Highlights • We aimed to assess lung fluid balance before and after gradual ascent to 5,150 m. • Lung diffusing capacity increased from sea-level to high-altitude; • Alveolar-capillary membrane ...conductance also increased from sea-level to high-altitude; • Gradual non-significant reduction in ultrasound lung comets with altitude; • Evidence of a decrease in interstitial lung fluid relative to at sea-level with gradual ascent to high-altitude.
Background & objectives: High-altitude pulmonary oedema (HAPE) continues to challenge the healthcare providers at remote, resource-constrained settings. High-altitude terrain itself precludes ...convenience of resources. This study was conducted to evaluate the rise in peripheral capillary saturation of oxygen (SpO2) by the use of a partial rebreathing mask (PRM) in comparison to Hudson's mask among patients with HAPE.
Methods: This was a single-centre, randomized crossover study to determine the efficiency of PRM in comparison to Hudson's mask. A total of 88 patients with HAPE referred to a secondary healthcare facility at an altitude of 11,500 feet from January to October 2013 were studied. A crossover after adequate wash-out on both modalities was conducted for first two days of hospital admission. All patients with HAPE were managed with bed rest and stand-alone oxygen supplementation with no adjuvant pharmacotherapy.
Results: The mean SpO2on ambient air on arrival was 66.92±10.8 per cent for all patients with HAPE. Higher SpO2values were achieved with PRM in comparison to Hudson's mask on day one (86.08±5.15 vs. 77.23±9.09%) and day two (89.94±2.96 vs. 83.39±5.93%). The difference was more pronounced on day one as compared to day two.
Interpretation & conclusions: Mean SpO2values were found to be significantly higher among HAPE patients using PRM compared to those on Hudson's mask. Further studies to understand the translation of this incremental response in SpO2to clinical benefits (recovery times, mortality rates and hospital stay) need to be undertaken.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
EGLN1 encoding HIF (hypoxia-inducible factor)-prolyl hydroxylase 2 plays a pivotal role in the HIF pathway and has emerged as one of the most intriguing genes with respect to physiology at HA (high ...altitude). EGLN1, being an actual oxygen sensor, appears to have a potential role in the functional adaptation to the hypobaric hypoxic environment. In the present study, we screened 30 polymorphisms of EGLN1, evaluated its gene expression and performed association analyses. In addition, the role of allelic variants in altering TF (transcription factor)-binding sites and consequently the replacement of TFs at these loci was also investigated. The study was performed in 250 HAPE-p HAPE (HA pulmonary oedema)-patients, 210 HAPE-f (HAPE-free controls) and 430 HLs (healthy Ladakhi highland natives). The genotypes of seven polymorphisms, rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252, differed significantly between HAPE-p and HAPE-f (P<0.008). The genotypes AA, TT, AA, GG, CC, AA and GG of rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252, prevalent in HAPE-p, were identified as risk genotypes and their counterpart homozygotes, prevalent in HLs, were identified as protective. EGLN1 expression was up-regulated 4.56-fold in HAPE-p (P=0.0084). The risk genotypes, their haplotypes and interacting genotypes were associated with up-regulated EGLN1 expression (P<0.05). Similarly, regression analysis showed that the risk alleles and susceptible haplotypes were associated with decreased SaO2 (arterial oxygen saturation) levels in the three groups. The significant inverse correlation of SaO2 levels with PASP (pulmonary artery systolic pressure) and EGLN1 expression and the association of these polymorphisms with SaO2 levels and EGLN1 expression contributed to uncovering the molecular mechanism underlying hypobaric hypoxic adaptation and maladaptation.
Almost one mountain trekker or climber out of two develops several symptoms of high altitude illness after a rapid ascent (> 300 m/day) to an altitude above 4000 m. Individual susceptibility is the ...most important determinant for the occurrence of high altitude pulmonary oedema (HAPE). Symptoms associated with HAPE are incapacitating fatigue, chest tightness, dyspnoea at the slightest effort, orthopnoea, and cough with due to haemoptysis in an advanced stage of the disease pink frothy sputum. The hallmark of HAPE is an excessively elevated pulmonary artery pressure (mean pressures of 35 and 55 mm Hg), which precedes the development of pulmonary oedema. Elevated pulmonary capillary pressure and protein- as well as red blood cell-rich oedema fluid without signs of inflammation in its early stage are characteristic findings. Furthermore, decreased fluid clearance from the alveoli may contribute to this non-cardiogenic pulmonary oedema. Immediate descent or supplemental oxygen and nifedipine are recommended until descent is possible. Susceptible individuals can prevent HAPE by slow ascent: an average gain of altitude not exceeding 400 m/day above an altitude of 2500 m. If progressive high altitude acclimatization is not possible, a prophylaxis with nifedipine should be recommended.
Mountain neurology Dekker, Marieke Cornelia Johanna; Wilson, Mark H; Howlett, William Patrick
Practical neurology
19, Številka:
5
Journal Article
Recenzirano
Mountain climbers may develop specific illnesses that largely depend on the altitude reached and the rate of ascent. The popularity of travel to high altitude destinations, extreme tourist activities ...and mountain climbing means that neurologists in low-altitude countries are increasingly likely to encounter neurological problems and disorders in people exposed to high altitude. Additionally, they may have to advise patients with pre-existing neurological conditions on the risks of ascent to altitude. This article focuses on neurological-related high-altitude illnesses: acute mountain sickness and high-altitude cerebral oedema, as well as high-altitude retinopathy and other neurological disorders. This overview combines current understood pathogenesis with the experience of managing altitude-related illness at the foot of Mount Kilimanjaro in northern Tanzania, the tallest free-standing mountain in the world.
Increased extravascular lung water (EVLW) is seen as B-lines on chest ultrasonography. In lowlanders ascending to altitude the time course, relationship with the patient's clinical status and factors ...affecting B-lines are still unclear. The aim was to monitor B-lines, clinical status and N-terminal B-type natriuretic peptide (NT-proBNP) during exposure to high altitude.
Chest ultrasonography, blood samples, cardiovascular parameters, and signs and symptoms of high altitude pulmonary oedema (HAPE) were prospectively assessed in 19 participants at baseline and after ascent to 3830 m (9, 24, 48, 72 h, and 8 days) by blinded investigators. Potential confounding factors (e.g. altitude variations, physical effort) were minimized. Generalized estimating equations were used to analyse factors associated with B-lines. B-lines changed with exposure to altitude (P = 0.006) in a parabolic-like pattern within the first 72 h; 10 of 18 participants (55.6%) had >5 B-lines at 24 h. B-lines were correlated with the number of signs and symptoms (partial coefficient = 0.372, P = 0.001). B-lines were associated with time (P = 0.038), sex (P = 0.013), and SpO2 (P = 0.042), but not with NT-proBNP (P = 0.546). The participant with a clinical diagnosis of HAPE had 23 B-lines.
B-lines during exposure to altitude seem to reflect the individual response to hypobaric hypoxia and represent clinically relevant alterations at high altitude, also in patients with HAPE. Similar to previous studies, our results support a non-cardiogenic aetiology of B-lines.
HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute ...to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b-245 α polypeptide) and GSTP1 (glutathione transferase Pi 1) are potential candidate genes for HAPE. In the present study, we investigated the polymorphisms -930A/G and H72Y (C/T) of CYBA and I105V (A/G) and A114V (C/T) of GSTP1, individually and in combination, in 150 HAPE-p (HAPE patients), 180 HAPE-r (HAPE-resistant lowland natives) and 180 HLs (healthy highland natives). 8-Iso-PGF2α (8-iso-prostaglandin F2α) levels were determined in plasma and were correlated with individual alleles, genotype, haplotype and gene-gene interactions. The relative expression of CYBA and GSTP1 were determined in peripheral blood leucocytes. The genotype distribution of -930A/G, H72Y (C/T) and I105V (A/G) differed significantly in HAPE-p compared with HAPE-r and HLs (P≤0.01). The haplotypes G-C of -930A/G and H72Y (C/T) in CYBA and G-C and G-T of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-p; in contrast, haplotypes A-T of -930A/G and H72Y (C/T) in CYBA and A-C of I105V (A/G) and A114V (C/T) in GSTP1 were over-represented in HAPE-r and HLs. 8-Iso-PGF2α levels were significantly higher in HAPE-p and in HLs than in HAPE-r (P=2.2×10(-16) and 1.2×10(-14) respectively) and the expression of CYBA and GSTP1 varied differentially (P<0.05). Regression analysis showed that the risk alleles G, C, G and T of -930A/G, H72Y (C/T), I105V (A/G) and A114V (C/T) were associated with increased 8-iso-PGF2α levels (P<0.05). Interaction between the two genes revealed over-representation of most of the risk-allele-associated genotype combinations in HAPE-p and protective-allele-associated genotype combinations in HLs. In conclusion, the risk alleles of CYBA and GSTP1, their haplotypes and gene-gene interactions are associated with imbalanced oxidative stress and, thereby, with high-altitude adaptation and mal-adaptation.
High altitude pulmonary oedema (HAPE) severely affects non‐acclimatized individuals and is characterized by alveolar flooding with protein‐ rich oedema as a consequence of blood‐gas barrier ...disruption. Limited choice for prophylactic treatment warrants effective therapy against HAPE. Keratinocyte growth factor‐2 (KGF‐2) has shown efficiency in preventing alveolar epithelial cell DNA damages in vitro. In the current study, the effects of KGF‐2 intratracheal instillation on mortality, lung liquid balance and lung histology were evaluated in our previously developed rat model of HAPE. We found that pre‐treatment with KGF‐2 (5 mg/kg) significantly decreased mortality, improved oxygenation and reduced lung wet‐to‐dry weight ratio by preventing alveolar‐capillary barrier disruption demonstrated by histological examination and increasing alveolar fluid clearance up to 150%. In addition, KGF‐2 significantly inhibited decrease of transendothelial permeability after exposure to hypoxia, accompanied by a 10‐fold increase of Akt activity and inhibited apoptosis in human pulmonary microvascular endothelial cells, demonstrating attenuated endothelial apoptosis might contribute to reduction of endothelial permeability. These results showed the efficacy of KGF‐2 on inhibition of endothelial cell apoptosis, preservation of alveolar‐capillary barrier integrity and promotion of pulmonary oedema absorption in HAPE. Thus, KGF‐2 may represent a potential drug candidate for the prevention of HAPE.
The pathophysiology of high-altitude illnesses has been well studied in normal individuals, but little is known about the risks of high-altitude travel in patients with pre-existing lung disease. ...Although it would seem self-evident that any patient with lung disease might not do well at high altitude, the type and severity of disease will determine the likelihood of difficulty in a high-altitude environment. The present review examines whether these individuals are at risk of developing one of the main forms of acute or chronic high-altitude illness and whether the underlying lung disease itself will get worse at high elevations. Several groups of pulmonary disorders are considered, including obstructive, restrictive, vascular, control of ventilation, pleural and neuromuscular diseases. Attempts will be made to classify the risks faced by each of these groups at high altitude and to provide recommendations regarding evaluation prior to high-altitude travel, advice for or against taking such excursions, and effective prophylactic measures.
Aims It is unknown whether subclinical high-altitude pulmonary oedema reduces spontaneously after prolonged altitude exposure. Continuous positive airway pressure (CPAP) removes extravascular lung ...fluids and improves haemoglobin oxygen saturation in acute cardiogenic oedema. We evaluated the presence of pulmonary extravascular fluid increase by assessing CPAP effects on haemoglobin oxygen saturation under acute and prolonged altitude exposure. Methods and results We applied 7 cm H2O CPAP for 30 min to healthy individuals after acute (Capanna Margherita, CM, 4559 m, 2 days permanence, and <36 h hike) and prolonged altitude exposure (Mount Everest South Base Camp, MEBC, 5350 m, 10 days permanence, and 9 days hike). At CM, CPAP reduced heart rate and systolic pulmonary artery pressure while haemoglobin oxygen saturation increased from 80% (median), 78–81 (first to third quartiles), to 91%, 84–97 (P < 0.001). After 10 days at MEBC, haemoglobin oxygen saturation spontaneously increased from 77% (74–82) to 86% (82–89) (P < 0.001) while heart rate (from 79, 64–92, to 70, 54–81; P < 0.001) and respiratory rate (from 15, 13–17, to 13, 13–15; P < 0.001) decreased. Under such conditions, these parameters were not influenced by CPAP. Conclusion After ascent excessive lung fluids accumulate affecting haemoglobin oxygen saturation and, in these circumstances, CPAP is effective. Acclimatization implies spontaneous haemoglobin oxygen saturation increase and, after prolonged altitude exposure, CPAP is not associated with HbO2-sat increase suggesting a reduction in alveolar fluids.
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