Individual effects of combination therapy on obstructive sleep apnea (OSA) severity. Combination therapy significantly reduced the overall supine apnea-hypopnea index (AHI) in all but one individual. Notably this individual had a low loop gain at baseline and a robust upper airway muscle response. However, with therapy, for reasons that are unclear, combination therapy unexpectedly increased loop gain (by 150%) and attenuated their upper airway muscle function (by 84%), which consequently widened the gap between V_arousal and V_active: such a widening is consistent with the increase in OSA severity observed. Black circles represent those patients considered nonresponders to therapy, whereas gray triangles represent responders (see text for definitions of responders/nonresponders). Of note, in six patients (approximately one-third of all unselected patients) OSA was completely resolved (AHI < 10 events/h) with combination therapy.