Category Archives: Acclimation

What happens to your body’s physiology when you move between low and high elevations?

Acclimation, Altitude Science, Backpacking, Child Growth & Development, Doc Talk, Exposure, Genetics, Health, High Altitude, High Altitude Training & Fitness, Medicine

Re-Entry HAPE: Leading Cause of Critical Illness in Mountain Teens

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Health care providers and people who live at altitude often believe that living in the mountains protects from altitude related illness. And yes, there are many ways the body acclimatizes over days, weeks, months, and years, as addressed in previous blog entries. However, as a physician who has practiced in high altitude communities for over 20 years, my personal observation that we are still at risk for serious complications was reenforced by a recent publication by Dr. Santiago Ucrós at the Universidad de los Andes School of Medicine in Santa Fe de Bogotá, Colombia. His article, High altitude pulmonary edema in children: a systemic review, was published in the journal Pediatric Pulmonology in August 2022. He included 35 studies reporting 210 cases, ages 0-18 years, from 12 countries.

A chart titled "HAPE in Children" illustrates cases of high altitude pulmonary edema by country.

Consistent with our experience in Colorado, the most common ages were 6-10 years and second most common 11-15 years. I have not seen or read any reports of adults affected. Cases included two deaths, which I have also seen here.

I receive reports on any of my patients seen in urgent or emergency care. Accidents, avalanches, and suicide attempts are what we think of first needing emergency care in the mountains. However, the most common critical condition is Reentry HAPE. This is a form of pulmonary edema that can occur in children who are returning from a trip to lower altitude. Think visiting Grandma during school break.  Dr. Ucrós’ review also confirms that all presentations of HAPE (classic, as in visitors, reentry, and HARPE, resident children with no history of recent travel) are more common in males by a 2.6 to 1 ratio. Analysis of time spent at lower altitude before the episode showed a range of 1.6 to 30 days with a mean of 11.3 days. Mean time between arrival and onset of symptoms for all types of HAPE was 16.7 hours. The minimum altitude change reported in a HAPE case was 520 meters (1700 feet), which is the difference between Frisco, CO (Summit County) and Kremmling, CO (Grand County, the next county over). A new form of HAPE in high altitude residents who travel to higher altitude was designated HL-HAPE in this review.  A case report will be featured in an upcoming blog interview with a Summit County resident who traveled to Mt. Kilimanjaro.

As with all cases of HAPE, the victims develop a cough, sound congested as the fluid builds up in their lungs, have fatigue, exercise intolerance, with rapid onset over hours of exposure to altitude, usually above 8000 ft or 2500m. Oxygen saturations in this paper ranged from 55 to 79%. My patients have been as low at 39% in the emergency room.  Children presenting earlier or with milder cases come to the office with oxygen saturations in the 80’s. An underlying infection such as a cold or influenza is nearly always present and considered a contributing factor. Everyone living or visiting altitude should have an inexpensive pulse oximeter which can measure oxygen on a finger. Access to oxygen and immediate treatment for values under 89 can be life-saving.

The recurrence rate for all types of HAPE is about 20%. Most children never have another episode, but some have multiple. Preventive measures include slower return to altitude, such as a night in Denver, acetazolamide prescription taken two days before and two days after, and using oxygen for 24-48 hours on arrival. Most families learn to anticipate, prevent, or treat early and don’t need to see a health care provider after the first episode.

On January 26, 2023 I met with Dr. Ucrós and other high altitude scientists including Dr. Christina Eichstaedt, genetics expert at the University of Heidelberg in Germany, Dr. Deborah Liptzen, pediatric pulmonologist, and Dr. Dunbar Ivy, pediatric cardiologist, both from the University of Colorado and Children’s Hospital of Colorado, and Jose Antonio Castro-Rodríguez MD, PhD from the Pontifica Universidad Católica in Santiago de Chile.

We discussed possible genetic susceptibility to HAPE and hypoxia in newborns at altitude with plans to conduct studies in Bogotá and Summit County, Colorado.

Acclimation, Altitude Science, Exposure, Genetics, Health, High Altitude, Sleep at Altitude

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

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Epigenetics slide from speaker at Hypoxia conference in La Paz Bolivia, 2022

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.3 To clarify, the most notable epigenetic change is the methylation of cytosine located 5’ to guanine, known as CpG dinucleotides.3 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.3 

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.4 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.4 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.4 

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.5 Both genes are responsible for cell proliferation and survival.5 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.

Acclimation, Altitude Science, Athletic Training, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Mountaineering

When Altitude gets High, does Stroke get higher?

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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.

Acclimation, Altitude Science, Athletic Training, Child Growth & Development, Doc Talk, Exposure, Health, High Altitude, High Altitude Training & Fitness, Medicine, Mountaineering

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

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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.

Acclimation, Altitude Science, Child Growth & Development, Doc Talk, Exposure, Health, High Altitude, Medicine

HARPE is the New HAPE

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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.

Acclimation, Altitude Science, Backpacking, Exposure, Health, High Altitude, High Altitude Training & Fitness, Medicine, Mountaineering, Technology

High-Altitude Pulmonary Edema is not just for tourists

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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/

Acclimation, Altitude Science, Athletic Training, High Altitude, High Altitude Training & Fitness, Hyperbaric Therapy, Technology

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

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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. 

Acclimation, Exposure, Health, High Altitude, High Altitude Training & Fitness

Non-Freezing Cold Injury

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Eighteen-year-old, NorAm skier, NCAA Division I Rugby player, and lover of the outdoors, presents to the clinic complaining of cold, painful hands. She states hands always feel cold, and in cold weather they are extremely painful. Blood tests to rule out vascular disease were normal. What could be the cause of this?

Normally, in cold weather our bodies work to keep essential organs functioning. Skin is not considered essential. When exposed to cold, blood vessels constrict, decreasing blood flow to the skin. Because the metabolic demand of our skin is low, more important organs like our heart and brain need the blood flow. Paradoxically, exposure to cooler temperatures like those below 15 degrees Celsius or 59 degrees Fahrenheit can cause cold-induced vasodilation. This allows blood to flow to the skin to help prevent more serious injury or frostbite. The vasodilation cycles in 5- to 10-minute intervals.

Nonfreezing cold injury (NFCI) occurs when tissues are damaged due to prolonged cooling exposure, but not freezing temperatures. NFCI is due to exposure of the extremities to temperatures around 0 to 15°C or 32 to 59°F, commonly the hands and feet. Current theory is that NFCI is due to a combination of vascular and neural dysfunction. With prolonged vasoconstriction, the skin experiences reduced blood flow with a neurological component influencing the damage as well.

Some patients living in cold environments like the Inuit, Sami people, and Nordic fisherman have a larger cold-induced vasodilation response and more rapid cycling. This is thought to decrease their risk of NFCI. Is it possible that patients who develop NFCI have a smaller and slower cycling of their cold-induced vasodilation? Could this be the issue with our patient with NFCI?  Further research is needed to learn more about NFCI and find better ways to treat it.

What we do know is there are 4 Stages of NFCI:

Stage 1: During the cold exposure – Loss of sensation, numbness, clumsiness. Usually painless unless rewarming is attempted.

Stage 2: Following cold exposure – occurs during and after rewarming. Skin can develop a mottled pale blue-like color, area continues to feel cold and numb, possible swelling. Usually lasts a few hours to several days.

Stage 3: Hyperemia – affected area becomes red and painful. Begins suddenly and lasts for several days to weeks.

Stage 4: Following hyperemia – affected areas appear normal but are hypersensitive to the cold. Areas may remain cold even after short exposure to the cold. This stage can last for weeks to years.

Mountains covered in pine forests reach up past tree line toward a deep blue sky spotted with fluffy white cumulous clouds over two people in bikinis standing on paddle boards reflected with the clouds in the dark water below them.

Outdoor paddle sports like kayaking and canoeing put patients at greatest risk due to the continual exposure to the cold, wet environment. It was thought that in order to have NFCI, one had to be exposed to both cold and wet environments. However, it has been shown that this is not always the case. Like in our patient, exposure to just cold environment can trigger the syndrome. Our 18-year-old patient is an avid skier and spends most of the winter on the mountain. It was also noted that she enjoys paddleboarding and kayaking, which were recognized as triggers for the hand pain. We are unable to determine exactly what caused our patient to develop this syndrome. But we do know it affects their life significantly.

 We choose to live in the mountains because of the things we love. Whether it is hiking, biking, skiing, kayaking, paddleboarding, or the hundreds of other activities offered in this area, we are at risk of NFCI. Currently, there is no good treatment for this syndrome. Prevention is  best. The purpose of this blog is to share information about staying healthy at high altitude. Sharing this information on the stages of NFCI with friends and family will help prevent this painful, debilitating syndrome.

Resources

Nonfreezing cold water (trench foot) and warm water immersion injuries. UpToDate. https://www.uptodate.com/contents/nonfreezing-cold-water-trench-foot-and-warm-water-immersion-injuries/print#:~:text=Nonfreezing%20cold%20injury%20%E2%80%94%20NFCI%20is,to%2059%C2%B0F)%20conditions. Accessed July 14, 2022.

Oakley B, Brown HL, Johnson N, Bainbridge C. Nonfreezing cold injury and cold intolerance in Paddlesport. Wilderness & Environmental Medicine. 2022;33(2):187-196. doi:10.1016/j.wem.2022.03.003

Rachel Cole is a Physician Assistant Student at Red Rocks Community College in Denver, Colorado. She originally grew up in Salt Lake City, Utah, where she learned to love the outdoors. She studied Biology at Western Colorado University in Gunnison, Colorado prior to PA school. She played soccer for the college and fell in love with Colorado and small mountain towns. When she is not studying for school, she enjoys skiing, hiking, backpacking, fishing, waterskiing, canyoneering, and any other activities that get her outside. After graduation she hopes to practice family medicine in a rural community in the mountains.

Acclimation, Child Growth & Development, Health, High Altitude, Medicine

Beneficial Effects of Chronic Hypoxia

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Living in Summit County, Colorado has its perks – residents are within a 20 to 40 minute drive to five world class ski resorts, and some of the most beautiful Rocky Mountain trail systems are accessible right out our back door. With the endless opportunities drawing residents outdoors to partake in physical activity, it comes as no surprise that Summit County is considered one of the healthiest communities in the country. However, there may be more than meets the eye when it comes to explaining this, as it also has something to do with the thin air.

As a Summit County native, you have likely heard the term “hypoxia” or “hypoxemia” mentioned a time or two. So what does this mean? Simply put, these words describe the physiological condition that occurs when there is a deficiency in the amount of oxygen in the blood, resulting in decreased oxygen supply to the body’s tissues. When this occurs in the acute setting, it may result in symptoms such as headache, fatigue, nausea, and vomiting. These are common symptoms experienced by those with altitude illness, also known as acute mountain sickness. While these symptoms can cause extreme discomfort and may put a huge damper on a mountain vacation, they are not usually life threatening. However, in a small number of people, development of more serious conditions such as a high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE) can occur. The treatment for all conditions related to altitude illness is oxygen, whether via return to lower elevations or by a portable oxygen concentrator that allows you to stay where you are. While altitude illness generally affects those who rapidly travel from sea level to our elevation, it has also been known to affect residents returning home to altitude, usually after a period of two or more weeks away. In a very small subset it can occur after a period of only a day or two. This generally occurs in those with a preexisting illness, where altitude exacerbates the condition.

While the acute effects of altitude can clearly have detrimental effects on one’s physical well-being, there is emerging research demonstrating that chronic hypoxia may actually come with several health benefits. Long time Summit County business owner and community pediatrician, Dr. Chris Ebert-Santos of Ebert Family Clinic in Frisco, has spent quite some time studying the effects of chronic high-altitude exposure, and recently attended and presented at the Chronic Hypoxia Symposium in La Paz, Bolivia, the highest capital city in the world.

It is important to first understand the adaptations that occur in our bodies as a result of long-term hypoxia. The ability to maintain oxygen balance is essential to our survival.

So how do those of us living in a place where each breath we take contains about ⅓ fewer oxygen molecules survive?

Simply put, we beef up our ability to transport oxygen throughout our body. To do this, our bodies, specifically the kidneys, lungs and brain increase their production of a hormone called erythropoietin, commonly known as EPO. This hormone signals the body to increase its production of red blood cells in the bone marrow. Red blood cells contain oxygen binding hemoglobin proteins that deliver oxygen to the body’s tissues. Thus, more red blood cells equal more oxygen-carrying capacity. In addition to increasing the ability to carry oxygen, our bodies also adapt on a cellular level by increasing the efficiency of energy-producing biochemical pathways, and by decreasing the use of oxygen consuming processes2. Furthermore, the response to chronic hypoxia stimulates the production of growth factors in the body that work to improve vascularization2, thus, increased ability for oxygenated blood to reach its destination. 

So, how can these things offer health benefit?

To start, it appears that adaptation to continuous hypoxia has cardio-protective effects, conferring defense against lethal myocardial injury caused by acute ischemia (lack of blood flow) and the subsequent injury caused by return of blood to the affected area3. The exact mechanism of how this occurs is not well understood, but it seems that heart tissue adapts to be better able to tolerate episodes of ischemia, making it more resistant to damage that could otherwise be done by decreased blood flow that occurs during what is commonly known as a heart attack. This same principle applied to ischemic brain damage when tested in rat subjects. Compared to their normoxic counterparts, rats pre-conditioned with hypoxia sustained less ischemic brain changes when subjected to carotid artery occlusion, suggesting neuroprotective effects of chronic hypoxia exposure4.

Additionally, it appears that altitude-adapted individuals may be better equipped to combat a pathological process known as endothelial dysfunction5. This process is a driving force in the development of atherosclerotic, coronary, and cerebrovascular artery disease. Altitude induces relative vasodilation of the body’s blood vessels compared to lowlanders2. A relaxing molecule known as nitric oxide, or NO, assists with causing this dilation, and in turn the resultant dilated blood vessels produce more of this compound5. The molecule has protective effects on the inner linings of blood vessels and helps to decrease the production of pro-inflammatory cytokines that damage the endothelium5. This damage is what kickstarts the cascade that leads to atherosclerosis in our arteries. Thus, a constant state of hypoxia-induced vasodilation may in fact decrease one’s risk of developing occlusive vascular disease. 

The topics mentioned above highlight a few of the proposed mechanisms by which chronic hypoxia may be beneficial to our health. However, do keep in mind that there are potential detrimental effects, including an increased incidence of pulmonary hypertension as well as exacerbation of preexisting conditions such as COPD, structural heart defects and sleep apnea, to name a few6. Research regarding the effects of chronic hypoxia on the human body is ongoing, and given its significance to those of us living at elevations of 9,000 feet and above, it is important to be aware of the impact our physical environment has on our health. Dr. Ebert-Santos is avidly involved in organizations dedicated to better understanding the health impacts of chronic hypoxia, and has several current research projects of her own that may help us to further understand the underlying science.

Kayla Gray is a medical student at Rocky Vista University in Parker, CO. She grew up in Breckenridge, CO, and spent her third year pediatric clinical rotation with Dr. Chris at Ebert Family Clinic. She plans to specialize in emergency medicine, and hopes to one day end up practicing again in a mountain community. She is an avid skier, backpacker, and traveler, and plans to incorporate global medicine into her future practice.

Citations

  1. Theodore, A. (2018). Oxygenation and mechanisms for hypoxemia. In G. Finlay (Ed.), UpToDate. Retrieved May 2, 2019, from https://www-uptodate-com.proxy.rvu.edu/ contents/oxygenation-and-mechanisms-of-hypoxemia?search=hypoxia&source=search_ result&selectedTitle=1~150&usage_type= default&display_rank=1#H467959
  2. Michiels C. (2004). Physiological and pathological responses to hypoxia. The American journal of pathology, 164(6), 1875–1882. doi:10.1016/S0002-9440(10)63747-9. Retrieved May 2, 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615763/ 
  3. Kolar, F. (2019). Molecular mechanism underlying the cardioprotective effects conferred by adaptation to chronic continuous and intermittent hypoxia. 7th Chronic Hypoxia Symposium Abstracts. pg 4. Retrieved May 2, 2019. http://zuniv.net/symposium7/Abstracts7CHS.pdf
  4. Das, K., Biradar, M. (2019). Unilateral common carotid artery occlusion and brain histopathology in rats pre-conditioned with sub chronic hypoxia. 7th Chronic Hypoxia Symposium Abstracts. pg 5. Retrieved May 2, 2019. http://zuniv.net/symposium7/Abstracts7CHS.pdf
  5. Gerstein, W. (2019). Endothelial dysfunction at high altitude. 7th Chronic Hypoxia Symposium Abstracts. pg 11. Retrieved May 7, 2019. http://zuniv.net/symposium7/Abstracts7CHS.pdf
  6. Hypoxemia. Cleveland Clinic. Updated March 7, 2018. Retrieved May 9, 2019. https://my.clevelandclinic.org/health/diseases/17727-hypoxemia
Acclimation, Altitude Science, Child Growth & Development, Genetics, Health, High Altitude

RSV: The Higher the Altitude, the Higher the Risk

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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.