Evaluation Of Diagnostic Criteria For Acute Mountain Sickness And The Preventive Effect Of Inhaled Corticosteroids

Acute mountain sickness （AMS） refers to a series of non-special clinic syndromesoccurring in people rapidly ascending to high altitude （HA） more than2500m, such asheadache, dizziness, nausea, emesis, fatigue or insomnia. The seriously affected will bethreatened by high altitude pulmonary edema （HAPE） or even high altitude cerebral edema（HACE）. As for AMS, except a few cases of HAPE and HACE, there is no diagnostic sign.AMS is probably related to hypobaric hypoxia of a plateau, which will lead to cerebralvasodilation or activation of nitric oxide through trigeminal vascular system, thus causingheadache. Moreover, headache itself can give rise to other symptoms, such as nausea andfatigue, leading to AMS. Besides, mild cerebral edema can also play a part in AMS.The number of visitors, mountaineers and frontier soldiers entering plateaus over3000m every year in China is large. Chinese researchers have done a lot of studies of AMS.However, there is inconsistence between Chinese diagnosis standard of AMS （AMS-CSS）and international standard diagnosis of Lake Louise for AMS （AMS-LLS）. Headache is notthe precondition for diagnosing AMS according to AMS-CSS. Additionally, differences inexpression between Chinese and English languages make it difficult to compare ourresearch findings of AMS with that of foreign AMS researches. Therefore, Chineseresearchers’ findings of AMS are unknown to the world. It is essential to compare the effectsof the two diagnosis systems on AMS incidence. With the increase of altitudes, humanarterial partial pressure of oxygen will gradually decrease, while pulse oxygen saturation（SpO₂） can be below80%in Morococha （4500m）, Peru. At present, it is in dispute whetherSpO₂can be a predictive factor to diagnose AMS because of disagreements among researchresults and lack of large-scale field studies.Gradual staged ascent to HA is not applicable for some emergencies, such asmobilization during a battle, disaster relief and so on. Therefore, chemoprophylaxis against AMS seems important. Acetazolamide is a safe and effective drug recommended byConsensus Guideline of Wilderness Medical Society for AMS prevention, which, however,is not available in China. Oral glucocorticoids are also effective for AMS prevention, butmay cause systematic side effects. Further study is needed to discover better drugs toprevent AMS. The safety and efficacy of long-term application of inhaled budesonide （IB）,an inhaled glucocorticoid, to children and adults with asthma has been verified. In this case,we hypothesize that IB can prevent AMS without systematic side effects caused by oralglucocorticoids.ObjectivesIn our study, we would like to observe the incidence of AMS under two differentstandards of AMS （AMS-CSS and AMS-LLS） in various ways into distinct altitudes ofplateaus, to know the relevance of SpO₂in different conditions and AMS, to determinewhether SpO₂is the predictive factor of AMS, and to study whether IB can prevent AMS.Methods1. Epidemiological survey on the incidence of AMS after ascent to3200m plateauby trainIn June2011,339subjects were recruited in this study. They took train from Xi’an,Shanxi province （345m） and then by bus to a settlement （3200m） within48hours. Theparticipants were divided into group1,2and3（n=88,91and160, respectively）. Eachgroup stayed at3200m for1,2and3nights, respectively. We adopted demography analysis,carried out AMS-LLS, AMS-CSS symptoms-sign investigation and measured their heartrate （HR）, blood pressure （BP） and SpO₂.2. Epidemiological survey on the incidence of AMS for those entering a higheraltitude area after3600m altitude acclimatizationIn August2011, this research enrolled67healthy Chinese males, who stayed at3600maltitude area for40days. We collected baseline data including demographic data, HR, BPand SpO₂. Then participants marched on by car for17days at HA with an average altitudeof3460m. They stayed the night at Lhasa （3650m） at the16thday. The next day, theytravelled to a higher altitude destination （4400m） in3hours.24hours later, the second data collection was performed. The participants stayed there for26days and then took train backto plain region.36days later, the third time data of deacclimatization was collected.3. Epidemiological survey on the incidence of AMS after ascent to3700m plateauby airIn June2012,1250young men participated in this research. They travelled fromChengdu Plain （500m） to3700m plateau within2².5h by air.24hours later, we collecteddemographic data, AMS-LLS and AMS-CSS questionnaires, HR, BP and SpO₂.4. Pilot study on inhaled budesonide for the prevention of AMSIn June2012,80healthy young men were recruited in this trial. One week beforesetting out to plateau, we collected baseline data of BP, HR and SpO₂at500m plain. Theywere randomized into four groups （20subjects for each group）. Each group was givendifferent medicine: IB, procaterol tablets, inhaled budesonide/formoterol （IBF） and placebo.They took medicines three days before an ascent from500m to3700m within2².5hoursby plane. They stopped taking any medicines after arrival. Then the participants fulfilledAMS-LLS questionnaire and measurement of BP, HR and SpO₂at20,70and120hoursafter exposure to high altitude. Pulmonary function test was carried out at20hours afterexposure.Results1. Epidemiology survey on the incidence of AMS at to3200mAccording to AMS-LLS and AMS-CSS, the incidence of AMS was17.11%（N=58）and29.79%（N=101） respectively （p <0.001）. There is significant association between twoscores （r=0.820, p <0.001）.58subjects were diagnosed as AMS （+） by AMS-LLS as wellas by AMS-CSS. Two criteria both showed that the incidence of AMS was lowest afterstaying in plateau for one day but highest after staying for two days. Among339subjects,the top-five symptoms were decreased activity ability （61.7%）, fatigue/weakness （49.05%）,dizziness （28.9%）, chest tightness （28.3%） and headache （27.4%）. There is no clearcorrelation between AMS-LLS or AMS-CSS scores and SpO₂levels （p>0.05）; there is nosignificant difference of SpO₂between AMS （-） and AMS （+） subjects.2. Epidemiology survey on the incidence of AMS for those entering a higheraltitude area after3600m altitude acclimatization The HR of67subjects was78.48±13.96bpm and SpO₂was90.88±2.25%after40-dayHA acclimatization. After entering a higher altitude plateau, the incidence of AMSdiagnosed by AMS-CSS was much higher than that diagnosed by AMS-LLS （56.92%vs.39.39%, p=0.045）.26subjects were diagnosed with AMS （+） by AMS-LLS as well as byAMS-CSS, the data was the same when the train is on3200m. AMS （-） and AMS（+）groups were divided by AMS-LLS and by AMS-CSS. When compared with two grouprespectively, there was no significant difference of SpO₂and HR （p>0.05）. After stay inplain for36days, subjects in Yangbajin diagnosed with AMS （+）by AMS-LLS still havedizziness （46.15%）, fatigue/weakness （42.31%）, headache （38.46%）, insomnia （34.62%）,gastrointestinal symptoms （7.7%） and other symptoms. Subjects in Yangbajin diagnosedwith AMS （+） by AMS-CSS still have fatigue/weakness （40.54%）, dizziness （37.84%）,headache （32.43%）, insomnia （29.73%）, gastrointestinal symptoms （5.4%） and othersymptoms. There were statistical differences of the HR and SpO₂among the three regions（3600m,4400m and300m）（p <0.001）.3. Epidemiology survey on the incidence of AMS after ascent to3700m plateau byairAccording to AMS-LLS and AMS-CSS, the incidence of AMS was60.39%（709/1174）and79.05%（928/1174）, respectively （p <0.001）. There is significant association betweenAMS-LLS score and AMS-CSS score （r=0.91, p <0.001）.709subjects were diagnosedwith AMS （+） by AMS-LLS as well as by AMS-CSS. There is clear difference of SpO₂among subjects without AMS, subjects with mild AMS and subjects with severe AMS （novs. mild: p=0.026; no vs. severe: p <0.001; mild vs. severe: p=0.042）. Headache was themain symptom after ascent to3700m by air. After stay for24h in3700m plateau, systolicblood pressure （SBP） increased （79.0±9.83vs.73.87±28.23mmHg, p <0.001）, diastolicblood pressure （DBP） increased （79.0±9.83vs.73.87±28.23mmHg, p <0.001）, SpO₂decreased （88.83±3.08%vs.98.09±1.03%, p <0.001） compared with that in plain.â–³SpO₂refers to the difference value of SpO₂in plateau and that in plain.â–³SpO₂in AMS （-）subjects is lower than that in AMS （+） subjects （AMS-CSS:8.79±2.75%vs.9.37±3.27%, p=0.036; AMS-LLS:8.81±2.85%vs.9.54±3.34%, p=0.001）. 4. Pilot study of inhaled budesonide in the prevention of AMSThere was no difference between the four groups in age, height, weight, BMI, smokinghistory, drinking history, SBP, DBP, HR and SpO₂. At20h after exposure to high altitude,there was great difference between the four groups in the incidence of AMS （p <0.05）.Compared with placebo, IB can effectively reduce the incidence of AMS （25%vs.70%, p <0.01） and severe AMS （5%vs.25%, p <0.05）.AMS incidence of the four groups decreased at72h after exposure to high altitude.AMS incidence of the IB group reduced from25%to5%（p=0.0507）, while AMSincidence of the placebo group decreased from70%to10%（p <0.05）. There was nosignificant difference of AMS incidence at72h between the IB and placebo groups （5%vs.10%, p>0.05）. The reduction of AMS incidence in the other two groups （IBF andprocaterol group） seemed insignificant （both from50%to30%, p>0.05）. In the IB group,SpO₂negatively correlated with AMS incidence （r=-0.45, p=0.0489）. At20hours afterexposure to high altitude, the reduction of SpO₂in AMS （+） subjects was greatly higherthan the that in AMS（-） subjects （-11±2.83%vs.-8.47±1.81%, p <0.05）. At20h afterexposure to high altitude, the four groups had no significant differences in pulmonaryfunction. Besides, pulmonary function did not differ between AMS （+） and AMS （-）subjects. During the whole follow-up period, the subjects tolerated all drugs well, with noobvious side effect reported.Conclusion1. The two kinds of diagnostic system for AMS, AMS-LLS and AMS-CSS, have theirpros and cons, similar with a little bit difference.2. In the three different ways to the plateau, and with the different target altitudes, theincidence of AMS diagnosed by AMS-CSS is higher than that diagnosed by AMS-LLS. TheAMS （+） patients diagnosed by AMS-LLS were included in that diagnosed by AMS-CSS,which indicated that the relationship between AMS-CSS and AMS-LLS is containing andbeing contained. But the role of vomiting in AMS-CSS is debatable.3. Both standards have been established for more than15years, and they are bothsubjective scales, which lack objective diagnostic indicators. More extensive fieldresearches are needed to build a better and more objective diagnostic system. 4. In different entry modes, ascent rates and target altitudes, SpO₂and the incidence ofAMS has different correlation.5. IB can effectively prevent AMS. Its mechanism may be partly related to theprevention of reduction of SpO₂at HA, but not to pulmonary function changes.