All posts by Dr. Chris

Pediatrician trained at University of Michigan Medical School, University of Hawaii and University of Chicago for residencies. Spent 20 years at the Commonwealth Health Center in Saipan, CNMI, before establishing Ebert Children's later Ebert Family Clinic in Frisco, CO in 2000. Published in the Journal of High Altitude Medicine and Biology

The Nobel Prize: Hypoxia studies Won in 2019!

The Nobel prizes are announced this month. Alfred Nobel invented dynamite in 1866. Within 30 years, Nobel made a large fortune from his invention. He demonstrated his passion for literature and science by creating a yearly prize to discoveries most beneficial to humankind. The five prize categories include physics, chemistry, medicine (physiology), literature and peace. The Nobel prize nominations are made by university professors, national assemblies, state governments, and international courts. The prize is awarded yearly to individuals who have discovered a new paradigm or a paradigm shift within their field. The prize recipients are declared on the first Monday of October of every year and the award is presented by the Nobel assembly on November 10th, the anniversary of Alfred Nobel’s death. The Nobel prize consists of a gold medal, a diploma of recognition of achievement, and a cash prize in the amount of $1 million U.S. dollars. 

There is no limit to the number of nominations that can be made or the number of times that an individual can be nominated. There were 400 candidates nominated in the field of medicine in 2019, all of which inspired, challenged, and demonstrated greatness in their field. In 2019 the Nobel Prize in Medicine honored three scientists for their discovery of the human body’s ability to adapt to low oxygen environments. 

Hypoxia is a state of which oxygen supply is insufficient for normal life functions, experienced by the human body at high altitude. Tissues and cells require a range of oxygen in order to survive. Oxygen is required by mitochondria, in all cells, to convert food into useable energy. “Otto Warburg, the recipient of the 1931 Nobel Prize in Physiology or Medicine, revealed that this conversion is an enzymatic process.” At low oxygen environments, as experienced at high altitude, the body must adapt in order to maintain basic cellular function. There are several mechanisms in the human body that increase oxygen concentration including breathing rate, regulated by the carotid body, increased heart rate, stimulated by the vagus nerve, and increased production of red blood cells (RBCs)  through the bone marrow, regulated by the kidney. 

The carotid body is a chemoreceptor near the carotid artery that detects oxygen, carbon dioxide and pH levels in the blood. At low oxygen, the carotid body relays an afferent (ingoing) signal to the the brain via the glossopharyngeal nerve. The medullary center in the brain then sends an efferent (outgoing) signal that increases the respiratory rate to maximize oxygen delivery to the brain. The carotid sinus is a baroreceptor near the aorta of the heart which senses changes in pressure. As pressure increases in the atmosphere, experienced at high altitude, the carotid sinus sends a signal along the vagus nerve to the brain which then increases the heart rate. “The 1938 Nobel Prize in Physiology or Medicine was awarded to Corneille Heymans for discoveries showing how blood oxygen sensing via the carotid body controls our respiratory rate by communicating directly with the brain.”

At low oxygen environments, the kidney increases production of erythropoietin, which stimulates RBC generation in the bone marrow,  called erythropoiesis, resulting in higher oxygen delivery to the brain and skeletal muscles needed at high altitude. Erythropoiesis was discovered in the early 20th century, however oxygen’s role in the process was not completely understood. The cell’s ability to sense and adapt to oxygen availability was discovered and explained by three scientists, William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza. 

2019 Nobel Prize, Physiology: 

Thanks to the work of Dr. Gregg L. Semenza and Sir Peter J. Ratcliffe, we now understand that the oxygen sensing mechanism that stimulates erythropoieten is present in all tissues, not just the kidney. Semenza conducted research on liver cells using gene-modified mice and found that a specific protein binds to an individual gene (the EPO gene), dependent upon oxygen availability. Semenza named the binding protein the Hypoxia-Inducible-Factor (HIF). The HIF protein was found to compose two transcription factors, HIF-1alpha and ARNT. In 1995, Semenza published his findings of the HIF protein. His work explained that when the body is at high oxygen environments, there is very little HIF-1alpha present within cells. At high oxygen availability, HIF-1alpha is rapidly degraded by a proteasome within cells. The degradation is signaled by a protein called ubiquitin which binds to HIF-1alpha at high oxygen, flagging HIF-1alpha for degradation by the proteasome. This process was recognized by the 2004 Nobel Prize in Chemistry, Aaron Ciechanover, Avram Hershko and Irwin Rose. 

The mechanism by which ubiquitin binds, causing the degradation of HIF-1alpha at high oxygen environments was explained by the work of William Kaelin, Jr. who conducted research on von Hippel-Lidau’s (VHL) disease. The VHL gene mutation causes an increased risk of cancer. Kaelin showed that the VHL gene encodes a protein that prevents the onset of cancer and was involved in controlling responses to hypoxia. VHL is part of a complex that labels proteins with ubiquitin. Ratcliffe discovered the physical interaction of the VHL gene with HIF-1alpha, causing degradation of the HIF-1alpha at normal oxygen levels. 

At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4). 


At hypoxic environments, HIF-1α is protected from degradation and accumulates in the nucleus, where it associates with ARNT and binds to specific DNA sequences (HRE) in hypoxia-regulated genes (1). At normal oxygen levels, HIF-1α is rapidly degraded by the proteasome (2). Oxygen regulates the degradation process by the addition of hydroxyl groups (OH) to HIF-1α (3). The VHL protein can then recognize and form a complex with HIF-1α leading to its degradation in an oxygen-dependent manner (4).

Kaelin and Ratcliffe’s research identified how oxygen levels regulate the interaction between VHL and HIF-1alpha. Their work demonstrated that at normal oxygen levels, hydroxyl groups are added to specific positions within HIF-1alpha, causing modification of the protein and allowing VHL to recognize and bind to HIF-1alpha, leading to degradation of the protein complex.  At high altitude, cells produce a greater amount of the HIF-1alpha protein which binds to the EPO gene, up-regulating the production of erythropoietin hormone, stimulating RBC production. Together, Semenza, Kaelin, and Ratcliffe explained the oxygen sensing mechanism.

Doc Talk: ALTITUDE AND THE EYES, AN INTERVIEW WITH DR. PAUL COOK, OD

Have you ever wondered why a bag of chips will swell almost to the point of bursting when you travel from a lower elevation?  As the altitude increases  the barometric pressure decreases. The difference between the high pressure inside the bag and the low pressure outside causes the bag to swell (and sometimes burst) to reach equilibrium with the surrounding environment.

The same concept applies to our biological tissue, including our eyes. Luckily there is not normally gas in our eyes, but there are procedures where air bubbles are injected into the eye, such as a vitrectomy: part of the vitreous humor of the eye is replaced with air so that a nearby site has the chance to heal. Common indications include a retinal detachment, macular hole or removal of scar tissue. It’s important to remain at the elevation your ophthalmologist or optometrist indicates because you don’t want your eye to suffer the same fate as a bag of chips!

This was one of many interesting things I learned while speaking with D. Paul Cook, OD and his wife and practice manager Karen Cook at Summit Eye Center on Main Street in beautiful Frisco, CO. The following is my interview with Dr. Cook, Karen Cook, and my preceptor Christine Ebert-Santos, MD, MPS.

How many years have you been practicing optometry in Frisco, CO?

I don’t recall the exact year, but I remember it was the year the Broncos lost the Superbowl.

Dr. Paul Cook at the entrance of Summit Eye Center.

I did a little research and this must have been either the 1986 or 1987 season, as the Broncos lost both of those Superbowls. Fortunately, those Superbowl losses were not a bad omen as Dr. Cook has successfully served the Frisco area every year since.

What conditions do you see commonly here at altitude?

One thing I see commonly here is recurrent corneal abrasions. The classic patient lives at a lower altitude and previously had a corneal abrasion. They received treatment but the abrasion site never completely heals. After arrival in the high country where it’s extremely dry that abrasion site dries up and becomes inflamed.

Usually what I do is give a bandage contact lens to cover up that recurrent corneal abrasion, which usually works, but if it’s extremely painful, we can use amniotic membrane, which is expensive. But it is effective.

The cornea is the outermost layer of the eye (if you don’t count the tear film). A corneal abrasion occurs when any foreign object scrapes the corneal surface. Symptoms include a foreign body sensation, pain, clear discharge, blurry vision and sensitivity to light. A corneal abrasion needs a healthy, moist environment in order to heal. You can see how the dryness that comes along with altitude could lead to a recurrent corneal abrasion.

I also see a fair amount of snow blindness, usually in the spring though.

I suppose it has to do with the sun being higher in the sky and people being out and about hiking. When people are out skiing in the cold winter they wear their goggles, but if it’s spring time and somebody’s hiking they might forget their glasses.

Snow blindness is only one potential cause of a disease called photokeratitis. Other causes are staring at the sun, looking at an arc welder, or catching too many refracted UV rays from surfaces such as sun, water, ice and snow. The pathophysiology for each disease is the same: too many UV rays are focused onto the cornea at one time which causes damage. Symptoms include pain, redness, blurriness, sensitivity to bright light, headache, and occasionally temporary vision loss. Treatment for photokeratitis caused by snow blindness is supportive, but the most important thing is resting your eyes. Try to get into a dark room and avoid anything that makes your eyes uncomfortable. In a few days your cornea should heal.

Prevention  is straightforward: wear sunglasses or ski goggles with adequate sun protection.

Are cataracts a more common condition at altitude?

Oh yes, because of sun exposure and our aging population here. The people of Summit County are so active, which increases their exposure to the damaging rays of the sun. We’re also treating cataracts so much sooner than we used to, so that’s part of what makes it more common.

Do you have any recommendations for healthy aging at altitude as it relates to the eyes?

Karen: Getting your annual eye exam. We always tell patients there are a lot of things we can do to preserve your vision, there’s almost nothing we can do to give it back to you.

So if you live in Frisco, CO and don’t have an optometrist, make sure to see Dr. Paul Cook!

Is blurry vision a common malady in patients that have recently received a LASIK procedure and then ascended to higher elevations?

I have not seen that with LASIK. About 30 years ago though there was a procedure called Radial Keratotomy (RK) that involved a surgeon making radial cuts on the cornea in order to correct nearsightedness. Those patients used to require one pair of glasses for where they lived at lower elevation and one pair of glasses at higher elevation. It’s not a procedure commonly done nowadays but patients that had RK roughly 30 years ago may have that problem.

LASIK stands for Laser Assisted In Situ Keratomileusis. It essentially means that the surgeon will use a laser to reshape the cornea so that the light refracting through it will be appropriately concentrated on the retina. LASIK is faster, cheaper, safer and more effective than RK. It has largely usurped RK for surgical treatment of nearsightedness or farsightedness.

What are some interesting cases you have seen over your years of practice?

I treated a patient that traveled from the Midwest and had a genetic condition called retinitis pigmentosa. Clinically that means the patient had limited peripheral vision at baseline.  He and his wife decided to hike the Colorado Trail. Unfortunately during the hike he developed blurred vision and ended up coming into my office. Turns out he had macular edema and I referred him to an ophthalmologist down in Denver because the altitude was probably the cause of his macular swelling. I called him a few weeks later and his vision had returned to normal.

Another  patient came into the office because his wife had noticed growths on his iris that turned out to be nevi (colloquially known as moles when they’re on the skin). So I dilated his eyes and noticed growths on his retina. I referred him down to oncology in Denver for a biopsy and it turned out to be melanoma. I think they’re closely monitoring that melanoma at this point. It’s uncommon to see cancers of the eye but I see them once every few years.

Dr. Cook performing an eye exam on me.

For my last question, do you have any general recommendations for residents or visitors?

Wear sunglasses, eat your vegetables, eat your fish at least two times per week, keep your cholesterol in check, keep your sugars in check, take breaks from looking at the computer, don’t sleep in your contacts, and see your optometrist once per year.

Seth Selby is a second-year physician assistant student at Des Moines University. He was raised in Eaton, CO and attended Colorado State University with a bachelor’s degree in Health and Exercise Science. Prior to PA school, Seth worked for 3 years as a Cardiovascular Technician at Boulder Community Hospital. In his spare time Seth loves backpacking, hunting, fishing, skiing and astronomy.

A conversation with Dr. Chris on neonatal oxygen levels at elevations 9000’ and above

My name is Austin Ethridge, I am a physician assistant student from Red Rocks Community College PA program who has been fortunate enough to have completed my pediatric rotation with Dr. Chris in Frisco, Colorado, this month. Dr. Chris has extensive experience providing care to the pediatric residents of Summit County, having established her practice here in 2000, following 20 years as a pediatrician on Saipan, in the Northern Mariana Islands, southeast of Japan. She has a unique perspective on high altitude health, having transitioned from sea level to the 8000′ and above elevations unique to Summit County. Since moving here, she has been advocating for more in-depth medical research regarding the needs specific to these high-altitude communities. We are here in her office today at the Ebert Family Clinic to discuss neonatal oxygen use in Summit County.

Dr. Chris, based on your experience, why do neonates need oxygen at a higher elevation? Is it because they need to acclimate?

Yes, that’s basically it, and smaller lung size at birth.

Yes, that’s what I read. Basically, the maternal physiology compensates for the higher altitude. When the infant is born, their lung size and physiology need to catch up to the altitude.

Based on your practice, when do you place neonates on oxygen?

Usually at 89% or below, but you see, that’s just it. Many parents ask why their children need to be on oxygen when neither themselves nor their siblings were on oxygen. One of the primary reasons that this has become more of an issue is the less invasive methods of measuring oxygen saturation in the blood. Before the 1990s, the only time to measure oxygen saturation in a newborn was if a concern for illness or pulmonary problems existed, which was completed by obtaining an arterial blood gas, a very invasive procedure. Do you know at what oxygen saturation level we begin to detect cyanosis in neonates?

Around75%, which means before the pulse oximeter used today, we had no idea if the infant’s oxygen saturation was in the 80s! Now that we have the pulse oximeter, we have access to so much more information. And this is why it is essential to determine the normal oxygen levels for these infants at higher elevations.

Does this include cyanosis or blue discoloration of the hands and feet, or is it just central as in the face and chest?

The blue discoloration of legs and arms do not count; this is very common and not concerning, only the discoloration of the trunk and face.

Yes, based on the articles that I have been reading while I have been here, there are not many studies that reflect normal oxygen saturation in neonates at a higher elevation. Most of the articles that I did find determined that newborn oxygen saturation is lower at elevations of around 6000’, with average values within the range of 89-96% SpO2 compared to greater than 97% at sea level. However, there could be a significant difference between 9000’-10000’ feet and the 6000’ in these studies.1-3

That is exactly right, and that is why I want to do a study here in Summit County to determine the average oxygen saturation at these altitudes.

On average, how many newborns do you place on oxygen in Summit County?

About 40% of newborns are placed on oxygen due to low oxygen levels at birth, and I would say that less than 5% will still need oxygen after their two-week visit; however, this rate may be higher in those that live at elevations of 10,000′ or greater. In general, studies have observed that the lowest oxygen levels tend to occur around the 4th day of life and then improve from this point onward. What is the main complication that we are worried about in infants that have low oxygen levels?

Pulmonary hypertension. At birth, when the fetal circulation is shunted back through the lungs, the pulmonary pressure decreases to allow this to happen. If the oxygen levels are too low, the vessels in the lungs may not dilate enough, and this could lead to elevated pulmonary pressures. I read an interesting study that found increased pulmonary pressures in Tibet children as measured by ECHO cardiogram until the age of 14. These pressures were noted to increase with increasing elevation but to decrease with increasing age. Generally, by the age of 14, the pulmonary pressures had normalized; the authors considered this to be a normal physiological response. However, it is worth noting that these children in the study came from generations of individuals that have always lived at these altitudes.4-5

That is correct. That is the difference between adaptation and acclimatization. Many of the children that live up here are acclimatized, meaning that their bodies have adapted on a physiological level, but their genetics remain the same. However, adaptation is observed in many families that have lived at high elevations for generations; in these instances, the changes have occurred at the genetic level.

That makes sense; so the data from some of those studies may not directly apply to the population here.

That is correct. Are we worried about brain damage in this setting of low blood oxygen levels?

No, I do not think so.

We are not! In fact, as an example of this: when I was in Saipan, there was a child that had a cyanotic, congenital heart defect that was unable to be repaired for social reasons. This child always appeared blue, and his oxygen saturation would have been very low. He did just fine in terms of development and progress in academics. There were no signs of developmental delay or any other neurological problems at all.

Are there any resources you recommend for parents whose newborn may need to be on oxygen?

Yes, I have a handout that I provide to all families whose infants are on oxygen. (View Dr. Chris’s handout here.)

Are there any red flags or signs that the newborns’ oxygen may not be high enough when they are sent home? Is there anything parents should look out for? I know that you mentioned the oxygen level needs to be as low as 75% before there are any signs of concerning central cyanosis.

No, there really are no clinical signs. A company called Owlet produces a sock for the newborn’s foot that monitors oxygen saturation. I am not sure how accurate this is, but if the parents really want to do something to monitor the oxygen level, this could be a way to do so. It is pretty expensive. On an aside, we are currently in communication with this company regarding future opportunities to conduct research using their product with regards to newborn oxygen saturation at higher elevations, so stay tuned for more developments on this topic.

Are there any risks to starting the infant on oxygen?

No, not at the level that these newborns are sent home on. In premature infants, there is a risk associated with oxygen therapy for eye and lung disease. However, these premature infants are placed on very high flow rates and positive pressures. The damage is actually caused by the pressures of the oxygen being too high. This is not the case for the newborns that we place on oxygen.

Are there any risks to infants or children growing up at high altitude?

Yes, there is some evidence of a very slight increased risk of pulmonary hypertension, but this is very rare.

Thank you so much for taking the time to discuss this, Dr. Chris!

References

  1. Ravert P, Detwiler TL, Dickinson JK. Mean oxygen saturation in well neonates at altitudes between 4498 and 8150 feet. Adv Neonatal Care. 2011 Dec;11(6):412-7. doi: 10.1097/ANC.0b013e3182389348. Erratum in: Adv Neonatal Care. 2012 Feb;12(1):27. PMID: 22123474.
  2. Morgan MC, Maina B, Waiyego M, Mutinda C, Aluvaala J, Maina M, English M. Oxygen saturation ranges for healthy newborns within 24 hours at 1800 m. Arch Dis Child Fetal Neonatal Ed. 2017 May;102(3):F266-F268. doi: 10.1136/archdischild-2016-311813. Epub 2017 Feb 2. PMID: 28154110; PMCID: PMC5474098.
  3. Bakr AF & Habib HS, Normal Values of Pulse Oximetry in Natewborns at High Altitude. Journal of Tropical Pediatrics 2005; 51(3) 170-173.
  4. Qi HY, Ma RY, Jiang LX, et al. Anatomical and hemodynamic evaluations of the heart and pulmonary arterial pressure in healthy children residing at high altitude in China. Int J Cardiol Heart Vasc. 2014;7:158-164. Published 2014 Nov 12. doi:10.1016/j.ijcha.2014.10.015
  5. Remien K, Majmundar SH. Physiology, Fetal Circulation. [Updated 2020 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539710/
  6. Thilo EH, Park-Moore B, Berman ER, Carson BS. Oxygen Saturation by Pulse Oximetry in Healthy Infants at an Altitude of 1610 m (5280 ft): What Is Normal? Am J Dis Child. 1991;145(10):1137–1140. doi:10.1001/archpedi.1991.02160100069025

Austin Ethridge is a second-year physician assistant student at the Red Rocks Community College Physician Assistant Program. Originally from the Colorado front range, Austin attended the University of Northern Colorado where he obtained both a bachelors and masters degree in chemistry prior to attending PA school. In his free time, Austin enjoys spending time with his friends and family, reading, and cycling.

COVID in Colorado Update: Reasons high altitude residents may be less susceptible

Last week we were privileged to have a Zoom discussion with two high altitude experts from the Instituto Pulmonar Y Patologia de la Altura (IPPA) founded in La Paz,  Bolivia in 1970. Dr Gustavo Zubieta-Calleja and Dr. Natalia Zubieta-DeUrioste answered our questions about their recently published article, Does the Pathogenesis of SAR-CoV-2 Virus Decrease at High Altitude?. They and the seven  coauthors presented data comparing COVID cases in high altitude areas of China, Bolivia and Ecuador showing a marked reduction in numbers compared to low altitude areas in the same countries, with dramatic, colorful topographic maps.

Drs. Zubieta-Calleja and Zubieta-DeUrioste and their colleagues theorized four reasons why altitudes above 2500 m could reduce the severity of the corona virus. (Note: Frisco, CO is at 2800 m, Vail 2500 m). As described in their previous paper published in March, the intense UV radiation at altitude as well as the dry environment likely reduce the viability of the virus in the air and on surfaces.

Dr. Zubieta-Calleja on a Zoom chat with Dr. Chris explaining a chart comparing UV exposure in La Paz, Bolivia (top line) and Copenhagen, Denmark (bottom line).
Dr. Chris with Dr. Gustavo Zubieta-Calleja and other altitude experts from the Hypoxia Conference in La Paz on the Camino Chacaltaya, which reaches an elevation of 17,785’/5421 m.

The low barometric pressure causes air particles to be spaced more widely, which would also decrease the viral particles inspired with each breath, reducing the severity and frequency of infections.

Furthermore, residents accustomed to chronic hypoxia may express reduced levels of angiotensin converting enzyme 2 (ACE2) in their lungs and other tissues. This enzyme has been found to be the entry path for the corona virus into cells where it replicates. Finally, the normal adaptation and acclimatization of populations with prolonged residence above 2500 meters may reduce the severity of the disease in individuals, and reduce mortality. This includes increased ventilation, improved arterial oxygen transport, and higher tissue oxygenation mediated by increased red blood cells produced under the influence of erythropoietin, which could be explored as a possible therapy.

Dr. Zubieta-Calleja with statistics reflecting the number of COVID-19 infections at different elevations in Bolivia. Note the most infections occur at a lower elevation.

As we stated in our interview quoted in the Summit Daily News March 17th, none of these factors can be relied upon to protect every individual. Therefore it is important to continue frequent hand washing, wearing masks, social distancing, and avoid touching your face.

COVID in the Mountains: What are the Risky Situations to Avoid as We Start Leaving Our Homes?

We are on the back slope of the epidemic, according to University of Massachusetts Dartmouth Professor of Biology Erin S. Bromage, Ph.D. He explains what to expect and where not to go in an article this week which was cited in the New York Times: The Risks-Know Them-Avoid Them. The bad news is that the back slope can have as many deaths as the upslope.

The good news is that you don’t get COVID outdoors, as long as you are not standing close to someone who might have the virus for a period of time, perhaps over ten minutes. Bromage reviews a series of epidemiologic studies tracing the spread of the disease in situations including standing outside talking to someone (one case), church choir practice (45 of 60 infected, 2 died), indoor sports, specifically a curling tournament in Canada where 24 of 72 attendees became ill, birthday parties and funerals (high rate of infection and many deaths related to hugging, kissing and sharing food), grocery stores (safe for shoppers but employees get infected), and restaurants (50% infection rate after sharing a meal with nine at the table). He also reported details about the spread of disease at meat packing plants, a call center and a medical conference.

The risk of infection increases with exposure to a larger number of virus particles over a longer period of time in a smaller space with poor air flow. This is why shopping and outdoor activities are not likely to be dangerous. Breathing releases a small number of virus, between 50-5000 droplets per breath. Talking expels more and  singing is definitely a means of spreading virus. A single cough releases 3000 droplets traveling 50 miles per hour, mostly falling rapidly to the ground. In contrast a sneeze may release 30,000 droplets at 200 MPH, many of which are smaller and stay in the air longer.

Dr. Bromage writes that 44% of infections come from people who have no symptoms at the time.  The virus can be shed up to five days before a person becomes ill. Most people contract COVID from a family member who brings it home. Children are three times less likely to become ill but three times more likely to spread the virus.

I wondered if the lower barometric pressure at altitude could cause viral particles to be less compact. I called Peter Hackett, MD of the Hypoxia Institute in Telluride and he agreed that theoretically the less dense air would not carry as many particles. We also discussed antibody tests, which are still experimental, not recommended and difficult to interpret. The population screened in Telluride showed a 0.5% positive rate, but when a disease has a low prevalence there are more false positives. They did blood tests on some 5,000 people early in the outbreak. They were not able to repeat the serology due to staffing problems at the lab where many technicians contracted the illness.

My advice is to wear masks anytime you are out of the house, except if you are biking, hiking, running where the viral particles will be dissipated rapidly. Wearing a mask during these activities is still a kind gesture  to reduce the anxiety of others. Continue with frequent hand washing, avoid touching your face, practice social distancing, and when the churches reopen we should hum instead of sing.

COVID-19 Update: Accordion Theory and Preparing for Next Steps

Today, I am going to share news gleaned from meetings and publications that address the importance of preventive care, returning to daycare, pulse oximetry as a screening tool for COVID, and the Accordion Theory.

Every Thursday the Children’s Hospital of Colorado presents a panel of experts with updates and answers to questions.

“Your offices are the safest place in the country,” they proclaimed. With social distancing many parents and patients are delaying routine care which has led to the largest drop in vaccination rates in 50 years. This could result in outbreaks of measles, whooping cough, pneumococcal and other infections. With the loss of revenue, small clinics may go out of business, and large clinics and hospitals are laying off workers by the hundreds. If there is a large outbreak of preventable disease, on top of a resurgence of COVID, there could be a devastating shortage of providers to care for the victims. Now is the time to call your clinic and set up appointments for check ups and vaccines. If you don’t feel safe yet you can do a Telehealth visit initially and schedule the vaccines and hands-on portion of the exam in a month.

Another reason not to delay preventive care is the increase in stress, isolation, and anxiety which can cause serious depression. We had a tragic teen suicide in the county this month. Students from middle school through college should be seen annually for mental and physical health screening as well as vaccines. One mother told me that the depression screening done at our office “saved my daughter’s life.”

More daycares are opening soon. Parents are asking me whether to send their child back. These facilities follow strict public health guidelines to prevent infection. Children are not likely to be affected by COVID. Any child with symptoms should be tested. Enrollment should be diminished due to parents preferring to keep their child at home.  However, if there is a high risk family member, I advise not to return to daycare yet.

School age children should be limited to playing with friends and family members who have been part of their social circle during the last two months. To borrow a slogan from the AIDS campaign, “KNOW YOUR NETWORK”.  This is not the time to expand friendships. There will be no team sports this summer. Children should play outside and not share toys or balls.

An emergency physician in New York, Richard Levitan, published an editorial in the NY Times on April 20 advocating the use of pulse oximeters to screen for COVID. Citing the many patients with low oxygen levels and abnormal x-rays who did not complain of trouble breathing, the delay in obtaining results and inaccuracy of the COVID testing, he sees the simple pulse oximeter as a source of immediate information as to who needs medical attention. I’ve been speaking and writing about this for weeks.

Finally, one of the panelists at Children’s mentioned the accordion phenomenon. As we reduce social distancing restrictions and open commerce and travel, there will inevitably be more cases of COVID. It is likely that restrictions will be imposed again, and this may occur in cycles during the next year(s). We may be able to decrease future shutdowns by wearing masks and gloves when we go out, using hand sanitizer, soap and water, not touching our face, covering our coughs and sneezes, and limiting exposure to large groups of people. I hope all these will be permanent behavior changes except the masks and the large groups (I love the Lake Dillon Amphitheater and the BBQ challenge).

Take care, stay engaged, and have another safe week!

COVID-19: Where Are We At Now?

A panel of experts at the University of Colorado School of Medicine had some good news this morning: we may have passed our peak here in Colorado.

Of the 8,675 cases there are 374 deaths. Less than 2% of those with the illness are under age 18, compared to the population of 22% children. This week there are only 4 children admitted to Children’s hospital with COVID-19, two in the ICU. There is a leveling-off of patients presenting to the hospitals and less ICU admissions.

So social distancing has flattened the curve and no hospitals were overextended or lacked ventilators. The initial R naught (the number of people infected from one individual) of each infected person spreading to 4 is now down to 1.5. A study from Singapore showed that 7% of cases came from presymptomatic persons. The infection can be transmitted 2 to 3 days before symptoms show. Of 121 healthcare workers exposed 35% developed symptoms but only 2.5% tested positive.

Our own experience with testing has been equally frustrating. The virus can be present for weeks but usually rapidly declines after 7 days. The PCR test (polymerase chain reaction test – the standard nasal swab being conducted to test for Corona virus) is said to be 75% accurate in detecting viral RNA. Even patients we’ve tested during the first 4 days of typical symptoms have been negative. Other viruses identified at Children’s Hospital in the last month include rhinovirus, adenovirus, enterovirus and human metapneumovirus, which can all cause fevers and respiratory illnesses.

However, many people we are treating have the unusual symptoms and course that seems unique to COVID. Not all have fever. They experience chills, fatigue, sore throat, then improve. A day later they are having chest tightness, trouble breathing, making it difficult to talk or walk, and upper abdominal pain. They feel worse at night and better in the morning. Symptoms can last for weeks. Lung specialists describe several different effects the virus can have. ARDS (adult respiratory distress syndrome) is a diffuse loss of protective protein that causes the air sacs to collapse. The pulmonary disease in the second week is described as a cytokine storm, where the immune system overreacts and damages the lungs.

Testing is less accurate when the prevalence of a disease is low. In Colorado 1.4% have been affected, in comparison with Wuhan where 5-10% were. Experts and individuals are waiting for antibody testing to see if they are immune and if so for how long. Immunity in similar infections has been shown to last anywhere between 3 weeks and 3 months, as opposed to diseases like measles and chickenpox which confer lifelong immunity.

Pediatricians are seeing few patients in the office these days, which raises the concern for a future epidemic of preventable diseases from a delay in vaccinations. Most clinics, like Ebert Family Clinic, are only seeing healthy patients or those with noninfectious complaints such as eczema and lacerations. Anyone with respiratory symptoms or fever is seen by Telehealth. This is effective because COVID, like most illnesses in the community, is usually mild and self-limited. Antibiotics are rarely indicated. A recent study showed that of several hundred children diagnosed with community-acquired pneumonia, those given antibiotics had the same outcomes at those who were not treated, with 4% of each group needing hospitalization for worsening symptoms.

Telehealth does not allow for auscultation of the heart and lungs (listening with a stethoscope), but the vital signs including oxygen saturation, heart rate and temperature along with the patient’s history usually give the provider enough information to make treatment and testing decisions. A face-to-face video interaction is ideal, protecting the patient and provider from exposure to infection. The expanded use of Telehealth is one of the good outcomes of this pandemic, especially in states like Colorado with far flung rural populations.

 The University of Colorado is doing 3000 telehealth visits daily. Specialists at Children’s are ramping up their services online while accepting the sickest patients in the state for inpatient care. They have the largest number of doctors in Colorado, many of whom are in research and can transfer to frontline and ICU duties. The University does 500 million dollars of sponsored research every year, with over 1000 studies. Many of these are on hold now, but with the capacity to initiate new trials within a week and laboratories adjacent to clinical care sites, CU has been tapped for many COVID-related studies. They are testing several antiviral drugs, including the new product from Gilead laboratories Remdesivir. There are also studies on disease modifying treatments such as steroids to prevent future problems caused by the infection. Other trials focus on sample collecting and processing. Some studies may show results within weeks but others take months or years to determine effect.

The University was one of the first centers to use convalescent plasma to treat COVID. The hope is that antibodies from previously-infected and recovered individuals can be lifesaving for severe cases, although the best timing of such treatment, originally used one hundred years ago in the influenza epidemic, is not yet determined. Plasma donations can be arranged by visiting the UC Health website. Since most people will not need hospitalization, instructions for home care can be found on the CDC website.

Vaccine development will proceed over the next 12 months. Until then, lifting of current social restrictions will depend upon having adequate and accurate testing to find cases early enough to quarantine patients and public health workers to trace contacts. Antibody testing must be done and repeated over months and years to determine susceptibility. Continued use of masks in public and the prohibition of large gatherings may continue for a year.

COVID VS HAPE: Experts Analyze Effect on Lungs

Dr. Chris with Dr. Eric Swenson from the University of Washington

An article published yesterday, April 13, 2020 in the Journal of High Altitude Medicine and Biology clarifies misconceptions in the media comparing high altitude pulmonary edema (HAPE)and COVID lung injury. The six authors include two critical care pulmonologists from the University of Washington: Andrew Luk MD and Eric Swenson MD, as well as Peter Hackett MD of the Hypoxia Institute in Telluride and the University of Colorado Altitude Research Center. Dr. Swenson is the editor of the journal and has given presentations in Summit County on altitude. Both Dr. Hackett and Dr. Swenson personally communicated with Dr. Chris yesterday.

Dr. Chris with Dr. Peter Hackett of the Hypoxia Institute in Telluride, CO

Severe viral pneumonia, as seen in COVID-19, can cause Adult Respiratory Distress Syndrome (ARDS) leading to respiratory failure and the need for ventilator support. As with HAPE, this is a form of non-cardiogenic pulmonary edema, where the air sacs in the lung fill with fluid due to conditions not related to heart failure, the most common cause of pulmonary edema. Other causes include bacterial pneumonia, near-drowning, nervous system conditions, re-expansion, and negative pressure edema. Radiographic findings are similar in all these cases with diffuse bilateral densities in the lungs. All these patients have severe hypoxia.

At altitude, hypoxia can lead to uneven pulmonary vascular constriction, (hypoxic pulmonary vasoconstriction or HPV). In the areas with the highest pressure, fluid leaks from capillaries into the alveoli. With COVID, alveolar inflammation reduces the protein surfactant that maintains expansion of the alveoli. The alveolar collapse causes hypoxemia, low blood oxygen. Severe viral and bacterial infections also cause inflammation in other organs, such as the liver, kidneys, and brain, which is not seen with HAPE.

Medications used to treat HAPE are not likely to be useful in treating COVID pneumonia and may have harmful effects such as increasing perfusion to damaged areas of the lung that are not oxygenated.

Both these conditions likely have large numbers of patients with mild symptoms who recover without seeing a medical provider. However, both HAPE and COVID can cause a sudden, rapid deterioration with severe hypoxia and death.

ACCESS TO A PULSE OXIMETER TO TRACK OXYGEN SATURATION IS VITAL.

Oxygen levels below 90% merit medical attention. Pulse oximeters can be purchased online, at drug stores, or at Ebert Family Clinic.

Doc Talk with Cardiologist Dr. Pete Lemis

Dr. Peter Lemis is a cardiologist in Summit County, CO. He sat down with us in December to share his experience treating heart patients in the mountains.

Summit County cardiologist Dr. Pete Lemis

I graduated medical school in ‘77, practiced internal medicine in New Rochelle, New York, the first county just north of the Bronx. Then I went to New Hampshire for three years. I was reading the New England Journal and saw an unexpected cardiology opening at Henry Ford Hospital in Detroit. Next I was in Pittsburg for 26 years practicing cardiology. Decided I wanted to retire to Colorado, so I built a vacation home here only to discover I didn’t have to wait to retire to move here, so I came five years ago. 

What is it about high altitude and the heart that makes it healthy for heart patients?

Summit is the fifth highest county in the US with the highest population of those counties. The 21 highest are all in Colorado. Lower air pressure means that although there is 21% oxygen in the atmosphere, there are fewer oxygen molecules. So every breath we take is giving us less oxygen, unless we breathe faster and deeper to make up for it, a natural tendency for people. They don’t even think about it. Some people have hypoxia without shortness of breath. Every once in a while, I’ll see a patient who moved to altitude for work or something, and they’re hypoxic. It is probably genetic that some people have a decreased central respiratory drive. 

These patients with low oxygen often are ordered to have an echocardiogram. When they first come up here, they usually won’t have pulmonary hypertension. For some, the decreased central respiratory drive develops not when they first move here, but years after they move here. They become more and more hypoxic without having the feeling of shortness of breath. They have the same physiological response that people with hypoxia get. Their pulmonary vessels are still being constricted, which is reversible if diagnosed and treated with oxygen supplementation during the first few years of high altitude living. If not treated they are likely to get scarring of their pulmonary vessels. The length of time for this to develop is different for different people, and is unpredictable.

For example, I had somebody just this week who’s been here about 2 years who has a resting oxygen saturation of about 82% at 60 years old. 

We can’t tell who is susceptible to this problem. There are likely some genetic factors involved. Dr. Johnson, who recruited me for my job in Summit County, has been here since 2008. He warned me about the issue of high altitude and hypoxia. Most doctors who are unfamiliar with life at high altitude think you adapt and that’s it. Dr. Johnson said to me, “wait three months and test yourself and your wife with an overnight oximetry to see if there’s hypoxia.” Based on that test I started using nocturnal oxygen and I sleep better when I use it. My wife doesn’t need it. Neither does her mother, who is 90 years old. Neither do my sons.

Awake, we’re able to maintain our oxygen levels, but at night when asleep most people who are here in Summit County have low oxygen. Hence my advice is to get a nocturnal pulse oximetry test. Low oxygen for several hours every night over the years can lead to pulmonary hypertension due to the narrowing of the pulmonary arteries. Then there is the question of what is normal: most high altitude studies were done in La Paz with indigenous, adapted populations as opposed to people living in the mountains of Colorado who have been here years or decades. (See what Dr. Chris has written on her collaboration with physicians and scientists in La Paz, Bolivia.)

We asked Dr. Lemis about arrhythmias at altitude. There are two categories-atrial (from the top chamber) and ventricular (from the bottom chamber).

Studies have shown that cardiac arrhythmias are increased initially, but people become acclimated after about 3 – 5 days and the risk returns to baseline. I don’t think these studies have been conducted over enough time. Hypoxia leads to an increase in arrhythmias. I see a lot of atrial fibrillation  and atrial flutter up here; plus, I send three to four patients a month for an electrical procedure to ablate some of the cardiac conduction pathways to get rid of their arrhythmias. Many patients experience relief from atrial arrhythmias when put on nocturnal oxygen.

JB is a 70 year old who has lived at high altitude for 14 years. He experienced atrial fibrillation several times after returning to Summit County from a trip to sea level. He wore a heart monitor for over a month to see how his heart was beating. He felt the atrial fibrillation was related to dehydration and has prevented further episodes, never needing a pacemaker or other treatment. Jim uses a device that monitors his oxygen and heart rate continually while he sleeps, downloading a written report in the morning.

Why do so many people who live up here have bradycardia?

I think because many are athletes. Athletes often have an efficient heart; I see just as many people who have tachycardia because they have low oxygen. Low oxygen causes higher levels of epinephrine. This stimulates their adrenal gland, which can increase their blood pressure. Many people have high blood pressure at high altitude because they have low oxygen. One of my criteria for testing someone for low oxygen at night is if they have high blood pressure.

Many people have central apnea during sleep at altitude caused by the brain’s blunted response to high CO2 and low O2. Similar to obstructive sleep apnea, this central sleep apnea can increase the risk of heart problems. Many people with obstructive sleep apnea here at high altitude need to have oxygen put into their CPAP machine so they get oxygen, rather than just air with continuous positive airway pressure.

There is less fatal ischemic heart disease up here. People tend to be healthier, more athletic. They’ve moved here for an active lifestyle. There’s less cigarette smoking, more exercise, generally better diet (not always), but people up here still have heart attacks. My impression is more of them survive their heart attacks because of their increased physical activity and healthy lifestyle. They have better collateral flow with more capillaries in the heart. They’re protected to some degree. The corollary to this is the fact that when visitors come here and have heart disease, I don’t think that their cardiologist back at low altitude understands high altitude risks and therefore are unable to provide appropriate medical advice. The same amount of exertion here is much harder on the heart, much more stressful to the heart, than it would be at low altitude. There’s something called a double product when you do an exercise test, related to blood pressure and heart rates. You get the same double product causing the same stress on the heart here as at low altitude, but it takes much less exertion to get to a specific double product. 

People who are accustomed to a certain work load at home come up here and try to do the same amount of exertion. If they have coronary artery disease, suddenly there is a middle aged guy with coronary disease having a cardiac ischemic event, perhaps even sudden cardiac death. 

Another important point is that people with known heart disease who live at low altitude, if they’re unstable at all, they shouldn’t be up here within three to six weeks of a heart attack. They should be able to pass a stress test at low altitude before coming to high altitude to visit.

Valvular heart disease patients who have not been treated with surgery, who don’t already live up here, shouldn’t come up here from lower altitude. People with heart failure can come up here if the failure is compensated.

For people who have trouble acclimating to high altitude in the short term, Diamox is quite useful. Using oxygen at night helps you acclimate as well. Diamox makes your blood a little acidotic which increases your respiratory drive.

Avoid alcohol when you first come to high altitude. Unfortunately people on vacation don’t do that. Alcohol is a respiratory suppressant. At high altitude the hypoxia and cold promotes diuresis, so people tend to get dehydrated. Anti-inflammatory drugs are useful in treating the acute altitude sickness for some people. During the first two or three days, try not to push your physical activity to the limits. Try to get a good amount of sleep.

I would say that I have way fewer heart failure patients [up here]. Because patients who develop advanced heart failure really do not do well here, so they tend to move away to lower altitude before that happens. I have younger patients as compared with my former Pittsburgh practice. I also have way fewer patients with COPD. Anything that causes chronic respiratory difficulties you will find a lot less of that up here. Plus, I’m working in an environment where there are less consultants. 

Back in Pittsburg, two thirds of my practice was taking care of patients in the hospital, so I would deal with patients who would come in with a heart attack, with a heart failure exacerbation, or other acute cardiac problem. Here in Summit County, those severely ill patients get transferred down to Denver, so I provide more in-office preventive or post-illness follow-up than I do care in the hospital. My patients who need advanced procedures (e.g. heart catheters, ablation for arrhythmias), I generally send them down to our sister hospital (St. Anthony in Lakewood). 

The cardiac surgeon who will do the bypass surgery usually knows that the patient returning to the mountains will have to be on oxygen for two weeks after surgery.


Gone, Gaper, Gone:COVID-19 April 3, 2020

April 1 is traditionally celebrated in Colorado’s mountain resort communities as “Gaper Day.” Locals dress in their finest 70’s and 80’s outdoor fashions and commemorate the tourists who stop in the middle of the mountain to stare at the beauty that surrounds us. This year travel is discouraged, so the tourists are gone. Here are some local updates on the pandemic to reinforce these directives from Governor Jared Polis.

One day this week, several residents were intubated and transferred to intensive care in Denver. Physicians at St. Anthony Summit Medical Center have access to an ICU and ventilators, but patients with severe respiratory symptoms and hypoxia have a better chance at lower altitude. Let’s hope the day doesn’t come when the Denver hospitals are full, leaving us no choice but to provide this care locally in our low-oxygen environment.

As of April 3, 29 people in have been hospitalized with COVID illnesses, ranging in ages from 20’s to 60’s. There have been 43 confirmed cases in Summit County, according to the Summit Daily News.   It’s here, it’s real, it’s dangerous to all.

Follow the footprints of the fox.

EVERYONE LIVING AT ALTITUDE SHOULD HAVE ACCESS TO A PULSE OXIMETER. You can buy this simple instrument at the pharmacies or call Ebert Family Clinic. You don’t need to go to the hospital if you are breathing normally and your oxygen is above 88%. You can call your doctor or the Ebert Family Clinic for a Telehealth assessment and advice. Our nurse practitioner Tara Taylor will be available 7 days a week between 9 am and 5 pm and Dr. Chris will answer calls and texts for parents and children 24/7. We all know to keep washing our hands: the Corona virus hates soap. Don’t touch your face.

And now I’m going to endorse recommendations from New York and other hard-hit locations: wear a mask and gloves when you go shopping. A bandana, ski mask, surgical mask, anything that reduces the spray of droplets from your mouth and the chance you will inhale these from others.  We are all wearing gloves to keep our hands warm this time of year anyways.

For your mental and physical health, get outside every day. Walk around your neighborhood. Exercise stimulates the immune system. Sunlight helps prevent depression. Look up at the mountains. Gaze at the stars. Let us all be gapers.

First tracks on the track.