Under normal physiological conditions, O2 transport is generally perfusion-limited, while it can become diffusion-limited in pathological states or during intense exercise.
The overall trend in the respiratory tract is for the epithelium to become progressively thinner as it approaches the alveoli (where it's extremely thin simple squamous epithelium) to facilitate gas diffusion.
Decreased atmospheric oxygen (PiO2) at high altitudes triggers various adaptation mechanisms in the respiratory system. Insufficient adaptation to the high altitude results in altitude sickness.