Alison,

Although there have only been a few studies specifically focused on the effects of oxygen desaturation due to altitude on cluster headaches, there have been a number of studies on the effects of reduced partial pressure of oxygen on cluster headaches, so it appears fairly clear, a relationship exists.  

Many of us get hit shortly after leveling off at altitude on commercial aircraft flights, just as many of us also suffer from an increased incidence of cluster headache attacks while sleeping.  There have been a number of studies done in this area where oxygen desaturation and elevated CO₂ levels in exhaled breath during reduced respiration rates while sleeping were found to be the probable source of provocation resulting in an increase in the incidence of cluster headache attacks.

As a retired Navy pilot, I'm very familiar with aviation physiology and aircraft pressurization systems.  Pilots flying tactical military jets are required to breathe 100% oxygen at all times as our cabin altitude is frequently above 10,000 feet where supplemental oxygen is required to prevent passing out from hypoxia (lack of oxygen).  At cruising altitudes between 30,000 ft and 40,000 ft it was common to see a cabin altitude pressure of 15,000 ft to 17,000 ft.

The cabins of commercial airliners are pressurized to maintain a cabin pressure equal to an altitude of less than 10,000 ft. at all times.  At normal cruising altitudes the cabin altitude in these aircraft is approximately 7,500 ft.  The reduction in the partial pressure of oxygen at this altitude is 23%.  The Naval Flight Surgeon's Manual has a table that indicates the reduction in the partial pressure of oxygen within the lung's alveoli is 32% at an altitude of 7,500 ft.  This same table states there is only a 7% reduction in the partial pressure of CO₂. This results in a major change in the ratio of oxygen to CO₂ at altitude.  

Given Denver is the mile high city, you and your husband are being exposed to the same reduction in the partial pressure of oxygen as well as the change in the ratio of oxygen to CO₂. While the change in altitude is likely to have only a minor effect on you, as a cluster headache sufferer, the elevation in altitude can have a major effect on your husband's cluster headache patterns.

Michael Berger and I have been researching the physiological effects of oxygen therapy as a cluster headache abortive over the last three years.  Soon after starting this research, we became aware of studies that indicated carbon dioxide (CO₂) appears to play a major role in the cluster headache triggering and abort mechanisms as well as oxygen.  We knew that when the oxygen concentration in the lungs and arterial bloodstream is higher than normal, the condition is called hyperoxia.  It’s well known in medicine that hyperoxia is a vasoconstrictor and there are several studies that clearly indicate it acts as an abortive for our cluster headache attacks.  Our research also revealed CO₂ plays an even greater role in cluster headache attacks as does the shift in arterial pH above or below the normal range of 7.35 to 7.45.

When lung and arterial CO₂ levels are above normal, the condition is called hypercapnia.  There's a large body of medical information that clearly indicates hypercapnia acts as a vasodilator.  As a vasodilator, hypercapnia tends to favor the cluster headache triggering mechanism.  This condition tends to make abortive therapies less effective and our attacks more frequent.  Hypercapnia also tends to make our attacks last longer and become more intense.  

CO₂ also dissolves in blood plasma the same way it does in carbonated beverages although not as much at normal atmospheric levels.  When this happens, CO₂ disassociates into carbonic acid.  When more CO₂ is dissolved in the blood plasma than normal, the acid content of the arterial blood rises and the pH drops below normal.

When lung and arterial CO₂ levels are below normal, the condition is called hypocapnia.  There are also a significant number of studies indicating hypocapnia acts as a vasoconstrictor.  As a vasoconstrictor, hypocapnia tends to make abortive medications and oxygen therapy more effective as well as reduce the frequency, duration, and intensity of our attacks.  As hypocapnia means less CO₂ is dissolved in the blood plasma than normal, the acid content of the arterial blood drops, and the pH rises above normal to an alkaline condition.  If this shift in pH is due to increased lung ventilation or hyperventilation, this condition is called respiratory alkalosis.

Now, when you add the fact that it isn't the lack of oxygen that makes us breathe faster and regulates our respiration rate, but rather the level of CO₂ in the arterial bloodstream, you can see that physical activity can act as a double edged sword with respect to our cluster headache attacks.  When arterial CO₂ levels are above normal, we start breathing like a big dog to reduce CO₂ levels back to normal.  When CO₂ levels are below normal, we breathe more slowly.

With this in mind, it's easy to see where claims that physical exercise can shorten the duration of cluster headache attacks for some, while it may make attacks worse for others.  The greater the physical activity, the more CO₂ our bodies produce and the faster we breathe to bring the excess CO₂ levels back to normal.  If we're breathing fast enough to keep CO₂ levels in the normal range or slightly below, there's a good chance that physical activity will reduce the duration and intensity of our cluster headache attacks.  If we're not ventilating our lungs fast enough to remove excess CO₂, the physical activity will tend to make our cluster headache attacks more painful and last longer.

This same physiological relationship between the exchange of oxygen and carbon dioxide in the lungs during respiration is also one of the important reasons many have difficulty when trying oxygen therapy to abort their cluster headache attacks.  In most cases where oxygen therapy fails to work effectively as an abortive, the oxygen flow rate is too low.  When a low oxygen flow rate is combined with the use of a non-rebreather mask that prevents room air from entering the lungs, the total flow rate per minute coming from the oxygen regulator equals the total lung ventilation in one minute.  

Even though an oxygen flow rate of 7 to 9 liters/minute may be sufficient to oxygenate blood hemoglobin to 100%, if the lung ventilation is not sufficient to reduce CO₂ levels back to or below normal, an abort may not be possible.

The heart plays an important role in this process as well and it tends to beat faster when arterial CO₂ levels are high than it does when arterial CO₂ levels are in the normal range.  When the heart beats faster, a greater volume of blood passes through the lungs allowing a greater exchange of oxygen and CO₂.

Michael and I developed the following graphic to illustrate the relative vasoactive effects of O₂, pH, and CO₂ as they relate to cluster headaches.

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As you can see, hyperoxia, an elevated pH, and hypocapnia all result in vasoconstriction just as hypoxia, a depressed pH, and hypercapnia result in vasodilation.  

This graphic also illustrates the benefit of using oxygen therapy at flow rates that support hyperventilation as a cluster headache abortive. As you can see, this method of oxygen therapy pushes all three of the vasoactive effects high into the green shaded areas that favor increased vasoconstriction.

I realize this is a long-winded response to your questions, but it should help explain some of the physiology behind an increase in cluster headache attacks at increased altitudes and while sleeping, as well as the use of oxygen therapy at sufficient flow rates to support hyperventilation in order to abort them.

Take care,

V/R, Batch