Samuel Verges

Background: Intermittent hypoxic training aims to enhance exercise performance and health, commonly assessed through maximal oxygen uptake ( V O ₂ max). Currently applied methods are live-high train-low (LHTL), live-low train-high (LLTH) and passive hypoxic conditioning (PHC). However, within these methods, numerous modes of application exist, and effectiveness is debated. Objective: To determine the effect of LHTL, LLTH and PHC on V O ₂ max in healthy participants, and identify factors associated with the amplitude of change in V O ₂ max. Methods: We conducted a systematic review with random-effects meta-analysis and meta-regression. Studies were identified through PubMed, EMBASE and Web of Science. We included controlled studies, calculating between-group standardised mean differences. Athlete and non-athlete populations were analysed separately. RoB2 was used to assess study quality and publication bias was investigated with funnel plots and the Egger’s test. Results: Of the 5244 identified studies, 62 were included for analysis, resulting in a sample size of 1332 participants (610 athletes, 722 non-athletes). LHTL increased V O ₂ max significantly more than control in athletes (mean difference [MD] = 2.17; 95% CI = 0.77, 3.56) but not in non-athletes (MD = 3.1; 95% CI = − 0.23, 6.43). LLTH did not increase V O ₂ max significantly more than control in athletes (MD = 0.89; 95% CI = − 0.27, 2.05) but it did in non-athletes (MD = 1.70; 95% CI = 0.85, 2.54). PHC did not increase V O ₂ max significantly more than control in athletes (MD = − 1.07; 95% CI = − 3.51, 1.37) but it did in non-athletes (MD = 2.26; 95% CI = 1.00, 3.52). Multivariate meta-regressions identified the severity, duration, and frequency of hypoxic exposure to be significantly associated with the change in V O ₂ max. Conclusions: LHTL showed a significant effect on V O ₂ max in athletic populations while LLTH and PHC showed a significant effect on V O ₂ max in non-athletic populations only. Future studies should target investigating which characteristics (e.g. severity, duration) of the hypoxic exposure are most beneficial.

Importance: Acute mountain sickness (AMS) is a common high-altitude illness partly preventable by acetazolamide, but sex-specific efficacy and tolerability have not been prospectively evaluated. Objective: To test the a priori hypothesis that preventive acetazolamide achieves a 20% greater relative risk reduction (RRR) of AMS in female vs male lowlanders ascending to 3600 m. Design: Randomized, double-blind, placebo-controlled, parallel-group trial conducted from March 2024 to August 2025; participants, outcome assessors, and statistician were blinded until analysis was complete. Setting: Baseline at 760 m in Bishkek and altitude exposure at the Kumtor High Altitude Facility (3600 m), Kyrgyz Republic. Participants: Healthy female and male low-altitude residents (age 18-44 years, BMI 18-30 kg/m2, residence 2500 m within 4 weeks. Intervention: Acetazolamide 125 mg or matching placebo twice daily, from 24 hours before ascent and throughout the 2-day, 2-night stay at 3600 m. Main Outcomes and Measures: Primary outcome was the between-sex difference in RRR of AMS, defined as a 2018 revised Lake Louise Score of 3 or higher including headache. Secondary outcomes included absolute risk reduction (ARR) and drug tolerability. Results: Of 303 randomized participants (180 females, 123 males; mean [SD] age, 23 [4] years), AMS incidence under placebo (n=155) was 34% (females 42% vs males 23%; P=.02) and under acetazolamide (n=148) was 24% (females 30% vs males 14%; P=.02). Overall RRR was 31% (95% CI, 0% to 52%) and ARR was 10% (95% CI, 0% to 22%). Sex-stratified RRR was 27% (95% CI, -9% to 52%) in females and 42% (95% CI, -28% to 74%) in males; between-sex RRR difference, -15% (95% CI, -65% to 57%). Females had a 4.8-fold higher risk of moderate-to-severe drug-related side effects than males. Conclusions and Relevance: Preventive acetazolamide reduced overall AMS incidence at 3600 m, but the pre-specified 20% greater RRR in females (trial powered at 90%) was not observed. The nearly 5-fold higher risk of moderate-to-severe side effects in females warrants further investigation of sex-specific dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT06499727

Sleep plays a pivotal role in athletes’ recovery and performance, yet research consistently shows that many athletes experience suboptimal sleep. Existing screening questionnaires typically rely on cut-off scores to classify athletes (e.g., good vs. poor sleepers), offering a limited and often simplistic view of sleep quality. By moving beyond these arbitrary thresholds, the present study adopts a person-centred approach to uncover distinct sleep profiles among elite athletes and explores how these profiles relate to well-being and ill-being. A total of 528 elite athletes (273 women) completed questionnaires assessing sleep, well-being, and ill-being. Sleep characteristics were measured using the Athens Insomnia Scale and the Pittsburgh Sleep Quality Index. Well-being was assessed using the Athlete Satisfaction Questionnaire subdimension for individual performance satisfaction, while ill-being was measured using the Burnout Assessment Tool short form adapted to the sport context. Latent profile analysis was then conducted to identify distinct sleep profiles, and multilinear regression analyses examined their associations with well-being and ill-being outcomes. Six distinct sleep profiles emerged. Two profiles, characterized by mean sleep durations of less than seven hours per night, were associated with significantly higher levels of ill-being and lower levels of well-being compared to other profiles. These findings highlight the importance of sleep duration, specifically the 7 h-threshold, in athletes’ psychological health. Sleep profiling offers a more nuanced and practical approach than conventional cut-off-based classifications, supporting individualised monitoring and interventions in elite sport.

High‐altitude chronic hypoxia can induce excessive erythrocytosis (EE, defined as a haemoglobin concentration of ≥21 g/dL in men), leading to hyperviscosity and promoting endothelial dysfunction. We aimed to assess whether EE affects the retinal vascular phenotype and the ophthalmological vascular response to CO ₂ . We conducted an ophthalmological cross‐sectional study among highlanders permanently living at 5100 m (La Rinconada, Peru). The central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and retinal vessel tortuosity were measured using semi‐automatic imaging software (VAMPIRE) from the diameters of the six largest arteries and veins on fundus images. Choroidal blood flow was assessed using laser Doppler flowmetry. Measurements were performed at rest and during a hypercapnic challenge (+10.1 ± 1.4 mmHg end‐tidal CO ₂ ) _. Among the 62 included highlanders, 38 (61%) had EE. Compared with non‐EE, highlanders with EE exhibited higher CRVE (278 ± 25 vs. 249 ± 24 µm, P  < 0.001), with no other significant ophthalmological differences. Resting CRVE was significantly correlated (all P ‐values < 0.001) with haematocrit ( r  = 0.56), haemoglobin concentration ( r  = 0.65), blood volume ( r  = 0.55) and the arterial partial pressure of carbon dioxide ( r  = 0.46). Hypercapnia led to a moderate overall decrease in CRVE (−8.6 ± 22.0 µm, P  = 0.02), without a specific effect of EE, and induced no other retinal vascular or choroidal blood flow changes in either group. We observed larger retinal vein diameters in EE highlanders compared with non‐EE. Although hypercapnia is known to increase retinal vessel diameter in healthy lowlanders, it selectively decreased CRVE in highlanders, irrespective of EE status. These findings suggest a retinal vascular dysfunction in highlanders, probably induced by chronic exposure to severe hypoxia.

Background and Objective: Severe hypoxemia, heightened dyspnea, and exercise limitation are hallmarks of fibrotic interstitial lung disease ( f ‐ILD). Standard O ₂ therapy (nasal prongs) fails, however, to correct hypoxemia with limited symptomatic benefits due to inspiratory flow‐patient demand mismatch. Nasal high‐flow O ₂ therapy (NHFO ₂ ) is a promising alternative, but the respective contribution of high‐flow and supplemental O ₂ to improved dyspnea and exercise tolerance remains unknown in f ‐ILD. Methods: Sixteen patients performed, in a randomized order, endurance tests (70% peak power) under 4 conditions: air, supplemental O ₂ (face mask, 9–12 L·min ⁻¹ ), NHF _air [50–70 L·min ⁻¹ ; inspired fraction of O ₂ (FiO ₂ ) = 0.21], NHFO ₂ (50–70 L·min ⁻¹ ; FiO ₂ = 0.5). Endurance time and O ₂ saturation (SpO ₂ ), breathing pattern (respiratory plethysmography) and dyspnea (Borg CR‐10) were compared across conditions. Results: Supplemental O ₂ (98 [2]%) and NHFO ₂ (99 [3]%) increased isotime SpO ₂ vs air (87 [17]%, p < 0.001). Exercise time improved on O ₂ and NHFO ₂ vs air and NHF _air (683[903], 690[1338], 346[247], 319[415]s, respectively, p < 0.001; O ₂ vs NHFO ₂ , p = 0.117). Supplemental O ₂ and NHFO ₂ reduced isotime ventilation vs air (47 ± 22, 44 ± 20, 63 ± 29 L·min ⁻¹ , p < 0.001), driven by lower respiratory rates (36 ± 9, 37 ± 8, 44 ± 10 br·min ⁻¹ , p < 0.001). Supplemental O ₂ and NHFO ₂ reduced isotime dyspnea vs air (4[3.5], 3.5[2.5], 7 [3], p < 0.001) and NHFO ₂ vs NHF _air (3.5[2.5] vs 6[1.5], p = 0.016). NHF _air lowered isotime ventilation (9.0 ± 6.2 L·min ⁻¹ , p = 0.012) but did not improve dyspnea and exercise time vs air. Conclusion: Supplemental O ₂ and NHFO ₂ improved dyspnea and exercise time at “iso‐O ₂ saturation” in severely hypoxemic f ‐ILD. Physiological benefits from supplemental O ₂ (including lower ventilation) are thus likely primary drivers of dyspnea relief and improved exercise tolerance on NHFO ₂ vs air in f ‐ILD. Clinical Trial Registration: NCT07129707 (registered at ClinicalTrials.gov ). image

Epidemiological evidence suggests that living at a moderate altitude (i.e. between 1000 and 2500 m) is associated with lower overall mortality, particularly from cardiovascular diseases. The underlying mechanisms have been scarcely investigated, although environmental and lifestyle factors likely play prominent roles. This review aims to shed light on two important modulators of cardiovascular health and mortality, that is, physical activity and body mass, and to explore how these factors interact with altitude. The lifestyle habits of people living at moderate altitudes have been shown to differ from individuals living at low altitudes. In addition the environmental conditions, notably the hypobaric hypoxia, at moderate altitudes influence the physiological parameters associated with these habits. Specifically engaging in the same physical activity at moderate altitude compared to low altitude results in enhanced cardiovascular responses and specific metabolic responses, potentially imparting benefits related to the cardiovascular system and body composition. Conversely mild hypobaric hypoxia can suppress appetite and food intake, leading to lower overall body mass and decreased risk of obesity. Exercise or sleep can accentuate the hypoxic stimuli at moderate altitudes and, like hypoxia conditioning, elicit adaptations such as improved oxygen supply, reduced dependence on oxygen and increased cellular/tissue resilience. These effects may prove beneficial for the cardiovascular and metabolic systems and contribute to lower mortality rates observed in moderate altitude residents. image

This study is the first to investigate the effects of IHC on CVR _CO2 over the short- and mid-term in elderly individuals. Contrary to our initial hypothesis, 8 wk of moderate IHC did not enhance CVR _CO2 at any time point.

Exercise limitation is a cardinal feature of fibrotic interstitial lung disease arising from pulmonary gas exchange, respiratory mechanical and cardio‐circulatory abnormalities. More recently, it has been recognized that impairment in locomotor muscle function (e.g., reduced muscle mass/strength or heightened fatigability) might also play a relevant contributory role. Exercise training as part of pulmonary rehabilitation is the most effective intervention to improve exercise tolerance, dyspnoea and quality of life in patients with fibrotic interstitial lung disease. Given that exercise training has modest effects on exertional ventilation, breathing pattern and respiratory muscle performance, improvement in locomotor muscle function is a key target for pulmonary rehabilitation in these patients. In the present narrative review, we initially discuss whether the locomotor muscles of patients might be exposed to negative risk factors. After offering corroboratory evidence on this matter (e.g., oxidative stress, inflammation, hypoxia, physical inactivity and medications), we outline their effects on skeletal muscle mass and functional properties. We finish by addressing the potentially beneficial effects of rehabilitative exercise training on these muscle‐centred outcomes, providing perspectives to facilitate or optimize the muscle benefits derived from this intervention. This narrative review, therefore, provides an up‐to‐date outline of the rationale for rehabilitative approaches focusing on the locomotor muscles in this patient population.