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Background: Hypoxia is a trigger for sympathetic activation and autonomic cardiovascular dysfunction. Pulmonary vascular disease (PVD) is associated with hypoxaemia, which increases with altitude. The aim was to investigate how exposure of patients with PVD to hypobaric hypoxia at altitude affects autonomic cardiovascular regulation., Methods: In a randomised crossover study, patients with PVD were studied for 1 day and one night at an altitude of 2500 m (hypobaric hypoxia) and low altitude at 470 m in a random order. Outcomes were heart rate variability (HRV) in the time domain and in the frequency domain (low frequency (LF)/high frequency (HF) and LF/HF) and heart rate (HR) during day and night and baroreflex sensitivity (BRS)., Results: In 25 patients with PVD (72% pulmonary arterial hypertension and 28% distal chronic thromboembolic pulmonary hypertension; mean±sd age 60.7±13.6 years), exposure to altitude resulted in significant increases in awake HR by 9.4 bpm (95% confidence interval (CI) 6.3-12.4, p<0.001) and nocturnal HR by 9.0 bpm (95% CI 6.6-11.4, p<0.001) and significant changes in awake and particularly nocturnal HRV indicating decreasing parasympathetic and increasing sympathetic activity (change in daytime LF/HF 1.7 (95% CI 0.6-2.8), p=0.004; nocturnal LF/HF 1.9 (95% CI 0.3-3.4), p=0.022) and a significant decrease in BRS (-2.4·mmHg -1 (95% CI -4.3- -0.4, p=0.024))., Conclusion: Exposure of PVD patients to altitude resulted in a significant change in HRV indicating an increase in sympathetic activity and a decrease in BRS. The relative change in HRV at altitude was more pronounced during sleep., Competing Interests: Conflict of interest: S. Ulrich reports grants or contracts from Swiss National Science Foundation, Zurich, and Swiss Lung League; unrestricted grants from Orpha Swiss and MSD, outside the submitted work; consulting fees from Orpha Swiss, MSD SA and Janssen SA, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Orpha Swiss, MSD SA, Janssen SA and Novartis SA, outside the submitted work; support for attending meetings and/or travel from Orpha Swiss, MSD SA, Janssen SA and Novartis SA, outside the submitted work; participation on a data safety monitoring or advisory board for Orpha Swiss, MSD SA and Janssen SA, outside the submitted work; leadership or fiduciary roles for the Swiss Society of Pulmonology, European Respiratory Society and Swiss Society of Pulmonary Hypertension, outside the submitted work. Conflict of interest: M. Lichtblau reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from MSD SA, outside the submitted work; support for attending meetings and/or travel from Orpha Swiss, Janssen and MSD, outside the submitted work; and participation on a data safety monitoring or advisory board for MSD SA, outside the submitted work. Conflict of interest: E.I. Schwarz reports receiving lecture fees from ResMed outside the submitted work and is Secretary of Assembly 4 of the European Respiratory Society (unpaid) outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

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.