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From the report:

When flying at high altitudes, the biggest fear for any crew member is succumbing to anoxia. Anoxia is the lack of breathable oxygen above 10,000 feet. The human body is adapted to an environment below 10,000 feet and whenever it goes above this altitude it requires supplemental oxygen to survive. To highlight this problem, Flight Surgeons and Physiologists found fatal and non-fatal anoxia occurring in operational aircraft from 1942 - 1944. While there was evidence of some mild cases during the first six months of operations in the Eighth Air Force, it was not until a death was reported that the problem got the needed attention. The seriousness of the problem was identified in the first two years of operations, from Aug 1942 through Aug 1944. During this time there had been a small number of deaths, but a larger number of non-fatal cases of anoxia.

Just flying a mission meant the chance of dying from a lack of oxygen.

The peak for anoxia cases came in November 1943
with an overall rate of 18.1 cases per 1,000 heavy bomber aircraft sorties.

The final aspect of physiological problems experienced by crews involves adaptation to the extreme cold of flying at 25-30,000 feet during their long missions. Here again, many unanticipated problems had to be overcome. Minus 30 to 50 degree temperatures were quite normal over northern Europe at 25,000 feet, the optimum altitude for heavy bombers. Frostbite, the predominant hazard, made the provision of suitable flight crew
clothing essential. The USAAF had developed electrically heated flying suits in 1940, but they only became available to gunners during the winter of 1942-43. The suits were completely unreliable, when subjected to the rigors of operational flying.

Another important piece of crew equipment found to be defective in the B-17 was the oxygen system. The early B-17s had the continuous flow type oxygen regulators. The Eighth AF had considerable trouble with this type of system because it had a tendency to allow the breath moisture to freeze and obstruct the oxygen flow. During many flights a crew member found himself constantly squeezing the O2 hoses just to break up ice crystals before they totally stopped the flow of oxygen. This deadly problem was immediately addressed because of crew complaints and cases of anoxia.

The entire USAAF had continuous flow type regulators until ~1944.

Of course all this exposure to altitude leads to a plethora of physiological problems. Today we recognize this leads to a decrease in the crews ability to safely operate the aircraft.

To highlight this problem one only needs to look at the data from 1944 in the Eighth AF:
there were 2562 aircraft accidents not related to combat, involving 2835 aircraft, and resulting in the death of 1692 persons. This amounts to seven accidents and 4.6 fatalities every day of the year.1

Pilot error was the primary cause of B-17 accidents in the Eighth AF. The most common forms of pilot error were: improper taxiing, leveling off too high, hitting too hard, overshooting the landing, and misuse of landing gear or flaps.

Pilot error in today’s aviation community indicates a problem with
crew training, physiological conditioning or crew fatigue.