% higher HVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001), higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001), and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025). One hundred and two (18.5%) of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR.ConclusionsThis is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

Sex‐linked difference in blood oxygen saturation

“…Another study not restricted to healthy volunteers included patients in an emergency room and did not exclude smokers, also found higher SpO 2 in females (0.7% higher in African American females and 0.6% higher in white females) . Recently, a study whose primary goal was to explore genetic factors related to the control of breathing, unexpectedly found higher SpO 2 in women compared to men. The difference between sexs was similar to our findings (98.0% ± 1.3% in females vs 96.6% ± 1.7% in males).…”

Percutaneous Closure of PFO in Patients with Reduced Oxygen Saturation at Rest and during Exercise: Short- and Long-Term Results

“…Dyspnea increases the tidal volume and thus normalizes the arterial saturation. As the reaction of the respiratory center on hypoxemia can differ, other patients will not react on hypoxemia and not become dyspneic [17].…”

Liberal Oxygen with Unreliable Unpredictable Flowrate Is the Root Cause of Unexplained Physiological Events in Combat aircraft

“…It has been shown that the primary driver of inhalation is a mechanism called "hypercapnic ventilatory drive", and "hypoxic ventilatory drive" is a secondary, back-up mechanism that stimulates breathing. (Dick, 1997, Goldberg, 2017 Hypercapnic drive forces exhalation in a very powerful, deep brain stem, primordial reflex. This is easily demonstrated in a typical individual who wishes to hold their breath for more than a minute.…”