Using modified Fenn diagrams to assess ventilatory acclimatization during ascent to high altitude: Effect of acetazolamide.

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self-administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide-free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. HIGHLIGHTS: What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide-free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

Comparison of mild physiological effects of surgical masks and N95 respirators over 60 min at rest.

Dead-space-associated rebreathing of expired air and heat trapping with use of surgical masks and N95 respirators may underlie anecdotal reports of adverse symptoms associated with medical face barriers. Limited data exist directly comparing the physiological effects of masks and respirators at rest. We assessed the short-term physiological effects of both barrier types over 60 min at rest, including face microclimate temperature, end-tidal gases, and venous blood acid-base variables. We recruited 34 participants into two trials: surgical masks (n = 17) and N95 respirators (n = 17). In a seated position, participants underwent a 10-min baseline without a barrier and then wore a standardized surgical mask or dome-shaped N95 respirator for 60 min, followed by a 10-min washout. We instrumented healthy human participants with a peripheral pulse oximeter ([Formula: see text]) and a nasal cannula connected to a dual gas analyzer for measurement of the pressure of end-tidal [Formula: see text] and [Formula: see text], with an associated temperature probe for face microclimate temperature. Venous (v) blood samples were obtained at baseline and following 60-min mask/respirator wearing to assess [Formula: see text], [HCO3-]v and pHv. Compared with baseline during/following 60 min, temperature, [Formula: see text], [Formula: see text], and [HCO3-]v were mildly but significantly higher, and [Formula: see text] and [Formula: see text] were significantly lower, but [Formula: see text] was unaffected. The magnitude of effects was similar between barrier types. Temperature and [Formula: see text] returned to baseline levels within 1-2 min following removal of the barrier. These mild physiological effects may underlie reports of qualitative symptoms while wearing masks or respirators. However, the magnitudes were mild, not physiologically relevant and reversed immediately with the removal of the barrier.NEW & NOTEWORTHY Anecdotal reports suggest mild physiological effects of wearing surgical masks and/or N95 respirators, including heat trapping and rebreathing of expired air. There are limited data directly comparing the physiological effects of wearing medical barriers at rest. We found that the time course and magnitude of changes to face microclimate temperature, end-tidal gases, and venous blood gases and acid-base variables were mild in magnitude, not physiologically relevant, equivalent between barrier types, and immediately reversible on removal.

Steady-state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide.

Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady-state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady-state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady-state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude-related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady-state measurements of resting ventilation (V̇I ; L/min), pressure of end-tidal (PET )CO2 (Torr), and peripheral oxygen saturation (SpO2 ; %) were measured. A stimulus index (SI; PET CO2 /SpO2 ) was calculated, and SSCD was calculated by indexing V̇I against SI. We found that (a) both V̇I and SSCD increased with ascent to 4240 m (day seven; V̇I : +39%, p < 0.0001, Hedges' g = 1.52; SSCD: +56.%, p < 0.0001, Hedges' g = 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇I : p = 0.02, Hedges' g = 1.04; SSCD: p = 0.02, Hedges' g = 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests.