SARS-CoV-2 Transmission during High-Altitude Field Studies.

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. 00:00-00, 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.

The effect of high altitude (2500†m) on incremental cycling exercise in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a randomised controlled crossover trial.

BACKGROUND: Our objective was to investigate the effect of a day-long exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: In a randomised controlled crossover trial, stable patients with PAH or distal CTEPH without resting hypoxaemia at low altitude performed two incremental exercise tests to exhaustion: one after 3-5 h at high altitude (2500 m) and one at low altitude (470 m). RESULTS: In 27 patients with PAH/CTEPH (44% females, mean±sd age 62±14 years), maximal work rate was 110±64 W at 2500 m and 123±64 W at 470 m (-11%, 95% CI -16- -11%; p<0.001). Oxygen saturation measured by pulse oximetry and arterial oxygen tension at end-exercise were 83±6% versus 91±6% and 6.1±1.9 versus 8.6±1.9 kPa (-8% and -29%; both p<0.001) at 2500 versus 470 m, respectively. Maximal oxygen uptake was 17.8±7.5 L·min-1·kg-1 at high altitude versus 20±7.4 L·min-1·kg-1 at low altitude (-11%; p<0.001). At end-exercise, the ventilatory equivalent for carbon dioxide was 43±9 at 2500 m versus 39±9 at 470 m (9%, 95% CI 2-6%; p=0.002). No adverse events occurred during or after exercise. CONCLUSIONS: Among predominantly low-risk patients with stable PAH/CTEPH, cycling exercise during the first day at 2500 m was well tolerated, but peak exercise capacity, blood oxygenation and ventilatory efficiency were lower compared with 470 m.

Hyperoxia improves exercise capacity in cardiopulmonary disease: a series of randomised controlled trials.

Background: The aim of this study was to investigate the overall and differential effect of breathing hyperoxia (inspiratory oxygen fraction (F IO2 ) 0.5) versus placebo (ambient air, F IO2 0.21) to enhance exercise performance in healthy people, patients with pulmonary vascular disease (PVD) with precapillary pulmonary hypertension (PH), COPD, PH due to heart failure with preserved ejection fraction (HFpEF) and cyanotic congenital heart disease (CHD) using data from five randomised controlled trials performed with identical protocols. Methods: 91 subjects (32 healthy, 22 with PVD with pulmonary arterial or distal chronic thromboembolic PH, 20 with COPD, 10 with PH in HFpEF and seven with CHD) performed two cycle incremental (IET) and two constant work-rate exercise tests (CWRET) at 75% of maximal load (Wmax), each with ambient air and hyperoxia in single-blinded, randomised, controlled, crossover trials. The main outcomes were differences in Wmax (IET) and cycling time (CWRET) with hyperoxia versus ambient air. Results: Overall, hyperoxia increased Wmax by +12 W (95% CI: 9-16, p<0.001) and cycling time by +6:13 min (4:50-7:35, p<0.001), with improvements being highest in patients with PVD (Wmax/min: +18%/+118% versus COPD: +8%/+60%, healthy: +5%/+44%, HFpEF: +6%/+28%, CHD: +9%/+14%). Conclusion: This large sample of healthy subjects and patients with various cardiopulmonary diseases confirms that hyperoxia significantly prolongs cycling exercise with improvements being highest in endurance CWRET and patients with PVD. These results call for studies investigating optimal oxygen levels to prolong exercise time and effects on training.

Hypoxia-altitude simulation test to predict altitude-related adverse health effects in COPD patients.

Background/aims: Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude. Methods: This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV1) 40-80% pred, oxygen saturation measured by pulse oximetry (S pO2 ) ≥92% and arterial carbon dioxide tension (P aCO2 ) <6 kPa. Patients underwent baseline evaluation and HAST, breathing normobaric hypoxic air (inspiratory oxygen fraction (F IO2 ) of 15%) for 15 min, at low altitude (760 m). Cut-off values for a positive HAST were set according to British Thoracic Society (BTS) guidelines (arterial oxygen tension (P aO2 ) <6.6 kPa and/or S pO2 <85%). The following day, patients travelled to HA (3100 m) for two overnight stays where ARAHE development including acute mountain sickness (AMS), Lake Louise Score ≥4 and/or AMS score ≥0.7, severe hypoxaemia (S pO2 <80% for >30 min or 75% for >15 min) or intercurrent illness was observed. Results: ARAHE occurred in 50 (66%) patients and 23 out of 75 (31%) were positive on HAST according to S pO2 , and 11 out of 64 (17%) according to P aO2 . For S pO2 /P aO2 we report a sensitivity of 46/25%, specificity of 84/95%, positive predictive value of 85/92% and negative predictive value of 44/37%. Conclusion: In COPD patients ascending to HA, ARAHE are common. Despite an acceptable positive predictive value of the HAST to predict ARAHE, its clinical use is limited by its insufficient sensitivity and overall accuracy. Counselling COPD patients before altitude travel remains challenging and best focuses on early recognition and treatment of ARAHE with oxygen and descent.

Morphological features useful in the differential diagnosis between undifferentiated carcinoma and gastrointestinal stromal tumor.

Undifferentiated (sarcomatoid) carcinomas may closely mimic gastrointestinal stromal tumors (GISTs) due to possible histological and immunohistochemical overlap between these two entities. To avoid unnecessary employment of a wide spectrum of immunohistochemical stainings and molecular genetics and thus decrease costs, finding simple morphological features to target further investigation of such neoplasms of the gastrointestinal tract would be helpful. Five cases classified as undifferentiated (sarcomatoid) carcinomas with a definite proof of the diagnosis, i. e. the presence of a differentiated carcinomatous component, were retrieved from archives of several institutions. For comparison, 84 cases of GIST mutated in KIT or PDGFRA genes served as the control group. Hematoxylin and eosin stained slides were evaluated for the presence of patterns which might discriminate between sarcomatoid carcinoma and GIST. Lymphatic invasion and entrapment of fat tissue strongly favor the diagnosis of undifferentiated carcinoma, as it was found in all or almost all cases of undifferentiated carcinoma, but in no GIST. Alternation of low- and high- grade areas, formation of angiosarcomatous-like spaces, and the presence of yolk sac-like areas were also detected in all cases of undifferentiated carcinoma, but only in 1.2%, 2.4% and 7.2% of the GISTs, respectively. Furthermore, DOG1 was negative in all cases of undifferentiated carcinoma. According to this study, the presence of the histological findings listed above should prompt extensive tumor sampling in order to find a differentiated carcinomatous component. However, due to the small number of cases of undifferentiated carcinoma available for the study, a larger multi-institutional study is warranted.