Short running head: Physiology of impaired gas exchange in BPD Descriptor: 14.3 Manuscript Body Word Count: 3639 At a Glance Commentary: Scientific Knowledge on the Subject: Assessment of impaired gas exchange may provide a continuous outcome measure for sensitive and equitable determination of severity of bronchopulmonary dysplasia (BPD). Previous gas exchange studies in BPD infants used small cohorts and targeted moderate-severe BPD. These studies show right shift of the peripheral oxyhemoglobin saturation (SpO2) versus inspired oxygen partial pressure (PIO2) curve and reduced ventilation-perfusion ratio reliably predict hypoxaemia in preterm infants breathing air, and further, that many infants also have a right-left shunt. What This Study Adds to the Field: We provide measures of right shift, ventilation/perfusion and shunt, across the full spectrum of lung disease in a large (n=219) group of preterm infants. Shift increases and ventilation/perfusion decreases with increased severity of BPD as defined by the NIH classification of BPD. Shunt is primarily a feature of infants with moderate-severe BPD who require supplemental oxygen. Non-invasive bedside assessment of shift, ventilation/perfusion and shunt provide physiological continuous outcome measures of severity of respiratory disease in very preterm infants with/without BPD independent of altitude and unit practices. Routine analysis of the SpO2/PIO2 curve may improve accuracy of BPD severity classification and provide a sensitive continuous outcome measure for clinical trials evaluating pulmonary outcomes.