Factors Associated with Fatigue in COVID-19 ICU Survivors.

PURPOSE: Approximately 30% of people infected with COVID-19 require hospitalization and 20% of them are admitted to an intensive care unit (ICU). Most of these patients experience symptoms of fatigue weeks post-ICU, so understanding the factors associated with fatigue in this population is crucial. METHODS: Fifty-nine patients [38-78 yr] hospitalized in ICU for COVID-19 infection for 32 [6-80] days including 23 [3-57] days of mechanical ventilation, visited the laboratory on two separate occasions. The first visit occurred 52 ± 15 days after discharge and was dedicated to questionnaires, blood sampling and cardiopulmonary exercise testing, while measurements of the knee extensors neuromuscular function and performance fatigability were performed in the second visit 7 ± 2 days later. RESULTS: Using the FACIT-F questionnaire, 56% of patients were classified as fatigued. Fatigued patients had worse lung function score than non- fatigued (i.e. 2.9 ± 0.8 L vs 3.6 ± 0.8 L; 2.4 ± 0.7 l vs 3.0 ± 0.7 L for forced vital capacity and forced expiratory volume in one second, respectively) and forced vital capacity was identified as a predictor of being fatigued. Maximal voluntary activation was lower in fatigued patients than non-fatigued patients (82 ± 14% vs 91 ± 3%) and was the only neuromuscular variable that discriminated between fatigued and non-fatigued patients. Patient-reported outcomes also showed differences between fatigued and non-fatigued patients for sleep, physical activity, depression and quality of life (p < 0.05). CONCLUSIONS: COVID-19 survivors showed altered respiratory function 4 to 8 weeks after discharge, that was further deteriorated in fatigued patients. Fatigue was also associated with lower voluntary activation and patient-reported impairments (i.e. sleep satisfaction, quality of life or depressive state). The present study reinforces the importance of exercise intervention and rehabilitation to counteract cardiorespiratory and neuromuscular impairments of COVID-19 patients admitted in ICU, especially individuals experiencing fatigue.

Making a virtue out of an evil: Are red blood cells from chronic mountain sickness patients eligible for transfusions?

We investigated highlanders, permanently living at an altitude of 5100 m and compared Chronic Mountain Sickness (CMS) patients with control volunteers. While we found differences in systemic parameters such as blood oxygen content, hematocrit, hemoglobin concentration, and blood viscosity, the mechanical and rheological properties of single red blood cells did not differ between the two investigated groups.

Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?

Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.

Impaired post-sleep apnea autonomic arousals in patients with drug-resistant epilepsy.

OBJECTIVE: Sudden and unexpected deaths in epilepsy (SUDEP) pathophysiology may involve an interaction between respiratory dysfunction and sleep/wake state regulation. We investigated whether patients with epilepsy exhibit impaired sleep apnea-related arousals. METHODS: Patients with drug-resistant (N = 20) or drug-sensitive (N = 20) epilepsy and obstructive sleep apnea, as well as patients with sleep apnea but without epilepsy (controls, N = 20) were included. We explored (1) the respiratory arousal threshold based on nadir oxygen saturation, apnea-hypopnea index, and fraction of hypopnea among respiratory events; (2) the cardiac autonomic response to apnea/hypopnea quantified as percentages of changes from the baseline in RR intervals (RRI), high (HF) and low (LF) frequency powers, and LF/HF. RESULTS: The respiratory arousal threshold did not differ between groups. At arousal onset, RRI decreased (-9.42%) and LF power (179%) and LF/HF ratio (190%) increased. This was followed by an increase in HF power (118%), p < 0.05. The RRI decrease was lower in drug-resistant (-7.40%) than in drug-sensitive patients (-9.94%) and controls (-10.91%), p < 0.05. LF and HF power increases were higher in drug-resistant (188%/126%) than in drug-sensitive patients (172%/126%) and controls (177%/115%), p < 0.05. CONCLUSIONS: Cardiac reactivity following sleep apnea is impaired in drug-resistant epilepsy. SIGNIFICANCE: This autonomic dysfunction might contribute to SUDEP pathophysiology.

Genetic polymorphisms and expression of Rhesus blood group RHCE are associated with 2,3-bisphosphoglycerate in humans at high altitude.

Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-altitude hypoxia, with longitudinal sampling at baseline, upon ascent to 5,100 m and descent to sea level. Results highlighted an association between erythrocyte levels of 2,3-bisphosphoglycerate (BPG), an allosteric regulator of hemoglobin that favors oxygen off-loading in the face of hypoxia, and expression levels of the Rhesus blood group RHCE protein. We then expanded on these findings by measuring BPG in RBCs from 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. These data informed a genome-wide association study using BPG levels as a quantitative trait, which identified genetic polymorphisms in the region coding for the Rhesus blood group RHCE as critical determinants of BPG levels in erythrocytes from healthy human volunteers. Mechanistically, we suggest that the Rh group complex, which participates in the exchange of ammonium with the extracellular compartment, may contribute to intracellular alkalinization, thus favoring BPG mutase activity.

Aspects clinico-neurophysiologiques des troubles du sommeil dans une population d'adultes jeunes entre 18-35 ans / Clinical-neurophysiological aspects of sleep disorders in a population of young adults aged 18-35 years

Contexte et objectifs : L'accès aux tests neurophysiologiques pour le diagnostic des Troubles du Sommeil (TS) est très limité dans les pays d'Afrique subsaharienne. La présente étude avait pour objectif de déterminer les caractéristiques épidémiologiques, cliniques et neurophysiologiques des (TS) dans un groupe de jeunes adultes. Méthodes : Il s'est agi d'une étude descriptive d'une série de cas, réalisée au centre de Médecine du sommeil et des maladies respiratoires de l'hôpital de la Croix-Rousse de Lyon du 1er janvier au 31 mars 2019. Les patients hospitalisés pendant cette période pour l'exploration d'un (TS) ont été sélectionnés. Etaient éligibles ceux dont l'âge était compris entre 18 et 35 ans, des deux sexes, ayant renseigné un questionnaire et ayant bénéficié au minimum d'une polysomnographie (PSG). Résultats : Quatre-vingt-onze patients étaient examinés. Les femmes étaient les plus affectées (59,3 %). Leur âge moyen était de 26,6 ± 5 ans. La PSG a incriminé le Syndrome d'Apnée Hypopnée Obstructive du sommeil (SAHOS) comme étiologie principale (66 %). Pour les patients sans SAHOS, 38,7 % avaient une PSG normale et la PSG avec d'autres tests de sommeil ont objectivé, pour le reste (61,3 %), d'autres types de (TS). La dépression (50,7 %) et la fatigue chronique (84,6 %) étaient très fréquentes. L'indice d'efficacité du sommeil était faible pour 70 % des patients avec SAHOS. Il y avait un déséquilibre de la durée des stades du sommeil, augmentée pour le sommeil lent léger et diminuée pour le sommeil lent profond dans la population avec SAHOS, tandis que la durée du sommeil paradoxal chez ceux sans SAHOS était augmentée. Conclusion Le SAHOS est fréquent dans cette formation hospitalière, avec des répercussions significatives à type de dépression et de fatigue chronique. Il est important que des mesures rendant accessible l'usage des tests d'exploration du sommeil particulièrement en Afrique au sud du Sahara, soient mises en place pour diagnostiquer ces troubles

Context and objective. Access to neurophysiological tests for diagnostic of sleep disorders (SD) is very limited in Sub-Saharan Africa countries. The objective was to determine the epidemiological, clinical and neurophysiological characteristics of SD in a young adult group. Methods. This was a descriptive serial cases study carried out at the Sleep Medicine and Respiratory Diseases Center of the CroixRousse hospital of Lyon between January 1st and March 31th, 2019. Patients hospitalized during this period with tests for SD were selected. Eligible were those aged between 18 and 35 years, both sexes, who completed a questionnaire and who received at least a polysomnography (PSG). Results. Ninety-one patients were involved. Women remained the most affected (59.3%). Mean age was 26.6±5 years. PSG incriminated obstructive sleep apnea (OSA) syndrome as the primary etiology (66%). For patients without OSA, 38.7% had normal PSG. For the remaining 61.3% of patients, other types of SD were found using PSG with various sleep tests. Depression (50.7%) was an important comorbidity, and chronic fatigue (84.6%) was the most frequent complaint. Sleep efficiency index was low for 70% of sleep apnea patients. There was an imbalance in the duration of sleep stages, with an increase in light slow-wave sleep in the OSA population and a decrease in their deep slow-wave sleep, while REM sleep duration in patients without OSA was increased. Conclusion: OSA was the primary etiology in our study, with significant repercussions like depression and chronic fatigue. Public health measures such as increasing access to the use of sleep exploration tests, especially in subSaharan Africa, should be put in place for the diagnosis of these sleep disorders and their consequences

Expedition 5300: limits of human adaptations in the highest city in the world.

Exposure to chronic hypobaric hypoxia imposes a significant physiological burden to more than 80 million humans living above 2500 m throughout the world. Among them, 50 000 live in the world's highest city, La Rinconada, located at 5000-5300 m in southern Peru. Expedition 5300 is the first scientific and medical programme led in La Rinconada to investigate the physiological adaptations and altitude-related health issues in this unique population. Dwellers from La Rinconada have very high haemoglobin concentration (20.3 ± 2.4 g/dL; n = 57) and those with chronic mountain sickness (CMS) exhibit even higher concentrations (23.1 ± 1.7 g/dL; n = 150). These values are associated with large total haemoglobin mass and blood volume, without an associated iron deficit. These changes in intravascular volumes lead to a substantial increase in blood viscosity, which is even larger in CMS patients. Despite these large haematological changes, 24 h blood pressure monitoring is essentially normal in La Rinconada, but some results suggest impaired vascular reactivity. Echocardiography revealed large right heart dilatation and high pulmonary arterial pressure as well as left ventricle concentric remodelling and grade I diastolic dysfunction. These changes in heart dimension and function tend to be more severe in highlanders with CMS. Polygraphy evaluations revealed a large reduction in nocturnal pulse oxygen saturation (median SpO2  = 79%), which is even more severe in CMS patients who also tended to show a higher oxygen desaturation index. The population of La Rinconada offers a unique opportunity to investigate the human responses to chronic severe hypoxia, at an altitude that is probably close to the maximum altitude human beings can permanently tolerate without presenting major health issues.

Unveiled central hypoventilation after tracheotomy in anti-IgLON5 disease: a case report.

Anti-IgLON5 disease is a recently described entity that has been associated with neurological symptoms and sleep disturbances including sleep breathing disorders. Sleep stridor as well as obstructive and less often central sleep apnea have been reported but rarely needing ventilation on tracheotomy. We report the case of a patient in whom obstructive sleep apnea with secondary development of dysphagia and recurrent aspiration pneumonia led to the diagnosis of anti-IgLON 5 disease. Acute respiratory failure due to laryngospasm required intubation and eventually tracheotomy. Yet hypoventilation persisted, and polysomnography demonstrated central sleep apnea alternating with sleep-related tachypnea. Nocturnal ventilation was thus reintroduced. The association of obstructive sleep apnea with dysphagia is a potential red flag for anti-IgLON5 disease, which remains an overlooked diagnosis. Breathing disorders can be complex in this context, with a mixed obstructive and central pattern whose central component can be unveiled after tracheotomy. This highlights the importance of closely monitoring sleep and respiration even after tracheotomy. CITATION: Tankéré P, Le Cam P, Folliet L, et al. Unveiled central hypoventilation after tracheotomy in anti-IgLON5 disease: a case report. J Clin Sleep Med. 2023;19(9):1701-1704.

Effects of a Maximal Exercise Followed by a Submaximal Exercise Performed in Normobaric Hypoxia (2500 m), on Blood Rheology, Red Blood Cell Senescence, and Coagulation in Well-Trained Cyclists.

Acute normoxic exercise impacts the rheological properties of red blood cells (RBC) and their senescence state; however, there is a lack of data on the effects of exercise performed in hypoxia on RBC properties. This crossover study compared the effects of acute hypoxia vs. normoxia on blood rheology, RBC senescence, and coagulation during exercise. Nine trained male cyclists completed both a session in normoxia (FiO2 = 21%) and hypoxia (FiO2 = 15.3% ≈ 2500 m). The two sessions were randomly performed, separated by one week, and consisted of an incremental and maximal exercise followed by a 20 min exercise at the first ventilatory threshold (VT1) on a home-trainer. Blood samples were taken before and after exercise to analyze hematological parameters, blood rheology (hematocrit, blood viscosity, RBC deformability and aggregation), RBC senescence markers (phosphatidylserine (PS) and CD47 exposure, intraerythrocyte reactive oxygen species (ROS), and calcium content), and blood clot viscoelastic properties. Hemoglobin oxygen saturation (SpO2) and blood lactate were also measured. In both conditions, exercise induced an increase in blood viscosity, hematocrit, intraerythrocyte calcium and ROS content, and blood lactate concentration. We also observed an increase in blood clot amplitude, and a significant drop in SpO2 during exercise in the two conditions. RBC aggregation and CD47 exposure were not modified. Exercise in hypoxia induced a slight decrease in RBC deformability which could be related to the slight increase in mean corpuscular hemoglobin concentration (MCHC). However, the values of RBC deformability and MCHC after the exercise performed in hypoxia remained in the normal range of values. In conclusion, acute hypoxia does not amplify the RBC and coagulation changes induced by an exercise bout.

Cardiorespiratory Fitness and Neuromuscular Function of Mechanically Ventilated ICU COVID-19 Patients.

OBJECTIVES: The aim of the current study was to investigate the level of cardiorespiratory fitness and neuromuscular function of ICU survivors after COVID-19 and to examine whether these outcomes are related to ICU stay/mechanical ventilation duration. DESIGN: Prospective nonrandomized study. SETTING: Patients hospitalized in ICU for COVID-19 infection. PATIENTS: Sixty patients hospitalized in ICU (mean duration: 31.9 ± 18.2 d) were recruited 4-8 weeks post discharge from ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients visited the laboratory on two separate occasions. The first visit was dedicated to quality of life questionnaire, cardiopulmonary exercise testing, whereas measurements of the knee extensors neuromuscular function were performed in the second visit. Maximal oxygen uptake (V o2 max) was 18.3 ± 4.5 mL·min -1 ·kg -1 , representing 49% ± 12% of predicted value, and was significantly correlated with ICU stay/mechanical ventilation (MV) duration ( R = -0.337 to -0.446; p < 0.01 to 0.001), as were maximal voluntary contraction and electrically evoked peak twitch. V o2 max (either predicted or in mL· min -1 ·kg -1 ) was also significantly correlated with key indices of pulmonary function such as predicted forced vital capacity or predicted forced expiratory volume in 1 second ( R = 0.430-0.465; p ≤ 0.001) and neuromuscular function. Both cardiorespiratory fitness and neuromuscular function were correlated with self-reported physical functioning and general health status. CONCLUSIONS: V o2 max was on average only slightly above the 18 mL·min -1 ·kg -1 , that is, the cut-off value known to induce difficulty in performing daily tasks. Overall, although low physical capacities at admission in ICU COVID-19 patients cannot be ruled out to explain the association between V o2 max or neuromuscular function and ICU stay/MV duration, altered cardiorespiratory fitness and neuromuscular function observed in the present study may not be specific to COVID-19 disease but seem applicable to all ICU/MV patients of similar duration.

Cardiac remodelling in the highest city in the world: effects of altitude and chronic mountain sickness.

AIMS: A unique Andean population lives in the highest city of the world (La Rinconada, 5100 m, Peru) and frequently develops a maladaptive syndrome, termed chronic mountain sickness (CMS). Both extreme altitude and CMS are a challenge for the cardiovascular system. This study aims to evaluate cardiac remodelling and pulmonary circulation at rest and during exercise in healthy and CMS highlanders. METHODS AND RESULTS: Highlanders living permanently at 3800 m (n = 23) and 5100 m (n = 55) with (n = 38) or without CMS (n = 17) were compared with 18 healthy lowlanders. Rest and exercise echocardiography were performed to describe cardiac remodelling, pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR). Total blood volume (BV) and haemoglobin mass were determined in all people. With the increase in the altitude of residency, the right heart dilated with an impairment in right ventricle systolic function, while the left heart exhibited a progressive concentric remodelling with Grade I diastolic dysfunction but without systolic dysfunction. Those modifications were greater in moderate-severe CMS patients. The mean PAP was higher both at rest and during exercise in healthy highlanders at 5100 m. The moderate-severe CMS subjects had a higher PVR at rest and a larger increase in PAP during exercise. The right heart remodelling was correlated with PAP, total BV, and SpO2. CONCLUSION: Healthy dwellers at 5100 m exhibit both right heart dilatation and left ventricle concentric remodelling with diastolic dysfunction. Those modifications are even more pronounced in moderate-severe CMS subjects and could represent the limit of the heart's adaptability before progression to heart failure.

The human blood transcriptome exhibits time-of-day-dependent response to hypoxia: Lessons from the highest city in the world.

High altitude exposes humans to hypobaric hypoxia, which induces various physiological and molecular changes. Recent studies point toward interaction between circadian rhythms and the hypoxic response, yet their human relevance is lacking. Here, we examine the effect of different high altitudes in conjunction with time of day on human whole-blood transcriptome upon an expedition to the highest city in the world, La Rinconada, Peru, which is 5,100 m above sea level. We find that high altitude vastly affects the blood transcriptome and, unexpectedly, does not necessarily follow a monotonic response to altitude elevation. Importantly, we observe daily variance in gene expression, especially immune-related genes, which is largely altitude dependent. Moreover, using a digital cytometry approach, we estimate relative changes in abundance of different cell types and find that the response of several immune cell types is time- and altitude dependent. Taken together, our data provide evidence for interaction between the transcriptional response to hypoxia and the time of day in humans.

Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world.

INTRODUCTION: Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude. METHODS: Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude. RESULTS: Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= -0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders. CONCLUSIONS: Lower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies.

Reduced Lung Diffusion Capacity Caused by Low Alveolar Volume and Restrictive Disease Are Common in Sickle Cell Disease

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Sex-related differences and effects of short and long trail running races on resting muscle-tendon mechanical properties.

The purpose of the study was to assess sex-related differences in resting mechanical properties and adaptations of skeletal muscles and tendons in response to trail running races of different distances using multi-site shear wave elastography assessments of the lower limb, force capacity and blood analyses. Sex differences in resting mechanical properties of knee extensor and plantar flexor muscles and tendons were characterized by shear wave velocity (SWV) measurements in healthy males (N = 42) and females (N = 25) trained in long-distance running. Effects of running distance on muscle and tendon properties were assessed in short (<60 km, N = 23) vs. long (>100 km, N = 26) distance races. Changes in isometric maximal voluntary contraction torque, serum C-reactive protein and creatine kinase activity were also quantified after running races. Higher SWV of relaxed triceps surae muscle was detected in females as compared to males before running races (+4.8%, p = 0.006), but the significant increases in triceps surae muscle group (+7.0%, p = 0.001) and patellar tendon SWV (+15.4%, p = 0.001) after short-distance races were independent of sex. A significant decrease in triceps surae muscle SWV was found after long-distance races in the whole experimental population (-3.1%, p = 0.049). Post-races increase in C-reactive protein and creatine kinase activity were significantly correlated to the relative decreases in triceps surae and quadriceps femoris skeletal muscle SWV (ρ = -0.56, p = 0.001 and ρ = -0.51, p = 0.001, respectively). Resting mechanical properties of muscles and tendons are affected by sex, and adaptations to trail races are related to running distance. Exercise-induced changes in resting skeletal muscle mechanical properties are associated with enhanced indirect markers of inflammation and muscle damage.

Shear-Stress-Gradient and Oxygen-Gradient Ektacytometry in Sickle Cell Patients at Steady State and during Vaso-Occlusive Crises.

Oxygen gradient ektacytometry (oxygenscan) measures the changes in red blood cell (RBC) deformability in normoxia and during deoxygenation. We investigated the changes in RBC deformability, measured by both oxygenscan and classical shear-stress-gradient ektacytometry, in 10 patients with sickle cell disease (SCD) during vaso-occlusive crisis (VOC) versus steady state. Oxygenscan and shear-stress-gradient ektacytometry parameters were also measured in 38 SCD patients at steady state on two different occasions. Shear-stress-gradient ektacytometry parameters, maximal RBC deformability at normoxia and the minimum RBC deformability during deoxygenation were lower during VOC compared to steady state. The oxygen partial pressure at which RBCs started to sickle (PoS) was not significantly affected by VOC, but the results were very heterogeneous: the PoS increased in 5 in 10 patients and decreased in 4 in 10 patients. Both oxygenscan and shear-stress-gradient ektacytometry parameters remained unchanged in patients at steady state between two sets of measurements, performed at 17 ± 8 months intervals. In conclusion, the present study showed that both oxygen gradient ektacytometry and shear-stress-gradient ektacytometry are sensitive to disease activity in SCD, and that both techniques give comparable results; however, the oxygen-dependent propensity of RBCs to sickle was highly variable during VOC.

Acid-base balance at high altitude in lowlanders and indigenous highlanders.

High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH (pHa) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations-where the latter are thought to be fully adapted to high altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders and Andean and Sherpa highlanders at various altitudes (∼3,800, ∼4,300, and ∼5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n = 7) had elevated pHa compared with Sherpas (n = 12; P < 0.01), but not to lowlanders (n = 16; 9 days acclimatized; P = 0.09); 2) at 4,300 m, lowlanders (n = 16; 21 days acclimatized) had elevated pHa compared with Andeans (n = 32) and Sherpas (n = 11; both P < 0.01), and Andeans had elevated pHa compared with Sherpas (P = 0.01); and 3) at 5,000 m, lowlanders (n = 16; 14 days acclimatized) had higher pHa compared with both Andeans (n = 66) and Sherpas (n = 18; P < 0.01, and P = 0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P = 0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.NEW & NOTEWORTHY Lowlander, Andean, and Sherpa arterial blood data were combined across five independent high-altitude expeditions in the United States, Nepal, and Peru to assess acid-base status at ∼3,800, ∼4,300, and ∼5,000 m. The main finding was that Andean and Sherpa highlander populations have more acidic arterial blood, due to elevated arterial carbon dioxide and similar arterial bicarbonate compared with acclimatizing lowlanders at altitudes ≥4,300 m.