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The Lung at high altitude: between physiology and pathology in Problems of high altitude medicine and biology

The lungs play a pivotal role in adaptation to high altitude. The increase in ventilation and the rise in pulmonary artery pressure are the first features of lung response to hypoxic exposure. At high altitude the lungs can also be affected by high-altitude pulmonary oedema, a severe form of acute mountain sickness. In healthy subjects the ascent to high altitude is also associated with alterations in lung function, which have been in part interpreted as an effect of extra vascular lung fluid accumulation. The patterns of respiratory function changes at high altitude are discussed, taking into account the body fluid movement and the increase in endothelial permeability induced by hypoxic exposure. As the problem of “respiratory” patients at high altitude is very important, a short summary of the guidelines for altitude exposure of asthmatic and COPD patients is reported at the end of the chapter.

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Relationship between individual ventilatory response and acute renal water excretion at high altitude

We tested the hypothesis that the individual ventilatory adaptation to high altitude (HA, 5050 m) may influence renal water excretion in response to water loading. In 8 healthy humans (33+/-4 S.D. years) we studied, at sea level (SL) and at HA, resting ventilation (VE), arterial oxygen saturation (SpO2), urinary output after water loading (WL, 20 mL/kg), and total body water (TBW). Ventilatory response to HA was defined as the difference in resting VE over SpO2 (DeltaVE/DeltaSpO2) from SL to HA. At HA, a significant increase in urinary volume after the first hour from WL (%WLt0-60) was observed. Significant correlations were found between DeltaVE/DeltaSpO2 versus %WLt0-60 at HA and versus changes in TBW, from SL to HA. In conclusion, in healthy subjects the ventilatory response to HA influences water balance and correlates with kidney response to WL. A higher ventilatory response at HA, allowing a more efficient water renal handling, is likely to be a protective mechanisms from altitude illness.

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Growth and nutritional status of Tibetan children at high altitude

Growth and development are clearly affected by high-altitude exposure to hypoxia, nutritional stress, cold or a combination of these factors. Very little research has been conducted on the growth and nutritional status of children living on the Tibetan Plateau. The present study evaluated the environmental impact on human growth by analyzing anthropometric characteristics of Tibetan children aged 8-14, born and raised above 4000 m altitude on the Himalayan massif in the prefecture of Shegar in Tibet Autonomous Region. Data on anthropometric traits, never measured in this population, were collected and the nutritional status was assessed. A reference data set is provided for this population. There was no evidence of wasting but stunting was detected (28.3%). Children permanently exposed to the high-altitude environment above 4000 m present a phenotypic form of adaptation and a moderate reduction in linear growth. However, it is also necessary to consider the effects of socioeconomic deprivation.

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Respiratory function at different altitudes

For the evaluation of a respiratory test at high altitude, several factors must be taken into account: the decreased barometric pressure, the decreased density of air and the degree of acclimatization which is related to the altitude and to the length of exposure. Several studies have shown a reduction in forced vital capacity (FVC) at high altitude and using simulated conditions, mainly related to an increase in pulmonary blood volume and development of interstitial edema. To assess the daily spirometric patterns during ascending to high altitudes we studied 17 healthy subjects at both Capanna Regina Margherita on the Italian Alps (4,559 m) and the Pyramid Laboratory in Nepal (5,050 m). Respiratory function tests were performed every day. Peak expiratory flow values significantly increased. The mean percent increase was 15% at 3,200 and 3,600 m and 26% at 4,559 m. FVC and MEF25 values showed a significant decrease (p < 0.005) during the first days above 3,500 m and improved only after several days spent above this altitude. For each subject the maximal reductions in FVC and maximal expiratory flow (MEF) at 25% of FVC however were found on different days. In our opinion, these data support the hypothesis that at high altitude the respiratory function can be affected by the presence of an increased pulmonary blood volume and/or the development of interstitial edema. The observed changes in forced expiration curves at high altitude seem to reflect the degree of acclimatization that is related to the individual susceptibility, to the altitude reached and to the duration of the exposure. These changes are transient and resolve after returning to sea level.

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The Lung at high altitude: between physiology and pathology in Problems of high altitude medicine and biology

The lungs play a pivotal role in adaptation to high altitude. The increase in ventilation and the rise in pulmonary artery pressure are the first features of lung response to hypoxic exposure. At high altitude the lungs can also be affected by high-altitude pulmonary oedema, a severe form of acute mountain sickness. In healthy subjects the ascent to high altitude is also associated with alterations in lung function, which have been in part interpreted as an effect of extra vascular lung fluid accumulation. The patterns of respiratory function changes at high altitude are discussed, taking into account the body fluid movement and the increase in endothelial permeability induced by hypoxic exposure. As the problem of “respiratory” patients at high altitude is very important, a short summary of the guidelines for altitude exposure of asthmatic and COPD patients is reported at the end of the chapter.

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Bronchial asthma and airway hyperresponsiveness at high altitude

The mountain climate can modify respiratory function and bronchial responsiveness of asthmatic subjects. Hypoxia, hyperventilation of cold and dry air and physical exertion may worsen asthma or enhance bronchial hyperresponsiveness while a reduction in pollen and pollution may play an important role in reducing bronchial inflammation. At moderate altitude (1,500-2,500 m), the main effect is the absence of allergen and pollutants. We studied bronchial hyperresponsiveness to both hyposmolar aerosol and methacholine at sea level (SL) and at high altitude (HA; 5,050 m) in 11 adult subjects (23-48 years old, 8 atopic, 3 nonatopic) affected by mild asthma. Basal FEV1 at SL and HA were not different (p = 0.09), whereas the decrease in FEV1 induced by the challenge was significantly higher at SL than at HA. (1) Hyposmolar aerosol: at SL the mean FEV1 decreased by 28% from 4.32 to 3.11 liters; at 5,050 m by 7.2% from 4.41 to 4.1 liters (p < 0.001). (2) Methacholine challenge: at SL PD20-FEV1 was 700 micrograms and at HA > 1,600 micrograms (p < 0.005). In 3 asthmatic and 5 nonasthmatic subjects plasma levels of cortisol were also measured. The mean value at SL was 265 nmol and 601 nmol at HA (p < 0.005). We suppose that the reduction in bronchial response might be mainly related to the protective role carried out by the higher levels of cortisol and, as already known, catecholamines.

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Respiratory and leg muscles perceived exertion during exercise at altitude

We compared the rate of perceived exertion for respiratory (RPE,resp) and leg (RPE,legs) muscles, using a 10-point Borg scale, to their specific power outputs in 10 healthy male subjects during incremental cycle exercise at sea level (SL) and high altitude (HA, 4559 m). Respiratory power output was calculated from breath-by-breath esophageal pressure and chest wall volume changes. At HA ventilation was increased at any leg power output by ? 54%. However, for any given ventilation, breathing pattern was unchanged in terms of tidal volume, respiratory rate and operational volumes of the different chest wall compartments. RPE,resp scaled uniquely with total respiratory power output, irrespectively of SL or HA, while RPE,legs for any leg power output was exacerbated at HA. With increasing respective power outputs, the rate of change of RPE,resp exponentially decreased, while that of RPE,legs increased. We conclude that RPE,resp uniquely relates to respiratory power output, while RPE,legs varies depending on muscle metabolic conditions.

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Relationship between individual ventilatory response and acute renal water excretion at high altitude.

We tested the hypothesis that the individual ventilatory adaptation to high altitude (HA, 5050 m) may influence renal water excretion in response to water loading. In 8 healthy humans (33+/-4 S.D. years) we studied, at sea level (SL) and at HA, resting ventilation (VE), arterial oxygen saturation (SpO2), urinary output after water loading (WL, 20 mL/kg), and total body water (TBW). Ventilatory response to HA was defined as the difference in resting VE over SpO2 (DeltaVE/DeltaSpO2) from SL to HA. At HA, a significant increase in urinary volume after the first hour from WL (%WLt0-60) was observed. Significant correlations were found between DeltaVE/DeltaSpO2 versus %WLt0-60 at HA and versus changes in TBW, from SL to HA. In conclusion, in healthy subjects the ventilatory response to HA influences water balance and correlates with kidney response to WL. A higher ventilatory response at HA, allowing a more efficient water renal handling, is likely to be a protective mechanisms from altitude illness.

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Problems of High Altitude Medicine and Biology

This book is directly derived from a NATO-sponsored international meeting on problems of high altitude medicine and biology, which was held on the shores of lake of Issyk-Kul, in Kyrghyzstan, in June 5-6, 2006. The meeting was remarkable by several aspects. The participants enjoyed the beauty of the blue waters of this 1610 m high sacred lake, with stunning view on the Tien Shan mountain range at a distance, and, most of all, the wonderful Kyrghyz hospitality and friendship. It was a surprise for several European and North and South-American scientists to discover the still on-going momentum high level altitude physiology research, which was extremely active but insufficiently acknowledged in this remote Central Asian country at the time of the USSR. Accordingly, the setting was perfect for numerous positive scientific interactions, exchanges of ideas, and structuring of new international collaborations. Overall, the meeting was an ideal mix of cell biology, integrative physiology and medical applications. Thanks to the efforts of both English and Russian speaking scientist participants, this comes out very well in this book. Hypoxia is and remains a major public health issue in many populated mountainous areas all over the world. We are sure that this book will be become a long-lasting essential reference.

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Bronchial asthma: advice for patients traveling to high altitude

This article examines the possibility of traveling to altitude for patients suffering from bronchial asthma. The mountain environment, the adaptations of the respiratory system to high altitude, the underlying pathophysiologies of asthma, and the recommendations for patients, according to altitude, are discussed. In summary, staying at low altitude has a significant beneficial effect for asthmatic patients, due to the reduction of airway inflammation and the lower response to bronchoconstrictor stimuli; for staying at moderate altitude, there is conflicting information and no clinical data; at high altitude, the environment seems beneficial for well-controlled asthmatics, but intense exercise and upper airway infections (frequent during trekking) can be additional risks and should be avoided. Further, in remote areas health facilities are often difficult to reach.

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