High-altitude Residents Research Articles

Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)

Abstract Introduction Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries. Aim To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru. Methods Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: <500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis. Results The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800). Conclusions Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.

Maternal AMPK pathway activation with uterine artery blood flow and fetal growth maintenance during hypoxia.

High-altitude (HA) hypoxia lowers uterine artery (UtA) blood flow during pregnancy and birth weight. Adenosine monophosphate kinase (AMPK) activation has selective, uteroplacental vasodilator effects that lessen hypoxia-associated birth weight reductions. In this study, we determined the relationship between AMPK-pathway gene expression and metabolites in the maternal circulation during HA pregnancy as well as with the maintenance of UtA blood flow and birth weight at HA. Residents at HA (2,793 m) versus low altitude (LA; 1,640 m) had smaller UtA diameters at weeks 20 and 34, lower UtA blood flow at week 20, and lower birth weight babies. At week 34, women residing at HA versus women residing at LA had decreased expression of upstream and downstream AMPK-pathway genes. Expression of the α1-AMPK catalytic subunit, PRKAA1, correlated positively with UtA diameter and blood flow at weeks 20 (HA) and 34 (LA). Downstream AMPK-pathway gene expression positively correlated with week 20 fetal biometry at both altitudes and with UtA diameter and birth weight at LA. Reduced gene expression of AMPK activators and downstream targets in women residing at HA versus women residing at LA, together with positive correlations between PRKAA1 gene expression, UtA diameter, and blood flow suggest that greater sensitivity to AMPK activation at midgestation at HA may help offset later depressant effects of hypoxia on fetal growth.NEW & NOTEWORTHY Fetal growth restriction (FGR) is increased and uterine artery (UtA) blood flow is lower at high altitudes (HA) but not all HA pregnancies have FGR. Here we show that greater UtA diameter and blood flow at week 20 are positively correlated with higher expression of the gene encoding the α1-catalytic subunit of AMP protein kinase, PRKAA1, suggesting that increased AMPK activation may help to prevent the detrimental effects of chronic hypoxia on fetal growth.

COVID-19 in the Tibet, China, the roof of the world: a comparative analysis of high-altitude residents and newcomers

BackgroundAfter a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders.MethodsThis multi-center cohort study conducted at the Third People’s Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis.ResultsNo fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups.ConclusionsHigh-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

The effects of bedroom microclimate regulation behaviors on sleep quality: A field study on the Qinghai-Tibetan Plateau

The environmental regulatory behaviors of humans have a myriad of effects on the microclimate of bedrooms and the quality of sleep. Due to the special geographical climate, proposing non-invasive optimal strategies for environmental regulation is of considerable significance to improve sleep quality among high-altitude residents. However, there is no report on the environmental regulatory behaviors of residents at high-altitudes. Conducted in the Qinghai-Tibet Plateau at an altitude of 3255m, this study investigated the environmental regulatory behaviors, bedroom microclimate, and sleep quality of 355 local residents over the course of one week, and analyzed the influence of the behaviors on the bedroom environment and sleep quality. Results from 1462 nights of monitoring revealed that residents of the Qinghai-Tibet Plateau prefer to sleep with doors or windows open in both winter and summer. Leaving the doors or windows open during summer led to a reduction in sleep time, rapid eye movement sleep and awakening time, which is the most prominent sleep issue at high-altitude, while in winter the percentage of deep sleep decreased with open doors or windows. The habit of humidification displayed a noticeable seasonal bias, with plateau residents being more inclined to adopt humidification measures in winter. Based on the results, this study recommends sleeping with doors or windows open without humidification in summer, while in the winter, humidification is necessary.

Electrocardiographic findings in a group of physically active young adults who reside at 2,600 meters above the sea level: an exploratory study

Purpose: The physiological adaptations to regular physical activity and hypobaric hypoxia associated with high-altitude residence are related to a series of cardiovascular adaptations that can generate electrocardiographic modifications. This study aimed to describe the principal findings and determine the mean values of the electrocardiographic parameters in a group of physically active young adults who reside at a high altitude. Methods: 49 young, physically active subjects (11 women) in a Sports Sciences program participated in the study. Each participant was subjected to a medical interview, a physical examination, and a resting electrocardiogram. Two physicians analyzed the electrocardiogram, searching for criteria of anatomical or physiological abnormalities; a descriptive analysis of the duration of waves and intervals and the amplitude of the T and P waves was also carried out. Results: The mean values of the electrocardiographic parameters were between the expected values. The principal findings involve sinus bradycardia and changes associated with the right side of the heart: incomplete right bundle branch block, right QRS axis deviation, and right ventricular hypertrophy. Conclusions: The findings of this study are related to other studies that describe changes in the right side of the heart in inhabitants of high altitude and sinus bradycardia in physically active subjects and, in some cases, in high-altitude residents. Every young dweller of the altitude who engages in physical activity should be submitted to a resting ECG, considering there is a high probability of finding asymptomatic changes in the ECG that could require further exploration. Keywords: Electrocardiogram, high altitude, hypoxia, exercise

Evaluation of the hemoglobin cutoff point for anemia in adult women residents of different altitudinal levels in Peru.

Anemia prevalence is high in countries where high proportion of the population lives at high altitude (HA) due perhaps to the unsuitability hemoglobin correction factor proposed by the WHO. The present study has been designed to evaluate a new approach to establish thresholds of hemoglobin (Hb) when defining anemia at HA. Cross-sectional study evaluating 217 women aged 18 to 75 years-old, residents of 2 cities at low altitude (LA) (130 and 150 meters) and 2 at HA (3800 and 4300 meters). Hb, pulse oxygen saturation (SpO2), arterial oxygen content (CaO2), and inflammatory markers were measured. Three definitions of anemia diagnoses were used: uncorrected Hb, WHO-corrected Hb, and Silubonde's criteria based on ferritin as a gold standard. STATA v18.0 was use for data analysis, p<0.05 indicated significant difference. HA residents present higher Hb values than at LA. Likewise, the highest area under the curve (AUC) ROC (Receiver Operating Characteristic) was observed for uncorrected Hb (AUC = 0.8595; CI95% 0.858-0.86) for the diagnosis of anemia using serum ferritin as the gold standard. Anemia prevalence was higher when using WHO-corrected Hb, 27%, and Silubonde's criteria, 41% (Hb cut-off of 11.10, 12.73, 15.80 and 16.60 g/dl for altitudes of 130, 150, 3800 and 4300 meters, respectively), than using uncorrected Hb to define anemia (7.7%). Serum Ferritin and CaO2 values are lower only in the group with anemia defined with uncorrected Hb than in the groups of anemia using the WHO-corrected Hb or the Silubonde´s criteria. The correction factor of hemoglobin for altitude of residence overestimates the prevalence of anemia in adult women. Likewise, CaO2 could be a potential marker to determine the transport of oxygen in LA and HA populations. Further studies in adult men are required to confirm the present findings.

Spirometry findings of chronic lung disease in high-altitude residents of Ladakh (&gt;11000 feet above sea level)

Ladakh is a hilly Himalayan dry desert, situated at an altitude of &gt;11000 feet. Studies have demonstrated that the spirometric values of high-altitude residents are significantly higher than those of low-landers. This is a retrospective observational study that analyzes the spirometry pattern in chronic lung diseases among people from Ladakh. Enrolled subjects were clinic-radiologically diagnosed and had at least one spirometry report. The spirometric parameters were analyzed for normal and abnormal patterns of lung function. The abnormal patterns were further classified into types of ventilator defects and their severity. A total of 122 cases were included, with 67 (55%) men. The mean age was 52.2±15.4 years. The most common diseases were chronic obstructive pulmonary disease (COPD) in 51 cases (41%), and asthma in 41 (33%). The median predicted percentage of forced vital capacity (FVC) was 116% (63-179%) with &gt;100% in 105 (85%) patients. The median predicted percentage of the forced expiratory volume in the 1st second (FEV1) was 113% (99-175%) with &gt;100% in 90 (74%) patients. FVC was reduced in 9 (7%) cases, normal in 62 (51%), and more than normal in 49 (42%), with 11 (9%) cases having &gt;150% of the predicted percentage. FEV1 was reduced in 9 (8%) cases, normal in 67 (55%), and more than normal in 46 (37%) cases, with &gt;150% predicted seen in 10 (8%) cases. Similarly, overall, the predicted percentages of both FVC and FEV1 were &gt;100% in all obstructive airway diseases as well as in the separate COPD and asthma subgroups. FVC and FEV1 amongst chronic lung disease patients from Ladakh were more than normal in the majority. These higher values of spirometry led to incorrect disease severity classifications and disease patterns. We propose that studies should be done to devise local reference equations for spirometry for Himalayan high-altitude residents of India.

Pulmonary vascular diseases at high altitude - is it safe to live in the mountains?

This review addresses the concern of the health effects associated with high-altitude living and chronic hypoxia with a focus on pulmonary hypertension. With an increasing global population residing at high altitudes, understanding these effects is crucial for public health interventions and clinical management. Recent literature on the long-term effects of high-altitude residence and chronic hypoxia is comprehensively summarized. Key themes include the mechanisms of hypoxic pulmonary vasoconstriction, the development of pulmonary hypertension, and challenges in distinguishing altitude-related pulmonary hypertension and classical pulmonary vascular diseases, as found at a low altitude. The findings emphasize the need for research in high-altitude communities to unravel the risks of pulmonary hypertension and pulmonary vascular diseases. Clinically, early and tailored management for symptomatic individuals residing at high altitudes are crucial, as well as access to advanced therapies as proposed by guidelines for pulmonary vascular disease. Moreover, identifying gaps in knowledge underscores the necessity for continued research to improve understanding and clinical outcomes in high-altitude pulmonary vascular diseases.

Prevalence of Chronic Obstructive Pulmonary Disease and Its Associated Risk Factors in Yunnan Province, China: A Population Based Cross-Sectional Study.

Chronic obstructive pulmonary disease (COPD) is a significant disease impacting health and quality of life. Yunnan Province, a major tobacco producer, lacks comprehensive COPD studies. The purpose of this study is to describe the epidemic situation of COPD in Yunnan province and explore its influencing factors. This study is a cross-sectional research conducted in a representative sample of adults aged 20 and older from 13 prefectures and cities in Yunnan Province, China. COPD was diagnosed using post-bronchodilator pulmonary function tests. Demographics were analyzed with descriptive statistics. The influencing factors of COPD were examined by using the multivariate logistic regression models. Our study found that high-risk individuals for COPD accounted for 20.30% of the screened population aged 20 and above, with a COPD prevalence of 27.18% among this high-risk group. Male had a higher prevalence (33.01%) than did female (16.35%; p<0.001 for sex difference). Additionally, the proportion of severe and extremely severe COPD cases in Yunnan Province was higher than the national average and other provinces. After considering the potential confounding variables, male (OR=2.291, 95% CI: 1.584-3.313), age (OR=1.501, 95% CI: 1.338-1.685), underweight (OR=1.747, 95% CI: 1.225-2.491), previous smoking (OR=1.712, 95% CI: 1.182-2.478), passive smoking (OR=1.444, 95% CI: 1.159-1.800), and a history of respiratory system diseases in childhood (OR=2.010, 95% CI: 1.346-3.001) were significantly associated with an increased risk of COPD. Conversely, being overweight (OR=0.636, 95% CI: 0.489-0.828), and residing in high-altitude counties (OR=0.445, 95% CI: 0.263-0.754) were negatively correlated with the risk of COPD. There is significant prevalence of COPD (27.18%) among high-risk population aged 20 and above in Yunnan Province, China. Apart from male, smoking, BMI and other known risk factors for COPD. We found that high-altitude residence had a lower prevalence of COPD. There is no significant difference in COPD prevalence between Han and ethnic minority populations.

#2489 The prevalence of chronic kidney disease in different altitude areas: results from the China multi-ethnic cohort study

Abstract Background and Aims Chronic Kidney Disease (CKD) poses a significant public health challenge with substantial implications for human well-being. In China, there are significant geographical differences in the prevalence of CKD, with the highest prevalence in the southwest region, which may be related to differences in geographical environment and lifestyle. This study aimed to investigate variances in the prevalence of CKD across different altitude areas in southwest China. Method In this cross-sectional study, we used data from the China Multi-Ethnic Cohort (CMEC). CMEC was established in five provinces of Southwest China and recruited a total of 99,556 participants between 2018 and 2019. Altitude information for each participant was extracted from the Shuttle Radar Topography Mission (SRTM) (version 4) data based on their residential address. To facilitate analysis, we categorized them into groups of low altitude (0-1499 m) and high altitude (≥1500 m). CKD was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Crude and age-standardized prevalence of CKD was calculated by using R. Results A total of 92,163 participants were included in the study, and 39.7% were men. Among the current cohort, 30,904 were high-altitude residents, and 61,259 were from low altitude. Among the participants, 1636 cases of CKD were identified, corresponding to a prevalence of 1.78%. We found, the prevalence of CKD in high altitude group was higher than that in low altitude group, and the former is 2.53%, the latter is 1.40%. The age-standardized prevalence were 1.35% and 2.73% for the low and high altitude groups, respectively, and 1.38% and 2.57% for the sex-standardized groups. Conclusion In southwestern China, the prevalence of CKD was higher in the high altitude group than the low altitude group. And after adjusting for age and gender, the prevalence of CKD remained lower in the low-altitude group, and the gap slightly increased.

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1±14.1mmolmol-1; aged 64.2±9.4years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ ]=0.155; ∼2500m simulated altitude) or normoxic conditions ( =0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P>0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P=0.10; P=0.08 respectively) for a medium beneficial effect (d=0.49; d=0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Tibetans exhibit lower hemoglobin concentration and decreased heart response to hypoxia during poikilocapnia at intermediate altitude relative to Han Chinese.

High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia. We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300m (∼4327ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ /ΔPetCO2 and ΔHR/ΔPetCO2, respectively). Male Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01). These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

RESIDENCE AT HIGH ALTITUDE IS ASSOCIATED WITH LOWER CONVENTIONAL AND AMBULATORY BLOOD PRESSURE THAN LIVING AT SEA LEVEL IN THE GENERAL POPULATION OF PERU. HIGHCARE-LAPS STUDY

Objective: Acute exposure to hypoxia at high altitude (HA) leads to an increase in blood pressure (BP) in healthy individuals and in hypertensive patients. Little is known, however, about the effect of long-term HA residence on BP. Available data based on conventional BP measurements are inconsistent and no general population studies using 24-h ambulatory BP monitoring (ABPM) have been conducted. Aim of HIGHCARE-LAPS was to compare BP levels and cardiovascular risk profile among population-based samples of subjects residing in Peruvian communities living at different altitudes. BP-related data are reported in this paper. Design and method: Study participants were recruited by sex- and age-stratified random multistage cluster sampling from the general adult population residing permanently in urban areas at different altitudes in Peru (Lima, &lt;500m, Huancayo 3287m, Juliaca 3824m, Cerro de Pasco 4330m). In all participants questionnaire-based information, conventional BP (3 seated measurements with a validated oscillometric device, HEM7121 OMRON, Japan), 24-hour ambulatory BP (A&amp;D TM2430, Japan) and laboratory variables were obtained. Results: The study included 206 lowlanders and 595 highlanders. Highlanders were slightly younger, had lower BMI, oxygen saturation and prevalence of antihypertensive medication use and higher haematocrit. In highlanders all conventional and ambulatory BP values were lower and heart rate values higher than in lowlanders. Comparisons between lowlander and highlander samples and for individual sites at different altitudes are reported in the Table. The difference in 24-hour systolic BP between highlanders and lowlanders remained significant (7.2 mmHg, p&lt;0.001) in a linear multiple regression model adjusting for age, sex, BMI, 24-hour heart rate, respiratory rate, and haematocrit. These covariates were selected by LASSO method from a set also including lifestyle-related variables. Conclusions: Permanent residence at high altitude is independently associated with lower conventional and ambulatory BP levels than low altitude residence in the general population of Peru. This relationship does not seem to be explained by lifestyle differences. Mechanisms behind this difference and its impact on cardiovascular risk should be further investigated. Also, comparative studies with other highland populations with different adaptive characteristics would allow to understand better the effects of HA residence on cardiovascular health.

Chest CT Scan Features of COVID-19 in a Hospitalized High-Altitude Population

There is a lack of knowledge regarding the type of lung compromise in high-altitude residents with COVID-19. This study aims to evaluate the lung compromise in chest CT scans of high-altitude dwellers hospitalized with COVID-19. Retrospective study that took place in "Daniel Alcides Carrión" Regional Hospital, located 3,250 meters above sea level in the city of Huancayo, Perú. 464 medical charts and chest CT images of hospitalized patients with confirmed COVID-19 from January to March 2021 were reviewed. The mean age was 56 years, 63.1% of the patients were male, and 85.8% of individuals had a CORADS 5. Ground glass infiltrates were found in 93.8% of the patients; alveolar consolidations were present in 86% and were usually bilateral. Thickened septa were described in 46%, lattice pattern in 38.8%, reticular components in 39%, and the crazy paving pattern in 36.9%. Most patients (84.5%) had central and peripheral lesions; only 4% had limited peripheral compromise, and 10% solely central distribution. The left posterior basal segment was the most affected pulmonary segment in 27% of the cases, and the right basal posterior in 26%. Less affected segments were the right and left apical (14% and 13%, respectively). Lung compromise in patients with COVID-19 in this high-altitude population was severe, with mostly bilateral compromise, increased diameter of the pulmonary artery, periaortic and subaortic lymph nodes enlargement, and extensive ground glass and alveolar lesions.

The ultrasound-based cardiac output monitoring is a useful tool to define baseline hemodynamic parameters in healthy permanent residents at high altitude: results of a monocentric pilot study.

Previous studies on the cardiac data of healthy permanent residents living in high-altitude regions such as Tibet and the Andes have yielded inconsistent findings and significant disparities. These discrepancies can be mainly attributed to the invasive methods conventionally used for parameter evaluation. However, with the introduction of cutting-edge ultrasound technology, there is now an innovative approach to addressing and reconciling these variations. In this pilot study, we employed an ultrasound-based cardiac output monitoring (USCOM) device to evaluate cardiac output and related hemodynamic variables in a group of 20 healthy high-altitude Andean residents (comprising 10 men and 10 women) aged between 26 and 35 years old. The monocentric study was carried out in La Paz, Bolivia, located between at an altitude of 3,600-4,000m. A total of 60 hemodynamic measurements were evaluated, accounting for three technical replicates per subject. Our results showed strong intrasubject reproducibility and revealed important differences related to both sex and hemodynamic parameters in highlanders compared to individuals residing at sea level. We conclude that USCOM represents a highly reliable technology for performing hemodynamic measurements in high-altitude residents. Our preliminary findings underscore the need for larger studies, encompassing larger sample sizes, specifically tailored to gender considerations, and extendable to broader highland populations. These findings have special significant implications for the management of hemodynamics in intensive care and postoperative settings, warranting further comprehensive research efforts.

Development and validation of clinically Mimicable model of frostbite injury-induced chronic pain

Frostbite, a debilitating condition, significantly affects the well-being of military veterans and high-altitude residents, causing severe clinical complications such as chronic pain that markedly impacts overall quality of life. There has been a notable increase in the development of pre-clinical models for studying frostbite injury, but their suitability for pain evaluation remains limited. The major hurdle in the development of novel therapeutics for the treatment of frostbite-induced chronic pain is the unavailability of well-established preclinical models. In this study, we employed deep-frozen magnets to induce frostbite injury and conducted validation for chronic pain through assessments of face, predictive, and mechanistic validity. Behavioral assays demonstrated that animals with frostbite injury exhibited significant mechanical, thermal & cold hypersensitivity in injured rats. Further, molecular analysis indicated that frostbite injury triggered the activation of TRP channels (TRPA1 and TRPM8), microgliosis, and increased neuroinflammation in the dorsal root ganglion (DRG) and spinal cord of rats. Notably, NR2B protein expressions were significantly upregulated in the DRG of injured rats, while no changes were observed in spinal NR2B expressions. Furthermore, the administration of ibuprofen (25, 50, and 100 mg/kg, i.p.) resulted in a significant improvement in behavioral, biochemical, and molecular alterations in frostbite-injured rats. Overall, results suggested that established frostbite model effectively recapitulates face, pharmacological, and mechanistic validity, highlighting its potential for screening future treatment modalities and exploring the intricate mechanisms associated with frostbite-induced chronic pain.

Mountains of research: Where and whom high-altitude physiology has overlooked.

High altitude is a natural setting in which to study human acclimatization and adaptation. Here, I identify where and in whom high-altitude physiology research has occurred. There has been a mismatch between countries with large high-altitude populations vs. where high-altitude research has been conducted. From 1970 to 2020, 83% of high-altitude physiology research took place in just seven countries: Nepal, China, USA, Peru, India, Bolivia and Italy. Collectively, these countries account for only 35% of the global population living above 2500m. Furthermore, high-altitude physiology research has predominantly studied low-altitude residents visiting high altitude and female participants are under-represented. Accordingly, the included populations are not necessarily a proportional representation of high-altitude residents. Here, I discuss how this influences our understanding of high-altitude adaptation. Finally, I highlight past initiatives to increase diversity in high-altitude research. By identifying the broad gaps in high-altitude physiology research, I propose exciting, inclusive opportunities to study human high-altitude physiology.

Distribution Characteristics and the Influencing Factors of High Altitude Deterioration in People Working in Tibet

To comprehensively investigate and analyze the distribution characteristics of high altitude deterioration (HADT) among people working in 7 cities of Tibet Autonomous Region, to examine the relevant influencing factors, and to provide baseline survey data for further research on HADT. A self-designed questionnaire was used to conduct a self-administered survey among employees in seven prefectures or cities (Lhasa City, Qamdo City, Shigatse City, Nyingchi City, Shannan City, Naqu City, and Ngari Prefecture) in Tibet. The respondents were selected through random cluster sampling. The survey covered 21 symptoms involving 4 systems of the human body, including the respiratory, nervous, circulatory, and digestive systems. The distributive characteristics of HADT (as manifested by maladaptation to high altitude) were described and Spearman's correlation was used to examine the influencing factors of maladaptation to high altitude. A total of 3 901 respondents were included in the sample analyzed in the study, including 2 107 (54%) native Tibetans and 1 794 (46%) immigrant Han people. There were 1 994 males (51%) and 1 907 females (49%). Their age ranged from 20 to 57 years, averaging (34.45±8.11) years. The subjects lived at a high altitude for a duration of 0.5 to 54 years, averaging (19.51±13.84) years. The overall rates of maladaptation for the 21 symptoms among native Tibetans and immigrant Han people were 60.10% (26 578/44 247) and 73.20% (27 565/37 674), respectively. The maladaptation rates of the native Tibetan population for the respiratory, nervous, circulatory, and digestive systems of the human body were all lower than those of the immigrant Han population (P<0.001). There were no significant differences in the maladaptation rates of employees from different regions of Tibet (66.21% for Ngari Prefecture, 65.02% for Qamdo City, 66.67% for Lhasa City, 62.29% for Shigatse City, 65.03% for Shannan City, 64.42% for Nyingchi City, and 61.65% for Naqu City). The type of high-altitude residents (i.e., being native Tibetan or immigrant Han) was the main influencing factor for high-altitude maladaptation of the respiratory, nervous, circulatory, and digestive systems (P<0.001). According to the findings of the correlation analysis, age, type of high-altitude residents, and the duration of residence at a high altitude were associated with high-altitude maladaptation of the respiratory system, while type of high-altitude residents was the only factor associated with maladaptation of the nervous system, circulatory system, and digestive systems. Age and duration of living at at high altitude had significant effect on self-perceived dyspnea, a type of maladaptation of the respiratory system (P<0.001). Duration of high-altitude residence had significant effect on cyanotic lips or redness in the cheeks, a type of maladaptation of the circulatory system, and self-perceived loss of appetite, a type of maladaptation of the digestive system (P<0.05). More attention should be given to the HADT among employees of public institutions and enterprises who are living in Tibet Autonomous Region and immigrant Han people, in particular, should pay special attention to the protection of their respiratory, nervous, circulatory, and digestive systems.

Comparative Study of Complete Blood Count Between High-Altitude and Sea-Level Residents in West Saudi Arabia.

The reduction in oxygen partial pressure at high altitudes leads to diminished oxygen saturation in the arteries, stimulating erythropoietin production and erythropoiesis to restore appropriate oxygenation. While many studies have explored acclimatization to high altitude and its effects on complete blood count (CBC) parameters, our research uniquely examined both male and female healthy individuals, emphasizing the novelty of gender-specific observations. We analyzed 1,160 individuals in Taif (Al Hada), east Saudi Arabia, a high-altitude region, and compared them to 1,044 counterparts in Jeddah, at sea level. Our results revealed significant variations in CBC parameters, including white blood count, red blood count, hemoglobin, hematocrit, platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, reflecting the body's hypoxic response. These variations were observed in both genders, with specific differences noted between males and females. For example, NEU (neutrophils), representing the absolute count of a type of white blood cell essential in the immune system's defense, showed significant variations for males. The male results show that the variation in males between the sea level and high altitudes indicated significant p-values for all CBC parameters except NEU between at sea level (Jeddah city), whose p-value was 0.8696, and at high altitude (Taif city, Al Hada). In contrast, MONO (monocytes), another type of white blood cell involved in immune response, and RBC (red blood cells), responsible for oxygen transport, were mentioned but did not show significant variations for females. The full results for females showed significant results (P<0.0001)for BASO, HCT, HGB, MCH, MCHC, MPV, PLT, RDW, and WBC between the sea-level altitude and high altitude for females. Also, EOS and LYM showed significant P-values of 0.0002 and 0.0001, respectively, while MONO, NEU, and RBC indicated no significance between the sea-level altitude and high altitude for females. The p-values of MONO, NEU, and RBC, respectively, were0.1907, 0.1259, and 0.0677. The results for both genders combined showed significant variations of all CBC parameters (P<0.0001) between the sea-level altitude and high altitude except for MONO, NEU, and RBC, which were not significant for both males and females, with p-values of 0.1589, 0.2911, and 0.0595, respectively. All unhealthy individuals were excluded from the study with any condition that would cause significant changes in CBC parameters and would skew the results, ensuring a focus on physiological adaptations in healthy subjects. By comparing healthy individuals and examining each gender separately, this study contributes valuable insights into high-altitude acclimatization, enhancing our understanding of physiological adaptations and potentially guiding health management in such environments within the normal range.

The impact of bedroom environment on sleep quality in winter and summer in the Qinghai-Tibetan plateau

The special climatic environment at high-altitude results in common sleep problems for the local inhabitants. Analyzing the relationship between bedroom environment and sleep at high-altitude is one way to improve sleep quality. This study investigated the bedroom environment and sleep quality of plateau dwellers in the Tibetan Plateau region in winter and summer respectively. One hundred and ninety-seven healthy local residents participated in a 1-week bedroom environment and sleep monitoring, resulting in a total of 690 person nights of valid data. The results showed that high-altitude environment caused more wakefulness after sleep onset compared to the NSF recommendation. Sleep of high-altitude residents in summer was associated with more environmental parameters in the bedroom. High Ta, high RH and high CO2 in summer exacerbated the decrease in sleep efficiency and deep sleep duration, with CO2 being the more dominant environmental factor. In winter, the dry environment reduced the length of light sleep for the highlanders, leaving them more sleep deprived when indoor heating was available.