I'm definately not an expert here, but I learnt a school that the level of CO2 in the atmosphere is important. The level of 02 is unlikely to drop much below 21% but even if CO2 concentration rises to 1% (from well below 0.1% in the atmosphere) it wil be very uncomfortable. (The scene in Das Boot where the crew have trouble breathing is more realistic than the likes of Stingray where subs run out of air like fuel.) Cabin air is recirculated. It is filtered to remove bugs, etc, but CO2 levels may well rise. Perhaps someone in the know could comment on this and correct me if neccesary.
Previous posts mention low levels of humidity in flight which can certainly affect nasal membranes. However I find high levels of humidity before the engines are started more uncomfortable. Most US airports and LHR T5 have external air conditioned air supplies, which are generally OK, but APUs can't always cope and some airlines save money but limiting APU use on the ground. I find that you are so more comfortable once you start getting engine bleed air into the cabin that I can nod off.