The aim of this prospective observational cohort study was to investigate relationships between acute mountain sickness (AMS) and physical and mental health during a high altitude expedition.
The aim of this prospective observational cohort study was to investigate relationships between acute mountain sickness (AMS) and physical and mental health during a high altitude expedition.
Forty-four participants (mean age, 34 ± 13 y; body mass index, 23.6 ± 3.5 kg·m2; 57% male) completed the Dhaulagiri base camp trek in Nepal, a 19-day expedition attaining 5,372 m. Participants self-reported the following daily physical and mental health: AMS (defined by Lake Louise diagnosis and individual and total symptom scores), upper respiratory symptoms, diarrhea, and anxiety, plus physiological and behavioral factors.
The rate of Lake Louise-defined AMS per 100 person days was 9.2 (95% CI: 7.2–11.7). All investigated illnesses except diarrhea increased with altitude (all p < 0.001 by analysis of variance). Total AMS symptom score was associated with a lower arterial oxygen saturation, higher resting heart rate, more upper respiratory and diarrhea symptoms, greater anxiety, and lower fluid intake (all p < 0.02 by longitudinal multiple regression analyses). However, only upper respiratory symptoms, heart rate, arterial oxygen saturation, and fluid intake predicted future AMS symptoms [eg, an increase in upper respiratory symptoms by 5 units predicted an increase in the following day's AMS total symptom score by 0.72 units (0.54–0.89)].
Upper respiratory symptoms and anxiety increasingly contributed to symptom burden as altitude was gained. Data were consistent with increased heart rate, decreased arterial oxygen saturation, reduced fluid intake, and upper respiratory symptoms being causally associated with AMS. Upper respiratory symptoms and fluid intake are the simplest targets for intervention to reduce AMS during high altitude exposure.
Many people travel to mountainous regions for work and recreation. In Nepal alone, over 130,000 foreigners visit each year to complete trekking and mountaineering activities of which half may get acute mountain sickness (AMS). However, general illnesses such as diarrhea and upper respiratory symptoms, and also psychological disturbances, contribute to ill health experienced at altitude.[3-5]
The intrusive nature of such general illnesses is likely to limit work capacity and enjoyment. There is also a substantial risk of having to be evacuated from expeditions due to such illnesses, and a small but real risk of such illnesses eventually resulting in death. Furthermore, conditions such as diarrhea, upper respiratory symptoms, and anxiety may be of considerable relevance to AMS since the conditions share many of the same symptoms (eg, nausea).[8, 9] Not only does this hamper diagnosis, but some authors have speculated that upper respiratory symptoms, diarrhea, or high anxiety may be causally related to AMS or share a common mechanism.[5, 10, 11]
However, whether exposure to high altitude environments per se actually increases incidence of diarrhea, upper respiratory symptoms, and anxiety remains unclear. Detailed description of these illnesses is lacking, and how these illnesses interact together is also unknown. Thus, the aim of the present investigation was to describe physical and mental health during a typical high altitude expedition. This study also aimed to explore relationships between illnesses and commonly implicated physiological factors, such as arterial oxygen saturation, heart rate, and fluid intake. Our hypotheses were that general physical (upper respiratory symptoms, diarrhea) and mental (anxiety) health would deteriorate with increasing altitude, and that presence of any illness symptoms or altered physiological parameters would increase AMS.
The study formed one of a series completed on the Medical Expeditions 2008 Hidden Valley Expedition to Nepal. The study exclusion criteria were age less than 18 years, inability to provide informed consent, and any uncontrolled medical condition. The study was approved by both the North West Wales Research Ethics Committee and the Nepal Health Research Council, and all participants provided written informed consent.
To enable the study of AMS and other common illness development over time, an observational prospective cohort study was completed. All participants completed a minimum 19-day (range: 19–24 d) expedition which included a 1-week baseline period at low altitude but under full expedition conditions, followed by ascent to at least 5,372 m (Figure 1). All participants completed the Dhaulagiri trek, which is the remotest and most difficult of the established trekking itineraries of Nepal, while 28 participants also climbed a technically easy peak of 6,035 m.
The expedition was split into four trekking groups, each with an individual nominated to supervise data collection. From the first day of the expedition, participants completed a physical and mental health diary. Immediately upon waking, prior to breakfast, and following a seated rest period of 2 minutes, participants self-reported the following: (1) AMS: symptoms were recorded using the Lake Louise scale, which recorded the severity of five items on a 0 to 3 Likert scale. Clinical diagnosis of AMS was defined as the Lake Louise definition of a total score ≥3 including headache, plus one other symptom. Scores for individual symptoms and total symptom scores were also calculated. (2) Stools: recorded using the Bristol Stool Scale, which recorded the consistency of motions on a 1 to 7 Likert scale with an extra question on the number of motions per day. Clinical diagnosis of diarrhea was defined in its strictest sense as loose stool (Bristol Stool Scale ≥ 6) at least three times within 24 hours. However, most people describe diarrhea as loose stool (Bristol Stool Scale ≥ 6) regardless of frequency, and stool consistency also gives a more accurate measure of intestinal transit time. Therefore, information on stool consistency alone was also calculated (a higher number indicated a looser stool). (3) Upper respiratory symptoms: recorded using a modified Jackson system, which detailed the severity of seven items (malaise, chilliness, sneezing, sore throat, runny nose, blocked nose, and cough) each on a 0 to 3 Likert scale (the headache score was removed). As there are no sufficiently sensitive and specific clinical definitions of presence or absence of upper respiratory infections,[20, 21] the Niemen method of defining presence of upper respiratory symptoms as any score above 1 was used. (4) Anxiety: recorded using the short form state-trait anxiety scale, which recorded the severity of six items on a 0 to 3 Likert scale (adapted from the usual 1–4 scale to ensure consistency with the other self-report measures). Alpha coefficients for the anxiety scale in the present study ranged from 0.83 to 0.92 (above the recommended value for psychological measures of 0.70). (5) Fluid intake: determined daily by using drink bottles of known volume and bead counters to record refills. Total fluid intake was also determined from 24-hour food and fluid diaries on day 3 (1,100 m) and day 13 (4,700 m), with food and fluid composition determined by computer software (Dietmaster; Lifestyles Technologies Inc, Phoenix, AZ, USA). Arterial oxygen saturation and resting heart rate: by finger tip pulse oximeter (9500, Onyx; Nonin, Plymouth, MN, USA), recorded when participants were sheltered from the wind, after wearing gloves and blinded to their results. The lowest and highest values observed over a 1-minute period were recorded and the mean calculated.
To achieve the study's first aim, for each illness, the individual symptom score and the total symptom score were calculated to provide daily expedition mean scores. Statistical differences between days were determined by repeated measures analysis of variance. Significant differences were followed up by Holm–Bonferroni procedures using 1,435 m as the baseline for comparison (the last day of the baseline period that exhibited normal arterial oxygen saturations). Also, for each illness, the expedition's daily sum of symptom scores (a marker of expedition symptom burden), daily and total expedition incidence (the number of individuals achieving criteria, when available, for clinical diagnosis), and event rates (expressed per 100 person days) were calculated. Participants with missing data were removed from these analyses.
To achieve the study's second aim, longitudinal linear regression analyses were performed using generalized estimation equations. The predictor variables were day of expedition, height gain, upper respiratory symptoms, stool consistency, anxiety symptoms, arterial oxygen saturation, heart rate, and fluid intake. In the first model, all expedition days were analyzed, and the outcome variable was total AMS symptoms. In the second model, the outcome measure was the cardinal symptom of AMS: high altitude headache; in the third logistic model, the outcome was AMS defined by Lake Louise diagnosis (as is also often investigated in hypoxia research). To determine whether predictor variables were consistent with being causally related to AMS, the first two models were rerun using a temporal time-lag technique. This involved the predictor variables at time-point t − 1 day being related to the outcome variable of AMS at time-point t and allowed determination of sequential temporality (ie, did the predictor variable change before the outcome variable?).
All statistical analyses were completed using SPSS version 18 (IBM Corporation, NY, USA), and statistical significance was accepted at p < 0.05. A sample size estimation conservatively assuming the use of a five-height repeated measures experiment indicated that 22 participants would be needed to produce a 90% chance of obtaining statistical significance at the 0.05 level for a difference between the most extreme heights of 0.7 standard deviations, a medium dispersion of height means, and an average correlation of 0.6 among the repeated measures.
The demographic and clinical data for the 44 analyzed participants are presented in Table 1. All medical conditions were well controlled and symptom free at the time of the expedition's departure. All participants were encouraged to continue normal medications, but altitude-specific prophylaxis/medications were discouraged.
|Age||34 ± 13|
|Gender||25 male, 19 female|
|Height (cm)||169 ± 7|
|Body mass (kg)||71 ± 12|
|Physical function (total n = 44)||Poor||0|
|Expedition experience (total n = 44)||None||7|
|Altitude experience (total n = 44)||None||7|
|High altitude illness history (n = 16)||Acute mountain sickness||15|
|High altitude pulmonary edema||1|
|Respiratory conditions (n = 10)||Smoker||0|
|Prescribed asthma inhaler||3|
|Asthma attack in previous 3 y||0|
|History of other relevant illnesses (n = 10)||Migraine||3|
Arterial oxygen saturations are shown in Figure 2 and reveal decreased arterial oxygen saturations from a height of 2,081 m. The lowest mean value was 79.0% ± 4.4% at 5,050c m. Fluid intake consumed from drink bottles also decreased as height was gained (F = 7.173, p < 0.001). Total fluid intake was 70 ± 18 mL/kg/d at 1,100 m and 48 ± 18 mL/kg/d at 4,700 m. Symptoms of diminished physical and mental health are described in Figures 3 and 4. Lake Louise symptom scores increased from the second day at 3,612 m and remained elevated until the third day at 5,050 m (Figure 3). Nineteen of 44 individuals (43%) had clinically defined AMS while above 2,476 m. The AMS maximum symptom score on any one day was 95 (from a possible range of 0–660) and occurred on the second day at 4,670 m. The peak incidence of clinically defined AMS was 11 of 44 participants, which occurred twice (on the second day at 4,670 m and on the first day at 5,050 m). The rate of AMS per 100 person days was 9.2 (95% CI: 7.2–11.7), and the average length of illness was 2.8 days (2.2–3.4 d). On the second day at 4,670 m when the maximum daily burden of AMS symptoms occurred, the total Lake Louise score comprised the following individual symptoms: difficulty sleeping (28%), headache (27%), fatigue (19%), gastrointestinal upset (16%), and dizziness (10%) (Figure 3). However, despite difficulty sleeping contributing substantially to the Lake Louise total score throughout the expedition, it was also the item that was least sensitive to increasing altitude and acclimatization.
Similar to AMS, upper respiratory symptoms increased from the second day at 3,612 m and remained elevated until the second day at 5,050 m (Figure 3). All the 43 individuals (100%) had upper respiratory symptoms at least once during the expedition. The maximum upper respiratory symptom score on any one day was 159 (from a possible range of 0–903) and occurred on the third day at 5,050 m. The peak incidence of presence of upper respiratory symptoms was 40 of 43 participants, which occurred on the second day at 5,050 m. The rate of upper respiratory symptoms per 100 person days was 74.4 (68.3–80.9), and the average length of illness was 11.3 days (9.8–12.8 d). On the second day at 3,612 m when the maximum daily burden of upper respiratory symptoms occurred, the total upper respiratory symptoms score comprised the following individual symptoms: runny nose (27%), blocked nose (17%), cough (16%), sneezing (12%), malaise (11%), chilliness (10%), and sore throat (8%) (Figure 3). Both sore throat and sneezing symptoms were unaltered by altitude. Of the remaining symptoms, runny nose, blocked nose, and cough were the most sensitive to altitude changes.
In contrast, stool consistency (Figure 4) showed the opposite relationship. More solid stool consistency was observed as the expedition progressed and altitude was gained. Nevertheless, 13 of 41 individuals (32%) had clinically defined diarrhea and 28 of 41 (68%) individuals had loose stools during the expedition. The peak incidence of clinically defined diarrhea (7 of 41 participants) occurred at 826 m. The rate of clinically defined diarrhea per 100 person days was 3.2 (2.0–4.8), and the average length of illness was 1.7 days (1.4–2.0 d). The rate of loose stools per 100 person days was 15.2 (12.5–18.4), and the average length of illness was 3.5 days (2.5–4.5 d).
Mean anxiety scores were significantly increased on three occasions, all of which were at high altitude (Figure 4). Forty-two of 43 individuals (98%) had anxiety symptoms at some point during the expedition. The maximum anxiety symptom score on any one day was 37 (from a possible range of 0–774) and occurred on the second day at 4,670 m. The peak incidence of anxiety was 33 of 43 participants, which also occurred on the second day at 4,670 m. The rate of anxiety per 100 person days was 64.8 (59.1–71.0), and the average length of illness was 11.3 days (9.6–13.0 d).
The first set of longitudinal regression models investigated relationships between predictor variables and AMS and explained between 14 and 31% of the variance in AMS, depending on method of AMS definition (Table 2). As can be seen from the significant p and β values (model 1 in Table 2), total AMS symptom score was positively correlated with upper respiratory symptoms, stool consistency (where a higher number = looser stool), and anxiety. Heart rate was also positively correlated with total AMS symptom score; in contrast, fluid intake was negatively correlated with total AMS symptom score. When investigating the symptom of high altitude headache alone (model 2 in Table 2), upper respiratory symptoms and stool consistency (where a higher number defines a looser stool) were correlated with headache severity, as did arterial oxygen saturation. However, when investigating presence or absence of clinically defined AMS (model 3 in Table 2), only upper respiratory symptoms (positive correlation) and arterial oxygen saturation (negative correlation) were significant predictors. Odds ratios suggested that a 1 unit increase in upper respiratory symptoms was associated with a 1.040 (1.005–1.262) significantly higher odds of having AMS; a 1 unit decrease in arterial oxygen saturation was associated with a 1.068 (1.000–1.141) significantly higher odds of having AMS.
|Model number and details||Model fit||Explained variance (%)||Predictors|
|1. Acute mountain sickness symptoms (total Lake Louise score). Days: 1–24 Heights: 826–5,050 m||1043||30.5||Intercept||0.569||−0.345||0.607|
|Arterial O2 saturation||0.582||−0.002||0.003|
|Resting heart rate||0.011*||0.014||0.006|
|Upper respiratory symptoms||> 0.001*||0.146||0.026|
|2. High altitude headache. Days: 8–24 Heights: 2,476–5,050 m||115||14.1||Intercept||0.005*||1.378||0.487|
|Arterial O2 saturation||>0.001*||−0.018||0.005|
|Resting heart rate||0.405||−0.002||0.002|
|Upper respiratory symptoms||0.013*||0.026||0.010|
|3. Acute mountain sickness present or absent (Lake Louise definition). Days: 8–24 Heights: 2,476–5,050 m||259||Logistic||Intercept||0.659||1.302||2.951|
|Arterial O2 saturation||0.048*||−0.066||0.034|
|Resting heart rate||0.705||0.006||0.016|
|Upper respiratory symptoms||0.039*||0.119||0.058|
Time-lag models, which investigated whether variables predicted AMS the following day as required to infer causality, explained between 10 and 24% of variance in AMS (Table 3). The following day's total AMS symptom score was positively correlated with upper respiratory symptoms (model 4 in Table 3). Heart rate and fluid intake also predicted future AMS symptoms. Thus, an increase of upper respiratory symptoms by 5 units would increase total AMS symptom score the following day by 0.72 units (0.54–0.89); an increase in heart rate of 10 beats per min would increase AMS score by 0.18 units (0.08–0.28); and a decrease of 10 mL per kg of body mass of fluid intake per day (∼710 mL per day) would increase total AMS score by 0.07 units (0.01–0.12). When investigating the symptom of high altitude headache alone, only arterial oxygen saturation was negatively correlated with the following day's headache severity (model 5 in Table 3). Thus, a decrease in arterial oxygen saturation of 5% would increase headache severity the next day by 0.06 units (0.02–0.10).
|Model number and details||Model fit||Explained variance (%)||Predictors|
|4. Acute mountain sickness symptoms (total Lake Louise score). Days: 2–24 Heights: 826–5,050 m||1051||24.0||Intercept||0.954||−0.030||0.518|
|Arterial O2 saturation||0.103||−0.005||0.003|
|Resting heart rate||>0.001*||0.018||0.005|
|Upper respiratory symptoms||>0.001*||0.143||0.018|
|5. High altitude headache. Days: 9–24 Heights: 2,476–5,050 m||122||10.6||Intercept||0.006*||1.066||0.391|
|Arterial O2 saturation||0.001*||−0.012||0.004|
|Resting heart rate||0.170||0.003||0.002|
|Upper respiratory symptoms||0.093||0.016||0.010|
This study is the first to use a longitudinal multiple regression analysis of daily illnesses and mental disturbances recorded during a relatively large expedition to high altitude. AMS affected almost half of the expedition participants, with up to one quarter having AMS on any day. However, AMS incidence alone underestimated the total illness symptom burden: all the participants also had upper respiratory symptoms, two thirds had loose stools and one third had diarrhea, and almost everyone reported mild anxiety. Upper respiratory symptoms increased as altitude was gained, and anxiety was also increased on certain days at high altitude. Detailed description of illnesses revealed that the variable contributing most to AMS symptom burden was difficulty sleeping. However, difficulty sleeping was also the least sensitive of the AMS symptoms to altitude change. The variables that contributed most to upper respiratory symptom burden were nasal and cough related, and these variables were the most sensitive of the upper respiratory symptoms to altitude change. Throughout the expedition, participants with increased AMS symptoms had poorer physical and mental health, higher heart rate, and lower fluid intake. Upper respiratory symptoms, heart rate, arterial oxygen saturations, and fluid intake also predicted AMS symptoms the following day, and thus, these predictor variables were consistent with being causally related to AMS. However, contrary to our hypotheses, this study found no increase in diarrhea with altitude, and no causal effect of diarrhea and anxiety on AMS.
The incidence of AMS in the present study is consistent with previous studies using similar ascent profiles, as recently reviewed. Although a landmark early study suggested no association between upper respiratory infections and AMS incidence, subsequent studies provided data consistent with a greater number of respiratory symptoms and diarrhea being associated with a greater number of symptoms and severity of AMS. Nevertheless, conclusive evidence that general illness caused AMS was still lacking. The present study thus extends previous findings by providing empirical support, using a longitudinal regression design that upper respiratory symptoms increase with altitude and are associated with AMS. Of course individuals may not be able to differentiate between symptoms of upper respiratory symptoms and AMS, as evidenced by the reporting of “AMS” symptoms at low altitude. This highlights that misdiagnosis may occur and incorrect treatment may be administered. Nevertheless, previous authors have suggested that upper respiratory symptoms may predispose to AMS.[5, 10] The exact cause for this relationship remains unclear, but if any upper respiratory symptoms are due to infection, then one plausible mechanism is that an immune response such as inflammation may increase AMS,[5, 29] although such a mechanism remains to be proven.
In contrast to upper respiratory symptoms, in the present study, diarrhea did not increase with altitude and was not causally associated with AMS. Similarly, anxiety was increased at altitude but inconsistently so, and like diarrhea was not causally associated with AMS. Although previous studies have shown relationships between diarrhea and anxiety with AMS, they could not establish whether data were consistent with causality as was tested in the present study. Possibly, diarrhea may cause symptoms such as dehydration headache rather than AMS per se, and anxiety may be a consequence, rather than a cause of AMS.
Previous authors have also suggested that arterial oxygen saturation may predict AMS susceptibility.[10, 30-32] However, arterial oxygen saturation testing has failed to gain widespread acceptance, and some authors[33, 34] have found that resting oxygen saturation may be inferior to other predictor variables of AMS, albeit often only acute exposure was investigated. The data presented herein provide empirical evidence that arterial oxygen saturation is reduced with AMS and when daily measures are obtained reveals that resting oxygen saturation also predicts future AMS symptoms. It has been speculated that such a relationship may be due to sub-clinical pulmonary edema. Similarly, elevated heart rate has been associated with AMS by some but not all authors; the current data which is supportive of the relationship is consistent with the hypothesis of altered autonomic cardiovascular control leading to AMS. Alternatively, some other factor which elevates heart rate may cause AMS symptoms, such as dehydration. Although data on hydration state and AMS is contradictory,[10, 13, 14] the current data suggest that fluid intake reduced AMS symptoms during the expedition as a whole. However, fluid intake had little effect when investigating more specific and conservative definitions of AMS, possibly because the majority of participants achieved an intake of at least 2 L per day, recently speculated as the minimum intake required to avoid AMS. On the other hand, these findings may be due to fluid intake reducing dehydration-associated headache rather than altitude-associated headache per se, a finding consistent with recent experimental studies suggesting that dehydration induces headaches of similar severity to hypoxia.
Weaknesses of the study include lack of clinician and microbiological diagnosis of illness. However, such methods to verify diagnosis of illness have recently been scrutinized and found lacking. While self-assessment may lead to underreporting of illness due to social desirability bias, controlling for this weakness would have been unlikely to improve accuracy of the health logs. Finally, this observational cohort study was non-interventional and did not include a control group. The longitudinal analysis that allowed estimation of causality and the multiple time-point baseline period at lower altitude, which was longer than accepted incubation periods for general illnesses, addressed this issue. Furthermore, the present study's control period, completed under expedition conditions and where individuals acted as their own controls, may be a stronger design than using a control group residing at low altitude but under non-expedition conditions.
In conclusion, upper respiratory symptoms and anxiety increasingly contributed to symptom burden as altitude was gained. Data were consistent with increased heart rate, decreased arterial oxygen saturation, reduced fluid intake, and upper respiratory symptoms being causally associated with AMS. These findings are of relevance to researchers investigating travel-associated illnesses common at altitude.
For those offering travel advice, the findings should be used to increase education of the potential incidence and burden of illness and mental disturbances in high-altitude environments, especially as some commercial companies seem to ignore recommended ascent rates making high altitude illness likely. The risk of diarrhea at low altitude compared to high altitude, most likely due to poor food hygiene, is important. It is also of interest that those with general AMS symptoms may have higher anxiety, and expedition leaders should be vigilant for such mental disturbances. The findings also offer alternative intervention targets to reduce risk and severity of AMS. If upper respiratory symptoms are at least in part due to infections, those visiting high altitude could use appropriate recovery strategies when performing arduous exercise, maintain good personal hygiene, ensure good nutrition, obtain adequate good quality sleep, reduce chances of infection transmission, and aggressively treat infections with appropriate medications, all of which may reduce upper respiratory symptoms and consequently alleviate AMS symptoms. Effective strategies to increase fluid intake, for example, by purifying and flavoring water, may help avoid general headache symptoms. Not only will this enhance productivity and enjoyment of altitude sojourners, but serious complications associated with these illnesses may then be reduced.
The authors gratefully acknowledge all participants and funders. This study was supported by Science in Sport (drinks supplement and funding for outcome measures), Ministry of Defense (Army) (funding for outcome measures), Mountain Equipment (researcher personal equipment), Panasonic United Kingdom (Toughbook laptops), Qatar Airways (Carriage), Polar United Kingdom, Optimal Performance, nSpire Health Inc, Vitech Scientific, and Digitalscales.com (all scientific equipment). The study funder played no part in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. This work is the opinion of the authors and not that of Science in Sport or Ministry of Defense (Army).
The authors state that they have no conflicts of interest to declare.