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Background: Obesity is a common chronic comorbidity of patients with COVID-19, that has been associated with disease severity and mortality. COVID-19 at high altitude seems to be associated with increased rate of ICU discharge and hospital survival than at sea-level, despite higher immune levels and inflammation. The primary aim of this study was to investigate the survival rate of critically ill obese patients with COVID-19 at altitude in comparison with overweight and normal patients. Secondary aims were to assess the predictive factors for mortality, characteristics of mechanical ventilation setting, extubation rates, and analytical parameters., Methods: This is a retrospective cohort study in critically ill patients with COVID-19 admitted to a hospital in Quito-Ecuador (2,850 m) from Apr 1, 2020, to Nov 1, 2021. Patients were cathegorized as normal weight, overweight, and obese, according to body mass index [BMI])., Results: In the final analysis 340 patients were included, of whom 154 (45%) were obese, of these 35 (22.7%) were hypertensive and 25 (16.2%) were diabetic. Mortality in obese patients (31%) was lower than in the normal weight (48%) and overweight (40%) groups, but not statistically significant (p = 0.076). At multivariable analysis, in the overall population, older age (> 50 years) was independent risk factor for mortality (B = 0.93, Wald = 14.94, OR = 2.54 95%CI = 1.58-4.07, p < 0.001). Ferritin and the neutrophil/lymphocyte ratio were independent predictors of mortality in obese patients. Overweight and obese patients required more positive and-expiratory pressure compared to normal-weight patients. In obese patients, plateau pressure and mechanical power were significantly higher, whereas extubation failure was lower as compared to overweight and normal weight., Conclusions: This preliminary study suggests that BMI was not associated with mortality in critically ill patients at high altitude. Age was associated with an increase in mortality independent of the BMI. Biomarkers such as ferritin and neutrophils/lymphocytes ratio were independent predictors of mortality in obese patients with COVID-19 at high altitude., (© 2023. The Author(s).)

Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of standardized protocols assuming similarity to severe acute respiratory syndrome (SARS-CoV-2). Understanding the histopathological and functional patterns is essential to better understand the pathophysiology of COVID-19 and then develop new therapeutic strategies. Epithelial and endothelial cell damage can result from the virus attack, thus leading to immune-mediated response. Pulmonary histopathological findings show the presence of Mallory bodies, alveolar coating cells with nuclear atypia, reactive pneumocytes, reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates, micro-abscesses, microthrombus, hyaline membrane fragments, and emphysema-like lung areas. COVID-19 patients may present different respiratory stages from silent to critical hypoxemia, are associated with the degree of pulmonary parenchymal involvement, thus yielding alteration of ventilation and perfusion relationships. This review aims to: discuss the morphological (histopathological and radiological) and functional findings of COVID-19 compared to acute interstitial pneumonia, acute respiratory distress syndrome (ARDS), and high-altitude pulmonary edema (HAPE), four entities that share common clinical traits, but have peculiar pathophysiological features with potential implications to their clinical management., Competing Interests: Competing interests None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Traveling to high altitudes for entertainment or work is sometimes associated with acute high altitude pathologies. In the past, scientific literature from the lowlander point of view was primarily based on mountain climbing. Sea level scientists developed all guidelines, but they need modifications for medical care in high altitude cities. Acute Mountain Sickness, High Altitude Pulmonary Edema, and High Altitude Cerebral Edema are medical conditions that some travelers can face. We present how to diagnose and treat acute high altitude pathologies, based on 51 years of high altitude physiology research and medical practice in hypobaric hypoxic diseases in La Paz, Bolivia (3,600 m; 11,811 ft), at the High Altitude Pulmonary and Pathology Institute (HAPPI - IPPA). These can occasionally present after flights to high altitude cities, both in lowlanders or high-altitude residents during re-entry. Acute high altitude ascent diseases can be adequately diagnosed and treated in high altitude cities following the presented guidelines. Treating these high-altitude illnesses, we had no loss of life. Traveling to a high altitude with sound medical advice should not be feared as it has many benefits. Nowadays, altitude descent and evacuation are not mandatory in populated highland cities, with adequate medical resources., (© 2022 Gustavo R. Zubieta-Calleja and Natalia Zubieta-DeUrioste, published by De Gruyter, Berlin/Boston.)

Introduction: Typical acute respiratory distress syndrome (ARDS) and severe coronavirus-19 (COVID-19) pneumonia share complex pathophysiology, a high mortality rate, and an unmet need for efficient therapeutics., Areas Covered: This review discusses the current advances in understanding the pathophysiologic mechanisms underlying typical ARDS and severe COVID-19 pneumonia, highlighting specific aspects of COVID-19-related acute hypoxemic respiratory failure that require attention. Two models have been proposed to describe the mechanisms of respiratory failure associated with typical ARDS and severe COVID-19 pneumonia., Expert Opinion: ARDS is defined as a syndrome rather than a distinct pathologic entity. There is great heterogeneity regarding the pathophysiologic, clinical, radiologic, and biological phenotypes in patients with ARDS, challenging clinicians, and scientists to discover new therapies. COVID-19 has been described as a cause of pulmonary ARDS and has reopened many questions regarding the pathophysiology of ARDS itself. COVID-19 lung injury involves direct viral epithelial cell damage and thrombotic and inflammatory reactions. There are some differences between ARDS and COVID-19 lung injury in aspects of aeration distribution, perfusion, and pulmonary vascular responses.

Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P50). In contrast to findings from in-vitro studies, we found a pH-related reduction in P50 in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Adaptation takes place not only when going to high altitude, as generally accepted, but also when going down to sea level. Immediately upon ascent to high altitude, the carotid body senses the lowering of the arterial oxygen partial pressure due to a diminished barometric pressure. High altitude adaptation is defined as having three stages: 1) acute, first 72 hours, where acute mountain sickness (CMS or polyerythrocythemia) can occur; 2) subacute, from 72 hours until the slope of the hematocrit increase with time is zero; here high altitude subacute heart disease can occur; and 3) chronic, where the hematocrit level is constant and the healthy high altitude residents achieve their optimal hematocrit. In the chronic stage, patients with CMS increase their hematocrit values to levels above that of normal individuals at the same altitude. CMS is due to a spectrum of medical disorders focused on cardiopulmonary deficiencies, often overlooked at sea level. In this study we measured hematocrit changes in one high altitude resident traveling several times between La Paz (3510 m) and Copenhagen (35 m above sea level) for the past 3 years. We have also studied the fall in hematocrit values in 2 low-landers traveling once from La Paz to Copenhagen. High altitude adaptation is altitude and time dependent, following the simplified equation: Adaptation=Time/Altitude where High altitude adaptation factor=Time at altitude (days)/Altitude in kilometers (km). A complete and optimal hematocrit adaptation is only achieved at around 40 days for a subject going from sea level to 3510 m in La Paz. The time in days required to achieve full adaptation to any altitude, ascending from sea level, can be calculated by multiplying the adaptation factor of 11.4 times the altitude in km. Descending from high altitude in La Paz to sea level in Copenhagen, the hematocrit response is a linear fall over 18 to 23 days.

Chronic mountain sickness (CMS) is a condition in which hematocrit is increased above the normal level in residents at high altitude. In this article we take issue with the "Consensus Statement On Chronic And Subacute High Altitude Diseases" of 2005 on two essential points: using a questionnaire to evaluate the symptoms of CMS to use the term "loss of adaptation" as opposed to "adaptation to disease in the hypoxic environment". We opine that CMS is rather an adaptive reaction to an underlying malfunction of some organs and no specific symptoms could be quantified. To substantiate our line of reasoning we reviewed 240 CMS cases seen at the High Altitude Pathology Institute in La Paz. Patients who had a high hematocrit (<58%) underwent pulmonary function studies in search for the cause of hypoxia: hypoventilation, diffusion alteration, shunts, and uneven ventilation-perfusion. The tests included arterial blood gas tests, chest x-rays, spirometry, hyperoxic tests, flow-volume curves, ventilation studies at rest and during exercise, ECG, exercise testing and doppler color echocardiography to assess heart structure and function. When correlated with clinical history these results revealed that CMS is practically always secondary to some type of anomaly in cardio-respiratory or renal function. Therefore, a questionnaire that tries to catalog symptoms common to many types of diseases that lead to hypoxia is flawed because it leads to incomplete diagnosis and inappropriate treatment. CMS, once again, was shown to be an adaptation of the blood transport system to a deficient organs' function due to diverse disease processes; the adaptation aimed at sustaining normoxia at the cellular level in the hypoxic environment at high altitude.

Chronic Mountain Sickness (CMS) patients have repeatedly been found to hypoventilate. Low saturation in CMS is attributed to hypoventilation. Although this observation seems logical, a further understanding of the exact mechanism of hypoxia is mandatory. An exercise study using the Bruce Protocol in CMS (n = 13) compared to normals N (n = 17), measuring ventilation (VE), pulse (P), and saturation by pulse oximetry (SaO(2)) was performed. Ventilation at rest while standing, prior to exercise in a treadmill was indeed lower in CMS (8.37 l/min compared with 9.54 l/min in N). However, during exercise, stage one through four, ventilation and cardiac frequency both remained higher than in N. In spite of this, SaO(2) gradually decreased. Although CMS subjects increased ventilation and heart rate more than N, saturation was not sustained, suggesting respiratory insufficiency. The degree of veno-arterial shunting of blood is obviously higher in the CMS patients both at rest and during exercise as judged from the SaO(2) values. The higher shunt fraction is due probably to a larger degree of trapped air in the lungs with uneven ventilation of the CMS patients. One can infer that hypoventilation at rest is an energy saving mechanism of the pneumo-dynamic and hemo-dynamic pumps. Increased ventilation would achieve an unnecessary high SaO(2) at rest (low metabolism). This is particularly true during sleep.

Pulse oximetry during breath-holding (BH) in normal residents at high altitude (3510 m) shows a typical graph pattern. Following a deep inspiration to total lung capacity (TLC) and subsequent breath-holding, a fall in oxyhemoglobin saturation (SaO(2) is observed after 16 s. The down-pointed peak in SaO(2) corresponds to the blood circulation time from the alveoli to the finger where the pulse oximeter probe is placed. This simple maneuver corroborates the measurement of circulation time by other methods. This phenomenon is even observed when the subject breathes 88% oxygen (PIO(2) = 403 mmHg for a barometric pressure of 495 mmHg). BH time is, as expected, prolonged under these circumstances. Thus the time delay of blood circulation from pulmonary alveoli to a finger is measured non-invasively. In the present study we used this method to compare the circulation time in 20 healthy male high altitude residents (Group N with a mean hematocrit of 50%) and 17 chronic mountain sickness patients (Group CMS with a mean hematocrit of 69%). In the two study groups, the mean circulation time amounted to 15.94 +/-2.57 s (SD) and to 15.66 +/-2.74 s, respectively. The minimal difference was not significant. We conclude that the CMS patients adapted their oxygen transport rate to the rise in hematocrit and blood viscosity.

This report describes the historical development in the clinical application of chemical variables for the interpretation of acid-base disturbances. The pH concept was already introduced in 1909. Following World War II, disagreements concerning the definition of acids and bases occurred, and since then two strategies have been competing. Danish scientists in 1923 defined an acid as a substance able to give off a proton at a given pH, and a base as a substance that could bind a proton, whereas the North American Singer-Hasting school in 1948 defined acids as strong non-buffer anions and bases as non-buffer cations. As a consequence of this last definition, electrolyte disturbances were mixed up with real acid-base disorders and the variable, strong ion difference (SID), was introduced as a measure of non-respiratory acid-base disturbances. However, the SID concept is only an empirical approximation. In contrast, the Astrup/Siggaard-Andersen school of scientists, using computer strategies and the Acid-base Chart, has made diagnosis of acid-base disorders possible at a glance on the Chart, when the data are considered in context with the clinical development. Siggaard-Andersen introduced Base Excess (BE) or Standard Base Excess (SBE) in the extracellular fluid volume (ECF), extended to include the red cell volume (eECF), as a measure of metabolic acid-base disturbances and recently replaced it by the term Concentration of Titratable Hydrogen Ion (ctH). These two concepts (SBE and ctH) represent the same concentration difference, but with opposite signs. Three charts modified from the Siggaard-Andersen Acid-Base Chart are presented for use at low, medium and high altitudes of 2500 m, 3500 m, and 4000 m, respectively. In this context, the authors suggest the use of Titratable Hydrogen Ion concentration Difference (THID) in the extended extracellular fluid volume, finding it efficient and better than any other determination of the metabolic component in acid-base disturbances. The essential variable is the hydrogen ion.