Steier, Joerg, Nic Cade, Ben Walker, John Moxham, and Caroline Jolley. Observational study of neural respiratory drive during sleep at high altitude. High Alt Med Biol. 18:242-248, 2017. AIMS:Ventilation at altitude changes due to altered levels of pO2, pCO2 and the effect on blood pH. Nocturnal ventilation is particularly exposed to these changes. We hypothesized that an increasing neural respiratory drive (NRD) is associated with the severity of sleep-disordered breathing at altitude. METHODS:Mountaineers were studied at sea level (London, United Kingdom), and at altitude at the Aconcagua (Andes, Argentina). NRD was measured as electromyogram of the diaphragm (EMGdi) overnight by a transesophageal multi-electrode catheter; results were reported for sea level, 3,380 m, 4,370 m, and 5,570 m. RESULTS:Four healthy subjects (3 men, age 31(3)years, body mass index 23.6(0.9)kg/m2, neck circumference 37.0(2.7)cm, forced expiratory volume in 1 second 111.8(5.1)%predicted, and forced vital capacity 115.5(6.3)%predicted) were studied. No subject had significant sleep abnormalities at sea level. Time to ascent to 3,380 m was 1 day, to 4,370 m was 5 days, and the total nights at altitude were 21 days. The oxygen desaturation index (4% oxygen desaturation index [ODI] 0.8(0.4), 22.0 (7.2), 61.4 (26.9), 144.9/hour, respectively) and the EMGdi (5.2 (1.9), 12.8 (5.1), 14.1 (3.4), 18.5%, respectively) increased with the development of periodic breathing at altitude, whereas the average SpO2 declined (97.5 (1.3), 84.8 (0.5), 81.0 (4.1), 68.5%, respectively). The average EMGdi correlated well with the 4%ODI (r = 0.968, p = 0.032). CONCLUSION:NRD sleep increases at altitude in relation to the severity of periodic breathing.