Fisiología respiratoria. Neumología de altura: saturación de oxígeno, edema pulmonar y pruebas de función pulmonar / Respiratory physiology - High -altitude pneumology: oxygen saturation, pulmonary edema and pulmonary function tests

En las alturas, sobre todo a 2500 metros sobre el nivel del mar, la cantidad absoluta de oxígeno va decreciendo y por lo tanto la cantidad disponible para el intercambio gaseoso disminuye, produciéndose una vasoconstricción hipóxica pulmonar (VHP). La VHP asociada a la hipoxia hipobárica de la altura produce un aumento de la presión pulmonar que es mayor en los lactantes y a mayores alturas. No hay valores únicos de saturación de oxígeno (SatO2) en la altura, porque ésta va disminuyendo según el mayor nivel de altura, aumenta con la edad, y la brecha entre la vigilia y sueño es grande (sobre todo en los primeros meses de vida). El 25% de los niños sanos que viven en altura tienen valores de SatO2 significativamente menores que el 75% restante. Los valores normales de los índices de apnea/hipopnea son distintos a los de nivel del mar. El edema pulmonar de las alturas es una patología frecuente, que se produce por un incremento desproporcionado en la VHP reflejando una hiperactividad del lecho vascular pulmonar ante la exposición aguda a la hipoxia hipobárica. Tiene cuatro fenotipos, es infrecuente en menores de 5 años y rara vez es mortal, la sospecha clínica y el manejo oportuno con oxigeno es la clave. Finalmente, en la altura los valores normales de la función pulmonar de la espirometría, oscilometría de impulso y capacidad de difusión son distintos que a nivel del mar.

At high altitude, especially > 2,500 meters above sea level, the absolute amount of oxygen decreases and therefore the amount available for gas exchange decreases, producing hypoxic pulmonary vasoconstriction (VHP). VHP associated with high-altitude hypobaric hypoxia produces an increase in pulmonary pressure that is greater in infants and at higher altitudes. There are no single values of oxygen saturation (SatO2) at altitude, because it decreases with the highest level of altitude, increases with age, and the gap between wakefulness and sleep is large (especially in the first months of life). Around 25% of healthy children living at altitude have SatO2 values significantly lower than the remaining 75%. The normal values of the apnea/hypopnea indices are different from those at sea level. High altitude pulmonary edema is a frequent pathology that is produced by a disproportionate increase in VHP reflecting hyperactivity of the pulmonary vascular bed in the face of acute exposure to hypobaric hypoxia, it has four phenotypes, it is uncommon in children under 5 years of age, and it is rarely fatal, the clinical suspicion and timely management with oxygen is the key. Finally, at high altitude, the normal values of lung function from spirometry, impulse oscillometry, and diffusing capacity are different from those at sea level.

Impact of Moderate Altitude on Lung Diseases and Risk of High Altitude Illnesses

ABSTRACT A large world population resides at moderate altitudes. In the Valley of Mexico (2240 m above sea level) and for patients with respiratory diseases implies more hypoxemia and clinical deterioration, unless supplementary oxygen is prescribed or patients move to sea level. A group of individuals residing at 2500 or more meters above sea level may develop acute or chronic mountain disease but those conditions may develop at moderate altitudes although less frequently and in predisposed individuals. In the valley of México, at 2200 m above sea level, re-entry pulmonary edema has been reported. The frequency of other altitude-related diseases at moderate altitude, described in skiing resorts, remains to be known in visitors to Mexico City and other cities at similar or higher altitudes. Residents of moderate altitudes inhale deeply the city's air with all pollutants and require more often supplementary oxygen.

Mechanisms and therapeutic drugs of high-altitude lung diseases / 药学实践杂志

The heavily harsh plateau environment including low pressure, hypoxia, cold, dryness and strong ultraviolet radiation, seriously threatens the physical and mental health of those who quickly enter the plateau area. Lungs are the sensitive organs for high altitude injury. High-altitude lung diseases include the acute high-altitude lung disease (i.e., high-altitude pulmonary edema), the chronic high-altitude lung disease (i.e., high-altitude pulmonary artery hypertension) and the high-altitude de-adapted reaction. This review summarizes the pathogenic mechanisms and the main therapeutic drugs of high-altitude lung diseases based on the recent research. Moreover, the related formulations and administration routes are also reviewed here. It will provide support and counsel for the diagnosis and treatment of high-altitude lung diseases.

Animal models of acute plateau disease / 中国药理学通报

Acute plateau disease refers to a variety of physiological and pathological reactions produced by the body in a short period of time after rapidly advancing into the high-pressure and low-oxygen plateau area with an altitude above 2 500 meters, mainly including acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (H A C E), which seriously affects the health of people in the acute plateau and even threats their lives. The establishment of an animal model of acute plateau disease with good reproducibility and a sound evaluation system are the basis of the research on acute plateau disease. Acute plateau disease is mainly caused by the low oxygen conditions on the plateau, so the animal model of acute plateau disease can be established in plateau environment simulation cabin or plateau field, simple breeding or animal treadmill assisted sports training. The indicators that indicate the success of the model establishment are commonly used blood gas, inflammation factors, organizational water content and pathological section. In this article, the animal models of acute plateau disease established in recent years are reviewed from the aspects of modeling environment, modeling methods and evaluation indicators.

Un ejemplo de respuesta adaptativa integrada: la aclimatación humana a la altitud / An example of integrated adaptive response: human acclimatization to altitude

Se describen las respuestas fisiológicas que el ser humano desarrolla en respuesta a la exposición a la altitud geográfica. Se describen no sólo las alteraciones debidas a una mala coordinación de los ajustes fisiológicos desencadenados durante la aclimatación a la altura sino también sus manifestaciones clínicas más relevantes. Se detallan los mecanismos moleculares subyacentes a tales respuestas y cómo su mejor conocimiento puede permitir aplicar la exposición intermitente a hipoxia como una herramienta útil para la resolución o alivio de determinadas alteraciones y patologías.

We depict the physiological responses developed by the human body in response to the exposure to geographic altitude. The main alterations due to a noncoordinated setup of the physiological adjustments triggered during the acclimatization at altitude are also described, as its most relevant clinical manifestations. The molecular mechanisms underlying such responses are detailed, and how a better knowledge of these processes can allow us to apply intermittent exposure to hypoxia programs as a useful tool for the resolution or relief of certain disorders and pathologies.

Protective effect of the Potentilla anserina polysaccharide on high altitude cerebral edema and high altitude pulmonary edema in rats / 国际药学研究杂志

Objective: To test the anti-plateau hypoxia effect of Potentilla anserina polysaccharide(PAP), Cynomorium songarieum Rupr. polysaccharide(SCRP), Sphallerocarpus gracilis polysaccharide(SGP)and Lilium brownii polysaccharide(LP), and then investigate the protective effect of most effective polysaccharide on the high altitude cerebral edema(HACE)and high altitude pulmonary edema(HAPE)in rats. Methods: PAP, CSRP, SGP and LP were prepared by the water extraction-alcohol precipitation method. The normobaric hypoxia test and acute hypoxia test were performed to find out the polysaccharide with the best anti-hypoxia effect and the related dose-dependent effect in mice. A large hypobaric hypoxia chamber stimulating 8000 m altitude was used to investigate pathological changes and water contents in rat brain and lung tissue before and after hypoxia, and the concerned oxidative stress and inflammation related parameters were also measured. The protective effect of PAP on the high altitude cerebral and pulmonary edema was evaluated by the rat model experiments. Results: PAP showed the best and dose-dependent anti-hypoxia effect among the four polysaccharides. The water content in brain and lung tissues of rats increased obviously in the hypoxia model(HM)group, and the brain tissue cell hierarchical fuzzy, lung tissue congestion and edema as well as the heavy inflammatory cell infiltration, widening of alveolar interval and thickening of alveolar wall were also found in the HM group. The enzymatic activity of SOD was notablely depressed, while both the MDA and IL-1β contents in brain and lung tissues remarkably increased(P<0.01)in the HM group. Com- pared with the HM group, the water content in the rat brain and lung tissues significantly decreased in each of the different dose PAP groups(P<0.05 or P<0.01), and the inflammatory cell infiltration, alveolar interval, and thickness of alveolar wall all notabely decreased in the HM group. Furthermore, the enzymatic activity of SOD increased, while both the MDA and IL-1β contents decreased, all significantly in the PAP groups than in the HM group(P<0.05 or P<0.01). Conclusion: PAP showed a good anti-hypoxia effect and effectively inhibited HACE and HAPE to exert a certain protective effect in a rat model.

Differential diagnosis of high altitude pulmonary edema and COVID-19 with computed tomography feature / 生物医学工程学杂志

To investigate the computed tomography (CT) characteristics and differential diagnosis of high altitude pulmonary edema (HAPE) and COVID-19, CT findings of 52 cases of HAPE confirmed in Medical Station of Sanshili Barracks, PLA 950 Hospital from May 1, 2020 to May 30, 2020 were collected retrospectively. The size, number, location, distribution, density and morphology of the pulmonary lesions of these CT data were analyzed and compared with some already existed COVID-19 CT images which come from two files, "Radiological diagnosis of COVID-19: expert recommendation from the Chinese Society of Radiology (First edition)" and "A rapid advice guideline for the diagnosis and treatment of 2019 novel corona-virus (2019-nCoV) infected pneumonia (standard version)". The simple or multiple ground-glass opacity (GGO) lesions are located both in the HAPE and COVID-19 at the early stage, but only the thickening of interlobular septa, called "crazy paving pattern" belongs to COVID-19. At the next period, some increased cloudy shadows are located in HAPE, while lesions of COVID-19 are more likely to develop parallel to the direction of the pleura, and some of the lesions show the bronchial inflation. At the most serious stage, both the shadows in HAPE and COVID-19 become white, but the lesions of HAPE in the right lung are more serious than that of left lung. In summary, some cloudy shadows are the feature of HAPE CT image, and "crazy paving pattern" and "pleural parallel sign" belong to the COVID-19 CT, which can be used for differential diagnosis.

Changes in corneal thickness in patients with high-altitude pulmonary edema after systemic oxygen therapy

Purpose: High-altitude pulmonary edema (HAPO) is an acute medical emergency occurring typically in lowlanders, who ascend rapidly to heights of 3000 m or more. It presents with marked dyspnea on exertion, fatigue with minimal-to-moderate effort, prolonged recovery time, and dry cough with manifestations of cyanosis, tachycardia, tachypnea, and temperature which generally does not increase beyond 38.5°C. The condition may be fatal if not treated in time with supplemental oxygen or hyperbaric oxygen or rapid descent to lower altitude. There is paucity in literature on changes in corneal thickness in HAPO. The effect of continued oxygen therapy on corneal thickness has also not been studied in detail. Hence, this study was conducted at high altitude among physician-confirmed HAPO cases. Methods: A case–control study was conducted at an altitude of 11,400 feet. Cases were patients suffering from HAPO and controls were patients admitted in hospital for low back pain, fractures, and minor surgical procedures. Central corneal thickness (CCT) was measured with an ultrasound pachymeter on day 1 of hospitalization and every day of hospital stay. Systemic oxygen concentration was also measured daily. Results: There was no statistically significant difference in corneal thickness between two groups at the onset of illness, but a significant decrease in CCT was found in both right and left eyes in HAPO cases when oxygen levels were increased by giving supplemental oxygen. Hierarchical modeling showed a decrease in 1.3 ?m in CCT with one unit increase in oxygen mmHg in cases. Conclusion: The findings of statistically insignificant difference in CCT between HAPO cases and controls and a decrease in CCT in HAPO cases on being treated with systemic oxygenation are points to ponder about.

Occurrence of high altitude cerebral edema (hace) and high altitude pulmonary edema (HAPO) simultaneously at 12000 ft: a rare phenomen

High altitude cerebral edema (HACE) and High altitude pulmonary edema (HAPO) are the most dreaded complications related to high altitude. Authors managed a case of HACE and HAPO simultaneously set at unusually low height (1200 ft) in a patient. The altitude was not too much to develop these comorbidities as studied earlier. Relationship with altitude was immaterial in our case. However, rapid ascent without proper acclimatisation, young and tender age, male sex and smoking were associated contributing factors. He was managed with standard protocol and descent to lower altitude.

High altitude pulmonary edema in children / 中国小儿急救医学

High altitude pulmonary edema(HAPE) occurs usually in plateau of low oxygen environ-ment,which is a non-cardiogenic pulmonary edema characterized by hypoxic pulmonary hypertension. Children HAPE has an acute onset and rapid progression.It always happens during the first 1 to 3 days ente-ring the plateau and has clear trigger factors such as upper respiratory tract infection,many physical labour and coldness. The pathogenesis is related with hypoxic pulmonary artery contraction,pulmonary epithelial dysfunction,inflammatory response,water transport imbalance in pulmonary epithelium,and genetic polymor-phism.The early symptoms include crying,breath holding,and dry cough. With the disease progressing, patients will present shortness of breath and expectoration of pink foam sputum,and even be unconscious, which results from cerebral edema and is mortal.The treatments of HAPE include bed rest,oxygen therapy, reduction of pulmonary arterial hypertension,hormone,diuresis,prevention of infection and so on.

Present Analysis of Off-indication Drug Use of Drugs for High Altitude Pulmonary Edema / 中国药房

OBJECTIVE:To analyze the situation of off-indication drug use of drugs for high altitude pulmonary edema (HAPE),and to provide reference for promoting rational drug use in medical institutions of plateau area and establishing relevant management process. METHODS:By taking"HAPE""treatment""Altitude illness""Treatment"as keywords,retrieving from CNKI,PubMed,Embase database during build up to Sept. 2017,drugs for HAPE were screened and extracted after reading the literatures. Drug package inserts of listed preparations were compared,summarized and analyzed. RESULTS:Drugs for HAPE in literatures were screened,and 16 kinds of drugs were summarized finally as nifedipine,sildenafil,tadalafil,aminophylline,etc. Indication of HAPE was not found in drug package inserts of those listed preparations. CONCLUSIONS:At present,there is a universal phenomenon of off-indication drug use of drugs for HAPE,and it is imminent to regulate the management of off-label drug use in the hospital. It is suggested to improve the off-label drug use management flow of drugs for HAPE so as to promote rational drug use.

Application of lung ultrasound examination in severe high altitude pulmonary edema / 中华危重病急救医学

Objective To investigate the application value of lung ultrasonic on severe high altitude pulmonary edema.Methods A prospective, single-blind, case-control study was conducted. Sixty patients with severe high altitude pulmonary edema admitted to Qinghai University Affiliated Hospital from February 2015 to May 2017 were enrolled. The patients were divided into 2500-3000 m group, 3000-3500 m group and 3500-4200 m group according to different altitudes,with 20 patients in each group. The acute physiology and chronic health evaluationⅡ(APACHEⅡ) score was recorded before and 12 hours and 24 hours after treatment. The arterial partial pressure of oxygen (PaO2) was determined by blood gas analysis, and the oxygenation index (PaO2/FiO2) was calculated. Bedside ultrasound scanning was used to determine B line number and pulmonary artery pressure (PAP), and B line score was calculated to reflect lung water content. The correlation between B line score and PaO2/FiO2, PAP and APACHEⅡ scores at each time point was analyzed by Pearson correlation analysis.Results None of 60 patients died or exited, all of them were enrolled in the final analysis. There was no significant difference in PaO2/FiO2, PAP, APACHEⅡ score or B line score among different altitudes groups (allP > 0.05). Repeated measurement variance analysis showed that the effects of different altitudes on PaO2/FiO2, PAP, APACHEⅡ score and B line score were not statistically significant (F value was 0.312, 0.014, 1.098, 0.236, andP value was 0.340, 0.791, 0.733, and 0.986, respectively). The PaO2/FiO2, PAP, APACHEⅡ score and B line score in all groups were improved obviously from 12 hours after treatment, and the improvements at 24 hours were more than those at 12 hours (allP < 0.05). Repeated measurement variance analysis showed that the effect at different time points on PaO2/FiO2, PAP, APACHEⅡ score and B line score was statistically significant (F value was 1844.270, 121.690, 1173.175, 19426.968, allP < 0.001). The interaction effects of different altitudes and different time points on PaO2/FiO2, PAP, APACHEⅡ score and B line score were not statistically significant (F value was 0.304, 0.404, 1.172, 1.403, andP value was 0.875, 0.805, 0.327, and 0.591, respectively). Pearson correlation analysis showed that there was a significant negative correlation between B line score and PaO2/FiO2 before and after treatment (r value was -0.579, -0.522, and -0.386, allP < 0.01), indicating that the more the B line, the more severe the pulmonary edema, and the worse the oxygenation; with the decrease in B line after treatment, the pulmonary edema was gradually alleviated, and oxygenation was gradually improved. There was a significant positive correlation between B line score and APACHEⅡ score before and 24 hours after treatment (r value was 0.484 and 0.536, bothP < 0.01), indicating that the more the B line, the more severe the patient; with the decrease in B line after treatment, the patient's condition improved after treatment. There was only a weak correlation between B line score and PAP at 24 hours after treatment (r = 0.317,P = 0.014), indicating that PAP was not a sensitive indicator in the degree of pulmonary edema in patients.Conclusions The more the B line in patients with severe high altitude pulmonary edema,the more severe of the pulmonary edema, and the more severe of the patient. There was no significant correlation between the B line score and PAP. Pulmonary ultrasonography can still be used not only in the plain and low elevation areas, but in the high altitude areas, as a reliable method to evaluate the severity of pulmonary edema.

The protective effect of rosiglitazone on the rats with high altitude pulmonary edema / 中华急诊医学杂志

Objective To investigate the protective effect of rosiglitazone on the rats with high altitude pulmonary edema.Methods Thirty-six SD rats were randomly (random number) divided into 6 groups (n =6 each):control group (Control),hypobaric hypoxia model group (HH),rosiglitazone groups (RSG) which were administered with 3 different doses [RSG-L:5 mg/ (kg · d),RSG-M:10 mg/ (kg·d),RSG-H:20 mg/ (kg· d)],dexamethasone group [Dex,4 mg/ (kg· d)].Rats were injected intraperitoneally with different doses of rosiglitazone (RSG),dexamethasone (Dex) or vehicle (Control and HH) for 3 days before placed in simulated altitude of 6 000 m hypobaric hypoxia animal chamber where the temperature and pressure were constant.After 72 h in the chamber,each rat was anesthetized.The water content of lung was determined with wet/dry weight ratio.Bronchoalveolar lavage fluid was measured by bradford method.The contents of GSH was measured by micro-ezymed labeled method.The contents of MDA was measured by TBA method.The enzymatic activities of SOD was measured by WST-1 method.The changes of the TNF-α,IL-6 and IL-10 in serum were determined by ELISA.Light microscope was used to observe the pathological changes of lung tissue.Results Compared with Control group,the wet/dry weight ratio of lung (5.08 ± 0.24) and total protein content of BALF (351.06 ± 44.55) μg/mL increased significantly (P ＜ 0.01) in HH group.There were red blood cells in the alveolar and interstitium,pink fluid exudation in the alveolar,the alveolar septum enhancement,and a large number of inflammatory cell infiltration;the SOD activity (10.65 ± 0.94) U/mgprot and the content of GSH (1.63 ±0.20) μmol/gprot in lung tissue were significantly decreased (P ＜ 0.01),the contents of MDA (2.1 5 ± 0.18) nmol/mgprot increased significantly (P ＜ 0.01),TNF-o (56.92 ± 2.87) pg/mL and IL-6 (217.80 ±48.01) pg/mL levels in serum were significantly increased (P ＜0.01),and IL-10 (76.85 ± 16.72) pg/mL level decreased (P ＜ 0.05).Compared with the HH group,the wet/dry ratio of lung and total protein content of BALF in different doses of rosiglitazone group significantly decreased (P ＜ 0.01),the pathological changes of the lung tissue was significantly improved,SOD activity and the content of GSH in lung tissue was significantly increased (P ＜ 0.01),the content of MDA decreased (P ＜ 0.01),The levels of TNF-α and IL-6 in serum were significantly decreased (P ＜ 0.01),while the IL-10 level was significantly increased (P ＜ 0.01).Conclusion Rosiglitazone could protect the high altitude pulmonary edema by alleviating the oxidative stress and inflammatory response.

Pathogenesis, prevention and treatment of high altitude pulmonary edema: Research advances / 国际药学研究杂志

High altitude pulmonary edema is a fatal acute non-cardiogenic pulmonary edema caused by the environment of low pressure and hypoxia, when people have their fast access to the plateau general elevation≥2500 m . It is a serious threat to human health. Pathogenesis of high altitude pulmonary edema is still not entirely clear and may be due to ventilation/perfusion imbalance, chemical receptors changes, water channel protein decreased, pulmonary microvascular changes and genes. Treatment of high altitude pulmonary edema should be mainly far away from the environment of low pressure and hypoxia as soon as possible, and comply with oxygen or take diuretics, hormones and other drugs reducing pulmonary artery pressure. This article describes the epidemiological characteristics, the studies of the pathogenesis and the methods of prevention and treatment of high-altitude pulmonary edema in order to provide a reference for the relevant medical staff and people engaged in activities plateau.

Pathogenesis,prevention and treatment of high altitude pulmonary edema:research advances / 国际药学研究杂志

High altitude pulmonary edema is a fatal acute non-cardiogenic pulmonary edema caused by the environment of low pressure and hypoxia,when people have their fast access to the plateau (general elevation≥2500 m). It is a serious threat to human health. Pathogenesis of high altitude pulmonary edema is still not entirely clear and may be due to ventilation/perfusion imbalance, chemical receptors changes, water channel protein decreased, pulmonary microvascular changes and genes. Treatment of high altitude pulmonary edema should be mainly far away from the environment of low pressure and hypoxia as soon as possible, and comply with ox?ygen or take diuretics, hormones and other drugs reducing pulmonary artery pressure. This article describes the epidemiological charac?teristics,the studies of the pathogenesis and the methods of prevention and treatment of high-altitude pulmonary edema in order to pro?vide a reference for the relevant medical staff and people engaged in activities plateau.

Comorbid cerebral and pulmonary edema at 7010 m/23000 ft: an extreme altitude perspective.

High Altitude Cerebral Edema (HACE) and High Altitude Pulmonary Edema (HAPE) are two dreaded altitude emergencies which can independently lead to complications. Two cases of suspected comorbid HACE and HAPE were managed at 5800 m/19000 ft in Karakoram Himalayas. Altitude acclimatization, purported to prevent high altitude illness, may not be protective. Comorbid HACE and HAPE at extreme altitude may present atypically necessitating high index of suspicion and prompt clinical decision making in challenging situations. One man HAPE bag/PHC is an excellent temporary measure in cases of delayed descent/evacuation. Due attention to extreme altitude emergencies is required in view of increased recreational, scientific and military activities at extreme altitude.

Research Progress in the Effect of Anti-high Altitude Plateau Pulmonary Edema of Rhodiola Capsules / 中国药师

Rhodiola capsules show the resistant effects on ischemia, anoxia, radiation, fatigue and virus and so on, and can im-prove the body immune function to relief the plateau symptoms such as fatigue and cerebral hypoxia. The influence mechanism of rhodi-ola capsules in the effect of anti-high altitude pulmonary edema was summarized in the paper.

Common High Altitudes Illnesses a Primer for Healthcare Provider.

Exposure to high altitude imposes significant strain on cardiopulmonary system and the brain. As a consequence, sojourners to high altitude frequently experience sleep disturbances, often reporting restless and sleepless nights. At altitudes above 3,000 meters (9,800 ft) almost all healthy subjects develop periodic breathing especially during NREM sleep. Sleep architecture gradually improves with increased NREM and REM sleep despite persistence of periodic breathing. The primary reason for periodic breathing at high altitude is a hypoxic-induced increase in chemoreceptor sensitivity to changes in PaCO2 – both above and below eupnea, leading to periods of apnea and hyperpnea. Acetazolamide improves sleep by reducing the periodic breathing through development of metabolic acidosis and induced hyperventilation decreasing the plant gain and widening the PCO2 reserve. This widening of the PCO2 reserve impedes development of central apneas during sleep. Benzodiazepines and GABA receptor antagonist such as zolpidem improve sleep without affecting breathing pattern or cognitive functions.

The relationship between rs1008438 polymorphism of HSP70 gene and high altitude pulmonary edema / 重庆医学

Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of rs1008438 in HSP70 promoter and the susceptibility of high altitude pulmonary edema (HAPE) .Methods The PCR‐DNA sequencing method was used to analyze gene distribution of rs1008438 in 100 HAPE patients and 200 healthy people ,and the relationship between dif‐ferent genotypes and HAPE was evaluated .Meanwhile ,HSP70 protein in cytoplasm and nuclei of white blood cells were detected by ELISA in patientgroup and healthy group .TNF‐α,IL‐1β and IL‐6 levels were analyzed by protein chip technology and EVI‐DENCE180 automatic chip reader .Results The TT ,GT ,and GG genetype frequencies of rs1008438 in HAPE patients and healthy controls were 76 .0% ,20 .0% ,4 .0% ,and 93 .0% ,6 .5% ,0 .5% ,respectively .The TT genetype frequency in HAPE patients was significantly lower than that in healthy control(P<0 .05) .The HAPE incidence rate in GT/GG genetype was 4 .195 times higher than that in TT genetype ,and the allele G can also significantly increase the prevalence of HAPE compared to T allele (OR=4 .178) .ELISA showed that HSP70 were higher in HAPE group of all genotypes than those in healthy control of the same geno‐type .And the nuclei/cytoplasm ratio of HSP70 in TT genotype was higher than that in GT/GG genotype .Protein chip showed that the levels of TNF α,IL‐1β,and IL‐6 in HAPE group were significantly higher than those in healthy control .Conclusion The poly‐morphism of rs1008438 is related to susceptibility of HAPE .Mutate genetype may change the promoter activity and increase the ex‐pression of HSP70 ,which induced HAPE .

Hipertensión y edema pulmonar de altura: Rol de la disfunción endotelial y de la programación fetal / Pulmonary hypertensión and lung edema at high altitude: Role of endothelial dysfunction and fetal programming

La altura constituye un fascinante laboratorio natural para la investigación médica. Si bien al principio el objetivo de la investigación en la altura fue la comprensión de los mecanismos de adaptación del organismo a la hipoxia y la búsqueda de tratamientos para las enfermedades relacionadas con la altura, durante la última década el alcance de esta investigación se ha ampliado considerablemente. Dos importantes observaciones han generado las bases para el crecimiento del alcance científico de la investigación en la altura. Primero, el hecho de que el edema pulmonar agudo de la altura constituye un modelo único para estudiar los mecanismos fundamentales de la hipertensión pulmonar y el edema pulmonar en humanos. Segundo, que la hipoxia ambiental asociada con la exposición a la altura facilita la detección de disfunción vascular pulmonar y sistémica en un estadio precoz. Aquí revisaremos los estudios que, capitalizando estas observaciones, han llevado a la descripción de nuevos mecanismos subyacentes del edema pulmonar y de la hipertensión pulmonar, y a la primera demostración directa de la existencia de una programación fetal sobre la disfunción vascular en humanos.

High altitude constitutes an exciting natural laboratory for medical research. While initially, the aim of high-altitude research was to understand the adaptation of the organism to hypoxia and find treatments for altitude-related diseases, over the past decade or so, the scope of this research has broadened considerably. Two important observations led to the foundation for the broadening of the scientific scope of high-altitude research. First, high-altitude pulmonary edema (HAPE) represents a unique model which allows studying fundamental mechanisms of pulmonary hypertension and lung edema in humans. Secondly, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary and systemic vascular dysfunction at an early stage. Here, we review studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning lung edema and pulmonary hypertension and to the first direct demonstration of fetal programming of vascular dysfunction in humans.