2009-2019: A comparative study on CMS of plateau migrants around ten years

In this study, CMS prevalence of people living on plateaus at altitudes of 3300-5400 m was surveyed. Comparative analysis was carried out with the same standard and the changes of CMS prevalence between the ten-year apart results were presented accurately. The in-depth analysis of CMS relevant inuencing factors provided a basis for prevention and diagnosis of CMS.


Abstract Background
Chronic mountain sickness (CMS), is a common disease occurred to people who migrate to plateau. Current CMS studies in different periods or areas have poor comparability due to the inconsistent diagnosis methods. Here we carried out a comparative study of the CMS prevalence in the year 2019 and 2009, to provide evidence for the prevention and diagnosis of CMS.

Methods
The Qinghai CMS Scoring System (Qinghai standard) was used to investigate the subjects who lived for at least months in the 3300-5400 m altitude area in 2019 and 2009, respectively. Their prevalence and symptom scores were also analyzed and statistically compared.

Results
The prevalence of CMS in 2019 survey subjects (15.60%) was signi cantly lower than that in 2009 (31.18%). The prevalence of dyspnea, venous dilatation, paresthesia, headache, tinnitus, and hemoglobin concentration reached 21g/dL or above decreased signi cantly among the survey subjects in 2019. The scores of cyanosis, venous dilatation, paresthesia, and headache signi cantly decreased in the 2019 survey subjects. But among the CMS patients, the sleep disturbance scores of the 2019 survey subjects increased signi cantly.

Conclusion
Compared to 2009, the health level of high altitude living population in 2019 has been signi cantly improved, indicating that the sleep research on high-altitude living population and the application of high altitude oxygen therapy has been effective in the past ten years. Among the CMS associated symptoms, sleep disturbance is an important indicator for the prevention and diagnosis of CMS, which deserves special attention.

Background
Chronic mountain sickness (CMS) is a disease that usually occurred in unacclimatized persons who live in areas above 2500 m for a long time. Typical symptoms of CMS include polycythemia, hypoxemia, breathlessness, palpitation, sleep disturbance, cyanosis, venous dilatation, headaches, tinnitus, and dizziness.
CMS survey is an important way to acknowledge the prevalence. However, studies in different periods or areas could not be compared properly due to the varied CMS diagnosis methods [1][2][3][4]. In this study, we used Qinghai standard to survey the prevalence of CMS in Chinese Han individuals who migrated to Qinghai-Tibetan plateau at an altitude of 3300-5400 m in 2009 and 2019. The same CMS diagnosis standard applied to the ten years apart surveys made the reasonable comparison be possible.
Characteristics of prevalence in both 2009 and 2019 were analyzed and the differences between these two results were compared more accurately owe to the application of the same standard. Besides, CMS diagnose criteria was also discussed.

Participants
The survey subjects were all male volunteers recruited from areas with an altitude of 3300-5400 m and totally 218 and 510 volunteers were recruited in 2019 and 2009, respectively. These participants lived in low altitude areas before (Anhui, Fujian, Gansu, Guangdong, Guangxi, Guizhou, Hebei, Henan, Hubei, Hunan, Jilin, Jiangsu, Inner Mongolia, Ningxia, Shandong, Shanxi, Shaanxi, Sichuan, Yunnan, Zhejiang and Chongqing provinces of China) and all migrated to the plateau for at least months. The basic information (Table 1) of subjects were obtained through questionnaires. The written informed consent was obtained from all subjects. No health care interventions were involved, and all data were anonymized.
Hb, oxygen saturation, and heart rate measurement The hemoglobin (Hb) concentration was measured by routine blood test. The nger blood oxygen saturation (SO 2 ) was measured by a handheld oximeter (TuffSat. GE Healthcare, London, England). The heart rate (HR) and blood pressure (BP) were measured by an electronic blood pressure monitor (HEM-7112. Omron, Kyoto, Japan).

Data analysis
The CMS prevalence between 2019 and 2009 was compared with the χ 2 test. The score of symptoms were compared with independent-samples t-test analysis and the prevalence of each symptom was compared with the χ 2 test between 2019 and 2009. Correlation of Hb with SO 2 was analyzed and the curve tting analysis was carried out. between the two batches of data, and the scores of which were signi cantly lower in 2019 than that in 2009 (Figure 1 A-D), while no signi cant difference was found in the scores of dyspnea/palpitation, sleep disturbance and tinnitus (Figure 1 E-G).
Further analysis of the symptom scores of the CMS patients revealed that there was no signi cant difference in the prevalence of all symptoms between the two years. In terms of symptom scores, compared to the year 2009, the score of sleep disturbance (p=0.015) among the CMS patients surveyed in 2019 were signi cantly increased (Figure 1 H), while the score of cyanosis (p=0.016) were signi cantly decreased (Figure 1 I).

Correlations between Hb concentration and SO 2
Analysis revealed that SO 2 signi cant related with Hb concentration. Quadratic curve was identi ed to be the best tting curve for the merged Hb and SO 2 results from 2019 and 2009 survey (

Discussion
Long time exposure to high altitude hypoxia might affect the health of people and cause CMS. In this study, CMS prevalence of people living on plateaus at altitudes of 3300-5400 m was surveyed.
Comparative analysis was carried out with the same standard and the changes of CMS prevalence between the ten-year apart results were presented accurately. The in-depth analysis of CMS relevant in uencing factors provided a basis for prevention and diagnosis of CMS.
People's health has improved over the past ten years In terms of the basic information of the survey respondents, compared to 2009, the average body weight of 2019 subjects was slightly heavier, which might re ect the improvement of living conditions over the past ten years. There was no signi cant difference in average altitude between the two batches of survey subjects. The survey subjects in 2019 lived on the plateau longer than those in 2009, but the BP and HR of the 2019 survey subjects were lower. In terms of CMS scores, the 2019 survey results were also signi cantly lower than those in 2009. The above results indicated that the health of the survey subjects in 2019 was better than that in 2009. In recent years, the health status of the plateau population has attracted more and more attention, and related research has gradually been carried out, especially the sleep study of plateau population [5], diagnosis of altitude sickness [6], oxygen therapy [7], optimization of physical examination indicators [8], et al. These may be an important reason for the signi cant improvement of the health. The results of the comparison of various symptoms showed that the increase in health attention of the people on plateau had the most obvious impact on cyanosis, venous dilatation, paresthesia and headaches, which signi cantly improved both in prevalence and severity.
Sleep disturbance may be an important factor in the occurrence of CMS The survey results in 2019 showed that dyspnea/palpitation, sleep disturbance and headache were the top three symptoms among all survey subjects. However, sleep disturbance became the most severe symptom among the CMS patients. The results indicated that dyspnea/palpitation and headache might be common symptoms caused by hypoxia, but sleep disturbance played a more important role in the occurrence of CMS. And this was consistent with the survey results in 2009. Decreased sleep quality caused by long-term sleep disturbance would make the body not get su ciently rest, which reduced the physical function, and then CMS was more likely to occur. It is worth mentioning that there is no signi cant difference in both severity or prevalence of sleep disturbance among the survey subjects, indicating that sleep disturbance might be more stable than the other symptoms in Qinghai standard. But at the same time, among the CMS patients, compared with 2009, the sleep disturbance scores of the CMS patients in 2019 were higher, which indicated that it was more serious. The above results suggested that sleep disturbance should be paid more attention to in the prevention and diagnosis of CMS. For the plateau residents, improvement of the sleep disturbance might be a prospective way to reduce the CMS prevalence.

Advice on CMS diagnosis
The Qinghai standard used in this survey scored the subjects according to the impression of the corresponding symptom severity in the CMS scale by the survey subjects themselves. Although there was a ten-year long time between the two survey results, dyspnea/palpitation, sleep disturbance and headache all showed high prevalence in both results, suggesting the consistency of the trend of CMSrelated symptoms. But at the same time, the score of cyanosis differed greatly between the two survey results. The results showed that there was no signi cant difference between the two batches of data in terms of Hb concentration. However, the blood oxygen saturation value of the 2009 survey object is slightly higher than that in 2019, but the severity of the cyanosis score shown in the 2009 survey result was signi cantly higher. We speculated that this might had a certain relation with the cyanosis evaluation standard. The cyanosis score was judged by the color of the ngernail and lips of the survey subjects. It was more intuitive than indicators such as headache and dyspnea, but it was also easier to make an overall difference by corresponding the same color depth to different scores. Therefore, a color comparison reference based on the relation between the hypoxia severity and cyanosis might be a way to avoid the overall difference in cyanosis scoring.
Analysis revealed that quadratic tting was the best tting method to describe the correlation of Hb concentration and SO 2 ( Table 2). Whether the data in 2019 and 2009 were merged or not, the tting curve was always a parabola with negative quadratic coe cients (Fig. 2), indicating that as the Hb concentration increased, the SO 2 showed a trend of increasing rst and then decreasing. When lived in hypoxic environment for a long time, the body would generate more erythrocyte and Hb to meet the oxygen demand and the SO 2 could be increased. However, if the low environmental partial pressure of oxygen couldn't meet the need of the body, the persistent chronic hypoxia of the body would happen, then may cause further increase in erythrocyte and Hb. As a result, more and more Hb would be generated but not fully oxygenated. According to the tting curve, the SO 2 level began to decrease when Hb concentration was lower than 21 g/dL, which mean that the body entered the decompensation period before the Hb concentration reached 21 g/dL. These results suggested that the diagnosis standard of Hb concentration might need to be adjusted to a lower value than 21 g/dL, but the new exactly judgement threshold need further study to determine.

Limitations
There were some limitations in this study. Participants in this study were all young male and whether the conclusions were available for female or older population was not sure. Besides, drinking and smoking, which might have effect on the body, were not considered in this study.

Conclusion
Long time plateau living makes people face with CMS, which could cause serious damage to the health.
In-depth study of the occurrence and development of CMS is very important for CMS prevention and diagnosis. According to the analysis of the ten-year apart CMS surveys, prevalence of CMS has been found decreased compared to ten years ago, and sleep disturbance, which revealed to be closely related to CMS, might be an important symptom and need to be taken seriously. Besides, the CMS diagnosis standard should also be discussed.