Konrad Ernst Bloch

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

Aim: We investigated the effect of an overnight-stay at high altitude (HA, 2500 m) on constant work-rate exercise test (CWRET) time and cardiorespiratory function in patients with pulmonary vascular disease (PVD) and the impact of supplemental oxygen therapy (SOT) in case of severe altitude-induced hypoxemia. Methods: In a randomized crossover trial, stable patients diagnosed with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PVD, PAH/CTEPH) performed a symptom-limited cycling CWRET at 470 m and after an overnight stay at 2500 m. For safety, patients with a SpO ₂ 30 min received SOT during the subsequent HA-stay. The primary outcome was CWRET-time, secondary outcomes were changes in ergospirometric parameters. Clinicaltrials.gov: NCT05107700 &NCT05112172. Results: Of 27 PVD-patients (44% female; mean age 62±14 y, 20 PAH, 7 distal CTEPH), 10 (37%) required SOT. Overall at HA versus 470 m, CWRET-time decreased to 292±181 s versus 454±411 s (mean difference −162 s, 95%CI −290 to −34 s; p=0.026), driven by patients without need for SOT (261±187 s versus 519±497 s; p=0.017), who revealed lower resting PaO ₂ (7.4±0.7 kPa versus 10.6±1.4 kPa, p2 -desaturation was not significantly different (−0.9%, 95%CI −3.9 to 2). In 10/27 patients needing SOT, SOT restored CWRET time to 470 m-values (344±170 s versus 345±167 s; p=0.990), corrected altitude-induced hypoxemia and attenuated hyperventilation. Conclusion: The majority of PVD-patients tolerated an overnight stay at 2500 m well. In those without need for SOT at HA, CWRET-time was reduced with increased hypoxemia and hyperventilation. In PVD-patients who received SOT due to severe nocturnal hypoxemia, SOT restored CWRET-time to 470 m levels and dampened the exercise-induced hypoxemia.

Background/Objectives: It is widely acknowledged that healthy highlanders (HL) present with significantly higher pulmonary arterial pressure (PAP) compared to healthy lowlanders (LL). However, whether this elevated PAP solely signifies a response to hypoxia at altitude or is also linked to right ventricular (RV) dysfunction is still unknown. Therefore, we assessed RV function in HL and LL using speckle-tracking-derived strain analysis. Methods: This case-control study evaluates echocardiographic RV free wall strain (RVFWS) in LL and HL in Kyrgyzstan. A RVFWS over −20% for men and a RVFWS of −21% for women were considered indicators of RV dysfunction. Subgroup analysis included individuals with and without risk for pulmonary hypertension (PH), defined as a TRV > 2.8 m/s. Results: A total of 59 participants (21 LL, 38 HL), with a mean ± SD age of 43 ± 8 versus 48 ± 10 years, were included and assessed at their living altitude. RVFWS in HL and LL was −27.3% ± 4.7 versus −27.0% ± 6.0 (mean difference 0.13%, 95%CI −2.65 to 2.92, p = 0.852). The conventional RV indices RV FAC (42% ± 6 vs. 38% ± 8), TAPSE (2.2 cm ± 0.2 vs. 2.0 cm ± 0.3), and TDI S’ (14.2 cm/s ± 1.9 vs. 12.1 cm/s ± 1.8), however, did differ significantly between LL and HL. HL with and without risk for PH did not differ in RVFWS and in the conventional RV indices. Conclusions: Despite significant differences in conventional RV markers, healthy highlanders generally did not differ in RVFWS compared with lowlanders, indicating maintained RV systolic function at high altitude. Our findings suggest that elevated PAP in HL reflects adaptation rather than RV dysfunction, underscoring the need for refined diagnostic criteria for clinically relevant high-altitude pulmonary hypertension.

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to altitude-related adverse health effects (ARAHE). Does structured self-monitoring (SSM) predict imminent ARAHE in COPD patients during altitude travel. Patients with moderate to severe COPD without chronic respiratory failure, living below 800 m, ascended by bus within 5 h to a clinic at 3100 m and stayed there for 2 days. During the altitude sojourn, patients regularly monitored themselves for symptoms of acute mountain sickness (AMS) and/or drops of pulse oximetry (SpO₂) to ≤84%, events designated as positive SSM. Measures of diagnostic accuracy of SSM in predicting subsequent ARAHE (defined as AMS Lake Louise score >4 and/or SpO₂ 30 min or 15 min and/or any condition requiring medical intervention) were computed. www.ClinicalTrials.org NCT03957759. Among 153 COPD patients (79 women, mean ± SD age 57 ± 10y) travelling to 3100 m, SSM was positive in 55 (36%), ARAHE occurred in 116 (76%). Concordance statistics indicated a diagnostic accuracy of SSM in predicting ARAHE of 0.65 (95%CI 0.58 to 0.72). In SSM positive patients, the odds ratio for ARAHE was 4.9 (95%CI 1.8 to 12.9). Positive and negative predictive values of SSM for ARAHE were 91% (95%CI 80 to 97) and 33% (95%CI 24 to 43). In exploratory analyses, supplementing SSM by nocturnal pulse oximetry with alarm capability enhanced diagnostic accuracy considerably (sensitivity improved from 43% to 73% concordance statistic increased to 0.80). Lowlanders with COPD ascending to 3100 m commonly experience ARAHE. Due to its high positive predictive value, performing SSM may allow patients to predict imminent ARAHE and take timely appropriate actions such as descend or use oxygen. Negative SSM does not reliably indicate a low risk of ARAHE.

Background: Exposure to high altitude triggers hypoxic pulmonary vasoconstriction with a rise in pulmonary artery pressure (PAP). This may lead to symptomatic pulmonary hypertension with impaired right heart function and exercise capacity. We investigated whether preventive acetazolamide treatment would attenuate the altitude‐induced PAP‐increase and hereby improve hemodynamics in nonacclimatized middle‐aged healthy lowland residents ascending to 3100 m. Methods: In this placebo‐controlled, double‐blind parallel trial, healthy lowland residents >40 years living P =0.087). Significant treatment effects with acetazolamide were detected for saturation by pulse oxymetry 2 (1 to 2)%, heart rate −5 (95% CI, −9 to −1)/minute, cardiac output −0.8 (95% CI, −1.3 to −0.4) L/min, oxygen delivery −123 (95% CI, −211 to −34) mL/min, and fractional area change of −4 (95% CI, −7 to −0)%. Conclusions: In healthy, middle‐aged lowland residents traveling to 3100 m, preventive acetazolamide tended to but did not significantly attenuate the altitude‐induced PAP‐increase. An alteration of hemodynamics and right heart function was observed resulting in a reduced overall oxygen delivery, which may counter the proven positive effects of acetazolamide on arterial oxygenation and acclimatization process. Registration: URL: https://clinicaltrials.gov ; Unique Identifier: NCT03540914.

Häfliger, Alina, Aline Buergin, Laura C. Mayer, Maamed Mademilov, Mona Lichtblau, Talantbek Sooronbaev, Silvia Ulrich, Konrad E. Bloch, and Michael Furian. Sex-specific difference in health-related altitude-effects and their prevention by acetazolamide. Data from a randomized controlled trial. High Alt Med Biol. 26:195–203, 2025. Background: Women are underrepresented in studies on acute mountain sickness (AMS), altitude-induced sleep-disordered breathing and preventive acetazolamide use. Methods: We analyzed sex-specific altitude-effects in participants of a randomized, placebo-controlled, double-blind trial in healthy lowlanders >40 years. Participants took 375 mg/day acetazolamide or placebo starting 24 hours before ascent to and while staying 2 days at 3,100 m. Main outcomes of this analysis were sex-specific incidence of AMS (Lake Louise score ≥3), nocturnal pulse oximetry (SpO ₂ ) and apnea–hypopnea index (AHI) at 3,100 m. Results: With placebo, 30 of 119 (25%) women and 4 of 51 (8%) men developed AMS ( p = 0.009 between sexes) at 3,100 m. Among women assigned to placebo, SpO ₂ (mean ± SE 84 ± 0%) and AHI (16.9 ± 1.3/h) in night 1 at 3,100 m were lower compared to men (SpO ₂ 86 ± 0%; AHI 28.3 ± 1.9/h), despite similar baseline values at 760 m. Mean between-sex difference in altitude-effects (women-men) in SpO ₂ was −1.4% (95% CI, −2.4 to −0.3%); AHI −10.7/h (95% CI, −15.7 to −5.7/h). The impact of acetazolamide on AMS was not significant for either sex but acetazolamide improved AHI in men (difference men-women, −9.8/h [95% CI, −16.8 to −2.7/h]). Conclusion: This study suggests sex-specific differences in altitude-induced hypoxemia, periodic breathing, AMS incidence, and in the response to preventive acetazolamide treatment.

Van Veelen, Michiel J., Rudolf Likar, Markus Tannheimer, Konrad E. Bloch, Silvia Ulrich, Michael Philadelphy, Barbara Teuchner, Thomas Hochholzer, Jacqueline Pichler Hefti, Urs Hefti, Peter Paal, and Martin Burtsche. Emergency Care for High-Altitude Trekking and Climbing. High Alt Med Biol. 26:70–86, 2025. Introduction: High altitude regions are characterized by harsh conditions (environmental, rough terrain, natural hazards, and limited hygiene and health care), which all may contribute to the risk of accidents/emergencies when trekking or climbing. Exposure to hypoxia, cold, wind, and solar radiation are typical features of the high altitude environment. Emergencies in these remote areas place high demands on the diagnostic and treatment skills of doctors and first-aiders. The aim of this review is to give insights on providing the best possible care for victims of emergencies at high altitude. Methods: Authors provide clinical recommendations based on their real-world experience, complemented by appropriate recent studies and internationally reputable guidelines. Results and Discussion: This review covers most of the emergencies/health issues that can occur when trekking or during high altitude climbing, that is, high altitude illnesses and hypothermia, freezing cold injuries, accidents, for example, with severe injuries due to falling, cardiovascular and respiratory illnesses, abdominal, musculoskeletal, eye, dental, and skin issues. We give a summary of current recommendations for emergency care and pain relief in case of these various incidents.

Background: The aim of this study was to investigate the acute effect of acetazolamide on pulmonary haemodynamics during exercise in patients with pulmonary vascular disease (PVD). Methods: Patients with PVD diagnosed as pulmonary arterial (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) underwent right-heart catheterisation with haemodynamic measurements at rest and during stepwise incremental cycling exercise 60 min after receiving intravenous acetazolamide (500 mg) or saline placebo in accordance with a double-blind, randomised-controlled, crossover design. The main outcomes were the difference between pulmonary vascular resistance (PVR) and its components mean pulmonary artery pressure (mPAP), cardiac output (CO) and pulmonary arterial wedge pressure (PAWP), during exercise, assessed by a mixed linear regression analysis. Results: A total of 24 patients (n=7 PAH, n=17 CTEPH; n=17 male) were included (mean± sd age 59±14 years). Treatment with acetazolamide compared with saline placebo showed the following average marginal effects during exercise: unchanged end-exercise power (mean difference −0.8 W, 95% CI −5.7–4.1 W; p=0.740), reduced mPAP (mean difference −1.7 mmHg, 95% CI −2.9– −0.5 mmHg; p=0.007), tendency to reduced CO (mean difference −0.3 L·min ⁻¹ , 95% CI −0.7–0.1 L·min ⁻¹ ; p=0.097), unchanged PVR (mean difference −0.1 Wood units (WU), 95% CI −0.3–0.2 WU; p=0.694), unchanged PAWP (mean difference 0.0 mmHg, 95% CI −0.2–0.3 mmHg; p=0.783) and unchanged mPAP/CO slope (mean difference 0.1 WU, 95% CI −1.0–1.3 WU; p=0.839). Conclusion: Intravenous acetazolamide was well tolerated and resulted in a significant but small decrease in mPAP, while CO, PVR and the pressure–flow slope during exercise were unchanged.

Background: In patients with COPD, preventive treatment with acetazolamide reduces adverse health effects during altitude travel. We investigated whether preventive acetazolamide treatment modifies exercise performance in COPD patients going to high altitude.Methods: In this randomised, double-blind trial, lowlanders with COPD, forced expiratory volume in 1 s (FEV₁) 40–80% predicted, were assigned to acetazolamide (375 mg per 24 h) or placebo treatment starting 24 h before ascent and while staying at 3100 m. Patients performed progressive cycling exercise to exhaustion at 760 m, before taking the study drug, and within 4 h after arrival at 3100 m. The primary outcome was the maximal power output (W_max).Results: 103 patients (32 women), mean±sdage 57.2±8.1 years, FEV₁66±11% predicted, were included in per-protocol analyses. In 53 patients receiving acetazolamide, W_maxand oxygen uptake (V′O_2max) at 760 m and 3100 m were 105±27 and 91±25 W, and 18.0±4.8 and 15.5±3.7 mL·min⁻¹·kg⁻¹(pmaxandV′O_2maxin 50 patients receiving placebo were 107±34 and 97±28 W, and 18.9±6.0 and 17.2±5.0 mL·min⁻¹·kg⁻¹(pmaxchanges were −3.0 W (−8.7 to +2.7, p=0.305) and inV′O_2maxchanges were −0.8 mL·min⁻¹·kg⁻¹(−2.1 to +0.5, p=0.213). Acetazolamide mitigated the altitude-induced reduction ofPaO₂by 0.7 kPa (0.1 to 1.3, p=0.016). At 3100 m, maximal work rate with respiratory exchange ratio ≤1 was greater with acetazolamide than with placebo by 10.1 W (4.0 to 16.2, p=0.022).Conclusions: In lowlanders with COPD, preventive treatment with acetazolamide did not modify the altitude-induced reduction in maximal work rate. However, acetazolamide enhanced arterial oxygenation and submaximal, moderate-intensity work capacity compared with placebo.

Grimm, Mirjam, Lucie Ziegler, Annina Seglias, Maamed Mademilov, Kamila Magdieva, Gulzada Mirzalieva, Aijan Taalaibekova, Simone Suter, Simon R. Schneider, Fiona Zoller, Vera Bissig, Lukas Reinhard, Meret Bauer, Julian Müller, Tanja L. Ulrich, Arcangelo F. Carta, Patrick R. Bader, Konstantinos Bitos, Aurelia E. Reiser, Benoit Champigneulle, Damira Ashyralieva, Philipp M. Scheiwiller, Silvia Ulrich, Talant M. Sooronbaev, Michael Furian, and Konrad E. Bloch. SARS-CoV-2 Transmission during High-Altitude Field Studies. High Alt Med Biol . 25:197–204, 2024. Background: Throughout the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, virus transmission during clinical research was of concern. Therefore, during high-altitude field studies performed in 2021, we took specific COVID-19 precautions and investigated the occurrence of SARS-CoV-2 infection. Methods: From May to September 2021, we performed studies in patients with chronic obstructive pulmonary disease (COPD) and in healthy school-age children in Kyrgyzstan in high-altitude facilities at 3,100 m and 3,250 m and at 760 m. The various implemented COVID-19 safety measures included systematic SARS-CoV-2 rapid antigen testing (RAT). Main outcomes were SARS-CoV-2-RAT-positive rate among participants and staff at initial presentation (prevalence) and SARS-CoV-2-RAT-positive conversion during and within 10 days after studies (incidence). Results: Among 338 participants and staff, SARS-CoV-2-RAT-positive prevalence was 15 (4.4%). During mean ± SD duration of individual study participation of 3.1 ± 1.0 day and within 10 days, RAT-positive conversion occurred in 1/237(0.4%) participants. Among staff working in studies for 31.5 ± 29.3 days, SARS-CoV-2-RAT-positive conversion was 11/101(10.9%). In all 338 individuals involved in the studies over the course of 15.6 weeks, the median SARS-CoV-2-RAT-positive incidence was 0.00%/week (quartiles 0.00; 0.64). Over the same period, the median background incidence among the total Kyrgyz population of 6,636 million was 0.06%/week (0.03; 0.11), p = 0.013 (Wilcoxon rank sum test). Conclusions: Taking precautions by implementing specific safety measures, SARS-CoV-2 transmission during clinical studies was very rare, and the SARS-CoV-2 incidence among participants and staff was lower than that in the general population during the same period. The results are reassuring and may help in decision-making on the conduct of clinical research in similar settings.