Effects of non‐steroid anti‐inflammatory drugs on the human hypoxic ventilatory response and acclimatization

Recent studies show that inflammation contributes to respiratory chemoreflex plasticity during chronic hypoxia. Ibuprofen (a non‐steroidal anti‐inflammatory drug, NSAID) prevents the normal time‐dependent increase in the hypoxic ventilatory response (HVR) in chronically hypoxic rats (Respir. Physiol. Neurobiol. 178: 381–386, 2011). We hypothesized that inflammatory pathways contribute to ventilatory acclimatization to hypoxia in humans also. To test this, we measured the isocapnic HVR in 5 subjects at sea level and at high altitude (3,800m) using a randomized, double‐blind, repeated measures protocol. Ibuprofen or placebo was administered (400mg TID) over 48 hours at sea level and over 48 hours at 3,800m. We measured HVR at 24 and 48 hours of treatment at sea level and 3,800m. Results showed no significant difference in the HVR between placebo and ibuprofen treatments at sea level. A significant increase in the HVR at altitude occurred with placebo, indicating normal ventilatory acclimatization. However, ibuprofen blocked the increase in HVR at altitude, showing significantly less HVR increase with ibuprofen versus placebo. The results may have implications for the treatment of acute mountain sickness at high altitude with NSAIDs. Supported by UC White Mt. Res. St., NIH RO1 HL‐ 081823 & 1P01 HL 098053.