Martin et al1 used a hypoxia altitude simulation test to propose a cut-off value of 85% oxygen saturation by pulse oximetry (Spo2) in infants breathing 14% oxygen at sea level; 7 infants had Spo2 ranging from 79 to 84%, while 12 infants had Spo2 ≥ 95%. This wide response was not predicted by baseline Spo2 percentage in air, emphasizing the need for measurements reflecting the continuum of underlying pathophysiology. Following British Thoracic Society2 recommendations that arterial oxygen saturation (Sao2) < 92% breathing air at sea level is an indication for in-flight oxygen administration, we found some adults with lung disease and Sao2 percentage above this cut-off who had profound hypoxemia (Sao2 ≤ 82%) during airline equivalent hypoxia.3 This is most likely to occur if the underlying pathophysiology is predominantly due to reduced ventilation-perfusion ratio (V̇/Q̇) rather than increased shunt.3 A simple modification to hypoxia altitude simulation test, whereby Spo2 percentage is plotted vs partial pressure of inspired oxygen (Pio2) during a stepwise reduction in inspired oxygen produces a curve whose shape reflects the dissociation curve but which is shifted to the right along the Pio2 axis in proportion to reduced V̇/Q̇.3 This rightward shift due to reduced V̇/Q̇ has a more profound effect than shunt on Spo2 percentage when Pio2 falls at altitude/in flight. Since the shape of the Spo2/Pio2 curve is affected differently by reduced V̇/Q̇ and shunt, these entities can be derived noninvasively from this curve. This approach can also be used in infants.4 Hence, adapting hypoxia altitude simulation test to derive V̇/Q̇ and shunt presents a continuum of physiologic impairment that may be of use when assessing fitness to fly.