Category Archives: Child Growth & Development

Children grow and develop differently at high altitudes than they do at sea level

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Unveiling the Hidden Risks of Living at High Altitude on our Kidney Health, and What it Might Mean for Your Child

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The hallmark concern for the body living at high altitude is low oxygen. We breathe in less, and thus less is sent throughout our blood stream to our tissues. We are quick to think about how this affects our heart and lungs, but what about our kidneys? What are our kidneys even responsible for?

Kidneys filter, reabsorb, and excrete our blood in the form of urine. They connect our cardiovascular system with our genitourinary system. The flow through the kidneys also helps monitor and adjust our blood pressure. Their importance is truly undervalued. When they receive less oxygen than preferred (hypoxia), they will become injured. Specifically, the glomerulus (term for the filter) will become affected. When this happens, it is not efficient at filtration, and protein will spill out into our urine (proteinuria), a key feature of High Altitude Renal Syndrome (HARS).

Zooming further in below

And even further…

Another issue involves uric acid, the chemical at fault for causing gout. Due to the filter injury sustained from low oxygen, uric acid excretion is affected. It can thus build up in our musculoskeletal system and other tissues. It is famous for causing red, swollen, and painful joints. The enzyme that helps create uric acid (xanthine oxidase) is also turned on by reactive oxygen species during hypoxia. This then causes further uric acid crystal deposition in our body. This can present in patients from adolescent years through adulthood, ranging from fleeting pain to amputations from severe bone infections. We have found that for younger patients, diet plays a lesser part than genetic predisposition and hypoxia.

So how is this treated? We are still researching the best course of action. We can treat with drugs that work by inhibiting the previously specified enzyme: xanthine oxidase. These include oral allopurinol, febuxostat, and even IV pegloticase infusions. But we are primarily focused on prevention and holistic care here, so we would prefer to use supplemental oxygen therapy for those that struggle to maintain oxygen saturations in the healthy ranges. Acetazolamide is also helpful in cases. This medication works to increase our respiratory drive, helping us breathe off CO2 and breathe in more oxygen. Contact us to see what method might be right for you.

This research was brought to us by a stroke of luck. A stranger on an airplane, and a son’s coworker. This stranger happened to be a nephrologist (kidney doctor) who is studying how altitude affects the kidneys. In working with him and his team at University of Colorado Anschutz, the team at Ebert Family Clinic in Frisco, Colorado (9000′) have been ordering broader lab panels (including uric acid) for their patients and seeking those with questionable renal labs. Another patient seen by the Ebert Family Clinic team has been severely impacted by gout. With multiple amputations before the patient’s 30th birthday, this case has motivated the health care team to prevent this from happening to others in their high altitude community.

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Carter Odean is a third-year medical student at Rocky Vista University. He was born and raised outside of Denver, Colorado before heading to Gonzaga University in Spokane, Washington where he studied biology and completed research on an invasive bee species there while playing club lacrosse. After graduating in 2019, he then came back to Denver to complete his Master’s in Biomedical Sciences at Regis University. After Regis, he started as a Clinical Research Coordinator at Anschutz Medical campus, working on multiple Diabetes Mellitus Type 2 research trials. He is in the Rural & Wilderness Track which is his favorite part about school. He plans to work as a rural Pediatrician or Family Medicine Physician. In his free time, you can find him dirt biking, fly fishing, skiing, and relaxing with friends and family. 

References

  1. Schoene, R.B. “High altitude renal syndrome: polycythemia, hyperuricemia, microalbuminuria, and hypertension.” High Alt Med Biol. 2002 Spring;3(1):65-73. doi: 10.1089/152702902753639371. PMID: 11949751.
  2. Bigham, A.W., Lee, F.S. “Tibetan and Andean patterns of adaptation to high-altitude hypoxia.” Hum Biol. 2014 Oct;86(4):321-37. doi: 10.3378/027.086.0401. PMID: 25700353; PMCID: PMC4438718.
  3. Beall, C.M., Cavalleri, G.L., Deng, L., et al. “Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders.” Proc Natl Acad Sci U S A. 2010 Mar 9;107(25):11459-64. doi: 10.1073/pnas.1002443107. Epub 2010 Feb 22. PMID: 20176925; PMCID: PMC2895106.
  4. Simonson, T.S., Yang, Y., Huff, C.D., et al. “Genetic evidence for high-altitude adaptation in Tibet.” Science. 2010 Sep 10;329(5987):72-5. doi: 10.1126/science.1189406. PMID: 20616233; PMCID: PMC3490534.
  5. Schoene, R.B., Swenson, E.R. “Cobalt-Induced Chronic Mountain Sickness: Pathophysiological Mechanisms and Genetic Susceptibility.” High Alt Med Biol. 2017 Mar;18(1):1-5. doi: 10.1089/ham.2016.0106. PMID: 28145824.Baillie, J.K., Bates, M.G., Thompson, A.A., et al. “Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude.” Chest. 2007 Dec;132(6):S275. doi: 10.1378/chest.132.6.275. PMID: 18079246.
  6. Yu, K.H., Wu, Y.J., Tseng, W.C., et al. “Risk of end-stage renal disease associated with gout: a nationwide population study.” Arthritis Res Ther. 2012 Jun 27;14(3):R83. doi: 10.1186/ar3818. PMID: 22738152; PMCID: PMC3446515.
  7. Bhat, A., Deshmukh, A., Anand, S., et al. “Acute Myocardial Infarction due to Coronary Artery Embolism in a Patient with Severe Hyperuricemia.” J Assoc Physicians India. 2019 Nov;67(11):90-91. PMID: 31801335.
  8. Khanna, D., Khanna, P.P., Fitzgerald, J.D., et al. “2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia.” Arthritis Care Res (Hoboken). 2012 Oct;64(10):1431-46. doi: 10.1002/acr.21772. PMID: 23024028.
  9. Schoene, R.B., Swenson, E.R. “Treatment of Cobalt-Induced Chronic Mountain Sickness.” High Alt Med Biol. 2017 Mar;18(1):74-77. doi: 10.1089/ham.2016.0135. PMID: 28145823.
  10. Schoene, R.B., Hackett, P.H., Henderson, W.R., et al. “High Altitude Medicine and Physiology, Fourth Edition.” CRC Press, 2007.
  11. Burtscher, M., Mairer, K., Wille, M., et al. “Risk of acute mountain sickness in tourists ascending to 4360 meters by cable car.” High Alt Med Biol. 2004 Summer;5(2):141-6. doi: 10.1089/1527029041352154. PMID: 15265307.
  12. Baumgartner, R.W., Bärtsch, P. “Chronic mountain sickness and the heart.” Prog Cardiovasc Dis. 2010 May-Jun;52(6):540-9. doi: 10.1016/j.pcad.2010.02.009. PMID: 20417390.
Acclimation, Altitude Science, Child Growth & Development, Doc Talk, Genetics, Health, High Altitude

The Frisco Score: A New Tool for Diagnosing HAPE

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by Madison Palmiero, PA-S

While HAPE may be a run-of-the-mill diagnosis for providers with years of experience practicing at altitude, it can be less straightforward for those who are unfamiliar with the condition. There are currently three recognized categories of HAPE. Classic HAPE (C-HAPE)  occurs when someone who resides at low altitude travels to high altitude and develops pulmonary edema. Re-entry HAPE (R-HAPE) occurs when high altitude residents travel to low altitude, then return to high altitude. High-altitude resident pulmonary edema (HARPE) occurs in high altitude residents without a change in altitude. HARPE is often brought on by an upper respiratory tract infection. 

HAPE and pneumonia can have similar presentations including shortness of breath, cough, fatigue, and malaise. Patients with either condition may have decreased oxygen saturation levels and abnormal findings on chest radiography. In response to this phenomena, Dr. Chris Ebert-Santos of Ebert Family Clinic in Frisco, Colorado (9000′) and Sean Finnegan, PA-C set out to develop a scoring system to differentiate the two diagnoses. If providers could easily differentiate between pneumonia and HAPE, this would shorten the time from presentation to diagnosis and would avoid unnecessary antibiotic use.

Dr. Chris and Sean Finnegan, PA-C summarized their research findings into a scoring system named the “Frisco Score”. They analyzed data from St. Anthony Summit Medical Center and associated clinics at or above ~2,760 meters above sea level from January 1, 2018 to May 30, 2023. The study looked at patients under the age of 19 who presented with hypoxemia or other respiratory concerns and had a chest x-ray performed and oxygen saturation measured. The final case review consisted of 138 total patients with 77 diagnosed with HAPE, 38 diagnosed with pneumonia, and 23 diagnosed with concomitant HAPE and pneumonia. Variables found to have no significance included gender, age, heart rate, and temperature. Variables with significance included respiratory rate, number of days ill, oxygen saturation, and chest x-ray findings. These significant variables were used to develop the Frisco Score. They do include a disclaimer that these findings are preliminary results on a small data set. Thus, as of yet, the Frisco Score should not be used on its own to make a diagnosis, but rather should be used as a clinical tool in differentiating conditions with similar presentations. 

Oxygen saturation varied greatly between patients with HAPE and those with pneumonia. Patients diagnosed with HAPE had an average oxygen saturation of 74% and those with pneumonia had an average of 92%. 

Patients who were diagnosed with HAPE had a higher average respiratory rate compared to those diagnosed with pneumonia.

 In patients diagnosed with HAPE, the duration of illness, or number of days ill, was shorter than those diagnosed with pneumonia. 

In comparison of chest x-rays, patients with HAPE were more likely to have diffuse findings and patients with pneumonia were more likely to have focal findings. 

Overall, there were no variables associated with a concomitant diagnosis of pneumonia and HAPE.

The asphalt road in the foreground leads past a sign for Common Spirit St. Anthony Summit Hospital just before the shelter over the entrance to a building labeled "ambulance" with deep green conifer forests stretching halfway up tall grey rocky mountains in the backgroundl.

In summary, patients diagnosed with HAPE had decreased oxygen saturation, increased respiratory rate, and diffuse findings on chest x-ray; while patients diagnosed with pneumonia had a longer duration of illness and focal findings on chest x-ray. The Frisco Score takes these variables into account to help differentiate a diagnosis of HAPE in children. Dr. Chris and Sean Finnegan, PA-C are currently presenting their findings at the 8th World Congress on Mountain and Wilderness Medicine in Snowbird, Utah. They hope that in the near future, the Frisco Score will be used to facilitate the diagnosis of HAPE by providers in high altitude communities state-wide.

References

1. Ebert-Santos, C. (2017). High-Altitude Pulmonary Edema in Mountain Community Residents. High Altitude Medicine & Biology, 18 (3), 278-284. https://doi.org/10.1089/ham.2016.0100

2. Ebert-Santos, C., Finnegan, S. (2024). Differentiating Pneumonia & HAPE in Children.

Acclimation, Altitude Science, Asthma, Child Growth & Development, COVID-19, Doc Talk, Exposure, Genetics, Health, High Altitude, Medicine, Mountaineering, Pandemic, Sleep at Altitude, Technology

Can I Ever Go Back Up To High Altitude Again? – Recurrence Risk of HAPE & HARPE

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by Taylor Kligerman, PA-S

Can I ever return to high altitude? Do I need to move down to a lower elevation?

Disease processes often differ at high altitudes. Some conditions have only been known to occur at high elevations. Most of the resources cited in this blog refer to ‘high altitude’ being at or above 2,500 meters or 8,200 feet.

Ebert Family Clinic in Frisco, Colorado is at 9,075 ft. Many areas in the immediate vicinity are over 10,000′, with some patients living above 11,000′. Two of the more common conditions seen in patients at Ebert Family Clinic are high altitude pulmonary edema (HAPE) and high altitude resident pulmonary edema (HARPE), similar conditions that affect slightly different populations in this region of the Colorado Rocky Mountains.

In “classic” HAPE, a visitor may come from a low-altitude area to Frisco on a trip to ski with friends. On the first or second day, the person notices a nagging cough. They might wonder if they caught a virus on the plane ride to Denver. The cough is usually followed by shortness of breath that begins to make daily tasks overwhelmingly difficult. One of the dangerous aspects of HAPE is a gradual onset leading patients to believe their symptoms are caused by something else. A similar phenomenon is seen in re-entry HAPE, where a resident of a high altitude location travels to low altitude for a trip and upon return experiences these same symptoms [1].

In HARPE, a person living and working here in Frisco may be getting ill or slowly recovering from a viral illness and notices a worsening cough and fatigue. These cases are even more insidious, going unrecognized, and so treatment is sought very late. Dr. Christine Ebert-Santos and her team at Ebert Family Clinic hypothesize that while residents have adequately acclimated to the high-altitude environment, the additional lowering of blood oxygen due to a respiratory illness with inflammation may be the inciting event in these cases.

In both cases, symptoms are difficult to confidently identify as a serious illness versus an upper respiratory infection, or simply difficulty adjusting to altitude. For this reason, Dr. Chris recommends that everyone staying overnight at high altitude obtain a pulse oximeter. Many people became familiar with the use of these instruments during the COVID-19 pandemic. The pulse oximeter measures what percent of your blood is carrying oxygen. At high altitude, a healthy level of oxygenation is typically ≥90%. This is an easy way to both identify potential HAPE/HARPE, as well as reassure patients they are safely coping with the high-altitude environment [2].

HAPE and HARPE are both a direct result of hypobaric hypoxia, a lack of oxygen availability at altitude due to decreased atmospheric pressures. At certain levels of hypoxia, we observe a breakdown in the walls between blood vessels and the structures in lungs responsible for oxygenating blood. The process is still not totally understood, but some causes of this breakdown include an inadequate increase in breathing rates, reduced blood delivered to the lungs, reduced fluid being cleared from the lungs, and excessive constriction of blood vessels throughout the body. These processes cause fluid accumulation throughout the lungs in the areas responsible for gas exchange making it harder to oxygenate the blood [3].

We do know that genetics play a significant role in a person’s risk of developing HAPE/HARPE. Studies have proposed many different genes that may contribute, but research has not, so far, given healthcare providers a clear picture of which patients are most at-risk. Studies have shown that those at higher risk of pulmonary hypertension (high blood pressure in the blood vessels of your lungs), are more likely to develop HAPE [4]. This includes some types of congenital heart defects [5,6]. High blood pressures in the lungs reach a tipping point and appear to be the first event in this process. However, while elevated blood pressures in the lungs are essential for HAPE/HARPE, this by itself, does not cause the condition. The other ingredient necessary for HAPE/HARPE to develop is uneven tightening of the blood vessels in the lungs. When blood vessels are constricted locally, the blood flow is shifted mainly to the more open vessels, and this is where we primarily see fluid leakage. As the blood-oxygen barrier is broken down in these areas, we may also see hemorrhage in the air sacs of the lungs [3].

One observation healthcare providers and scientists have observed is that HAPE/HARPE can be rapidly reversed by either descending from altitude or using supplemental oxygen. Both strategies increase the availability of oxygen in the lungs, reducing the pressure on the lungs’ blood vessels by vasodilation, quickly improving the integrity of the blood-oxygen barrier.

In a preliminary review of over 100 cases of emergency room patients in Frisco diagnosed with hypoxemia (low blood oxygen content) Dr. Chris and her team have begun to see trends that suggest the availability of at-home oxygen markedly reduces the risk of a trip to the hospital. This demonstrates that patients with both at-home pulse oximeters and supplemental oxygen have the capability to notice possible symptoms of HAPE, assess their blood oxygen content, and apply supplemental oxygen if needed. This stops the development of HAPE/HARPE before damage is done in the lungs. In the case of many of our patients, these at-home supplies prevent emergencies and allow patients time to schedule an appointment with their primary care provider to better evaluate symptoms.

Additionally, Dr. Chris and her team have observed that patients with histories of asthma, cancer, pneumonia, and previous HAPE/HARPE are often better educated and alert to these early signs of hypoxia and begin treatment earlier on in the course of HAPE/HARPE, reducing the relative incidence identified by medical facilities. There are many reasons to seek emergent care such as low oxygen with a fever. Patients with other existing diseases causing chronically low oxygen such as chronic lung disease may not be appropriately treated with  supplemental oxygen, although this is a very small portion of the population. Discussions with healthcare providers on the appropriate prevention plan for each patient will help educate and prevent emergency care visits in both residents and visitors.

A young child with short brown hair and glasses with dark, round frames wears a nasal canula for oxygen.

Studies of larger populations have yet to be published. A review of the case reports in smaller populations suggests that the previously estimated recurrence rate of 60-80% is exaggerated. This is a significant finding as healthcare providers have relied on this recurrence rate to make recommendations to their patients who have been diagnosed with HAPE. A review of 21 cases of children in Colorado diagnosed with HAPE reported that 42% experienced at least one recurrence [7]. This study was conducted by voluntary completion of a survey by the patients (or their families) which could lead to significant participation bias affecting the results. Patients more impacted by HAPE are more likely to complete these surveys. Another study looking at three cases of gradual re-ascent following an uncomplicated HAPE diagnosis showed no evidence of recurrence. The paper also suggested there may be some remodeling of the lung anatomy after an episode of HAPE that helps protect a patient from reoccurrence [8]. Similar suggestions of remodeling have been proposed through evidence of altitude being a protective factor in preventing death as demonstrated by fatality reports from COVID-19[9].

Without larger studies and selection of participants to eliminate other variables like preexisting diseases, we are left to speculate on the true rate of reoccurrence based on the limited information we have. Strategies to reduce the risk of HAPE/HARPE such as access to supplemental oxygen, pulse oximeters, and prescription medications [10] are the best way to prevent HAPE/HARPE. Research should also continue to seek evidence of individuals most at risk for developing HAPE/HARPE [11].

A woman with reddish-brown, straight hair just below her shoulders, wears a white coat over a mustard-colored shirt, smiling.

Taylor Kligerman is a third-year medical student at Rocky Vista University with plans to complete a residency in emergency medicine. She was born and raised in Flossmoor, IL, and became interested in medicine following her first medical mission trip to Gonaïves, Haiti in 2010. Taylor has extensive experience in wilderness and remote emergency medicine. Before starting medical school, she was certified as a wilderness EMT and gained experience in remote areas of Canada and Western North Carolina on whitewater expeditions and as a volunteer with local search and rescue. Her personal interests include camping, skiing, and all paddle sports.

References

  1. Ucrós S, Aparicio C, Castro-Rodriguez JA, Ivy D. High altitude pulmonary edema in children: A systematic review. Pediatr Pulmonol. 2023;58(4):1059-1067. doi:10.1002/ppul.26294
  2. Deweber K, Scorza K. Return to activity at altitude after high-altitude illness. Sports Health. 2010;2(4):291-300. doi:10.1177/1941738110373065
  3. Bärtsch P. High altitude pulmonary edema. Med Sci Sports Exerc. 1999;31(1 Suppl):S23-S27. doi:10.1097/00005768-199901001-00004
  4. Eichstaedt C, Benjamin N, Grünig E. Genetics of pulmonary hypertension and high-altitude pulmonary edema. J Appl Physiol. 2020;128:1432
  5. Das BB, Wolfe RR, Chan K, Larsen GL, Reeves JT, Ivy D. High-Altitude Pulmonary Edema in Children with Underlying Cardiopulmonary Disorders and Pulmonary Hypertension Living at Altitude. Arch Pediatr Adolesc Med. 2004;158(12):1170–1176. doi:10.1001/archpedi.158.12.1170
  6. Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol. 2018;19(1):91-98. doi:10.1089/ham.2017.0096
  7. Kelly TD, Meier M, Weinman JP, Ivy D, Brinton JT, Liptzin DR. High-Altitude Pulmonary Edema in Colorado Children: A Cross-Sectional Survey and Retrospective Review. High Alt Med Biol. 2022;23(2):119-124. doi:10.1089/ham.2021.0121
  8. Litch JA, Bishop RA. Reascent following resolution of high altitude pulmonary edema (HAPE). High Alt Med Biol. 2001;2(1):53-55. doi:10.1089/152702901750067927
  9. Gerken J, Zapata D, Kuivinen D, Zapata I. Comorbidities, sociodemographic factors, and determinants of health on COVID-19 fatalities in the United States. Front Public Health. 2022;10:993662. Published 2022 Nov 3. doi:10.3389/fpubh.2022.993662
  10. Luks A, Swenson E, Bärtsch P. Acute high-altitude sickness. European Respiratory Review. 2017;26: 160096; DOI: 10.1183/16000617.0096-2016
  11. Dehnert C, Grünig E, Mereles D, von Lennep N, Bärtsch P. Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude. European Respiratory Journal 2005;25(3):545-551; DOI: 10.1183/09031936.05.00070404
Accessibility, Acclimation, Altitude Science, Asthma, Child Growth & Development, Doc Talk, Exposure, Genetics, Health, High Altitude, Medicine

Hypoxia in the Emergency Department: Preliminary Analysis of Data from the Highest Atitude Population in North America & Children with Hypoxia

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Hypoxia is a common presentation at the emergency department for the St Anthony Summit Medical Center, located at 2800 meters above sea level (msl) in Colorado. Children under 18 are brought in with respiratory symptoms, trauma, congenital heart and lung abnormalities, and high altitude pulmonary edema (HAPE). Many complain of shortness of breath and/or cough and are found to be hypoxic, defined as an oxygen saturation below 89% on room air for this elevation. Patients who live at altitude may perform home pulse oximetry and arrive for treatment and diagnosis of known hypoxia. Extensive and ongoing analysis of the data from children found to be hypoxic in the emergency department raises many questions, including how residents vs nonresidents present, how often  these cases are preceded by febrile illness and what chief complaint is most frequently cited. 

Understanding the presentation of hypoxia in children at altitude can help ensure that healthcare providers are following a comprehensive approach with awareness of the overlapping symptoms of HAPE, pneumonia and asthma. Below is a graphic summary of 36 cases illustrating the clinical, social and geographic factors contributing to hypoxia at altitude in residents and visitors. A further analysis of over 200 children with hypoxia presenting to the emergency room at 9000 feet is underway including x-ray findings.

The graphs below were created by the author, using data extracted directly from a review of patient charts (specifically, those of children presenting to the local hospital in Summit County, Colorado (9000 feet) with hypoxia).

Graphs 1-4 show chief complaints of cough (CC) and shortness of breath (SOB) compared by age and by residence (residence includes altitudes above 2100 msl, the front range (a high altitude region of the Rocky Mountains running north-south between Casper, Wyoming and Pueblo, Colorado) averaging 1500 msl, and out of the state of Colorado) 

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Graphs 5-6 show presence of fever by residence and by age 

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Graphs 7-8 show presence of asthma by residence and by age 

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Graphs 9 and 10 show lowest oxygen by age at admission and lowest O2 organized by days spent in the county (residents are excluded from this data). 

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Erin Snyder is a new graduate physician assistant who graduated this fall after spending her final rotation in Frisco with the Ebert clinic. She is now working in pediatric hematology at Children’s Hospital Colorado. And her free time she enjoys skiing, hiking and spending time with her cat Charlie.

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

Doc Talk: Physician Altitude Experts on High Altitude Pulmonary Edema (HAPE)

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One of our students recently came across a comprehensive publication on high altitude pulmonary edema (HAPE) on reputable point-of-care clinical resource UpToDate.com1, citing Christine Ebert-Santos, MD, MPS, the founder of highaltitudehealth.com.

Emergency medicine physician at Aspen Valley Hospital and medical director for Mountain Rescue Aspen since 1997 Dr. Scott A. Gallagher2 and emergency physician and altitude research pioneer Dr. Peter Hackett3 introduce the resource warning, “Anyone who travels to high altitude, whether a recreational hiker, skier, mountain climber, soldier, or worker, is at risk of developing high-altitude illness.”

Ebert-Santos’s (known affectionately to her patients and mountain community as “Dr. Chris”) own research is referenced in the article’s discussion of epidemiology and risk factors noting an additional category of HAPE among “children living at altitude who develop pulmonary edema with respiratory infection but without change in altitude,”4 whereas the two other recognized categories (classic HAPE and re-entry HAPE) typically happen in response to a change in altitude.

The article continues with figures illustrating how ascending too quickly or too much can dramatically increase risk: “HAPE generally occurs above 2500 meters (8000 feet) and is uncommon below 3000 meters (10,000 feet) … The risk depends upon individual susceptibility, altitude attained, rate of ascent, and time spent at high altitude. in those without a history of HAPE, the incidence is 0.2 percent with ascent to 4500 meters (14,800 feet) over four days but 6 percept when ascent occurs over one to two days. In those with a history of HAPE, recurrence is 60 percent with an ascent to 4500 meters over two days. At 5500 meters (18,000 feet), the incidence ranges between 2 and 15 percent, again depending upon rate of ascent.”

Dr. Chris discusses her experience treating her pediatric patients at high altitude in more depth in an interview with pediatric emergency medicine physician Dr. Alison Brent from Colorado Children’s Hospital for the podcast Charting Pediatrics.

Dr. Gallagher and Dr. Hackett’s article is available on UpToDate with a subscription.

References

  1. https://www.uptodate.com/contents/high-altitude-pulmonary-edema?source=autocomplete&index=0~1&search=HAPE ↩︎
  2. https://www.aspenhospital.org/people/scott-a-gallagher-md/ ↩︎
  3. https://www.highaltitudedoctor.org/dr-peter-hackett ↩︎
  4. Ebert-Santos, C. High-Altitude Pulmonary Edema in Mountain Community Residents. High Alt Med Biol 2017; 18:278. ↩︎
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Interview with Dr. Christine Ebert-Santos on High Altitude Pulmonary Edema

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by Cody Jones, Summit Daily News

“‘The first sign is usually a cough,’ Ebert-Santos said. ‘Followed by shortness of breath with any effort — even just walking — and fatigue. You just want to lie on the couch.’

If left untreated the early warning signs of high altitude pulmonary edema can rapidly progress into having fluid build up in the lungs, which will then lead to a patient’s oxygen saturation levels rapidly decreasing. If the individual does not seek treatment quickly, the condition can be fatal.”

Read the whole article here.

Accessibility, Acclimation, Altitude Science, Child Growth & Development, Diabetes, Exposure, Genetics, Health, High Altitude, Medicine, Mountaineering

The Impact of High Altitude on Diabetes Diagnosis: The Relationship between Hemoglobin A1c and Fasting Plasma Glucose

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Type 2 Diabetes (T2D) has emerged as a global concern, with its prevalence steadily increasing. The test of choice to diagnose and monitor T2D is hemoglobin A1c (HbA1c), which tracks average blood sugar levels over the last three months. Normal HbA1c levels are below 5.7%, 5.7% to 6.4% indicates prediabetes, and 6.5% or higher indicates diabetes. Within the prediabetes range, high HbA1c levels increase the risk of developing T2D. Additionally, levels above 6.5% correlate with greater risk for diabetes complications.1 Fasting Plasma Glucose (FPG) is an additional test that indicates an immediate blood sugar level following a period of fasting. Normal FPG levels are below 100 mg/dL (5.5 mmol/L), 100 to 125 mg/dL (5.6 to 6.9 mmol/L) suggests prediabetes, whereas 126 mg/dL (7 mmol/L) or higher generally indicates diabetes.2 Because HbA1c provides an overview of blood sugar levels spanning the past 2-3 months, it offers a more comprehensive insight into blood sugar management and is the preferred diagnostic test for T2D.3 Recent studies are unveiling discrepancies between HbA1c and glucose testing, prompting discussions on specific diagnostic criteria for different populations.

People living at high altitude experience unique physiological adaptations, such as higher hemoglobin levels and specific glucose metabolism patterns. Acknowledging these adaptations, a 2017 study by Bazo-Alvarez et. al sought to evaluate the relationship between HbA1c and FPG among individuals at sea level compared to those at high altitude.

The study analyzed data from 3613 Peruvian adults without diagnosed diabetes from both sea level and high altitude (>3000m). The mean values for hemoglobin, HbA1c, and FPG differed significantly between these populations. The correlation between HbA1c and FPG was quadratic at sea level but linear at high altitude, suggesting different glucose metabolism patterns. Additionally, for an HbA1c value of 48 mmol/mol (6.5%), corresponding mean FPG values were significantly different: 6.6 mmol/l at sea level versus 14.8 mmol/l at high altitude.

Tall, snowy mountain peaks rise in the distance over rows of deep green pine trees growing out of the hills around a bike. path in the foreground.

This significant difference in predictive values suggests potential controversy in utilizing HbA1c as a diagnostic tool for diabetes in high altitude settings. Using HbA1c at altitude potentially underdiagnoses and under treats patients. To ensure a more accurate diagnosis of T2D at high altitude, reevaluating diagnostic criteria, possibly leaning towards FPG or oral glucose tolerance testing (OGTT) might be necessary.

In conclusion, this study emphasizes the need for careful consideration when diagnosing diabetes in high-altitude regions. Future research is warranted, including studies replicating the findings of the cross-sectional study by Bazo-Alvarez and longitudinal studies exposing the long-term effects of the diagnostic discrepancy of HbA1c in high altitude patients. This additional data will ensure accurate diagnosis and appropriate management of diabetic patients at high altitude.

References

  1. Centers for Disease Control and Prevention. A1C Test. Accessed 12/26/23. Available from: https://www.cdc.gov/diabetes/managing/managing-blood-sugar/a1c.html
  2. World Health Organization. Fasting Blood Glucose. Accessed 12/26/23. Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/2380#:~:text=When%20fasting%20blood%20glucose%20is,separate%20tests%2C%20diabetes%20is%20diagnosed   
  3. Sherwani, S.I., et al. 2016. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark. Insights. 2016 Jul; 11: 95-104. DOI: 10.4137/BMI.S38440.
  4. Bazo-Alvarez, J. C., et al. Glycated haemoglobin (HbA1c) and fasting plasma glucose relationships in sea-level and high-altitude settings. Diabet. Med. 2017 Jun; 34(6): 804-812. DOI: 10.1111/dme.13335.

Ambra Saurini is a second-year physician assistant student at Red Rocks Community College in Arvada, CO. She was born and raised in Denver, but Italian is her first language and she spent summers visiting her grandparents in Italy. She received her undergraduate degree in integrative physiology from the University of Colorado at Boulder. Before PA school, she worked as a research assistant in the Sleep and Development Lab at CU and as a medical assistant at Panorama Orthopedics and Spine Center. In her free time, she enjoys trying new restaurants and coffee shops, hiking, and spending time outside with her two-year old daughter, Chiara.

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What is Acute Mountain Sickness?

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Acute mountain sickness (AMS) is a condition that can occur when individuals ascend to high altitudes rapidly, typically above 2,500 meters (8,200 feet). The symptoms of AMS are due to the body’s struggle to adapt to the decreased oxygen levels at higher elevations. More specifically, the symptoms are caused by cerebral vasodilation that occurs in response to hypoxia, in an attempt to maintain cerebral perfusion.1

The typical symptoms of AMS include headache, nausea, vomiting, anorexia, and fatigue. In children the symptoms are less specific including increased fussiness, crying, poor feeding, disrupted sleep, and vomiting. Symptom onset is usually 6-12 hours after arrival to altitude but this can vary.

AMS affects children, adults, males and females equally, with a slight increased incidence in females. It is difficult to believe, but physical fitness does not offer protection against AMS. However, people who are obese, live at low elevation, or undergo intense activities upon arrival to elevation are at increased risk.1

Treatments for Acute Mountain Sickness

Descending

Descending and decreasing altitude is a vital treatment for people with severe symptoms of AMS. By decreasing altitude there will be more oxygen in the air and symptoms will not be as severe..2 

Oxygen

Since the main cause of AMS is hypoxia, oxygen supplementation is an effective treatment when descent is not wanted or possible. Supplemental oxygen even at .5L to 1L per hour can be effective in reducing symptoms.1  It can be prescribed for short periods of time or to be used only during sleep  In the central Colorado Rockies, this may be a practical solution for “out of towners” who have traveled up to the town of Leadville (10,158’/3096m) for vacation, but in an austere environment supplemental oxygen may not be a reasonable treatment option. There should be symptomatic improvement within one hour.

Acetazolamide

Acetazolamide is a carbonic anhydrase inhibitor which causes increased secretion of sodium, potassium, bicarb, and water. This mechanism of actions lends beneficial to the treatment of AMS because it decreases the carbonic anhydrase in the brain. 3There is evidence to support the use of acetazolamide in the prevention of AMS, but minimal evidence pointing towards it’s role in treatment. Dosing is inconsistent but is usually prescribed at 125-250mg BID.

Hyperbaric Therapy

Many people consider hyperbaric chambers to be large structures in hospitals, however there are portable and lightweight hyperbaric chambers that can be used in austere environments or during expeditions. The mechanism of action of hyperbaric therapy is a simulated decrease in elevation, of approximately 2500 meters. These chambers will remove symptoms within approximately one hour of use but symptoms are likely to return. They are useful in the field but not frequently required in a hospital setting.1

Lynde Tucker is a third year medical student who grew up in Lake Tahoe California, and moved to Colorado for medical school. She is grateful for the opportunity to be back living in the mountains and working in a mountain community.

References

  1. https://www.uptodate.com/contents/acute-mountain-sickness-and-high-altitude-cerebral-edema?search=acute%20mountain%20sickness&source=search_result&selectedTitle=1~15&usage_type=default&display_rank=1#H35
  2. https://my.clevelandclinic.org/health/diseases/15111-altitude-sickness
  3. https://www.uptodate.com/contents/acetazolamide-drug-information?search=acetazolamide%20altitude&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#F129759
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Maternal Exercise and Its Effect on the Development of High-Altitude Pulmonary Hypertension in Children

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by Julia Wu, PA-S

Every newborn I have managed while rotating at Ebert Family Clinic in Frisco, Colorado at 9000′ has needed oxygen supplementation. It is known that at high altitudes, there is a lower oxygen concentration in the air, which poses challenges to our bodies. What exactly happens, and what are the consequences of chronic high-altitude exposure? There are approximately 140 million people that live at high altitudes, defined as at least 2500 meters above sea level, who are affected by chronic hypoxic conditions.1 In this article, I will focus on how hypoxia — low levels of oxygen in the blood — affects pregnant women, alters fetal to newborn transition and development, and whether cardiorespiratory exercise by mothers during pregnancy can prevent diseases such as high-altitude pulmonary hypertension (HAPH) development in offspring.  

Pulmonary hypertension (PH) is abnormally high blood pressure in the pulmonary arteries. PH is classified into 5 groups based on the cause. High-altitude pulmonary hypertension (HAPH) is Group III PH and defined as mean pulmonary arterial pressure (PAP) ≥25 mm Hg. Chronic high-altitude hypoxia can lead to the development of HAPH, which has adverse effects on the heart from right ventricular wall thickening to reduced cardiac output, and eventual right heart failure and death. HAPH can occur in utero, so it’s imperative to understand how hypoxia affects mothers and their fetuses during and after birth.2

During pregnancy, the fetus doesn’t breathe air and the lungs are not used. The fetus receives all its oxygen and nutrition needs from the mother’s blood, which flows through the blood vessels in the umbilical cord to the placenta and then to the baby.3 Circulating blood bypasses the lungs by flowing in different pathways through openings called shunts that close at birth to allow for adult circulation. In utero, the baby’s lungs fill with a special fluid that helps the lungs grow.4 The fluid in the lungs, in combination with naturally thicker pulmonary vascular and pulmonary vessel vasoconstriction from low PO2, causes higher vascular resistance in pulmonary circulation that allows for the diversion of blood away from the lungs through the shunts.2 At low altitudes, in the first few days after birth, the high PAP in the lungs drops. The sharp drop in PAP is due to “expansion of the lungs, pulmonary vasodilation from higher PO2, a gradual receding of fluid, a thinning of pulmonary vascular smooth muscle, and… closing of the [shunts]”. This process is known as cardiopulmonary transition. However, at altitude, perinatal hypoxia negatively affects cardiopulmonary transition. The elevated pressures in the pulmonary arteries and vascular resistance persist into early childhood delaying cardiopulmonary transition, which can have developmental consequences such as HAPH and right heart failure, as discussed.

It was discovered that cardiopulmonary transition delay is linked to a high-altitude hypoxia-induced proinflammatory state within the pulmonary vasculature that leads to pulmonary artery remodeling and HAPH. Hypoxia activates or upregulates transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NK-kB), that signals for inflammatory mediators such as hypoxia-inducible factors (HIF). HIF-1a inhibits mammalian target of rapamycin (mTOR). mTOR signaling has an important role in cell metabolism, cell proliferation, and survival, thus inhibiting mTOR prevents “non-proliferative branching and elongation of conducting airways and fluid removal from the lungs,” which contributes to increases in pulmonary vascular resistance and lung development during the cardiopulmonary transition and the onset of newborn gas exchange. 2,5 HIF also contributes to the uncontrolled proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMC) which is also a crucial contributing factor to pulmonary vessel wall thickening, pulmonary vascular remodeling, and vascular resistance. 5 Metabolic studies showed that chronic hypoxia not only increased the expression of these proinflammatory molecules and mediators but also reduced anti-inflammatory products like omega-3 fatty acids.2

Studies have shown that cardiorespiratory exercise reduces proinflammatory markers and increases anti-inflammatory stimulus in healthy and HAPH populations.2 However, exercise training is not sufficient to reverse PAH, so we need to prevent HAPH from developing in utero with maternal exercise.  The American College of Obstetrics and Gynecologists (ACOG) recommends resistance training twice a week and moderate-intensity cardiorespiratory training daily for a total of 150 minutes a week. Studies showed that pregnant women who followed this recommendation had a 25% reduced risk of developing conditions like gestational diabetes and hypertension that contribute to compromised uterine blood flow and fetal hypoxic conditions. At low altitudes, exercise by pregnant mothers leads to benefits such as decreased fat mass, leptin, oxidative stress, pulmonary valve defects, aortic valve defects and inflammation, and increased neurogenesis in the fetus. Some animal studies at high altitudes showed that offspring of physically active pregnant rodents also received similar benefits from maternal exercise. The offspring were protected against proinflammatory stressors evidenced by low levels of inflammatory mediators, which protected them against the inflammatory processes that drive pulmonary artery remodeling and pressures that lead to HAPH. Further animal studies should be conducted to further explore the possibilities that maternal exercise can counteract the inflammatory changes and prevent HAPH development in fetus and newborns.

Resources

  1. Mirrakhimov AE, Strohl KP. High-altitude Pulmonary Hypertension: an Update on Disease Pathogenesis and Management. The Open Cardiovascular Medicine Journal. 2016; 10: 19-27. doi: 10.2174/1874192401610010019
  2. Leslie E, Gibson AL, Gonzalez Bosc LV, Mermier C, Wilson SM, Deyhle MR. Can Maternal Exercise Prevent High-Altitude Pulmonary Hypertension in Children?. High Altitude Medicine & Biology. 2023; 24: 1-6. https://doi.org/10.1089/ham.2022.0098
  3. 2023. Blood Circulation in the Fetus and Newborn. Stanford Medicine Children’s Health. https://www.stanfordchildrens.org/en/topic/default?id=blood-circulation-in-the-fetus-and-newborn-90-P02362
  4. 2023. Transient tachypnea- newborn. Icahn School of Medicine at Mount Sinai. https://www.mountsinai.org/health-library/diseases-conditions/transient-tachypnea-newborn#:~:text=As%20the%20baby%20grows%20in,start%20removing%20or%20reabsorbing%20it.
  5. He S, Zhu T, Fang Z. The Role and Regulation of Pulmonary Artery Smooth Muscle Cell in Pulmonary Hypertension. International Journal of Hypertension. 2020; 2020: 1478291. doi: 10.1155/2020/1478291
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HAFE: High-Altitude Flatus Expulsion

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Often, at high altitude we hear complaints of gas pain and increased flatus in our infant population. Parents often wonder, are we doing something wrong? Is my child reacting to breastmilk, or showing an intolerance to certain foods?  Actually there is another explanation for increased flatus and gas pain in the high-altitude region of Colorado. 

The term HAFE was coined by Dr. Paul Auerbach and Dr. York Miller and published in the Western Journal of Medicine in 1981. Their discovery began In the summer of 1980, when the two doctors were hiking in the San Juan Mountains of Colorado on a quest to summit three 14ers. During their ascent they noticed that something didn’t smell right! As the pair continued to emit noxious fumes, they began to put their scientific brains to work and discovered HAFE. The symptoms include an increase in frequency and volume of flatus, or in other terms an increase in toots! We all have familiarity in watching our bag of potato chips blow up when reaching altitude or our water bottle expanding as we head into the mountains. This reaction is due to a decrease in barometric pressure. Based on Boyle’s law, decreased barometric pressure causes the intestinal gas volume to expand, thus causing HAFE (Skinner & Rawal, 2019).

A graphic illustrating how Boyle's law works: the pressure of a gas increases as its volume decreases.

To my surprise, a gas bubble the size of a walnut in Denver, Colorado (5280 ft) would be the size of a grapefruit in the mountain region of Summit County, CO (8000+ ft)! Trapped gas is known to lead to discomfort and pain. The use of simethicone may have merit in mitigating the effects of HAFE. Simethicone works by changing the surface tension of gas bubbles, allowing easier elimination of gas. This medication, while benign, can be found over the counter and does not appear to be absorbed by the GI tract (Ingold, C. J., & Akhondi, H., 2022). 

While this phenomenon may not be as debilitating as high-altitude pulmonary edema (HAPE), it deserves recognition, as it can cause a significant inconvenience and discomfort to those it inflicts. As the Radiolab podcast explained in their episode The Flight Before Christmas , expelled gas in a plane or car when driving up to the mountains can be embarrassing. While HAFE can be inconvenient, it is a benign condition and a matter of pressure changes rather than a disease or pathological process. We would love to talk more about HAFE at Ebert Family Clinic if you have any questions or concerns!

A bald eagle flies over a misty settled into the valley against the blue-green pine forest of a mountain.
A bald eagle flies toward its nest atop a bare lodgepole pine.

As always, stay happy, safe, and healthy 😊

Taylor Hollingsworth is finishing her final semester as a family nurse practitioner (FNP) student at Georgetown University. Originally from the east coast, Taylor plans to start her FNP career in North Carolina close to family. She has a passion for pediatric and family wellness and has worked as a pediatric intensive care unit nurse for 6 years! In her free time, Taylor loves to hike, fly fish, run, and spend time with her fiancé Logan. 

References

Auerbach, P. & Miller, Y. (1981). High altitude flatus expulsion. The Western Journal of Medicine, 134(2), 173-174.

Chemistry Learner. (2023). Boyle’s Law. https://www.chemistrylearner.com/boyles-law.html

Ingold, C. J., & Akhondi, H. (2022). Simethicone. StatPearls Publishing. 

McKnight, T. (2023). The Flight Before Christmas [Audio podcast]. Radiolab. https://radiolab.org/episodes/flight-christmas

Skinner, R. B., & Rawal, A. R. (2019). EMS flight barotrauma. StatPearls Publishing.