Citations

Background: Hypoxia challenges the regulation of arterial oxygenation (SaO 2 ), eliciting a compensatory increase in ventilation ([Formula: see text]E) to preserve blood-gas homeostasis. However, the ability to maintain blood-gas homeostasis during hypoxic exercise may differ between sexes due to differences in chemoreflex drive and the mechanical capacity to augment ventilation. The purpose of this study was to evaluate sex differences in ventilatory and blood-gas responses to progressive hypoxia during moderate walking exercise. Specifically, we asked whether females would be more susceptible to hypoxemia. We hypothesized that females would exhibit a smaller ventilatory response and a less steep ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) compared with males, resulting in a greater reduction in SaO 2 during progressive hypoxia. Methods: Twenty-six physically active adults (15M: age 35.3±9.4; [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 36.2±9.0; [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) were studies during two visits. Visit 1: we determined the participants’ maximal oxygen uptake ([Formula: see text]O 2 max) during an incremental treadmill test. Visit 2: participants walked at ~50% of their [Formula: see text]O 2 max while we reduced the fraction of inspired oxygen (FiO 2 ) progressively every 5 minutes (0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). Arterial blood samples were collected from a brachial artery catheter during the final 30 seconds of each stage; cardiometabolic and ventilatory data were averaged over the final minute of each stage. The test ended when peripheral oxygen saturation (SpO 2 ) fell below 70%. Because 0.13 FiO 2 was the lowest stage completed by all participants, Δ responses were calculated from 0.21 to 0.13 FiO 2 . Independent t-tests compared Δ responses between sexes; data are mean±SD, significance was set at p < 0.05. Results: There was no significant difference in ΔSaO 2 between sexes across hypoxia (M: −22.0±3.7%; F: −22.8±5.5%; p = 0.89). Males had higher arterial oxygen content (CaO 2 ) than females across all stages (M: 20.6±1.2 to 16.0±1.4 mL O 2 ·dL -1 ; F: 18.5±1.1 to 13.8±2.0 mL O 2 ·dL -1 ), but the ΔCaO 2 during hypoxia was not significantly different between sexes (M: −4.6±0.7; F: −4.7±1.4 mL O 2 ·dL -1 ; p = 0.86). Similarly, there was no significant difference in the change in arterial CO 2 (ΔPaCO 2 ) between sexes (M: −5.8±1.5 mmHg; F: −6.5±3.6 mmHg, p = 0.51). In contrast, males exhibited a significantly greater increase in ventilation (Δ[Formula: see text]E: +13.9±4.2 L·min -1 ) than females (+8.6±2.7 L·min -1 ; p = 0.003). Consequently, the ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) was steeper in males (−2.46±0.66 L·min -1 ·mmHg -1 ) compared with females (−1.57±0.68 L·min -1 ·mmHg -1 ; p = 0.004). However, when Δ[Formula: see text]E was expressed relative to maximal ventilatory capacity (%[Formula: see text]Emax), there was no sex difference (M: 8.8±2.6% vs F: 8.3±2.8%; p = 0.68). Conclusion: Females were not more susceptible to hypoxemia than males; both sexes showed comparable reductions in SaO 2 during moderate exercise in progressive hypoxia. Reductions in PaCO 2 were also similar, indicating comparable ventilatory drive. Although males exhibited a larger absolute increase in [Formula: see text]E and a steeper ventilatory CO 2 -response, this difference disappeared when Δ[Formula: see text]E was expressed relative to %[Formula: see text]Emax. These findings indicate that apparent sex differences in ventilation during hypoxia largely reflect differences in ventilatory capacity rather than true differences in oxygenation or ventilatory drive. Taken together, these findings challenge the assumption that females are inherently more susceptible to hypoxemia or have a lower ventilatory drive than males during moderate hypoxic exercise. Funding: NIH T32 DK007352, UL1 TR002377 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: During hypoxic exercise, oxygen transport becomes increasingly challenged as oxygen availability decreases. As the inspired oxygen fraction (FiO 2 ) decreases, peripheral oxygen saturation (SpO 2 ) gradually declines, then drops rapidly upon reaching the steepest point of the sigmoidal shaped, oxyhemoglobin dissociation curve. This reduction in FiO 2 creates a distinct SpO 2 “breakpoint,” which likely represents the threshold at which compensatory mechanisms, such as increases in ventilation and cardiac output, can no longer maintain arterial oxygenation. Several physiological factors may modulate this breakpoint, including hemoglobin concentration, blood volume, and ventilatory capacity. This study aimed to determine the SpO 2 breakpoint during steady-state, submaximal, hypoxic exercise and examine whether factors like sex, age, and fitness level influence the SpO 2 breakpoint. We hypothesized that SpO 2 breakpoints would differ by sex, age, and fitness level, with earlier breakpoints visible in females, older adults, and those with higher aerobic fitness. Methods: Twenty-six physically active adults (15M: age 35±9 yrs, [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 38±10 yrs, [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) participated in a two-day study. Day one: participants performed a treadmill [Formula: see text]O 2 max test. Day two: participants walked at a steady state of ~50% of their [Formula: see text]O 2 max, for 40 minutes, while FiO 2 was progressively reduced every 5 minutes in a stepwise fashion (0.25, 0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). The test was terminated when SpO 2 dropped below 70%. SpO 2 was measured continuously using a clinical-grade oximeter. Analysis was performed in RStudio by first determining each participant’s individual SpO 2 vs time breakpoint. Male and Female breakpoints were compared to assess sex-based differences. To evaluate whether SpO 2 breakpoint timing differed by age or fitness level, participants were then divided into tertiles for each variable. Age tertiles were derived from the sample distribution of chronological age, and fitness tertiles were defined using [Formula: see text]O 2 max (L/min). Mean breakpoint times were compared between the highest and lowest tertiles for both age and fitness. Mean SpO 2 breakpoints were compared between groups using independent sample t-tests. Significance was set to p< 0.05. Results: The overall mean breakpoint occurred at an SpO 2 of 90.7±2.8% during the 0.17 FiO 2 stage. No significant sex differences were observed in breakpoint SpO 2 and timing (M: SpO 2 = 90.7±2.7%, time = 18.6 min; F: SpO 2 = 90.7±3.0%, time = 17.7 min; p = 0.961). Age did not significantly influence breakpoint (younger tertile [21-30 yrs] SpO 2 = 91.0±2.4%, time = 18.4 min; older tertile [41-60 yrs] SpO 2 = 91.1±2.4%, time = 17.2 min, p = 0.953). Additionally, fitness level showed no significant difference on breakpoint (low fitness [1.91-3.01 L/min]: SpO 2 = 90.3±3.1%, time = 17.8 min; high fitness [4.38-5.25 L/min]: SpO 2 = 90.4±2.9%, time = 19.2 min; p = 0.992). Conclusion: During a hypoxic, steady state walking exercise, at ~50% [Formula: see text]O 2 max, we observed no difference in the peripheral oxygen saturation breakpoint, across sex, age, and fitness level. This may suggest that moderate exercise in hypoxia does not sufficiently challenge the cardiopulmonary system for individual variations in oxygen transport to influence the breakpoint. These findings imply that the SpO 2 breakpoint, during hypoxic exercise, may represent a physiological marker of the upper limit for maintaining oxygen saturation in healthy adults. Applying this protocol to identify SpO 2 breakpoints may offer insights for improving pharmacological interventions and our understanding of clinical populations with impaired oxygen transport. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

e23014 Background: The number of annual global cancer deaths is rising and the majority of this burden, for a multitude of reasons, falls in low- and middle- income countries (LMICs). With the United Nations’ 3rd and 17th Sustainable Development Goals in mind (which include by 2030 “reduce by one third premature mortality from non-communicable diseases” and “partnership for the goals”) a survey was undertaken at the UK’s two largest comprehensive cancer centres to scope individual and team endeavours to work with colleagues in less well-resourced countries. Methods: Employees at the Royal Marsden Foundation Trust (RM) and Institute of Cancer Research (ICR) in London and Surrey, UK and The Christie NHS Foundation Trust (Christie), Manchester were invited to complete a survey to capture collaborative clinical care, research, education and training. Results: Responses were received from 520 multidisciplinary individuals across the 2 centres to two similar questionnaires. A large number had experience of working in some capacity in, or in collaboration with an LMIC. At the RM 14.62% of respondees were currently working with colleagues in LMICs. At The Christie 13.22% of staff had experience of working in LMICs in a supportive capacity. Those currently collaborating with colleagues in LMICs were working in a wide range of countries across Asia, Africa and South America in a range of initiatives spanning clinical care, research, education and training. Of those who answered the survey 64% at The Christie said they’d like to hear more about opportunities to be involved in supporting global health care, and 89% at RM/ICR said they’d be interested in joining a collaborative group working on global oncology initiatives at the institutions. Conclusions: This survey highlights the body of willing, interested individuals keen to work with colleagues in LMICs to improve cancer outcomes. The launch of the UK Global Cancer Network in 2020 will build upon these two surveys with a planned national survey of global health and cancer work undertaken by individuals in 2021.

AbstractThe purpose of this systematic review and meta‐analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID‐19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID‐19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full‐text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta‐analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = −0.49 days [95% CI = −3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID‐19.