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Special Issue "Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients"

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (10 May 2023) | Viewed by 12123

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Special Issue Editors

Prof. Dr. Martin Burtscher

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Guest Editor

Department of Sport Science, University of Innsbruck, Fürstenweg 185, A-6020 Innsbruck, Austria
Interests: exercise physiology; extreme environments; high-altitude medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Sébastien Baillieul

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Guest Editor

INSERM, Laboratoire HP2 (U 1300), Grenoble Alpes University and Sleep Laboratory, CHU Grenoble Alpes, France
Interests: sleep medicine; physiology; neurology; rehabilitation medicine; altitude; hypoxia

Dr. Michael Furian

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Guest Editor

Pulmonology Department, University of Zurich, Zürich, Switzerland
Interests: human physiology; altitude; hypoxia; cardiorespiratory diseases

Special Issue Information

Dear Colleagues,

Low arterial oxygen content, termed hypoxemia, is often closely linked to respiratory or cardiovascular diseases or environmental conditions (high altitude, air travel). Hypoxemia has broad clinical and physiological consequences. It leads to insufficient availability of oxygen in tissues (hypoxia) and, therefore, may alter brain functionality, induce tissue remodeling and destruction, result in organ dysfunction and might promote progression of morbidity and mortality.

Diseases associated with hypoxemia are highly prevalent (COVID-19, chronic obstructive pulmonary disease, pulmonary hypertension, sleep apnea syndrome). Moreover, millions of people are living at high altitude places worldwide (8 million alone in Bogotá, 2640 m, Columbia). Intriguingly, current recommendations in patients with COPD recommend long-term oxygen therapy when the resting PaO₂ value is <7.3 kPa (55 mmHg) or SaO₂ <89 %, independent of living altitude. Moreover, the lack of well-designed studies complicates recommendations for patients with pre-existing cardiopulmonary diseases planning mountain sojourns, as well as treatments of patients permanently living at high-altitude places. On the other side, hypoxemia is not always deleterious; therefore, patients with ischemic heart disease might have a lower mortality rate when living at higher altitude (Ezzatti 2012, J Epidemiol Community Health). In accordance, millions of people migrate to higher altitudes, but not all of them have hypoxemic maladaptations; therefore, the pathways of hypoxemia are multifactorial and need more attention.

This Special Issue has the following aims:

1) To provide deep insights into the consequences of hypoxemia and hypoxia on the clinical, physiological and molecular level in humans.

2) To connect multiple areas of research and to improve evidence-based medicine in patients and highlanders suffering from hypoxemia.

3) To acquire a comprehensive understanding; to be able to improve current recommendations to prevent, treat or promote hypoxemia; to counsel patients planning to fly or live at high altitude; to protect healthy highlanders from suffering damage from chronic hypoxemia and hypoxia.

To accomplish these aims, we invite all research performed in humans focusing on the clinical, physiological and molecular level in any disease or condition related to or caused by hypoxemia and hypoxia. We welcome all forms of submissions: original research articles and review articles.

Prof. Dr. Martin Burtscher
Dr. Sébastien Baillieul
Dr. Michael Furian
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hypoxia
hypoxemia
oxygen deficit
altitude
hypobaric hypoxia
normobaric hypoxia

Published Papers (10 papers)

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Editorial

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Special Issue “Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients”

and

J. Clin. Med. 2022, 11(13), 3904; https://doi.org/10.3390/jcm11133904 - 05 Jul 2022

Viewed by 1051

Abstract

This editorial of the Special Issue “Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients” aims to draw more attention to the broad and diverse field of hypoxia research and serves as an invitation for research groups to share their most [...] Read more.

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

Research

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Open AccessArticle

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders

and

J. Clin. Med. 2023, 12(8), 2872; https://doi.org/10.3390/jcm12082872 - 14 Apr 2023

Viewed by 549

Abstract

Background: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric–hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. Methods: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Results: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. Conclusions: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric–hypoxic conditions should be considered when planning training and physical activity at altitude. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Effects of Acute Hypoxia on Heart Rate Variability in Patients with Pulmonary Vascular Disease

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J. Clin. Med. 2023, 12(5), 1782; https://doi.org/10.3390/jcm12051782 - 23 Feb 2023

Viewed by 774

Abstract

Pulmonary vascular diseases (PVDs), defined as arterial or chronic thromboembolic pulmonary hypertension, are associated with autonomic cardiovascular dysregulation. Resting heart rate variability (HRV) is commonly used to assess autonomic function. Hypoxia is associated with sympathetic overactivation and patients with PVD might be particularly vulnerable to hypoxia-induced autonomic dysregulation. In a randomised crossover trial, 17 stable patients with PVD (resting PaO₂ ≥ 7.3 kPa) were exposed to ambient air (FiO₂ = 21%) and normobaric hypoxia (FiO₂ = 15%) in random order. Indices of resting HRV were derived from two nonoverlapping 5–10-min three-lead electrocardiography segments. We found a significant increase in all time- and frequency-domain HRV measures in response to normobaric hypoxia. There was a significant increase in root mean squared sum difference of RR intervals (RMSSD; 33.49 (27.14) vs. 20.76 (25.19) ms; p < 0.01) and RR50 count divided by the total number of all RR intervals (pRR50; 2.75 (7.81) vs. 2.24 (3.39) ms; p = 0.03) values in normobaric hypoxia compared to ambient air. Both high-frequency (HF; 431.40 (661.56) vs. 183.70 (251.25) ms²; p < 0.01) and low-frequency (LF; 558.60 (746.10) vs. 203.90 (425.63) ms²; p = 0.02) values were significantly higher in normobaric hypoxia compared to normoxia. These results suggest a parasympathetic dominance during acute exposure to normobaric hypoxia in PVD. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Effect of Acetazolamide on Postural Control in Patients with COPD Travelling to 3100 m Randomized Trial

Philipp M. Scheiwiller

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J. Clin. Med. 2023, 12(4), 1246; https://doi.org/10.3390/jcm12041246 - 04 Feb 2023

Viewed by 652

Abstract

Patients with chronic obstructive pulmonary disease (COPD) may be susceptible to impairments in postural control (PC) when exposed to hypoxia at high altitude. This randomized, placebo-controlled, double-blind, parallel-design trial evaluated the effect of preventive acetazolamide treatment on PC in lowlanders with COPD traveling to 3100 m. 127 lowlanders (85 men, 42 women) with moderate to severe COPD, aged 57 ± 8 y, living below 800 m, were randomized to treatment with acetazolamide 375 mg/d starting 24 h before ascent from 760 m to 3100 m and during a 2-day sojourn in a clinic at 3100 m. PC was evaluated at both altitudes with a balance platform on which patients were standing during five tests of 30 s each. The primary outcome was the center of pressure path length (COPL). In the placebo group, COPL significantly increased from (mean ± SD) 28.8 ± 9.7 cm at 760 m to 30.0 ± 10.0 cm at 3100 m (p = 0.002). In the acetazolamide group, COPL at 760 m and 3100 m were similar with 27.6 ± 9.6 cm and 28.4 ± 9.7 cm (p = 0.069). The mean between-groups difference (acetazolamide-placebo) in altitude-induced change of COPL was −0.54 cm (95%CI −1.66 to 0.58, p = 0.289). Multivariable regression analysis confirmed an increase in COPL of 0.98 cm (0.39 to 1.58, p = 0.001) with ascent from 760 to 3100 m, but no significant effect of acetazolamide (0.66 cm, 95%CI −0.25 to 1.57, p = 0.156) when adjusting for several confounders. In lowlanders with moderate to severe COPD, an ascent to high altitude was associated with impaired postural control and this was not prevented by acetazolamide. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Validation of Noninvasive Assessment of Pulmonary Gas Exchange in Patients with Chronic Obstructive Pulmonary Disease during Initial Exposure to High Altitude

J. Clin. Med. 2023, 12(3), 795; https://doi.org/10.3390/jcm12030795 - 19 Jan 2023

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Abstract

Investigation of pulmonary gas exchange efficacy usually requires arterial blood gas analysis (aBGA) to determine arterial partial pressure of oxygen (mPaO₂) and compute the Riley alveolar-to-arterial oxygen difference (A-aDO₂); that is a demanding and invasive procedure. A noninvasive approach (AGM100), allowing the calculation of PaO₂ (cPaO₂) derived from pulse oximetry (SpO₂), has been developed, but this has not been validated in a large cohort of chronic obstructive pulmonary disease (COPD) patients. Our aim was to conduct a validation study of the AG100 in hypoxemic moderate-to-severe COPD. Concurrent measurements of cPaO₂ (AGM100) and mPaO₂ (EPOC, portable aBGA device) were performed in 131 moderate-to-severe COPD patients (mean ±SD FEV₁: 60 ± 10% of predicted value) and low-altitude residents, becoming hypoxemic (i.e., SpO₂ < 94%) during a short stay at 3100 m (Too-Ashu, Kyrgyzstan). Agreements between cPaO₂ (AGM100) and mPaO₂ (EPOC) and between the O₂-deficit (calculated as the difference between end-tidal pressure of O₂ and cPaO₂ by the AGM100) and Riley A-aDO₂ were assessed. Mean bias (±SD) between cPaO₂ and mPaO₂ was 2.0 ± 4.6 mmHg (95% Confidence Interval (CI): 1.2 to 2.8 mmHg) with 95% limits of agreement (LoA): −7.1 to 11.1 mmHg. In multivariable analysis, larger body mass index (p = 0.046), an increase in SpO₂ (p < 0.001), and an increase in PaCO₂-PETCO₂ difference (p < 0.001) were associated with imprecision (i.e., the discrepancy between cPaO₂ and mPaO₂). The positive predictive value of cPaO₂ to detect severe hypoxemia (i.e., PaO₂ ≤ 55 mmHg) was 0.94 (95% CI: 0.87 to 0.98) with a positive likelihood ratio of 3.77 (95% CI: 1.71 to 8.33). The mean bias between O₂-deficit and A-aDO₂ was 6.2 ± 5.5 mmHg (95% CI: 5.3 to 7.2 mmHg; 95%LoA: −4.5 to 17.0 mmHg). AGM100 provided an accurate estimate of PaO₂ in hypoxemic patients with COPD, but the precision for individual values was modest. This device is promising for noninvasive assessment of pulmonary gas exchange efficacy in COPD patients. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Sex-Specific Difference in the Effect of Altitude on Sleep and Nocturnal Breathing in Young Healthy Volunteers

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J. Clin. Med. 2022, 11(10), 2869; https://doi.org/10.3390/jcm11102869 - 19 May 2022

Viewed by 1423

Abstract

Importance: To date, there is no established evidence of sex-specific differences in altitude-induced sleep-disordered breathing (SDB) during polysomnography-confirmed sleep. Objective: The aim of this study was to investigate whether differences in sex play a pivotal role in incidences of SDB and acute mountain sickness (AMS) when staying overnight at high altitude. Design: This was a prospective cohort study. Setting: Participants underwent overnight polysomnography (PSG) and clinical assessment in a sleep laboratory at 500 m and two consecutive days at 3270 m. Participants: The participants comprised 28 (18 women) healthy, young, low-altitude residents with a median (interquartile range) age of 26.0 (25.0, 28.0) years. Exposures: Altitude exposure. Main outcomes and Measures: The primary outcome was altitude-induced change in the PSG-confirmed apnea–hypopnea index (AHI) at 3270 m compared to 500 m between men and women. Secondary outcomes included sex differences in other parameters related to SDB, sleep structure, AMS, psychomotor vigilance test reaction time and parameters from arterial and venous blood analyses. Results: The median (interquartile range) AHIs at 500 m and 3270 m on night 1 and on night 2 were 6.5/h (3.6, 9.1), 23.7/h (16.2, 42.5) and 15.2/h (11.8, 20.9) in men, respectively, and 2.2/h (1.0, 5.5), 8.0/h (5.3, 17.0) and 7.1/h (4.9, 11.5) in women, respectively (p < 0.05 nights 1 and 2 at 3270 m vs. 500 m in men and women). The median difference (95% CI) of altitude-induced change in AHI (3270 m night 1 compared to 500 m) between men and women was 11.2/h (1.9 to 19.6) (p < 0.05). Over the time course of 2 days at 3270 m, 9 out of 18 (50%) women and 1 out of 10 (10%) men developed AMS (p < 0.05 women versus men). Conclusions and Relevance: This prospective cohort study showed that men were more susceptible to altitude-induced SDB but that they had a lower AMS incidence when staying for 2 days at 3270 m than women. These findings indicate that sex-related prevention and intervention strategies against SDB and AMS are highly warranted. Trial Registration: This trial was registered at the Chinese Clinical Trial Registry; No. ChiCTR1800020155. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Cardiorespiratory Adaptation to Short-Term Exposure to Altitude vs. Normobaric Hypoxia in Patients with Pulmonary Hypertension

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J. Clin. Med. 2022, 11(10), 2769; https://doi.org/10.3390/jcm11102769 - 14 May 2022

Cited by 4 | Viewed by 1355

Abstract

Prediction of adverse health effects at altitude or during air travel is relevant, particularly in pre-existing cardiopulmonary disease such as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH, PH). A total of 21 stable PH-patients (64 ± 15 y, 10 female, 12/9 PAH/CTEPH) were examined by pulse oximetry, arterial blood gas analysis and echocardiography during exposure to normobaric hypoxia (NH) (F_iO₂ 15% ≈ 2500 m simulated altitude, data partly published) at low altitude and, on a separate day, at hypobaric hypoxia (HH, 2500 m) within 20–30 min after arrival. We compared changes in blood oxygenation and estimated pulmonary artery pressure in lowlanders with PH during high altitude simulation testing (HAST, NH) with changes in response to HH. During NH, 4/21 desaturated to SpO₂ < 85% corresponding to a positive HAST according to BTS-recommendations and 12 qualified for oxygen at altitude according to low SpO₂ < 92% at baseline. At HH, 3/21 received oxygen due to safety criteria (SpO₂ < 80% for >30 min), of which two were HAST-negative. During HH vs. NH, patients had a (mean ± SE) significantly lower PaCO₂ 4.4 ± 0.1 vs. 4.9 ± 0.1 kPa, mean difference (95% CI) −0.5 kPa (−0.7 to −0.3), PaO₂ 6.7 ± 0.2 vs. 8.1 ± 0.2 kPa, −1.3 kPa (−1.9 to −0.8) and higher tricuspid regurgitation pressure gradient 55 ± 4 vs. 45 ± 4 mmHg, 10 mmHg (3 to 17), all p < 0.05. No serious adverse events occurred. In patients with PH, short-term exposure to altitude of 2500 m induced more pronounced hypoxemia, hypocapnia and pulmonary hemodynamic changes compared to NH during HAST despite similar exposure times and P_iO₂. Therefore, the use of HAST to predict physiological changes at altitude remains questionable. (ClinicalTrials.gov: NCT03592927 and NCT03637153). Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Tent versus Mask-On Acute Effects during Repeated-Sprint Training in Normobaric Hypoxia and Normoxia

Aldo A. Vasquez-Bonilla

Daniel Rojas-Valverde

Adrián González-Custodio

Rafael Timón

and

Guillermo Olcina

J. Clin. Med. 2021, 10(21), 4879; https://doi.org/10.3390/jcm10214879 - 22 Oct 2021

Cited by 3 | Viewed by 1398

Abstract

Repeated sprint in hypoxia (RSH) is used to improve supramaximal cycling capacity, but little is known about the potential differences between different systems for creating normobaric hypoxia, such as a chamber, tent, or mask. This study aimed to compare the environmental (carbon dioxide (CO₂) and wet-globe bulb temperature (WGBT)), perceptual (pain, respiratory difficulty, and rate of perceived exertion (RPE)), and external (peak and mean power output) and internal (peak heart rate (HRpeak), muscle oxygen saturation (SmO₂), arterial oxygen saturation (SpO₂), blood lactate and glucose) workload acute effects of an RSH session when performed inside a tent versus using a mask. Twelve well-trained cyclists (age = 29 ± 9.8 years, VO₂max = 70.3 ± 5.9 mL/kg/min) participated in this single-blind, randomized, crossover trial. Participants completed four sessions of three sets of five repetitions × 10 s:20 s (180 s rest between series) of all-out in different conditions: normoxia in a tent (RSNTent) and mask-on (RSNMask), and normobaric hypoxia in a tent (RSHTent) and mask-on (RSHMask). CO₂ and WGBT levels increased steadily in all conditions (p < 0.01) and were lower when using a mask (RSNMask and RSHMask) than when inside a tent (RSHTent and RSNTent) (p < 0.01). RSHTent presented lower SpO₂ than the other three conditions (p < 0.05), and hypoxic conditions presented lower SpO₂ than normoxic ones (p < 0.05). HRpeak, RPE, blood lactate, and blood glucose increased throughout the training, as expected. RSH could lead to acute conditions such as hypoxemia, which may be exacerbated when using a tent to simulate hypoxia compared to a mask-based system. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Open AccessArticle

Predictors of Hypoxemia and Related Adverse Outcomes in Patients Hospitalized with COVID-19: A Double-Center Retrospective Study

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J. Clin. Med. 2021, 10(16), 3581; https://doi.org/10.3390/jcm10163581 - 14 Aug 2021

Cited by 4 | Viewed by 1591

Abstract

Hypoxemia is a hallmark of coronavirus disease 2019 (COVID-19) severity. We sought to determine predictors of hypoxemia and related adverse outcomes among patients hospitalized with COVID-19 in the two largest hospitals in Jerusalem, Israel, from 9 March through 16 July 2020. Patients were categorized as those who developed reduced (<94%) vs. preserved (≥94%) arterial oxygen saturation (SpO₂) within the first 48 h after arrival to the emergency department. Overall, 492 hospitalized patients with COVID-19 were retrospectively analyzed. Patients with reduced SpO₂ were significantly older, had more comorbidities, higher body surface area (BSA) and body mass index (BMI), lower lymphocyte counts, impaired renal function, and elevated liver enzymes, c-reactive protein (CRP), and D-dimer levels as compared to those with preserved SpO₂. In the multivariable regression analysis, older age (odds ratio (OR) 1.02 per year, p < 0.001), higher BSA (OR 1.16 per 0.10 m², p = 0.003) or BMI (OR 1.05 per 1 kg/m², p = 0.011), lower lymphocyte counts (OR 1.72 per 1 × 10³/μL decrease, p = 0.002), and elevated CRP (1.11 per 1 mg/dL increase, p < 0.001) were found to be independent predictors of low SpO₂. Severe hypoxemia requiring ventilatory support, older age, and pre-existing comorbidities, including underlying renal dysfunction and heart failure, were found to be significantly associated with in-hospital mortality. These findings suggest that assessment of predictors of hypoxemia early at the time of hospitalization with COVID-19 may be helpful in risk stratification and management. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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Review

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Effects of Acute Exposure and Acclimatization to High-Altitude on Oxygen Saturation and Related Cardiorespiratory Fitness in Health and Disease

Michael Furian

Markus Tannheimer

and

Martin Burtscher

J. Clin. Med. 2022, 11(22), 6699; https://doi.org/10.3390/jcm11226699 - 12 Nov 2022

Viewed by 1169

Abstract

Maximal values of aerobic power (VO₂max) and peripheral oxygen saturation (SpO₂max) decline in parallel with gain in altitude. Whereas this relationship has been well investigated when acutely exposed to high altitude, potential benefits of acclimatization on SpO₂ and related VO₂max in healthy and diseased individuals have been much less considered. Therefore, this narrative review was primarily aimed to identify relevant literature reporting altitude-dependent changes in determinants, in particular SpO₂, of VO₂max and effects of acclimatization in athletes, healthy non-athletes, and patients suffering from cardiovascular, respiratory and/or metabolic diseases. Moreover, focus was set on potential differences with regard to baseline exercise performance, age and sex. Main findings of this review emphasize the close association between individual SpO₂ and VO₂max, and demonstrate similar altitude effects (acute and during acclimatization) in healthy people and those suffering from cardiovascular and metabolic diseases. However, in patients with ventilatory constrains, i.e., chronic obstructive pulmonary disease, steep decline in SpO₂ and V̇O₂max and reduced potential to acclimatize stress the already low exercise performance. Finally, implications for prevention and therapy are briefly discussed. Full article

(This article belongs to the Special Issue Clinical and Physiological Consequences of Hypoxia/Hypoxemia in Healthy Subjects and Patients)

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