The major findings of our present study were as follows: 1) In the fast ascent cohort, the prevalence of AMS was 68.4% and 56.1% at 3700 m, which decreased to 21.4% and 14.3% when further ascending to 4400 m, as diagnosed by the old LLS and new LLS, respectively; 2) In the slow ascent cohort, the prevalence of AMS was 30.3% and 25.7% at 3450 m, which increased to 36.6% and 32.2% when further ascending to 4100 m, as diagnosed by the old LLS and new LLS, respectively; 3) AMS-related symptoms such as headache, dizziness, and fatigue were the leading symptoms after the initial ascent to 3700 m or 3450 m and were still the main symptoms after further ascending to 4100 m in the slow ascent cohort but not to 4400 m in the fast ascent cohort; and 4) the ascent protocol was the primary factor that affected the incidence of AMS and related symptoms, showing that the slow ascent protocol was protective during the initial ascent but became a risk factor after further ascending to a higher altitude.
AMS is a common medical problem that affects the well-being of a large population. A recent systematic review summarized the published incidences of AMS from 53603 subjects, which demonstrated that the median AMS incidence was 60% in randomized trials, 51% in cohort studies, and 32% in cross-sectional studies. The results from the multivariate analysis suggested that the study design, mode of ascent, maximum altitude, population, and geographical location were significantly associated with the incidence of AMS . Indeed, our present data on AMS prevalence were higher or lower than those of previous studies mainly in the population characteristics, mode of ascent, altitude reached and AMS definitions. Similar to our protocol, it had been reported that the incidence of AMS was 84% among tourists who ascended directly to 3740 m by airplane, whereas the incidence of AMS was 61% in subjects who ascended to the same altitude from < 3000 m by foot , which was consistent with our present results that subjects ascending to HA by plane reported more frequent AMS than with other protocols. Furthermore, previous results showed that the overall incidence of AMS was 53% after ascending to 4243 m altitude at Pheriche in the Himalayas of Nepal. It had also been reported that the prevalence of acute mountain sickness was 9% at 2850 m, 13% at 3050 m, and 34% at 3650 m ; the latter of the three values was comparable with our prevalence in the slow ascent cohort at 3450 m. Moreover, it had been demonstrated that the incidence of AMS was 59% of children trekking at 3952 m (Jade Mountain, Taiwan), which was consistent with our results that the most common AMS symptom was headache, followed by fatigue, sleep disorders, dizziness or lightheadedness and gastrointestinal upset .
After arriving at a new altitude above 2500 m in unacclimated individuals, AMS patients usually developed a group of nonspecific symptoms. Among these various symptoms, headache was the defining and indispensable symptom for AMS diagnosis . After sequencing the 15 clinical symptoms reported in our present study, the main symptoms of AMS, including headache, dizziness and fatigue, remained as the cardinal symptoms after the initial ascent to 3700 m by plane or 3450 m by bus, which was consistent with previous results . However, after further ascending to 4400 m in the fast ascent cohort, fatigue, headache and dizziness were no longer the leading symptoms, and their incidence was also lower than that in the slow ascent cohort after further ascending to 4100 m, which suggested that the fast ascent protocol might be more effective in attenuating the incidence of AMS-related symptoms than the slow ascent protocol when subjects further ascended to a higher altitude after a short term of staying at the intermediate altitude. Additionally, activity reduction, which was not a symptom for AMS diagnosis, was another more frequent complaint. Consistently, a previous review claimed that individuals with AMS were frequently incapacitated . Although insomnia had been excluded from the newly revised AMS diagnostic criteria, the incidence of insomnia was still prevalent, as previously described, and was more frequent in the fast ascent cohort than in the slow ascent cohort in our study.
Consistently, the incidence of AMS was highly correlated with the speed of ascent and age, but not sex or previous altitude experience . A previous systematic review summarized that the fast ascent protocol had an OR of 4.69 (95% CI, 2.79–7.90), whereas a slow ascent protocol had an OR of 0.30 (95% CI, 0.20–0.44) for the incidence of AMS, which was highly consistent with our present results during the initial ascent to 3700 m or 3450 m by plane or by bus, respectively. In addition, compared with non-smokers, smokers showed a lower incidence of AMS, suggesting that smoking slightly lowers the risk of AMS but impairs long-term altitude acclimation during prolonged HA exposure , which was similar to our present findings that smoking was a protective factor for AMS in subjects who rapidly ascended to 3700 m, but increased the risk for AMS in a prolonged HA exposure in the slow ascent cohort at 4100 m. However, our data suggested that the associations of smoking and AMS were uncertain and depended on the ascent protocol, altitude attained and diagnostic criteria. Indeed, a previous meta-analysis also showed that there were no consistent results demonstrating that cigarette smoking acted as either a protective factor against or a risk factor for AMS .
It had been recommended that AMS could be prevented by ascending slowly at altitudes above 3000 m and taking a rest day every 3–4 days . Such a protocol had been described as a “staged ascent”, which had been considered the best method for AMS prevention . Indeed, our present data also demonstrated that the incidence of AMS was definitely lower in the slow ascent cohort than in the fast ascent cohort after their initial ascent to an intermediate altitude. A previous report showed that 2 days of staging at an intermediate altitude lowered the incidence of AMS compared with the direct ascent group . However, such approaches did not reduce the incidence of AMS with a rapid ascent to higher altitudes . Therefore, the results from studies aiming to identify the benefit of intermittent hypoxic exposures for AMS prevention were somewhat conflicting for subjects planning a further ascent to higher altitudes. In our present study, the results from the field study at HA indicated that there was no significant impact of the slow ascent protocol combined with 3 days of staging at an intermediate altitude on the incidence of AMS after a further ascent to above 4000 m. Interestingly, although the incidence of AMS was high in subjects after the fast ascent to the initial altitude by plane, the number of subjects suffering from AMS after a further ascent to a higher altitude was significantly lower than that of the initial ascent in the fast ascent cohort and that of a further ascent in the slow ascent cohort. These findings might imply a novel strategy for AMS prevention in individuals travelling to or working at HA when a further ascent to a higher altitude was needed.
There were also several limitations. First, the enrolled participants were young, healthy men, and whether the established results can extend to other types of individuals or circumstances (such as women, older adults, children) is still unknown. Second, the effects of other modes of transport (such as the train) on the incidence of AMS under the present conditions are also unknown. Third, the classification of AMS was based on a self-report without an immediate medical control, which might lead to possible classification bias. Finally, due to the reality of the field study at HA, the target altitudes were not absolutely the same between the two cohorts. Theoretically, the incidence of AMS would be higher in subjects at higher target altitudes ; thus, our conclusions would be even more affirmative if the target altitudes of further ascent were the same in the two cohorts.