I agree about the importance of human factors in hot and high flying, even though I have never actually done it!
The South Western US is a favourite holiday destination of mine (fly-drive, but after all the recent threads I hope to fly-drive-fly next time!).
Sight-seeing around areas such as the Grand Canyon, Yosemite and Big Bear (7000 to 9000 ft asl) the shortness of breath after a jog from the car to a view point is really noticeable (OK, so I am not particularly fit).
The effect seems to be cumulative over a few days at altitude leading to tiredness, poor concentration and irritability (Mrs TG particularly prone to the latter
).
Tall Guy.