Symptoms Of Acute Mountain Sickness Research Articles

Intravenous Iron Supplementation May Protect Against Acute Mountain Sickness: A Randomized, Double-Blinded, Placebo-Controlled Trial

Acute mountain sickness (AMS) is a common and disabling condition that occurs in healthy individuals ascending to high altitude. Based on the ability of iron to influence cellular oxygen sensing pathways, we hypothesized that iron supplementation would protect against AMS. To examine this hypothesis, 24 healthy sea-level residents were randomized to receive either intravenous iron(III)-hydroxide sucrose (200 mg) or saline placebo, before ascending rapidly to Cerro de Pasco, Peru (4340 m). The Lake Louise scoring system was used to assess incidence and severity of AMS at sea level and on the first full day at altitude. No significant difference in absolute AMS score was detected between the two groups either at baseline or at high altitude. However, the mean increase in AMS score was 65% smaller in the iron group than in the saline group (p<0.05), and the change in AMS score correlated negatively with the change in ferritin (R=-0.43; p<0.05). Hematocrit and arterial oxygen saturation were unaffected by iron. In conclusion, this preliminary randomized, double-blinded, placebo-controlled trial suggests that intravenous iron supplementation may protect against the symptoms of AMS in healthy volunteers.

Effects of Oxygen Supplementation on Acute Mountain Sickness Symptoms and Functional Capacity During a 2-Kilometer Walk Test on Chajnantor Plateau (5050 Meters, Northern Chile)

The aim of this study was to test the hypothesis that administration of low-flow oxygen will improve physical performance in subjects unacclimatized to altitude. We evaluated the effects of oxygen supplementation on functional capacity and acute mountain sickness (AMS) symptoms in young, healthy male and female subjects who performed a 2-km fast walk test following rapid ascent to the Chajnantor plateau (5050 m above sea level) in Northern Chile. The participants were randomly distributed into 2 groups according to oxygen supplementation levels: 1 or 3 L O(2) · min(-1). Within each group, males and females were evaluated separately. A preliminary walk test was carried out at sea level on a 100-m long, flat track with 10 U-turns. For the first walk at altitude, subjects carried the supplementary oxygen system but did not breathe the oxygen. Subjects received oxygen through a facemask the following day during the second test. The nights prior to altitude tests were spent at 2400 m in San Pedro de Atacama. Supplementary oxygen administration during a 2-km walk test significantly improved walking times at 5050 m. We also observed a significant improvement in AMS symptoms. As expected, however, performance was poorer at altitude compared to test values at sea level, despite supplementary oxygen administration. Our findings demonstrate the beneficial effects of supplementary oxygen administration on physical capacity, reducing the incidence of AMS and, thus, improving health and safety conditions for high altitude workers following rapid ascent, when adequate acclimatization is not possible.

Acute Mountain Sickness in Travelers Who Consulted a Pre‐Travel Clinic

The main objective of this study was to investigate the incidence and predictors of acute mountain sickness (AMS) in travelers who consulted a pre-travel clinic and the compliance with advices concerning this condition. A post-travel questionnaire was sent to clients of five travel clinics who planned to climb above 2,000 m. The response was 77% and the data of all 744 respondents who stayed above 2,500 m were used for the analysis. Eighty-seven percent (646) read and understood the written advices on AMS. The incidence of AMS was 25% (184), and the predictors were previous AMS [odds ratio (OR) 2.2], female sex (OR 1.6), age (OR 0.98 per year), maximum sleeping altitude (OR 1.2 per 500 m), and the number of nights between 1,500 and 2,500 m (OR 0.9 per night). Eighty-seven percent of respondents understood the written advices about AMS but 21% did not read or understand the use of acetazolamide. Forty percent spent less than two nights between 1,500 and 2,500 m and 43% climbed more than 500 m/d once above 2,500 m. Acetazolamide was brought along by 541 respondents (72%) and 116 (16%) took it preventively. Of those with AMS 62 (34%) took acetazolamide treatment and 87 (47%) climbed higher despite AMS symptoms. The average preventive dose of acetazolamide was 250 mg/d, while the average curative dose was 375 mg/d. We found no relation between acetazolamide prevention and AMS (p = 0.540). The incidence of AMS in travelers who stayed above 2,500 m was 25%. Predictors were previous AMS, female sex, age, maximum overnight altitude, and the number of nights between 1,500 and 2,500 m. Only half of these travelers followed the preventive and curative advices and 21% did not read or understand the use of acetazolamide. We found no preventive effect of a low dose of acetazolamide in this retrospective observational study.

Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study

The pathophysiology of acute mountain sickness (AMS) is unknown. One hypothesis is that hypoxia induces biochemical changes that disrupt the blood-brain barrier (BBB) and, subsequently, lead to the development of cerebral edema and the defining symptoms of AMS. This study explores the relationship between AMS and biomarkers thought to protect against or contribute to BBB disruption. Twenty healthy volunteers participated in a series of hypobaric hypoxia trials distinguished by pretreatment with placebo, acetazolamide (250 mg), or dexamethasone (4 mg), administered using a randomized, double-blind, placebo-controlled, crossover design. Each trial included peripheral blood sampling and AMS assessment before (-15 and 0 h) and during (0.5, 4, and 9 h) a 10-h hypoxic exposure (barometric pressure = 425 mmHg). Anti-inflammatory and/or anti-permeability [interleukin (IL)-1 receptor agonist (IL-1RA), heat shock protein (HSP)-70, and adrenomedullin], proinflammatory (IL-6, IL-8, IL-2, IL-1β, and substance P), angiogenic, or chemotactic biomarkers (macrophage inflammatory protein-1β, VEGF, TNF-α, monocyte chemotactic protein-1, and matrix metalloproteinase-9) were assessed. AMS-resistant subjects had higher IL-1RA (4 and 9 h and overall), HSP-70 (0 h and overall), and adrenomedullin (overall) compared with AMS-susceptible subjects. Acetazolamide raised IL-1RA and HSP-70 compared with placebo in AMS-susceptible subjects. Dexamethasone also increased HSP-70 and adrenomedullin in AMS-susceptible subjects. Macrophage inflammatory protein-1β was higher in AMS-susceptible than AMS-resistant subjects after 4 h of hypoxia; dexamethasone minimized this difference. Other biomarkers were unrelated to AMS. Resistance to AMS was accompanied by a marked anti-inflammatory and/or anti-permeability response that may have prevented downstream pathophysiological events leading to AMS. Conversely, AMS susceptibility does not appear to be related to an exaggerated inflammatory response.

Exercise in Normobaric Hypoxia Exacerbates Symptoms of Acute Mountain Sickness But Does Not Impact Mood State in Middle-Aged Males

Exercise in Normobaric Hypoxia Exacerbates Symptoms of Acute Mountain Sickness But Does Not Impact Mood State in Middle-Aged Males

Pro: Headache Should Be a Required Symptom for the Diagnosis of Acute Mountain Sickness

The diagnosis of acute mountain sickness (AMS) continues to pose problems to altitude sojourners, physicians, and researchers because of its subjective nature relying essentially on a subject’s appreciation of the presence and severity of symptoms (Roach and Kayser, 2007). Even though AMS is characterized by an ensemble of symptoms (Hackett and Roach, 2001), headache has been recognized as its key symptom at least since Ravenhill’s description in 1911 (Ravenhill, 1913). He described the experiences of ‘‘a majority of newcomers . . . . wake up the next morning with a severe frontal headache . . . . . any attempt at exertion increases the headache, which is nearly always confined to the frontal region.’’ This central role of headache was codified in the current version of the Lake Louise Questionnaire (Roach et al., 1993) that states that a ‘‘diagnosis of AMS is based on a recent gain in altitude, at least several hours at the new altitude, and the presence of headache and at least one of the following symptoms: gastrointestinal upset (anorexia, nausea or vomiting), fatigue or weakness, dizziness or lightheadedness and difficulty sleeping.’’ All surveys of AMS identify headache as the predominant and most prevalent symptom. Singh et al. (1969) noted from a survey of 1925 soldiers rapidly transported to high altitude that ‘‘Headache was not only the commonest but also the most persistent symptom.’’ In a study of 146 trekkers with AMS, Hackett et al. observed the following predominance of headache compared to other symptoms: headache (96%), insomnia (70%), anorexia (38%), nausea (35%), dizziness (27%), excessive breathlessness on exertion or at rest (25%), headache unrelieved by analgesics (26%), reduced urine (19%), marked lassitude (13%), vomiting (14%), incoordination (11%) (Hackett et al 1976). And finally, in a large survey at moderate altitudes, Honigman et al. confirmed the importance of headache in AMS with 62% of 3158 conference attendees reporting moderate to severe headache, and the next most common complaint being sleep disturbance at 31%, and anorexia at 11% and vomiting at only 3% (Honigman et al., 1993). Thus it seems clear that for AMS the cardinal symptom is headache in all studies, in all populations, and at a wide range of altitudes. Our position is that from a research perspective there are important advantages to defining AMS as a collection of symptoms that includes, always, a headache. The same is obviously not true for clinical management of altitude illness. This contrast between the needs for research versus best practice in clinical care forms the basis of our stance. In spite of several decades of sustained research efforts, the basic pathophysiology of AMS still remains elusive. We believe that a focus on high altitude headache will help unravel the puzzle of the pathophysiology of AMS. By stipulating for research purposes that headache be included in the definition of AMS, scientists seek to increase signal-to-noise ratio in AMS subjective symptom reporting. Unfortunately, subjective perception and reporting of symptoms is currently the only way to diagnose and quantify AMS. An example of excess noise is that without obligatory headache, a research subject who had a very bad night sleep and is dizzy at the time of completing the questionnaire could have a ‘‘severe’’ AMS score. Yet we know from several studies that poor sleep at altitude is not necessarily related directly to AMS. And dizziness can be secondary to hypoxemia, or to hypohydration, a common, non-AMS-related phenomenon at high altitude. Similarly, nausea and vomiting can be associated with the onset of AMS, or secondary to a bad headache of any cause, especially migraine, and in the field can also be secondary to gastrointestinal infection. Thus, obligatory presence of headache in the research scoring of AMS symptoms serves an important role by increasing the likelihood that the central symptom of AMS, first reported so clearly by Ravenhill, remains the focus of research studies. It should be noted that

Year in review 2010: Interstitial lung diseases, acute lung injury, sleep, physiology, imaging, bronchoscopic intervention and lung cancer

Year in review 2010: Interstitial lung diseases, acute lung injury, sleep, physiology, imaging, bronchoscopic intervention and lung cancer

Effects of acetazolamide and dexamethasone on cerebral hemodynamics in hypoxia

Previous attempts to detect global cerebral hemodynamic differences between those who develop headache, nausea, and fatigue following rapid exposure to hypoxia [acute mountain sickness (AMS)] and those who remain healthy have been inconclusive. In this study, we investigated the effects of two drugs known to reduce symptoms of AMS to determine if a common cerebral hemodynamic mechanism could explain the prophylactic effect within individuals. With the use of randomized, placebo-controlled, double-blind, crossover design, 20 healthy volunteers were given oral acetazolamide (250 mg), dexamethasone (4 mg), or placebo every 8 h for 24 h prior to and during a 10-h exposure to a simulated altitude of 4,875 m in a hypobaric chamber, which included 2 h of exercise at 50% of altitude-specific VO(2max). Cerebral hemodynamic parameters derived from ultrasound assessments of dynamic cerebral autoregulation and vasomotor reactivity were recorded 15 h prior to and after 9 h of hypoxia. AMS symptoms were scored using the Lake Louise Questionnaire (LLQ). It was found that both drugs prevented AMS in those who became ill on placebo (~70% decrease in LLQ), yet a common cerebral hemodynamic mechanism was not identified. Compared with placebo, acetazolamide reduced middle cerebral artery blood flow velocity (11%) and improved dynamic cerebral autoregulation after 9 h of hypoxia, but these effects appeared independent of AMS. Dexamethasone had no measureable cerebral hemodynamic effects in hypoxia. In conclusion, global cerebral hemodynamic changes resulting from hypoxia may not explain the development of AMS.

Increased Insulin Requirements During Exercise at Very High Altitude in Type 1 Diabetes

OBJECTIVESafe, very high altitude trekking in subjects with type 1 diabetes requires understanding of glucose regulation at high altitude. We investigated insulin requirements, energy expenditure, and glucose levels at very high altitude in relation to acute mountain sickness (AMS) symptoms in individuals with type 1 diabetes.RESEARCH DESIGN AND METHODSEight individuals with complication-free type 1 diabetes took part in a 14-day expedition to Mount Meru (4,562 m) and Mount Kilimanjaro (5,895 m) in Tanzania. Daily insulin doses, glucose levels, energy expenditure, and AMS symptoms were determined. Also, energy expenditure and AMS symptoms were compared with a healthy control group.RESULTSWe found a positive relation between AMS symptoms and insulin requirements (r = 0.78; P = 0.041) and AMS symptoms and glucose levels (r = 0.86; P = 0.014) for Mount Kilimanjaro. Compared with sea level, insulin doses tended to decrease by 14.2% (19.7) (median [interquartile range]) (P = 0.41), whereas glucose levels remained stable up to 5,000 m altitude. However, at altitudes >5,000 m, insulin dose was unchanged (36.8 ± 17 vs. 37.6 ± 19.1 international units [mean ± SD] P = 0.75), but glucose levels (7.5 ± 0.6 vs. 9.5 ± 0.8 mmol/L [mean ± SD] P = 0.067) and AMS scores (1.3 ± 1.6 vs. 4.4 ± 4 points [mean ± SD] P = 0.091) tended to increase. Energy expenditure and AMS symptoms were comparable in both groups (P = 0.84).CONCLUSIONSOur data indicate that in complication-free individuals with type 1 diabetes, insulin requirements tend to increase during altitudes above 5,000 m despite high energy expenditure. This change may be explained, at least partly, by AMS.

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.

Polymorphisms of Hypoxia-Related Genes in Subjects Susceptible to Acute Mountain Sickness

Background: The occurrence of acute mountain sickness (AMS), which develops in some individuals who ascend to altitudes above 2,500 m, may be associated with 4 hypoxia-related genes (HIF-1, VEGFA, HSP-70 and eNOS). Objectives: The aim of our study was to investigate the potential role of the 4 hypoxia-related genes in AMS pathogenesis. We therefore evaluated single-nucleotide polymorphisms (SNPs) of the genes in an association study using a case-control design. Methods: At an altitude of 4,600 m, 64 male Chinese patients with AMS, defined according to the Lake Louise consensus criteria, were compared to 64 Chinese men free of symptoms of AMS. Clinical data, such as age, history of diseases, oxygen saturation (SpO₂) and heart rate, were obtained. Genotypes of selected SNPs of these genes in patients were compared with those in controls. Results: The mean SpO₂ and heart rate of the AMS and control groups were similar before ascent to high altitude (p = 0.79, p = 0.62) but, 24 h after ascent, the mean SpO₂ of the AMS group was significantly lower than that of the control group (p = 0.001), and the mean heart rate of the AMS group was significantly higher than that of the control group (p = 0.001). Twenty-eight of the 48 SNPs investigated were successfully genotyped, and SNP allele frequencies were obtained. The rs3025039 SNP and the haplotype (rs1413711, rs833070 and rs3025000) in the VEGFA gene were significantly associated with AMS (p = 0.0435 and 0.024, respectively). Conclusions: Our study demonstrates a possible association between the VEGFA gene and AMS. We conclude that VEGFA may have an important role in the AMS process.

High-altitude exposure and its effects on special populations

Altitude illness is a spectrum of conditions that affect the majority of travelers to high elevations (>8200 ft [2500 m]). The rapid decrease in arterial oxygen saturation with increasing altitude is the physiologic basis for this group of disorders. Many travelers to high altitudes will experience symptoms of acute mountain sickness including headache, fatigue, dyspnea, and dizziness. Prolonged exposure can result in more serious pulmonary, central nervous system, and circulatory disorders. Core treatments for most altitude-related illnesses include descent, rest, medications, and supportive care. Children and travelers with chronic diseases are more susceptible to altitude illness compared with the general population. Pregnant women residing at high altitudes are at increased risk for pregnancy-induced hypertension, preeclampsia, and low-birth-weight infants. Early recognition and treatment of altitude illness can prevent life-threatening situations. Primary care physicians should counsel patients traveling to high altitudes about altitude illness and discuss medications available for mountain sickness prophylaxis.

Ophthalmodynamometry for ICP prediction and pilot test on Mt. Everest

BackgroundA recent development in non-invasive techniques to predict intracranial pressure (ICP) termed venous ophthalmodynamometry (vODM) has made measurements in absolute units possible. However, there has been little progress to show utility in the clinic or field. One important application would be to predict changes in actual ICP during adaptive responses to physiologic stress such as hypoxia. A causal relationship between raised intracranial pressure and acute mountain sickness (AMS) is suspected. Several MRI studies report that modest physiologic increases in cerebral volume, from swelling, normally accompany subacute ascent to simulated high altitudes.Objectives1) Validate and calibrate an advanced, portable vODM instrument on intensive patients with raised intracranial pressure and 2) make pilot, non-invasive ICP estimations of normal subjects at increasing altitudes.MethodsThe vODM was calibrated against actual ICP in 12 neurosurgical patients, most affected with acute hydrocephalus and monitored using ventriculostomy/pressure transducers. The operator was blinded to the transducer read-out. A clinical field test was then conducted on a variable data set of 42 volunteer trekkers and climbers scaling Mt. Everest, Nepal. Mean ICPs were estimated at several altitudes on the ascent both across and within subjects.ResultsPortable vODM measurements increased directly and linearly with ICP resulting in good predictability (r = 0.85). We also found that estimated ICP increases normally with altitude (10 ± 3 mm Hg; sea level to 20 ± 2 mm Hg; 6553 m) and that AMS symptoms did not correlate with raised ICP.ConclusionvODM technology has potential to reliably estimate absolute ICP and is portable. Physiologic increases in ICP and mild-mod AMS are separate responses to high altitude, possibly reflecting swelling and vasoactive instability, respectively.

Effect of hypohydration and altitude exposure on aerobic exercise performance and acute mountain sickness

Hypoxia often causes body water deficits (hypohydration, HYPO); however, the effects of HYPO on aerobic exercise performance and prevalence of acute mountain sickness (AMS) at high altitude (ALT) have not been reported. We hypothesized that 1) HYPO and ALT would each degrade aerobic performance relative to sea level (SL)-euhydrated (EUH) conditions, and combining HYPO and ALT would further degrade performance more than one stressor alone; and 2) HYPO would increase the prevalence and severity of AMS symptoms. Seven lowlander men (25 ± 7 yr old; 82 ± 11 kg; mean ± SD) completed four separate experimental trials. Trials were 1) SL-EUH, 2) SL-HYPO, 3) ALT-EUH, and 4) ALT-HYPO. In HYPO, subjects were dehydrated by 4% of body mass. Subjects maintained hydration status overnight and the following morning entered a hypobaric chamber (at SL or 3,048 m, 27°C) where they completed 30 min of submaximal exercise immediately followed by a 30-min performance time trial (TT). AMS was measured with the Environmental Symptoms Questionnaire-Cerebral Score (AMS-C) and the Lake Louise Scoring System (LLS). The percent change in TT performance, relative to SL-EUH, was -19 ± 12% (334 ± 64 to 278 ± 87 kJ), -11 ± 10% (334 ± 64 to 293 ± 33 kJ), and -34 ± 22% (334 ± 64 to 227 ± 95 kJ), for SL-HYPO, ALT-EUH, and ALT-HYPO, respectively. AMS symptom prevalence was 2/7 subjects at ALT-EUH for AMS-C and LLS and 5/7 and 4/7 at ALT-HYPO for AMS-C and LLS, respectively. The AMS-C symptom severity score (AMS-C score) tended to increase from ALT-EUH to ALT-HYPO but was not significant (P = 0.07). In conclusion, hypohydration at 3,048 m 1) degrades aerobic performance in an additive manner with that induced by ALT; and 2) did not appear to increase the prevalence/severity of AMS symptoms.

Impaired Cerebral Autoregulation in Acute Mountain Sickness: Incidental Yet Adaptive?

To the Editor: Subudhi et al1 recently demonstrated that dynamic cerebral autoregulation (CA) became progressively impaired when volunteers were exposed to the hypoxia of simulated high-altitude, although this was unrelated to the onset of neurological symptoms ascribed to acute mountain sickness (AMS). Although their study describes some important findings, the authors’ interpretation of similar studies conducted by our groups2,3 warrants clarification and provides an opportunity to offer complementary insight into alternative mechanisms. The authors discuss deficiencies with the design and interpretation of our findings, thus “…making it difficult to draw conclusions regarding …

Physical and Physiological Effects on Otoacoustic Emissions in Hypobaric Hypoxia

Tinnitus and dizziness are symptoms of acute mountain sickness. We investigated the mechanism by which high altitude (i.e. hypobaric hypoxia) affects inner ear function by measuring transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) under conditions of normobaric normoxia (1,013 hPa; 760 mm Hg) and hypobaric hypoxia (540 hPa; 405 mm Hg). The possibility that air pressure effects on the eustachian tube impacted our findings was excluded by the use of tympanograms. The nonphysiological effects of hypobaric hypoxia on TEOAE and DPOAE were also assessed using an ear simulator. Under conditions of hypobaric hypoxia, both TEOAE and DPOAE levels were reduced. The amount of reduction that occurred was approximately 4 dB in the total echo power and signal-to-noise ratio of the TEOAE, and in the 2f₁ – f₂ element level of the DPOAE. Stimulus levels that were measured using an ear simulator were also reduced by approximately 4 dB under conditions of hypobaric hypoxia. These results do not indicate that stimulus levels affected TEOAE and DPOAE levels because these levels were actually only slightly affected by changes in the stimulus level. Instead, this reduction was likely due to the nonphysiological hypobaric effects of the sound pressure emitted from the tympanic membrane. We conclude that the impact of hypobaric hypoxia on cochlear function was negligible up to pressures of 540 hPa.

Asthma in Patients Climbing to High and Extreme Altitudes in the Tibetan Everest Region

Objectives: The aim of this study was to investigate the behavior of asthma in patients traveling to high and extreme altitudes. Methods: Twenty-four Dutch patients with mild asthma did a trekking at high and extreme altitudes (up to 6410 m = 21030 ft) in the Tibetan Everest region. Asthma symptoms, use of asthma medication, symptoms of acute mountain sickness, spirometry, peripheral oxygen saturation, and heart rate were measured at 1300 m (baseline), and at 3875, 4310, 5175, and 6410 m. Asthma symptoms were assessed by means of a modified version of the Asthma Control Test. Symptoms of acute mountain sickness were scored by the Lake Louise self-report questionnaire. The expedition staff, consisting of seven healthy persons, acted as a control group. Results: In both asthmatics and controls, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) decreased with increasing altitude, whereas FEV1 as percent of FVC (FEV1%FVC) did not change. In both groups, peak expiratory flow (PEF) increased with increasing altitude. In general, differences in spirometric values between asthmatics and controls were not significant. Asthma symptoms did not change with increasing altitude. During ascent, less than half of the asthma patients increased their medication use. According to the Lake Louise score, no acute mountain sickness occurred, except for in the asthma group at 6410 m, which showed mild acute mountain sickness at that altitude. As expected, peripheral oxygen saturation decreased with increasing altitude in asthmatics and controls, differences between the two groups not being significant. In general, heart rate (at rest) did not change with altitude, except for an increase in asthmatics at 6410 m. Conclusions: These results suggest that traveling to high and extreme altitudes is safe for patients with mild asthma.

Auswirkungen akuter Höhenexposition: Welche Höhe ist gesundheitlich verträglich?

Exposures to natural and simulated altitudes are combined with a reduction of the available oxygen (hypoxia) and may provoke health problems or even emergencies. Although millions of people are living at high altitudes, are regularly or occasionally performing mountain sport activities, are transported by airplanes, and are increasingly frequently exposed to hypoxia at their workplace, e.g. with fire control systems, there is no consensus about the level of hypoxia which is well tolerated by most of human beings. Thus, the present mini review tries to define such a level. This review indicates that although humans show adaptive responses even to altitudes below 2000 m or corresponding normobaric hypoxia (FiO2: >16%) most of these subjects without severe pre-existing diseases well tolerate altitudes up to 3000 m (FiO2: 14.5%). If at all, symptoms of acute mountain sickness may develop in some persons after a minimum exposure time of about 6 hours. This also applies to children, elderly persons and pregnant women. Physical activity and unusual environmental conditions may increase the risk to get sick. Also patients with not severe cardiovascular, respiratory or metabolic diseases well tolerate such levels of altitude. However, individual differences in responses to hypoxia have to be considered and can at least partly be tested by simple hypoxia challenge tests. For safety reasons altitudes up to 2700 m or normobaric hypoxia up to FiO2 values of 15% are proposed to be well tolerated by most humans who are not severely diseased.

Prospective, Double-Blind, Randomized, Placebo-Controlled Comparison of Acetazolamide Versus Ibuprofen for Prophylaxis Against High Altitude Headache: The Headache Evaluation at Altitude Trial (HEAT)

High altitude headache (HAH) is the most common neurological complaint at altitude and the defining component of acute mountain sickness (AMS). However, there is a paucity of literature concerning its prevention. Toward this end, we initiated a prospective, double-blind, randomized, placebo-controlled trial in the Nepal Himalaya designed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH. Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg, acetazolamide 85 mg, or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity, AMS incidence and severity on the Lake Louise AMS Questionnaire (LLQ), and visual analog scale (VAS). Two hundred sixty-five of 343 subjects completed the trial. HAH incidence was similar when treated with acetazolamide (27.1%) or ibuprofen (27.5%; P = .95), and both agents were significantly more effective than placebo (45.3%; P = .01). AMS incidence was similar when treated with acetazolamide (18.8%) or ibuprofen (13.7%; P = .34), and both agents were significantly more effective than placebo (28.6%; P = .03). In fully compliant participants, moderate or severe headache incidence was similar when treated with acetazolamide (3.8%) or ibuprofen (4.7%; P = .79), and both agents were significantly more effective than placebo (13.5%; P = .03). Ibuprofen and acetazolamide were similarly effective in preventing HAH. Ibuprofen was similar to acetazolamide in preventing symptoms of AMS, an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness.

Nocturnal Periodic Breathing during Acclimatization at Very High Altitude at Mount Muztagh Ata (7,546 m)

Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m). To investigate whether periodic breathing persists during prolonged stay at very high altitude. A total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19-20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained. Nocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5-8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing. Our field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system. Clinical trial registered with www.clinicaltrials.gov (NCT00514826).