Category Archives: Altitude Science

Are Epigenetics the Bridge to Permanent Physiologic Adaptations in Organisms Living at High Altitude?

The CDC defines epigenetics as “the study of how your behaviors and environment can cause changes that affect the way your genes work… epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a sequence.”1 Examples of epigenetic changes include methylation, histone modifications, and non-coding RNAs. Researchers have postulated the involvement of epigenetics in an organism’s adaptations to hypoxic high-altitude environments. After looking into this topic, I questioned if epigenetics may be the bridge to the permanent physiologic alterations in organisms living at high altitudes. 

Hypoxia Inducible Factor-1 (HIF-1) is a nuclear transcription factor activated in hypoxia states, and regulates several oxygen-related genes. The role of epigenetics, specifically methylation of HIF-1 in the expression of the erythropoietin gene, in states of hypoxia was researched. Erythropoietin was chosen due to it being a widely known protein that stimulates erythropoiesis in states of hypoxia. It was confirmed that HIF-1 binds to a HIF-1 binding site (HBS) on the erythropoietin enhancer and will induce transcription of erythropoietin.2 CpG methylation in the HBS interferes with HIF-1 binding, thus inhibiting the activation of transcription of erythropoietin.2  They also found that there were several other oxygen-related genes that were susceptible to similar epigenetic changes.2 Another study investigating HIF-1 and its binding to HIF-1 response element (HRE) upstream to a target gene confirmed the potential for epigenetic changes, specifically methylation. They found that this HIF-1 binding site has a CpG dinucleotide, making it inherently susceptible to methylation.To clarify, the most notable epigenetic change is the methylation of cytosine located 5’ to guanine, known as CpG dinucleotides.Again, they reported that methylation of the CpG island in the HIF-1 binding site upstream of the target gene, erythropoietin, was negatively correlated with its expression.

Furthermore, research on epigenetic changes in rats exposed to long and short-term intermittent hypoxic environments and their room air recovery treatments suggests there is a long-term effect in rats exposed to long-term intermittent hypoxia.4  Rats were exposed to short-term (10 days) and long-term (30 days) intermittent hypoxia resembling obstructive sleep apnea oxygen profiles.The short-term hypoxic rats treated for 10 days at room air reversed their altered carotid body reflexes including hypertension, irregular breathing, and increased sympathetic tone. While the long-term hypoxia rats treated for 30 days at room air did not have a reversal of altered carotid body reflexes.There were similar results in reactive oxygen species (ROS) and antioxidant enzyme (AOE) levels. The long-term hypoxia rats had increased levels of ROS and decreased AOEs in their recovery periods compared to the short-term hypoxia rats.

Erythropoietin is not the only oxygen-related gene that is affected. For example, a study looked at the methylation profiles of Tibetan and Yorkshire pigs under high-altitude hypoxia. IGF1R and AKT3 were two notable differentially methylated genes found to have high expression and low methylation levels in Tibetan pigs that suggest a role in adaptation to hypoxic environments.Both genes are responsible for cell proliferation and survival.Tibetan pigs are known to have become physiologically adapted to their high-altitude hypoxic environment over generations and epigenetic changes were verified in the genome-wide sequence ran in this study.5 This study alludes that epigenetics is not only a bridge but may be a part of the permanent physiologically selected adaptations to ensure survival at high altitudes.

In conclusion, research demonstrates a variety of epigenetic changes that are taking place in these high-altitude hypoxic environments. The research suggests that they may likely be tissue-specific as well. There are definite knowledge gaps in the exact roles that epigenetics may play in hypoxic environments and gene expression. There is room for more research and identifying alterations to epigenetics to improve human physiologic adaptations to hypoxia. 

References 

1. Centers for Disease Control and Prevention. What is Epigenetics. https://www.cdc.gov/genomics/disease/epigenetics.htm. Accessed December 30th, 2022.

2. Wenger, R.H., Kvietikova, I., Rolfs, A., Camenisch, G. and Gassmann, M. (1998), Oxygen-regulated erythropoietin gene expression is dependent on a CpG methylation-free hypoxia-inducible factor-1 DNA-binding site. European Journal of Biochemistry, 253: 771-777. https://doi.org/10.1046/j.1432-1327.1998.2530771.x

3. Yin H, Blanchard KL. DNA methylation represses the expression of the human erythropoietin gene by two different mechanisms [published correction appears in Blood 2000 Feb 15;95(4):1137]. Blood. 2000;95(1):111-119.

4. Nanduri J, Semenza GL, Prabhakar NR. Epigenetic changes by DNA methylation in chronic and intermittent hypoxia. Am J Physiol Lung Cell Mol Physiol. 2017;313(6):L1096-L1100. doi:10.1152/ajplung.00325.2017

5. Zhang B, Ban D, Gou X, et al. Genome-wide DNA methylation profiles in Tibetan and Yorkshire pigs under high-altitude hypoxia. J Anim Sci Biotechnol. 2019;10:25. Published 2019 Feb 5. doi:10.1186/s40104-019-0316-y

A woman in a white coat with long, dark, straight hair below her shoulders smiles.

Emily Paz is a third-year medical student at Rocky Vista University College of Osteopathic Medicine and is looking forward to pursuing a career in orthopedics. She is from the central coast of California and earned her Bachelor of Science degree in General Biology from the University of California San Diego. She worked in an emergency department as an EMT after her undergraduate education which reaffirmed her passion and curiosity for medicine. In her free time, she enjoys snowboarding, practicing Muay Thai, cooking, and spending time with family and friends.

When Altitude gets High, does Stroke get higher?

Does altitude increase or decrease risk of strokes? As one review put it, “Due to limited literature, lack of large series, and controlled studies, the understanding of stroke at high altitude is still sketchy and incomplete”. What is clear is that stroke at high altitude can often be misdiagnosed (or underdiagnosed), due to the similarity of initial presentation with high altitude cerebral edema (HACE). Both conditions present with imbalance or ataxia, and both can present with focal neurological deficits.  There are few large urban populations at high altitude (Addis Ababa in Ethiopia is 7,726 ft), so medical providers have fewer resources.  Without the ability to perform neuroimaging with a CT scan or MRI in a timely manner a diagnosis of HACE vs. stroke could be uncertain. HACE often causes global cerebral dysfunction, differentiating it from an early stroke before the onset of focal symptoms can and often does prove challenging. 

While the prevalence of strictly hemorrhagic and ischemic strokes at high altitude remains murky, it is known that exposure to high altitude can result in conditions such as TIA, cerebral venous thrombosis (CVT), seizures, and cranial nerve palsies. Most of the research that has been done on strokes is focused on “moderate” and “high” altitudes, as opposed to “very high” or “extremely high” altitudes. As such, there is very little research on populations living at 3500m or higher. There was at least one tangible piece of evidence indicating that the higher the elevation, the earlier the mean onset of stroke – Dhiman et al. (2018) found that at an elevation of 2,000m, the mean age of onset of stroke was 62 years. The age decreased to a mean of 57.9 years at 2,200m in another study (Mahajan et al. (2004)). Yet another study (Razdan et al. (1989)) found 10.9% of the patients in their sample suffered strokes aged < 40, though this was at an altitude of only 1,530m. Some reports suggest higher stroke prevalence at higher altitudes, and at a strikingly young age – between age 20 and age 45.

Student presentation on stroke at altitude at Colorado Medical Society meeting 2022

There have been mixed results on the effect that altitude has on strokes. One systematic review study found 10 studies displaying an increase in stroke prevalence with higher altitude, 5 other studies showing that altitude was actually protective against stroke, and 2 studies in which the results were ambiguous. This study and other sources alluded to the fact that poorer stroke outcomes at higher altitude may be due to polycythemia and increased viscosity of blood. Specifically, Ortiz-Prado et. al noted that “living in high-altitude regions (>2500m) increases the risk of developing thrombosis through hypoxia-driven polycythaemia which leads to a hypercoagulation unbalance”, which was associated with increased risk for stroke. Ortiz-Prado et. al noted that most of their info came from “very few cross-sectional analyses”. These analyses did find “a significant association between living in high-altitude regions and having a greater risk of developing stroke, especially among younger populations”. When the effects of altitude on stroke were broken down by race (Gerken, Huber, Barron, & Zapata, 2022) it was found to be protective in some populations (Whites, African Americans), but detrimental in other populations (Hispanics, Asian-Pacific, and American-Indian). Going back to the work of Ortiz-Prado et. al, altitude increased the risk of stroke at elevations above 3500m, when the time spent at this elevation was at least 28 days, and more so in younger persons (below the age of 45). At lower elevations, between 1500m and 3500m, increased / easier acclimatization and adaptation to hypoxia seemed to offer protective effects against the risk of stroke. Chronic exposure to hypoxia at high altitude triggers adaptive / compensatory mechanisms, such as higher pulmonary arterial flow and improved oxygen diffusing capacity. Ortiz-Prado et. al concluded that a window of ideal elevation seems to exist – below an altitude of 2000m the adaptive mechanisms do not seem to be sufficient to yield a protective effect – however, above 3500m, adaptive mechanisms may actually become maladaptive (excessive polycythemia & blood stasis), yielding a higher risk for stroke. A lack of any adaptation (i.e. in altitude naïve persons) was even more detrimental at such high altitudes, with the authors concluding that “above 3500–4000m, the risk of developing stroke increases, especially if the exposure is acute among non-adapted populations” (Ortiz-Prado et. al, 2022).

Strokes are more common in males compared to females, and this held true at altitudes of 3380m, 4000m, and 4572m. In addition to the standard vascular risk factors such as hypertension, smoking, and diabetes, the higher incidence of polycythemia in persons living at high altitude is thought to play a role. One study (Jha et al. (2002)) found that 75% of the patients in their sample who had suffered strokes had some form of polycythemia – this was at an altitude of 4270m. (Dr. Christine Ebert-Santos of Ebert Family Clinic in Frisco, Colorado at 2743m suspects everyone who lives at altitude has polyerythrocythemia as more accurately described by Dr. Gustavo Zubieta-Calleja of La Paz, Bolivia at 3625m.)

Only about 2% of the world’s population resides at what is considered “high altitude”. Given the current world population (over 8 billion, 5 million), that is still over 160,100,000 people. The sheer number of people that may be at increased risk of stroke is all the more reason for us to act, and act soon, to get more research done. This is further exemplified by the fact that “cerebrovascular events or stroke is the second leading cause of death worldwide, affecting more than 16 million people each year” (Ortiz-Prado et. al). Guidelines need to be implemented to assist in the diagnosis and treatment of stroke at high altitude, to help differentiate it from related conditions such as HACE, giving patients the standard of care that they need and deserve. While a fascinating topic, stroke seems to be delegated to the sidelines in the mountains, cast aside by culprits such as HAPE, HACE, altitude sickness, and hypoxia. More research, more resources, and more funding need to be funneled into understanding stroke at higher altitudes. Overall, it is clear living at or even exposure to higher altitudes can result in a multitude of neurological symptoms, and that a higher incidence of stroke may yet be one of them.

References

Maryam J. Syed, Ismail A. Khatri, Wasim Alamgir, and Mohammad Wasay. Stroke at Moderate and High Altitude. High Altitude Medicine & Biology.Mar 2022.1-7. http://doi.org.mwu.idm.oclc.org/10.1089/ham.2021.0043

Current World Population – https://www.worldometers.info/world-population/ 

Ortiz-Prado E, Cordovez SP, Vasconez E, Viscor G, Roderick P. Chronic high-altitude exposure and the epidemiology of ischaemic stroke: a systematic review. BMJ Open. 2022;12(4):e051777. Published 2022 Apr 29. doi:10.1136/bmjopen-2021-051777

Gerken, Jacob (MS), Huber, Nathan (MS), Barron, Ileana (MD, MPH-S), Zapata, Isain (PhD). “Influence of Elevation of Stroke and Cardiovascular Outcomes”. Poster presented at a conference in Colorado, in 2022.

Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058702/ https://www-liebertpub-com.mwu.idm.oclc.org/doi/full/10.1089/ham.2021.0043

Born in Salt Lake City, Utah, Piotr Poczwardowski has also lived in Upstate New York, Florida, and Colorado (where he spent the 13 years prior to moving to Glendale for PA school). While attending the University of Denver, he volunteered at a nearby hospital Emergency Department, and also participated in a study abroad program in Italy. After earning a degree in Psychology, he worked as both a Primary Care Medical Scribe and Neurology MA. His main hobbies include skiing, watching movies, hiking, swimming, playing video games, reading, and playing ping pong. Piotr has also volunteered at the Sky Ridge Medical Center Emergency Department and secured a job as a Primary Care Medical Scribe after graduating from the University of Denver in 2018. Piotr is now attending Midwestern University’s PA program in Glendale, AZ.

Going Home to the Mountains Can Be Dangerous: Re-Entry HAPE (High Altitude Pulmonary Edema)

Louie was excited to get out on the slopes after spending Thanksgiving with family in Vermont. He got tired early and felt his breathing was harder than usual, leaving early to go home and rest. As a competitive skier he thought that was strange. But he was getting over a cold. He could not have imagined that in 24 hours he would be in the emergency room, fighting for his life.

Louie experienced a dangerous condition, set off by altitude, and inflammation from his “cold”, that caused his lungs to fill with fluid.  His oxygen saturation was 54 % instead of the normal 92, he had been vomiting and feeling very weak and short of breath. His blood tests showed dehydration, hypoxemia and acute kidney injury. His chest x-ray looked like a snowstorm. He was transferred to Children’s Hospital in Denver and admitted to the intensive care unit.

The diagnosis of Re-entry HAPE was confirmed by echocardiogram showing increased pressures in his lungs. He improved rapidly with oxygen and low altitude.

Re-entry HAPE is not rare, affecting several Summit County children every year.  Many do not come to medical attention because after their first episode parents carefully monitor their oxygen and have a concentrator available in their home when they return from travel. 

Medical providers may not be aware of this risk, expecting that children living at altitude are acclimatized. (See previous blog entry on Acclimatization vs. Adaptation, April 17, 2019) Re-entry HAPE seems to occur mostly in children between the ages of 4 and 15. Inflammation, such as a viral respiratory infection, seems to play a role.  Trauma may also predispose a returning resident to Re-entry HAPE, as described in our blog post from February 5, 2018, Re-entry HAPE in High Altitude Residents.

Louie agreed to share his story on our blog to help educate medical personnel and families living in the mountains about this dangerous condition. Further research will help define who is at risk.  The University of Heidelberg recently published an article on the genetics of pulmonary hypertension (HARPE is the New HAPE) and is interested in testing families here who have had more than one person affected by HAPE.

Altitude Promotes Better Survival Rates in Critically Ill Obese Patients with COVID-19: A Presentation from the Chronic Hypoxia Symposium

The 8th Chronic Hypoxia Symposium is recently took place in La Paz, Boliva, and I had to pleasure of hearing Dr. Jorge Luis Velez’ presentation on altitude, obesity, and COVID-19 survival rates. Dr. Velez is an intensive care doctor and the head of critical medicine at Pablo Arturo Suarez Hospital in Quito, Ecuador, as well as being a professor at the Central University of Ecuador. With Quito being the second highest in elevation capital in the world at 9,350 feet, Dr. Velez understands the effects of altitude on the human body.

https://cdn.boundtree.com/assets/btm/University/Articles/ArticleHeroMobile-To-intubate-or.jpg

Dr. Velez conducted a study among 340 unvaccinated adult patients with severe COVID-19 infections requiring intubation. Of the 340 patients, 45% were obese, 43% were overweight, and 12% were of normal weight. The results of the study showed that obese patients had significantly reduced mortality rates and higher rates of successful extubation when compared to the overweight and normal weight groups. Successful extubation is commonly described as extubation without the need for re-intubation within 72 hours. Obese patients were found to have a 31.17% mortality rate and an 81.03% rate of successful extubation. Overweight patients were found to have a 40.14% mortality rate and a 73.00% rate of successful extubation. Patients of normal weight were found to have a 48.72% mortality rate and a 53.85% rate of successful extubation.

https://www.vidawellnessandbeauty.com/wp-content/uploads/2021/11/obesity-and-covid.png

These results are surprising given that obesity is a widely accepted risk factor for high severity COVID-19 infections and increased mortality. Other factors that may have contributed to the increased survival rates of obese patients with severe COVID-19 infections is that in their study, the obese patients happened to be on average younger and a higher proportion of males. Despite variables in age and sex, Dr. Velez still concludes with statistical significance that “patients with obesity had a 52% less probability of dying in relation to those of normal weight.”

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Despite this emerging research, we still recommend maintenance of a healthy weight and lifestyle, as the effects of a healthy weight have been extensively researched and proven to be beneficial for a heart health, joint health, mental health, sleep, the digestive system, and more.

Family Nurse Practitioner Ana Sofia Bedoya administering the new bivalent COVID-19 vaccine to Dr. Chris in her office at Ebert Family Clinic in Frisco, CO.

Looking for other ways to protect yourself from COVID-19?

The new bivalent vaccine uses the same technology with upgraded protection against the omicron variant. The vaccine is the best way to reduce risk for you and your family during the holiday season, as well as protecting from reinfection if you’ve already had COVID-19.

References

Luis Velez, J., 2022. Altitude Promotes Better Survival Rates in Critically Ill Obese Patients with COVID-19.

Artime, C. A. A., & Hagberg, C. A. H. (2014, June). Tracheal Extubation. Respiratory Care, 59(6), 991–1005. https://rc.rcjournal.com/content/respcare/59/6/991.full.pdf#:~:text=Successful%20extubation%20is%20dependent%20on%20two%20factors%3A%20the,a%20planned%20extubation8%3B%20however%2C%20this%20definition%20does%20not

Cameron Santiago is a second-year Physician Assistant Student at Red Rocks Community College in Arvada, CO. He grew up in Colorado Springs and received his undergraduate degree in Biology from Colorado State University. Prior to PA school, he was an inpatient phlebotomist and urgent care technician. In his free time, he enjoys fishing, hiking, and spending time with his dogs and family.

HARPE is the New HAPE

It took ten years for me to convince high altitude experts that children living in the mountains get high altitude pulmonary edema (HAPE) without leaving home. My observations were published in 2017 in the Journal of High Altitude Medicine and Biology,

High-Altitude Pulmonary Edema
in Mountain Community Residents

This week Dr. Jose A Castro-Rodriguez MD PhD ATSF discussed HAPE in children at the 8th World Hypoxia conference in La Paz including the now renamed high altitude resident pulmonary edema (HARPE) in his presentation.

Dr. Castro-Rodriguez emphasized the importance of recognizing the three forms of HAPE, including reentry HAPE when children return to the mountains from vacation, since these can be life threatening.

My work has been cited in articles by pulmonologists Deborah Liptzin and Dunbar Ivy from Children’s Hospital of Colorado and geneticist Christine Eichstaedt and her team at the University of Heidelberg.

At Ebert Family Clinic we give every patient/family a free pulse oximeter. The ability to measure the oxygen saturation of anyone with cough, congestion, or fatigue can facilitate early treatment with oxygen and prevent visits to the emergency room, hospital and intensive care unit.

I recently received first prize for a poster presentation on HARPE at the fall Colorado Medical Society meeting, and second prize for a poster on Trauma and HAPE.

For more information about HAPE, HARPE and Trauma-related HAPE, see previous blog entries.

References

Ebert-Santos C. High-Altitude Pulmonary Edema in Mountain Community Residents. High Alt Med Biol. 2017 Sep;18(3):278-284. doi: 10.1089/ham.2016.0100. Epub 2017 Aug 28. PMID: 28846035.

Giesenhagen AM, Ivy DD, Brinton JT, Meier MR, Weinman JP, Liptzin DR. High Altitude Pulmonary Edema in Children: A Single Referral Center Evaluation. J Pediatr. 2019 Jul;210:106-111. doi: 10.1016/j.jpeds.2019.02.028. Epub 2019 Apr 17. PMID: 31005280; PMCID: PMC6592742.

Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol. 2018 Mar;19(1):91-98. doi: 10.1089/ham.2017.0096. Epub 2018 Feb 22. PMID: 29470103; PMCID: PMC5905943.

Eichstaedt CA, Mairbäurl H, Song J, Benjamin N, Fischer C, Dehnert C, Schommer K, Berger MM, Bärtsch P, Grünig E, Hinderhofer K. Genetic Predisposition to High-Altitude Pulmonary Edema. High Alt Med Biol. 2020 Mar;21(1):28-36. doi: 10.1089/ham.2019.0083. Epub 2020 Jan 23. PMID: 31976756.

High-Altitude Pulmonary Edema is not just for tourists

HAPE can affect long term locals too. There is no specific test to diagnosis HAPE leading to delayed treatment or improper treatment, including death.

HAPE is defined as fluid accumulation in the lungs when an individual spends about 48 hours at elevations of 8,200 feet or higher. This can occur when 1) tourists who are not accumulated to high altitudes appropriately 2) locals who re-enter high altitude after being at lower elevation for a period of time or 3) long term residents who develop an illness.

What are the signs and symptoms you ask? Exhaustion, dyspnea on exertion, productive cough, tachypnea, tachycardia, low oxygen saturation levels, and crackles upon lung assessments are the most common to be seen. These are very generic symptoms and resemble many other diseases, such as pneumonia and asthma, leading to misdiagnosis and improper treatment.

How is HAPE treated?

The answer is simple, oxygen. The body is being deprived of oxygen and is unable to feed our cells. By giving oxygen (either through an artificial source or returning to lower elevation) and allowing the body to rest, the body is able to meet its demand for oxygen and symptoms resolve. If one receives oxygen and symptoms do not improve, there is most likely an underlying cause that is contributing to the symptoms unrelated to HAPE.

A pulse oximeter is the easiest way that one can monitor their oxygen levels at home. This device can be purchased over the counter, relatively inexpensive, and easy to use. By placing the pulse oximeter on one’s finger, the device will read the individual’s oxygen level which should be greater than 90% (when at altitude). The heart rate will also be recorded which tends to be between 60-100 beats per minute when at rest for adults.

References

A new mechanism to prevent pulmonary edema in severe infections. Lung Disease News. (n.d.). Retrieved September 2, 2022, from https://lungdiseasenews.com/2015/01/14/researchers-discover-a-new-mechanism-to-prevent-pulmonary-edema-in-severe-infections/

Bhattarai, A., Acharya, S., Yadav, J. K., & Wilkes, M. (2019). Delayed-onset high altitude pulmonary edema: A case report. Wilderness & Environmental Medicine, 30(1), 90–92. https://doi.org/10.1016/j.wem.2018.11.002

Fixler, K. (2017, October 12). Colorado doctor: Health effects of living in mountains unknown to medical establishment. SummitDaily.com. Retrieved September 2, 2022, from https://www.summitdaily.com/news/summit-county-doctor-makes-a-case-for-high-altitude-disorder-that-affects-even-the-acclimated/

Interview with Retired Fighter Pilot Andrew Breithaupt: Altitude Earth and Sky

I had the honor of interviewing Andrew Breithaupt who recently retired from US Customs and Border Protection in the Department of Homeland Security where he served as an Air Interdiction Agent piloting multiple types of aircraft.  He currently serves as a Lieutenant Colonel on active duty for the US Army, stationed in Minneapolis, MN.  He began Army flight school in 1992 to become a helicopter pilot, ultimately qualifying in 4 different types of Army helicopters including the UH-1H, OH-58, AH-1, and the AH-64 Apache for which he became an Instructor Pilot training new Army aviators at Fort Rucker, Alabama.  Later he began his transition to fixed-wing aircraft in the civilian community. After nearly 10 years of Army active duty and multiple overseas tours, he was selected to enter service for US Customs and Border Protection where he served as a federal law enforcement agent for over 20 years, retired in December of 2021.  He holds his commercial pilot license for single engine & multi-engine fixed wing as well as rotorcraft with instrument privileges and aircraft type ratings. He has over 30 years of aviation experience and more than 2,500 hours of flight time over his career. I sat down to chat with him about his accomplished career and learn more about his aviation and altitude expertise.

In army flight school, specifically aeromedical training, he was taught the effects of aviation on the body. One of the first lessons they learned in their training was how to recognize the early warning signs of hypoxia. These include shortness of breath, dysphoria, nausea, vomiting and lightheadedness. This type of training is often done in altitude chambers, so trainees can experience these effects before they are in the air, including how aviation can affect your vestibular senses. A position change as simple as looking down to change a radio or instrument can completely disorient a pilot due to the change in direction of the fluid within the inner ear against the cilia. This can lead to the sensation that the plane has rotated and flying sideways. They are taught to trust their instruments because an overcorrection can lead to what they teach in flight school as a “death spiral.” The training is often done in a Barany Chair and simulates vestibular senses experienced during flight.

Elevation in Summit County, Colorado ranges from 7,947 feet to 14,270 feet, the highest peak being Gray’s Peak. With people living as high as 11,200 feet, as Andrew does at his home in Blue River located south of of Breckenridge, CO.  Andrew shared some very interesting aviation altitude requirements which might surprise some. He spent much of his career operating non-pressurized helicopters and Federal Aviation Regulations prohibited him from going between 10,000 feet to 12,000 feet for more than 30 minutes without oxygen. When flying above 12,000 feet, pilots are required to have supplemental oxygen regardless of the amount of time spent at that elevation depending on the category of aviation being conducted such as commercial operations. This is according to the CFR (Code of Federal Regulations) Part 135 which governs commercial aircraft operations. How interesting is it that pilots have these regulations, yet many people who live in Summit County or those summiting 14ers (peaks at 14,000 ft. or above) are at or above these elevations with no supplemental oxygen on a daily basis. When flying private aircraft, CFR part 91.211 specifies flight crew can fly without pressurization or supplemental O2 below 14,000 feet and passengers below 15,000 feet.

While in the Army, Andrew would rarely operate aircraft above 8,000 feet and would typically not have supplemental oxygen on board. They were trained to begin descent immediately if they were to notice the early signs of hypoxia. Keeping a pilot’s license requires strict annual or even semi-annual FAA physicals and continued training to ensure their bodies can withstand the effects of aviation.  As you can imagine those holding these licenses are some of the most fit men and women in the country.  Andrew rarely felt the effects of altitude even with altitude changes as great as 8,000 feet coming from sea level. He would typically remain at these elevations for two hours or less piloting non-pressurized aircraft.

To give some perspective, when you hop on a commercial flight for your next adventure these planes typically fly around 28,000 to 36,000 feet of elevation. When beginning the ascent, the aircraft pressure stabilizes at 6,000 to 8,000 feet, approximately when the dreaded “popping of the ears” is felt. Supplemental oxygen and quick donning masks are required on all these aircraft in case depressurization were to occur due to the rapid hypoxia which would occur at such high altitudes.

Andrew moved to Summit County in November of 2021 from Stafford, VA with his wife and five sons ages 24, 22, 19, 14, and 11.  Andrew and his family spent a significant amount of time in Summit County for snowboarding and skiing competitions and quickly fell in love with the area prior to spending the last 5 years living in Stuttgart, Germany. This is when they decided one day, they would become full-time residents of the county. They moved here for the “people, climate and lifestyle,” a combination I am learning is hard to beat outside of Summit County. With ski and snowboard season right around the corner, he and his family are excited to get back out on the slopes.   Andrew currently travels between his home in Blue River and Minneapolis for his position in the Army. With each trip back he feels his body more quickly adjust to the altitude changes. Thank you for your service Andrew, and welcome to the community!

Ellie Martini grew up in Richmond, VA and is currently a second-year Physician Assistant student at Drexel University in Philadelphia, PA. She completed her undergraduate degree at The College of William and Mary in Williamsburg, VA where she received her BS in Biology. Before PA school she worked as a rehab tech and medical scribe at an addiction clinic. In her free time she enjoys hiking, biking, group fitness, traveling and spending time with friends and family. 

Watch Out for Flying Discs: How High Altitude Changes Flight

by Laundon Transue, PA-S

Have you ever played disc golf? Maybe you know someone who has. Or maybe you’ve seen it from a distance. Perhaps you were taking a walk through a park or on a hiking trail and noticed a warning sign: “You Are Now Entering a Disc Golf Course – Watch Out for Flying Discs.” It can be a dangerous sport.

It’s just like golf, but with frisbees. Only instead of putting your ball into a hole in the ground, you throw your disc into an odd looking metal basket situated on top of a pole with a bunch of chains hanging from it. Maybe you’ve seen one such basket on your stroll through the park and thought “What is that thing?” That’s disc golf.

I learned to play this game in the forests and hills of Northern California, close to sea-level. Colorado is home to some of the best disc golf courses in the country, so I was excited to venture out and experience them after moving here. However, I could tell immediately that something was wrong the first time I played a round in Summit County – my discs were not flying like they used to!

How exactly were they flying differently? It was hard to say, I just knew they weren’t flying like I was expecting them to. It was throwing my game off. I’ve learned quickly that life at over 9,000 ft has all sorts of challenges not faced by sea-level dwellers. After a few rounds of disc golf up here and feeling like I had to learn how to play all over again, I wondered if my new high altitude environment had something to do with why my discs were misbehaving.

I set out to better understand the physics behind how discs fly through the air and how altitude affects these characteristics.

A lightweight flying disc traveling through the air is very sensitive to the atmosphere. At sea-level there is increased air density, so flying objects encounter more air resistance. As elevation increases, air density decreases, and there is less resistance in the air for flying objects to encounter. So yes, high altitude does cause flying objects to fly differently, but there’s a lot more to the story when it comes to disc golf.

Disc golf is a challenging game. The goal is to throw a ⅓ lb plastic disc hundreds of feet through the air across rough terrain while avoiding trees, hills, ponds, and eventually land in that odd metal basket, hopefully doing so in fewer throws than it takes your friends.

The fun part is throwing the disc far. Flying discs can travel much, much further than most other objects thrown by hand such as a baseball or football. The world record for throwing a golf disc stands at over 1,100 ft.

The hard part is throwing the disc accurately. Unlike a spherical object, the trajectory of a flying disc is not something easily graphed and calculated in your Physics 101 class. A ball thrown up in the air follows a relatively predictable parabolic path largely determined by the force of gravity acting on the sphere. It goes up, it comes down, easy-peasy.

The force of gravity also applies to a spinning disc as it flies. However, the unique shape of the disc, and the rotational torque (spin) acting on it, makes for a much more complex physics problem to solve. Disc golf is all about solving this physics problem in real time and in the real world.

As an object, such as a disc, flies through the air, it is constantly bumping into gas particles in the atmosphere which gradually slow the disc down until it eventually comes to a stop on the ground, this is wind (air) resistance. Also, the shape of a spinning disc thrown through the air generates lift, similar to the wings of an airplane. This means the air passing around the disc as it’s flying exerts an upward force which keeps the disc aloft longer, and this is why discs can be thrown so much further than a sphere. In summary, the air particles a disc encounters on its flight are responsible for both slowing down the disc due to air resistance, and for keeping the disc aloft due to lift. Fascinating!

Now here’s where it gets really complicated. You see, flying discs do not travel in a straight line. A disc thrown through the air will actually travel in an S-shaped line. If thrown by a right handed player, a disc will spin clockwise when viewed from above. When a disc leaves the golfer’s hand the clockwise spin will cause it to first start to drift to the right, then as the disc slows down it will start to drift back to the left, before finally landing on the ground. This property of flying discs to travel in an S-shaped line is termed stability.

Stability is a result of rotational torque and unequal air pressures generated on opposite sides of the disc. Think about the clockwise spinning disc described above. The left side of the disc (at the 9 o’clock position) is spinning into the wind, in the same vector as the trajectory of the disc. The right side of the disc (at the 3 o’clock position) is spinning away from the wind, in the opposite vector of the disc’s flight. This results in a high air pressure system on the left side of the disc, and a low air pressure system on the right side. Higher air pressure on the left means greater lift on the left. That unequal lift result is a gradual drifting of the disc to the right as it flies, and this is the first half of the S-shaped flight path caused by a disc’s stability.

To understand the second half of stability, we need to introduce another concept called gyroscopic precession. This is another complicated piece of physics, but it’s the same principle that keeps you from falling when riding on a hoverboard, and it’s what allows helicopters to maneuver around in the air. Gyroscopic precession says that if you apply a perpendicular force  to a spinning object, that force will be seen 90 degrees away in the direction of spin from where the force was applied. So if we have a clockwise spinning disc, and we apply an upward force at the 12 o’clock position, the disc will feel an upward force at the 3 o’clock position. Another example would be if we applied a downward force at the 7 o’clock position, then the disc would feel a downward force at the 10 o’clock position.

After the disc has traveled through the air for a bit it will start to slow down due to wind resistance. This means the disc will be moving at a slower velocity through the air, and will also be spinning at a slower rate. Slower speed through the air means less lift force acting on the disc and the disc will start to fall toward the ground. When the disc starts to fall, instead of the front of the disc slicing straight through the air like it did when it first left the golfer’s hand, the directional force of the air starts to push upward underneath the front of the disc. In other words, the disc is falling onto the air while it flies forward, and the air is now applying an upward force against the front of the disc.

So our disc is spinning clockwise, and now there is an upward force applied at the front of the disc (12 o’clock), then according to gyroscopic precession, the disc should feel an upward force at the 3 o’clock position (the right side of the disc). This upward force on the right side of the disc causes it to drift back toward the left until it eventually slows down to the point of landing on the ground.

Okay, that was a lot, let’s put it all together! A golf disc is thrown by a right handed player. The disc starts out flying through the air very fast and spinning at a high rate in a clockwise direction. The fast spinning disc creates higher pressure on the left side than the right due to air resistance. This left side pressure lifts and pushes the disc to the right as it’s flying. The disc starts to slow down and begins to fall, resulting in an upward force of air against the front of the disc. This upward air force produces a gyroscopic force 90 degrees away at the 3 o’clock position. The upward force on the right side of the disc causes it to fly back toward the left while the disc continues to slow and eventually lands on the ground.

Now that we know how discs are supposed to fly and how the atmospheric forces determine a disc’s flight, what changes should we expect to see when playing disc golf at high altitude?

At 9,000+ ft elevation there are significantly fewer gas particles in the atmosphere for discs to bump into during their flight. A disc will have less air resistance to deal with. That means it should fly faster and further, right? Not necessarily.

Remember, the atmosphere not only slows the disc down due to air resistance, it also provides the lift that keeps the disc up in the air for so long. Less gas particles in the atmosphere also mean less lift force.

So do discs fly shorter, further, or the same distance at high altitude? The answer is, it depends. Again, flying discs are a much more complicated physics problem than a flying baseball. Discs may fly further or shorter distances at high altitude compared to sea-level, but it depends on the type of disc, the player, and a whole host of other environmental factors such as specific elevation, temperature, humidity, and the direction of the wind.

What we can say, however, is that discs do fly differently at altitude. The shape of the S-path a disc takes at high altitude will look different due to the reduced air density, and this can spell trouble for a disc golfer who’s expecting their disc to turn right but instead it turns left.

During the first half of the stability S-curve, the disc is normally pushed toward the right due lift pressure created by air resistance. At high altitude less air resistance means less lift pressure generated during this first half of the S-curve, so the disc doesn’t move toward the right as much.

The second half of the S-curve is also changed. As we said before, less atmosphere mens less lift, so the disc will start to fall from its flight path sooner at high altitude. That means the upward air force on the front of the disc that results when it starts to fall will also occur sooner in the disc’s flight. Remember, this is the force that is felt by the disc 90 degrees away on the right side of the disc and pushes the disc to the left for the final part of its flight path.

At high altitudes discs drift less toward the right during the first half of their S-curve, and they begin the second half of their S-curve sooner along their flight path. The result is discs fly not so much in an S-shaped path, but rather a J-shaped, or hook-shaped path.

There you have it, High Altitude Disc Golf in a nut-shell. It was initially very frustrating when I started playing disc golf in Summit County. High altitude disc golf forces you to think about each hole and and each shot differently than you might at sea-level. The thin air changes the game dramatically, but that’s what I love most about disc golf. It’s a game that is virtually impossible to master, constantly challenges you, and can be enjoyed outside in the most beautiful and most extreme environments. Pick out a disc at your local sporting goods store and give it a try.

RSV: The Higher the Altitude, the Higher the Risk

Respiratory syncytial virus, RSV, is a common disease that predominantly affects infants and children throughout the world. Symptoms include mild fever, runny nose, coughing, and wheezing (CDC, 2021 and is the leading cause of bronchiolitis and pneumonia in children under the age of 1 in the United States. Because of this high risk of lower respiratory symptoms RSV is also the leading cause of hospitalizations within this age group (Sanofi Pasteur, 2021). Testing for RSV is quick and easy. Children under the age of 5 can be tested for RSV with a nasal swab and rRT-PCR test, similar to COVID-19 home tests (CDC, 2021) available at clinics and emergency rooms. . Unfortunately, preventing the spread of RSV and keeping these hospitalization rates to a minimum is more difficult at higher elevations.

One of our patients during admission after being diagnosed with RSV earlier in the day.

Higher elevations affect the body in many ways. The human body physiologically adapts within seconds of exposure to higher altitudes. Respiratory rate increases in order to compensate for the lower amount of oxygen circulating within the body (Scott, 2018). Within days to weeks, the body begins to acclimate to the higher altitude and this hypoxic state by maintaining this increased ventilation rate and increasing the amount of hemoglobin in the body (Scott, 2018). Due to the combination of effects on ventilation and oxygenation, managing respiratory infections like RSV becomes more difficult.

  The correlation between rates of RSV and higher altitudes has been studied more in recent years. It is hypothesized that the physiological changes that the body undergoes at higher altitude predisposes children to respiratory illnesses including RSV (Shi et al., 2015). In one study done in Colorado, the incidence of RSV within the population was higher than those at moderate and lower elevation areas. The rates of hospitalization increased 25% with children under the age of 1 and up to 53% with children between 1 and 4 (Choudhuri et al, 2006). Data shows that as altitude increases, the incidence of RSV increases, with elevations over 2500m considered as a modest predictor of RSV-related hospitalizations. The incidence of morbidity associated with RSV increases with higher elevation as well (Wu et al., 2015). This increased morbidity is attributed to the thick secretions that is caused by the virus. Since infants breathe through their nose until age 3, this collection of mucus causes respiratory issues including pauses in breathing with cyanosis called apnea. With studies showing the increased incidence, hospitalizations, and morbidity of RSV at higher altitudes, diagnoses of RSV should not be downplayed in children living at high altitudes.

Photo of the same patient as above on home oxygen after being discharged from the hospital.

It is important for providers and parents to be aware of the higher risk for more severe disease progression faced by children who reside at higher altitudes. Parents should recognize the symptoms of RSV and practice proper handwashing techniques to prevent the further spread of this disease within the community. Health care providers within these high-altitude areas should consider additional interventions and treatments such as home oxygen or nasal suctioning which may be beneficial to preventing hospitalizations due to RSV. Dr. Chris advises parents with older children in daycare or preschool to consider keeping them home during RSV season (November-April) when they have a new baby in the house. Although it is imperative to properly diagnose and treat RSV to avoid hospitalizations, obtaining a chest x-ray and treating with medications like albuterol or steroids is unnecessary. Ultimately, although RSV is a benign disease to most, in areas of higher elevation, it must be taken seriously order to prevent unfavorable outcomes.

References

Centers for Disease Control and Prevention. (2021, September 24). Symptoms and care of RSV (respiratory syncytial virus). Centers for Disease Control and Prevention. Retrieved April 28, 2022, from https://www.cdc.gov/rsv/about/symptoms.html 

Choudhuri, J. A., Ogden, L. G., Ruttenber, A. J., Thomas, D. S., Todd, J. K., & Simoes, E. A. (2006). Effect of altitude on hospitalizations for respiratory syncytial virus infection. Pediatrics, 117(2), 349–356. https://doi.org/10.1542/peds.2004-2795

Sanofi Pasteur. (2021). Rethink RSV. Retrieved April 28, 2022, from https://www.rethinkrsv.com/

Scott, B. (2018, June 13). How does altitude affect the body? Murdoch University. Retrieved April 28, 2022, from https://www.murdoch.edu.au/news/articles/opinion-how-does-altitude-affect-the-body#:~:text=Many%20people%20who%20ascend%20to,lethargy%2C%20dizziness%20and%20disturbed%20sleep 

 Shi, T., Balsells, E., Wastnedge, E., Singleton, R., Rasmussen, Z. A., Zar, H. J., Rath, B. A., Madhi, S. A., Campbell, S., Vaccari, L. C., Bulkow, L. R., Thomas, E. D., Barnett, W., Hoppe, C., Campbell, H., & Nair, H. (2015). Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta-analysis. Journal of iglobal health, 5(2), 020416. https://doi.org/10.7189/jogh.05.020416

Wu, A., Budge, P. J., Williams, J., Griffin, M. R., Edwards, K. M., Johnson, M., Zhu, Y., Hartinger, S., Verastegui, H., Gil, A. I., Lanata, C. F., & Grijalva, C. G. (2015). Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru. PloS one, 10(6), e0130233. https://doi.org/10.1371/journal.pone.0130233

Claire Marasigan is a 2nd year PA student currently studying at Midwestern University in Glendale, Arizona. Claire has lived her entire life in Arizona and went to Grand Canyon University for her undergraduate degree in Biology. Prior to PA school, she was a medical scribe trainer at St. Joseph’s Hospital in Phoenix. In her free time, she loves to cook, try new restaurants with friends, and play with her dog, Koji. 

Kids Living at Altitude are Built Different: How Phenotypic Variations in Pediatric Patients Born at Altitude Help Them Compensate for Their Hypoxic Environment

One of the phenomena I experienced while caring for pediatric patients in Summit County was the image of a [1] child with an oxygen saturation of 83% who wasn’t in any respiratory distress. This got me thinking: do adaptations in children exposed to chronic hypoxia at altitude prepare them to encounter an episode of acute hypoxia?

It turns out this phenomenon has been studied previously. Children permanently residing at high altitudes exhibit phenotypic variations to help them adapt to their chronically hypoxic environment. According to de Meer, K., et al., for those children living at altitudes greater than 3000m above sea level since gametogenesis, the opportunities for phenotypic plasticity are particularly excellent.

These changes in phenotypic expression have led to both theorized and proven physiologic differences in oxygen uptake, transport, systemic circulation, and consumption, allowing them to overcome the effects of chronic high-altitude hypoxia.

The lower partial pressure of oxygen causes high-altitude hypoxia to those who are visiting from lower altitudes. With less oxygen in the air, increased respiratory effort would be required to maintain the same oxygen levels as those children living at sea level. However, children living at altitude have physiologic increases in ventilation, lung compliance, and pulmonary diffusion, which help negate the need for augmented respiratory effort.

To conserve respiratory rate, increases in lung compliance and tidal volume have been observed in children living at altitude. In one study by Mortola, J. P., et al., lung compliance and tidal volume remained increased even while participants were on 100% supplemental oxygen.      This suggests that this is a permanent physiological adaptation in kids living at altitude.2

Additionally, children living at altitude are more efficient at delivering oxygen to their tissues. An increase in pulmonary diffusion capacity facilitates this improved efficiency. Pulmonary diffusion capacity is determined by the surface area available for diffusion. Assuming all other anatomic variables are the same in highlanders and lowlanders[2] , this increased capacity can only be explained by an increase in the number and size of alveoli.1 To study this possibility, researchers compared the lung volumes and chest dimensions of children exposed to chronic hypoxia at altitude since birth to those of children living at sea level and found that lung volumes and chest dimensions of children residing at altitude indeed were greater.

Despite this opportunity for increased oxygen uptake by the lungs of children living at altitude, the partial pressure of oxygen in their blood is still substantially lower. This decrease in arterial blood oxygen concentration that is associated with hypoxia encourages the kidneys to release erythropoietin, which subsequently stimulates the production of erythrocytes contributing to an increased erythrocyte and hemoglobin concentration in children living at altitude. Elevated hemoglobin concentration leads to a relative increase in arterial oxygen saturation, which compensates for the lower availability of oxygen at altitude.1

Despite the witnessed phenomenon of the ability of children living at altitude to adapt to acute hypoxia, it is still debated whether chronic hypoxemia in this population results in decreased oxygen consumption. New research has concluded that previously observed decreases in oxygen metabolism in newborns at altitude are reactions to acute stress and hypoxia and should not be considered an effect of chronic exposure to hypoxia.1 In other words, the ability of children living at altitude to decrease ventilation during an episode of acute hypoxia is due to a decrease in tissue metabolism only during that event of respiratory stress.

Like most things in life, these advantages do not come without consequences. Humans exposed to chronic hypoxia are prone to pulmonary hypertension; in fact, phenotypic, physiological changes in tidal volume and lung diffusion that improve oxygen uptake contribute to pulmonary hypertension. However, unlike children who develop pulmonary hypertension unrelated to altitude, highland children often present with a less severe clinical picture and fewer irreversible complications.1

Children born and residing at altitude offer a window into a world of medical phenomena that are little understood. The more we know about the physiological differences in this population, the better we can serve them as clinicians.

References

  1. de Meer, K., et al. “Physical Adaptation of Children to Life at High Altitude.” European Journal of Pediatrics, vol. 154, no. 4, Apr. 1995, pp. 263–72. Springer Link, https://doi.org/10.1007/BF01957359.
  2. Mortola, J. P., et al. “Compliance of the Respiratory System in Infants Born at High Altitude.” The American Review of Respiratory Disease, vol. 142, no. 1, July 1990, pp. 43–48. PubMed, https://doi.org/10.1164/ajrccm/142.1.43.

Lauren Thompson is a second-year Physician Assistant Student at Drexel University in Philadelphia. She is here all the way from sunny sea level, Florida, where she got her degree in Psychology with a minor in Biology from Florida State University. She is currently completing her clinical rotation, which has taken her all over the country with her feline and canine companions, Duke and Remi. Before PA school, Lauren worked as a Certified Nursing Assistant at a local hospital and a Medical Assistant at a pediatric specialty clinic. Outside of medicine, Lauren enjoys traveling, spending time with her animals, singing karaoke, playing disc golf, and taking in all of what mother nature has to offer, whether it’s hiking, skiing, diving, or enjoying the beach.