HIIE led to an increase in B-lines at altitude after subacute exposure but not during acute exposure at equivalent simulated altitude. This may indicate pulmonary interstitial edema.

The aim was to assess the effect of high altitude on the development of new immune memory (induction) using a contact sensitization model of in vivo immunity. We hypothesized that high-altitude exposure would impair induction of the in vivo immune response to a novel antigen, diphenylcyclopropenone (DPCP). DPCP was applied (sensitization) to the lower back of 27 rested controls at sea level and to ten rested mountaineers 28 hours after passive ascent to 3777 m. After sensitization, mountaineers avoided strenuous exercise for a further 24 hours, after which they completed alpine activities for 11-18 days. Exactly 4 weeks after sensitization, the strength of immune memory induction was quantified in rested mountaineers and controls at sea level, by measuring the response to a low, dose-series DPCP challenge, read at 48 hours as skin measures of edema (skinfold thickness) and redness (erythema). Compared with control responses, skinfold thickness and erythema were reduced in the mountaineers (skinfold thickness,-52%, p=0.01, d=0.86; erythema, -36%, p=0.02, d=0.77). These changes in skinfold thickness and erythema were related to arterial oxygen saturation (r=0.7, p=0.04), but not cortisol (r<0.1, p>0.79), at sensitization. In conclusion, this is the first study to show, using a contact sensitization model of in vivo immunity, that high altitude exposure impairs the development of new immunity in humans.

The overestimation of HRpeak by commonly used age-derived predictive equations in normobaric hypoxic conditions suggests that despite possible contraindications researchers should directly measure HRpeak whenever possible if it is to be used to prescribe exercise intensities.

The VT appears to be a suitable physiological parameter for exercise prescription in normobaric hypoxia up to an altitude of 4,000 m.

Acetazolamide (Az) is widely used to prevent and treat the symptoms of acute mountain sickness (AMS) but whether it alters exercise capacity at high altitude is unclear. Az (250 mg twice daily) or placebo were administered to 20 healthy adults (age range, 21-77 years) in a double-blind, randomized manner. Participants ascended over five days to 4559 m, before undertaking an incremental exercise test to exhaustion on a bicycle ergometer, with breathby-breath gas measurements recorded using a portable gas analysis system. Maximum power output (P max ) was reduced on Az compared with placebo (p=0.03), as was maximum O 2 uptake (VO 2max ) (20.7 vs 24.6 mL/kg/min; p=0.06) and maximum expired CO 2 (VCO 2max ) (23.4 vs 29.5 mL/kg/min; p=0.01).Comparing individuals matched for similar characteristics, Az-treated participants had smaller changes than placebo-treated participants in minute ventilation (88 vs 116 L/min: p=0.05), end tidal O 2 (6.6 vs 9.3 mm Hg: p=0.009), end-tidal CO 2 (-2.3 vs -4.2 mm Hg: p=0.005), VO 2max (9.8 vs 13.8 mL/kg/min; p=0.04) and VCO 2max (14.7 vs 20.8 mL/kg/min; p=0.009). There was a negative correlation between the mean ages of paired vs placebo-treated individuals and differences in P max reductions from base-line to altitude (r =-0.83: p<0.005) and HR max at altitude (r=-0.71; p=0.01). Glomerular filtration rate (measured at sea-level) declined with increasing age (r=-0.69; p=0.001). Thus, 250mg of Az twice daily reduced exercise performance, particularly in older individuals. The age-related effects of Az may reflect higher tissue concentrations due to reduced drug clearance in older people.Key words: acute mountain sickness, high altitude, acetazolamide, exercise, age not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/105726 doi: bioRxiv preprint first posted online Feb. 3, 2017; New and noteworthy:We have identified a reduction in exercise performance (maximum power output and VO 2max ) at high altitude in individuals given commonly prescribed doses of acetazolamide for acute mountain sickness. This reduction was greater in older people (>50 years) possibly due to reduced renal clearance of the drug. Results indicate that it may be appropriate for older people to use smaller doses of acetazolamide at altitude. Introduction: