The Smell of Hypoxia: using an electronic nose at altitude and proof of concept of its role in the prediction and diagnosis of acute mountain sickness.

Electronic nose (e-nose) devices may be used to identify volatile organic compounds (VOCs) in exhaled breath. VOCs generated via metabolic processes are candidate biomarkers of (patho)physiological pathways. We explored the feasibility of using an e-nose to generate human "breathprints" at high altitude. Furthermore, we explored the hypothesis that pathophysiological processes involved in the development of acute mountain sickness (AMS) would manifest as altered VOC profiles. Breath analysis was performed on Sherpa and lowlander trekkers at high altitude (3500 m). The Lake Louise Scoring (LLS) system was used to diagnose AMS. Raw data were reduced by principal component (PC) analysis (PCA). Cross validated linear discriminant analysis (CV-LDA) and receiver-operating characteristic area under curve (ROC-AUC) assessed discriminative function. Breathprints suitable for analysis were obtained from 58% (37/64) of samples. PCA showed significant differences between breathprints from participants with, and without, AMS; CV-LDA showed correct classification of 83.8%, ROC-AUC 0.86; PC 1 correlated with AMS severity. There were significant differences between breathprints of participants who remained AMS negative and those whom later developed AMS (CV-LDA 68.8%, ROC-AUC 0.76). PCA demonstrated discrimination between Sherpas and lowlanders (CV-LDA 89.2%, ROC-AUC 0.936). This study demonstrated the feasibility of breath analysis for VOCs using an e-nose at high altitude. Furthermore, it provided proof-of-concept data supporting e-nose utility as an objective tool in the prediction and diagnosis of AMS. E-nose technology may have substantial utility both in altitude medicine and under other circumstances where (mal)adaptation to hypoxia may be important (e.g., critically ill patients).

Sublingual microcirculatory blood flow and vessel density in Sherpas at high altitude.

Anecdotal reports suggest that Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, despite exhibiting lower arterial oxygen content than acclimatized lowlanders. This study tested the hypothesis that Sherpas exposed to hypobaric hypoxia on ascent to 5,300 m develop increased microcirculatory blood flow as a means of maintaining tissue oxygen delivery. Incident dark-field imaging was used to obtain images of the sublingual microcirculation from 64 Sherpas and 69 lowlanders. Serial measurements were obtained from participants undertaking an ascent from baseline testing (35 m or 1,300 m) to Everest base camp (5,300 m) and following subsequent descent in Kathmandu (1,300 m). Microcirculatory flow index and heterogeneity index were used to provide indexes of microcirculatory flow, while capillary density was assessed using small vessel density. Sherpas demonstrated significantly greater microcirculatory blood flow at Everest base camp, but not at baseline testing or on return in Kathmandu, than lowlanders. Additionally, blood flow exhibited greater homogeneity at 5,300 and 1,300 m (descent) in Sherpas than lowlanders. Sublingual small vessel density was not different between the two cohorts at baseline testing or at 1,300 m; however, at 5,300 m, capillary density was up to 30% greater in Sherpas. These data suggest that Sherpas can maintain a significantly greater microcirculatory flow per unit time and flow per unit volume of tissue at high altitude than lowlanders. These findings support the notion that peripheral vascular factors at the microcirculatory level may be important in the process of adaptation to hypoxia.NEW & NOTEWORTHY Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitude, yet the physiological mechanisms underlying this tolerance remain unknown. In our prospective study, conducted on healthy volunteers ascending to Everest base camp (5,300 m), we demonstrated that Sherpas have a higher sublingual microcirculatory blood flow and greater capillary density at high altitude than lowlanders. These findings support the notion that the peripheral microcirculation plays a key role in the process of long-term adaptation to hypoxia.