Epidemiological Study of Chronic Mountain Sickness in Natives of Spiti Valley in the Greater Himalayas

Abstract

Negi, Prakash Chand, Sanjeev Asotra, Ravi Kumar, Rajeev Marwah, Arvind Kandoria, Neeraj Kumar Ganju, Rajesh Sharma, and Rajeev Bhardwaj. Epidemiological study of chronic mountain sickness in natives of Spiti Valley in the Greater Himalayas. High Alt Med Biol 14:220–229, 2013.— Aims: This study determined the prevalence of chronic mountain sickness (CMS) and its predisposing factors among natives of Spiti Valley in the northern state of Indian Himalayas. A cross-sectional survey study was conducted in natives of Spiti Valley aged ≥20 years residing at altitudes of 3000 to 4200 meters. CMS was diagnosed using Qinghai criteria. Demographics, behavioral characteristics, specified symptoms of CMS were recorded, including BP, anthropometrics, evidence of RHF, PAH, and severe cyanosis. ECG, echocardiography, PFT, and Sao₂ were recorded, and Hb level was estimated with the cyanmethhemoglobin method. Results: 694 subjects free of cardiorespiratory diseases were analyzed. Prevalence of CMS was 28.7%, (95% C.I. of 25.9%–32.8%) and was higher in women than in men (36.6% vs. 15.7%, p<0.001). Erythrocythemia and hypoxemia were recorded in 10.5% and 7.5%, respectively. Age, truncal obesity, female gender, altitude of residence, and physical activity index were independent predictors of CMS with z statistics of 4.2, 2.29, −3.7, 2.8, and −2.8, respectively, and were statistically significant p<0.001. 6.2% of the surveyed population had HAPH. Conclusion: 28.7% (95% C.I. of 25.9%–32.8%) of the natives of the Spiti Valley in the Indian Himalayas are affected with CMS. Higher prevalence of CMS amongst women needs further studies. Westernized lifestyle appears to have predisposition to CMS.

Introduction

Chronic mountain sickness (CMS) is the phenotypic expression of mal-adaptations to physiological stress of hypobaric hypoxia among natives and lifelong residents of high altitude, free of apparent underlying cardiorespiratory diseases that may result from impaired hypoxic ventilatory response, diffusion abnormalities, and perfusion-ventilation inequality. As per the Chinese Medical Association* for high altitude medicine and the Consensus Statement by ad hoc committee of the International Society for Mountain Medicine** on chronic high altitude diseases, CMS manifests as excessive erythrocytosis, hypoxemia, various neuropsychiatric symptoms, and may or may not be associated with severe pulmonary arterial hypertension (PAH) and right heart failure (RHF). Patients of CMS are disabled with impaired memory, headache, breathlessness, fatigue, disturbed sleep, anorexia, and tinnitus that affect the quality of life; some patients may have a vascular element where severe PAH may lead to congestive heart failure (CHF) and death (Penaloza et al, 1971a, 1971b). The physiological derangements observed in CMS subside after descent to low altitude and thus is the only effective treatment of CMS to date (Maria Rivera et al., 2007), although respiratory stimulants such as medroxyprogesterone (Zhou et al., 1983) and acetazolamide have been used (Kryger et al., 1983; Richalet et al., 2005, 2008).

However, option of descent to low altitude is not feasible in a great majority of these high landers due to socioeconomic reasons. Globally about 140 million people reside at altitudes higher than 2500 m. Mountainous regions of the worlds are vast and have residents in the Andes in South America, Rocky Mountains in North America, and Himalayas in Asia. Prevalence of chronic mountain sickness among natives of high altitude is influenced by ethnicity (Wu et al., 1998a, 1992), altitude of residence (Wu et al., 1998a), and ancestral history of colonization to the mountainous regions (Moore, 2001; Wu et al., 1998a). Tibetans have the longest ancestral history of about 25,000 years, followed by Andeans of about 10,000 years, European of 200 years, and Han Chinese of 50 years (Heath et al., 1981; Moore, 2001; Pei et al., 1989; Wu et al., 1987, 1992). The natives of high altitude with the longest ancestral history of living at high altitude are more likely to be genetically and phenotypically better adapted than the civilizations with shorter ancestral history through the phenomenon of natural selection (Heath et al., 1981; Moore, 2001; Pei et al., 1989; Wu T.Y et al 1987, 1992). Prevalence of CMS amongst native Tibetans, Han Chinese immigrated to Qinghai plateau in Tibet (Wu 1998a), and Quechua Andeans have been reported to be 1.21%, 5.57%, and 15.6%, respectively (Monge et al., 1992), though the diagnostic criteria used may not have been identical in these epidemiological studies.

Prevalence of high altitude pulmonary hypertension (HAPH) is reported to be higher in Andeans than in Tibetans (Yang et al., 1985; Wu et al., 1998b, 1999). The pattern of adaptive responses along the cascades of oxygen transport from atmosphere to mitochondria varies amongst Tibetans and Andeans, although the ultimate goal is the same (Beall 2000; Ge et al., 1995; Wu et al., 1998b; Xia et al., 2000; Zhang et al., 1999).

The burden, distribution characteristics, and predisposing factors have never been studied in natives of the Spiti Valley, located geographically southwest of Tibetan plateau in northern India. The Spiti Valley is spread over an area of 710,111 hectares and altitude of residence of about 3000–4200 meters. Climate is mostly dry and cold, and temperature varies from −30 to +20°C, with snow in winters and sparse rain during rainy season. The main source of livelihood is agriculture (hplahaulspiti.nic.in/fact_file.htm). The traditional diet of natives of Spiti is Thupa prepared from barley cereal floor, dried green leaves, and beans locally grown, mutton, butter, and salt as per taste. Consumption of salt tea is traditionally prevalent. Due to the global warming effect in the last 30–40 years, the pattern of agriculture produce is changing. In regions situated at an altitude of about 3000 to 3200 meters, apples are grown as a cash crop, apart from peas and potatoes, which are grown in all regions of Spiti. Thus, there is a socioeconomic gradient across the altitude of residence and influence of urbanized lifestyle is more prevalent in lower regions. The present epidemiological study was conducted to determine the prevalence, distribution characteristics, and predisposing factors of CMS amongst the natives of Spiti Valley.

Materials and Methods

Study population and sampling methods

The study population was sampled by a stratified random cluster method. Based on altitude of residence, the study population was stratified into group I to group III, at an altitude of more than 4000 meters, 3500–4000 meters, and 3000–3500 meters, respectively. The population of Spiti as of December 31, 2008, was 9464, as obtained from the office of Additional Commissioner, Kaza, Spiti, with a population of 3667, 3805, and 1782 in the respective altitude groups. The villages under each altitude group were listed and were selected using a random number table. As a part of a comprehensive epidemiological study of cardiovascular (CV) risk factors, cardiovascular diseases (CVD), and chronic mountain sickness (CMS) in natives of Spiti Valley, 1500 subjects age 20 years and above were targeted to be screened. The sample size selected from each altitude group was based on probability proportional to population of respective altitude groups. From the selected village, all individuals age 20 years and above consenting to participate were screened. Informed consent from each participant was obtained. The study protocol was approved by ethical committee of IGMC Shimla, HP. Subjects found to have no underlying cardiorespiratory diseases and having all the laboratory data required for diagnosis of CMS after screening were enrolled for analysis. The diagnosis of CMS was made using revised Chinese Association of Mountain Medicine quantitative scoring criteria (Wu et al., 1992).

Sao₂ of less than 85% was taken as the cut-off value for hypoxemia, and Hb levels of more than 21 gm/dL in men and more than 19 gm/dL in women were taken as the cut-off values for diagnosing erythrocythemia and were awarded a CMS score of 3 for each. A symptom-based CMS symptom score that did not include Hb was also derived and compared between the group included for analysis and the group excluded from analysis due to lack of Hb/So₂ data. The screening of the study subjects were conducted in two stages.

Stage I

Information related to demographics, health behavior, and anthropometrics to record waist circumference, weight, and height were recorded by trained field investigators by house-to-house visits in selected villages using WHO STEP I and II instruments following appropriate guidelines. Field investigators were trained in IGMC Shimla for one month to administer WHO STEP I and II instruments and were pretested in outdoor patients. Qualities of data recording were certified by principal investigator (P.I.) at the end of training period of one month before the actual survey study was started.

Stage II

screening was done by a team of two consultant cardiologists, one senior resident cardiology, and trained lab technicians from the State Medical College Shimla, HP. The clinical examinations were carried out in primary health centers (PHC)/rest houses of respective altitude groups. Thus for Group I it was conducted in PHC Losar and Kibber, for Group II at PHC Sagnam, for Group III at Sub center Mane and at Rest house at Poh and Lari, respectively. Clinical examinations involved recording of history of any cardiorespiratory diseases as per structured questionnaires. One investigator in each team was assigned the task of recording symptoms and signs related to CMS, as per revised Chinese Medical Association criteria on mountain medicine following standard operating protocol (designed by investigators after deliberations at depth) to document presence and its severity to maintain the uniformity in scoring CMS symptoms and signs. BP was measured twice with a gap of 2–3 minutes with a mercury sphygmomanometer, and average value was taken as the BP value. Clinical examination of the cardiorespiratory system involved any evidence of CHF, PAH, respiratory and structural heart diseases. Each subject were subjected to blood tests in a fasting state to estimate Hb level using cyanmethhemoglobin with Hb calorimeter after calibrating with standard solution for validation of the calorimeter, recording of 12-lead ECG, measurement of Sao₂ using hand-held pulse oximeter Nyco model after 2–3 minutes of resting comfortably; the reading was taken after about 30–45 sec of its application to cleaned index finger when reading displayed on LCD screen showed a stable value. The pulmonary function test (PFT) was performed by trained PFT technicians from the Department of Pulmonary Medicine from IGMC Shimla (State Medical College) using a Spirolab 111 PFT machine. The system was calibrated daily before performing PFT using a 300 cc syringe. Subjects were made to observe procedure while being performed by the fellow subject so that they could understand the procedure well; full efforts were made by the subjects as per instructions given by the PFT technician while performing the test. Once two satisfactory spirometer curves were obtained, the study was terminated and was used for analysis. Forced expiratory volume (FEV1), forced vital capacity (FVC), and ratio of FEV1/FVC, percentage of predicted FEV1, FVC and ratio of FEV1/FVC were recorded.

The consultant cardiologist in the team performed echocardiography with portable echo machine Cx 50 of Philips Medical System using 2.5 MHZ phased array probe to rule out any structural heart disease, to assess LV function, and to record any evidence of PAH by recording TR velocity in subjects with TR Doppler signals in color flow imaging, and pulmonary flow acceleration time by recording the pulse Doppler spectral at right ventricular outflow tract (RVOT). Echocardiography was performed in the left lateral decubitus position recording parasternal long axis (PLAX), parasternal short axis (PSAX), apical 4 and 2 chamber views. In selected cases, a subcostal window was used. All the 694 subjects included for final analysis had an echocardiogram done. Only 65 subjects had an evaluable TR jet, and PFAT was evaluated in 589 subjects with an evaluable pulmonary Doppler signal.

The data were recorded in the EpiInfo data recording template by a data entry operator. The accuracy of data recording was crosschecked by rechecking the entire entered data by investigators from the source document; any errors found were corrected. Data cleansing was done by filtering the values of the variable entered, and any outliers found were deleted. Data were analyzed using Statistical software EpiInfo version 3.4.3.

Statistical analysis

Sample size of the study population was estimated considering the population of Spiti 9464 as per census information available on December 31, 2008, from the Office of Additional Commissioner Kaza Spiti. The prevalence of CMS was assumed to be 5%, with worst accepted prevalence of 2% at 99% confidence level was 338. Using a cluster correction factor of 2, the approximate sample required was about 650. The characteristics of the study population are reported as percentages and mean±SD for categorical variables and continuous variables, respectively. The distributions of categorical characteristics were described at the level of 95% confidence interval. The significance of the differences in distributions of proportions of categorical characteristics amongst group with and without CMS were compared by Chi square test and continuous variable with unpaired t test, Mann Whitney, and Fisher exact tests as appropriate. Risk associated with various sociodemographic and biological CV risk factors as predisposing factors for CMS was estimated by calculating risk ratio and 95% confidence intervals of the RR. The risk factors found to have significant association with CMS was entered in logistic regression model to determine the independent predictors of CMS. Significance of age-related changes in trends in Hb, Sao₂, and indices of PFT were analyzed using ANOVA. Two-tailed significance at level of <0.05 was taken as statistical significance.

Results

A total of 1654 natives, aged 20 years and above, were screened. 84 subjects were excluded due to presence of cardiorespiratory diseases (chronic obstructive airway disease (COAD): 21; pulmonary TB: 27; rheumatic heart disease (RHD): 13; congenital heart disease (CHD): 4; coronary artery disease (CAD): 7; hypertensive heart disease (HHD): 3; FEV1/FVC <70% in 7; and dilated cardiomyopathy (DCM): 2). 876 subjects were excluded from analysis due to absence of Hb estimation and/or lack of Sao₂ data. The final 694 subjects representing 41.7% of the total screened subjects were analyzed. Comparison of study population included and the group excluded did not reveal any difference in distribution of gender and CMS symptom score (males: 37.1% vs. 37.5%, p<0.87; and CMS symptom score 3.7±2.8 vs. 3.9±2.8, p<0.2). However, the mean age of the group excluded was lower than the group included (38.6±13.9 vs. 40.8±14.3, p<0.001).

Clinical characteristics of study population

Details of demographic, health behavior, and clinical characteristics of study population are described in Table 1. Briefly, the study population was characterized by mean age of 39.9±13.9 years; 37.7% were males, 61.8% were literate, and farming was the major occupation (63%), followed by employment either in government or in the private sector (19.6%). Women were more engaged in farming than men (75.4% vs. 42.6%, p<0.001). 7.2% and 8.2% of the study population consumed tobacco and alcohol, respectively, and were mostly men than women. 25.1% were overweight or obese (BMI >23 kg/m²) and prevalence of obesity was not different in men and women (34.6% vs. 19.4%, p=0.35). Truncal obesity was observed in 42.8% and was significantly higher in women than in men (57.9% vs. 17.8%, p<0.001). 32.0% were hypertensives and 2.8% were found to be diabetics. Cognitive impairment (63.7%) was the most common symptom of CMS, followed by headache (51%), breathlessness (50%), fatigue (33.3%), sleep disturbances (25.5%), tinnitus (22.2%), and anorexia (14.4%). All the symptoms were more prevalent among women as compared to men. Cyanosis was observed in 31.6% of the population and was more common in women. The mean symptom score of CMS was 3.6±2.7 and was significantly higher in women than men (4.1±2.8 vs. 2.8±2.3, p<0.001). The cumulative CMS Score including the scores for erythrocythemia and hypoxemia was 4.1±3.2. The mean cumulative CMS score was significantly higher in women than in men (4.6±3.3 vs. 3.1±2.6, p<0.001). The mean CMS symptom score in the group with CMS was 7.0±2.2. There was no significant difference in the CMS scores among men and women in the CMS group. The mean CMS symptom score was 6.4±1.7, 9.4±2.3, and 12.6±2.5 in the CMS group with mild, moderate, and severe CMS, respectively. There was no statistically significant difference in the mean CMS score among men and women in each category CMS.

Table 1.

Clinical Characteristics of Study Population

Characteristics	Overall population N=694	Males 261 (37.7%)	Females 433 (62.3%)	P value
1. Demographics
Age (Mean±sd)	691 (39.9±13.9)	260 (39.9±12.5)	431 (40.0±14.7)	0.48
Literacy (%) (N=654)	404 (61.7%)	200 (81%)	204 (50.2%)	<0.0001
Occupation:(N=659)
Farmers (%)	415 (63.0%)	106 (42.6%)	309 (75.4%)	0.001
Employed (%)	129 (19.6%)	87 (34.9%)	42 (10.2%)
Altitude of residence (meters)
>4000	234 (33.8%)	74 (28.4%)	160 (37.0%)	0.02
3500–4000	282 (40.6%)	104 (39.8%)	177 (41.0%)	0.83
3000–3500	178 (25.6%)	83 (31.8%)	95 (22.0%)	0.005
2. Behavioral
Tobacco consumers (%) N=656	47 (7.2%)	42 (17.0%)	5 (1.2%)	0.001
Alcohol consumers (%) N=649	52 (8.0%)	42 (17.4%)	10 (2.5%)	0.001
Physical activity Index (N) (mean±sd)	620 (1976.6±579)	236 (1869.1±636)	384 (2042.7±531)	0.001
Obesity(%) N=684	172 (25.1%)	89 (34.6%)	83 (19.4%)	0.001
Truncal obesity (%) N=673	288 (42.8%)	45 (17.8%)	243 (57.9%)	0.001
Hypertension (%) N=692	222 (32%)	85 (32.6%)	131 (31.8%)	0.89
Diabetes (%) N=631	18 (2.8%)	11 (4.6%)	7 (1.8%)	0.07
3. Physical examination
BMI N (mean±sd)	685 (21.0±3.2)	257 (21.8±3.5)	427 (20.6±2.8)	0.001
Waist circumference N (mean±sd)	673 (81.8±8.6)	252 (82.3±9.0)	420 (81.5±8.2)	0.29
SBP N (mean±sd)	693 (127.9±20.0)	261 (127.8±18.4)	431 (127.0±20.9)	0.2
DBP N (mean±sd)	693 (83.7±14.1)	261(84.3±13.6)	431 (83.4±14.4)	0.43
4. CMS symptoms and signs
Anorexia	100 (14.4%)	20 (7.7%)	80 (18.5%)	<0.0001
Breathlessness	347 (50.0%)	116 (44.4%)	230 (53.2%)	0.01
Fatigue	231 (33.3%)	65 (24.9%)	166 (38.4%)	0.0001
Headache	354 (51.0%)	99 (37.9%)	254 (58.8%)	<0.00001
Cognitive impairment	442 (63.7%)	156 (59.8%)	285 (66.0%)	0.05
Sleep disturbances	177 (25.5%)	52 (19.9%)	125 (28.9%)	0.003
Tinnitus	154 (22.2%)	46 (17.6%)	108 (25.0%)	0.01
Cyanosis	219 (31.6%)	72 (27.6%)	147 (34.4%)	0.03
5. Oxygen transport system
% predicted FEV1 N (mean±sd)	562 (89.6±25.7)	341 (91.0±27.9)	221 (87.6±21.9)	0.2
% predicted FVC N (mean±sd)	562 (83.2±26.3)	341 (85.0±28.6)	221 (80.3±22.1)	0.11
% predicted FEV1/FVC N (mean±sd)	561 (107.3±23.4)	341 (107.3±22.2)	220 (107.3±25.1)	0.9
FEV1 N (mean±sd)	561 (2.5±0.7)	220 (2.8±0.7)	341 (2.2±0.6)	0.001
FVC N (mean±sd)	561 (2.6±0.8)	219 (3.0±0.8)	341 (2.4±0.7)	0.001
FEV1/FVC N (mean±sd)	561 (87.9±21.9)	221 (90.0±17.5)	340 (86.6±24.3)	0.8
Hb (gm%) N (mean±sd)	694 (15.5±3.2)	261 (16.2±3.1)	432 (15.1±3.1)	0.001
SaO₂ (%) N (mean±sd)	694 (89.3±3.7)	261 (89.4±3.6)	432 (89.2±3.7)	0.7
6. CMS SCORE
CMS Symptom Score N (mean±sd)	694 (3.6±2.7)	261 (2.8±2.3)	432 (4.1±2.8)	0.001
Cumulative CMS Score N (mean±sd)	681 (4.1±3.2)	255 (3.1±2.6)	425 (4.6±3.3)	0.001
CMS Symptom score in CMS group	199 (7.0±2.2)	41 (6.8±2.1)	158 (7.0±2.2)	0.6
CMS Symptom Score in Mild CMS	165 (6.4±1.7)	38 (6.4±1.5)	127 (6.4±1.7)	0.9
CMS symptom score in Mod CMS	31 (9.4±2.3)	2 (10.5±0.7)	29 (9.3±2.4)	0.5
CMS symptom Score in Severe CMS	3 (12.6±2.5)	1 (15.0±0)	2 (16.5±2.1)	0.1
7. PAH
TR gradient (mmHg) N (mean±sd)	65 (28.3±9.9)	17 (30.2±14.2)	48 (27.6±7.9)	0.89
PFAT (msec.) N (mean±sd)	589 (121.1±25.3)	225 (117.7±23.4)	364 (123.2±26.2)	0.8

N, Number of study subjects with data available for analysis.

Hb, arterial oxygen saturations levels and indices of pulmonary function (Table 1)

The mean Hb level was 15.5±3.2 and was significantly higher in men than in women (16.2±3.1 vs. 15.1±3.1, p<0.001). Mean arterial oxygen saturation was 89.3%±3.7% and was not different between men and women (89.4%±3.6 vs. 89.2%±3.7, p<0.7). The mean values of FEV1, FVC, and FEV1/FVC in the study population were 2.5±0.7, 2.6±0.8, and 87.9±21.9, respectively. The FEV1, FVC was significantly higher in males compared with females (2.8±0.7 vs. 2.2±0.6 and 3.0±0.8 vs. 2.4±0.7), respectively, p<0.001. However, the ratio of FEV1/FVC was not different between men and women (90.0±17.5 vs. 86.6±23.3, p<0.8). Percentage predicted FEV1, FVC, and ratio of FEV1/FVC was similar in men and women (91.0±27.9 vs. 87.6±21.9, p<0.2), 85.0±28.6 vs. 80.3±22.1, p<0.11) and 107.3±22.2 vs. 107.3±25.1, p<0.9), respectively.

Prevalence of polycythemia, hypoxemia, and HAPH

The prevalence of erythrocythemia was 10.5% (95% C.I. of 8.4–13.1%) and hypoxemia was 7.5% (95% C.I. of 5.7–9.8%). Although there was a trend of higher prevalence of erythrocythemia and hypoxemia in women than in men, it was statistically not significant (12.3% vs. 7.7%, p<0.055 and 8.3% vs. 6.1%, p<0.35, respectively). Prevalence of HAPH based on TR gradient of >50 mmHg was 6.2% (95% C.I. of 1.7–15.0%) and was 12.1% (95% C.I. of 9.6–15.5%) as estimated by using criteria of pulmonary flow acceleration time recorded at RVOT of <90 msec. Prevalence of HAPH estimated by either of the criteria was not significantly different between men and women (Table 2).

ECG changes of RV overload

ECG features of RV overload in the form of R/S in V1 of >1, T wave inversion in lead V1 and V2, and QRS axis deviation to >90 was 6.2%, 1.6%, and 11.9%, respectively. Prevalence of ECG features of RV Stain was not significantly different between men and women (Table 2).

Age-related trends in changes in indices of oxygen transport system in women and men

There was a trend of significant increase in the levels of Hb in women with age (p<0.04). However, no significant change in the levels of Hb with age was observed in men (p>0.6). The SPo₂ level declines significantly with age in both sexes (p<0.001 and p<0.002, respectively). No significant change in indices of pulmonary functions with age was observed in both women and men (Table 6a,b).

Table 6A.

Changes in Trends of Indices of Oxygen Transport System Across Age Groups in Women

Age groups (years)	20 – 29	30 – 39	40 – 49	50 – 59	>60	P value
Number of subjects	115	113	85	64	54
Hb [N (Mean±SD)]	115 (14.5±3.0)	113 (15.7±3.6)	85 (14.8±2.8)	64 (15.4±3.0)	54 (15.3±2.9)	0.04
Sao2 [N (Mean±SD)]	115 (90.8±2.7)	113 (89.4±3.0)	85 (90.0±2.5)	64 (87.5±4.5)	54 (86.4±4.8)	0.001
% Predicted FEV1 [N (Mean±SD)]	90 (90.5±25.3)	91 (91.5±26.7)	67 (91.3±28.4)	52 (91.0±27.5)	40 (89.9±36.2)	0.99
% predicted FVC [N (Mean±SD)]	90 (84.2±23.8)	91 (85.8±28.1)	67 (86.4±29.8)	52 (85.4±30.7)	40 (81.7±35.3)	0.93
% Predicted FEV1/FVC [N (Mean±SD)]	90 (109.9±14.1)	91 (101.8±32.7)	67 (109.1±32.7)	52 (110.1±15.9)	40 (108.0±24.2)	0.34

Table 6B.

Changes in Trends of Indices of Oxygen Transport System Across Age Groups in Men

Age groups	20 – 29	30 – 39	40 – 49	50 – 59	>60	P value
Number of subjects	59	73	76	30	22
Hb [N (Mean±SD)]	59 (16.5±3.1)	73 (16.5±3.6)	76 (16.5±2.5)	30 (15.9±3.0)	22 (15.6±2.9)	0.6
Sao2 [N (Mean±SD)]	59 (90.1±2.7)	73 (90.0±2.8)	76 (89.3±3.0)	30 (89.0±3.3)	22 (86.0±7.5)	0.002
% Predicted FEV1 [N (Mean±SD)]	53 (88.7±13.8)	65 (88.5±22.3)	61 (86.9±23.2)	24 (88.2±29.9)	17 (83.3±24.8)	0.91
% predicted FVC [N (Mean±SD)]	53 (79.6±15.0)	65 (81.8±23.7)	61 (80.0±21.4)	24 (80.8±30.4)	17 (79.0±26.0)	0.99
% Predicted FEV1/FVC [N (Mean±SD)]	53 (103.6±31.4)	65 (110.8±16.4)	60 (110.8±16.4)	24 (100.2±37.5)	17 (108.4±9.7)	0.59

Prevalence of CMS and its predisposing factors (Tables 2 –5)

28.7% (95% C.I. of 25.9–32.8%) had CMS while 4.9% (95% C.I. of 3.2–7.8%) had moderate to severe CMS. Distribution characteristics of CMS in study population revealed CMS was significantly more prevalent amongst females (36.6% vs. 15.7%, p=0.001), illiterates, farmers, population residing at higher altitudes, people with truncal obesity, and hypertension. The mean age of population with CMS was significantly higher than population without CMS (47.1±14.8 vs. 37.1±12.4, p<0.001) and as expected, the Hb level of population with CMS was significantly higher than the population without CMS (16.4±3.9 vs. 15.2±2.8, p<0.001). The population mean of physical activity index (1881.1±578 vs. 2011.6±576, p<0.02), arterial Sao₂ 88.0±4.9 vs. 89.9±2.9, p<0.001) and indices of pulmonary functions, for example, FEV1 (2.2±0.8 vs. 2.5±0.7, p<0.001), FVC (2.4±0.8 vs. 2.7±0.8, p<0.001), and a ratio of FEV1/FVC (91.9±7.3 vs. 93.2±6.9, p<0.001) were significantly lower amongst CMS group than group without CMS. Modeling of these variables into logistic regression analysis to determine the independent predictors of CMS revealed age, female sex, altitude of residence at altitude group II, physical inactivity, and central obesity were independent predictors of CMS with Z statistic of 4.2 (p<0.0001), −3.75 (p<0.0002), 2.84 (p<0.004), −2.83 (p<0.004), and 2.29 (p<0.02).

Table 2.

Prevalence of CMS, Erythrocythemia, Hypoxemia, HAPH, and Gender Distribution

	Overall N=694 % (95% C.I.)	Males N=261 (37.7%) % (95% C.I.)	Females N=433 (62.3%) % (95% C.I.)	R.R. (95% C.I.)	P value
Prevalence of CMS	28.7 (25.4 – 32.2)	15.7 (11.5 – 20.7)	36.6 (32.1 – 41.3)	0.75 (0.68 – 0.82)	0.001
Mild CMS:	23.8 (20.7 – 27.9)	14.6 (10.5 – 19.4)	29.4 (25.2 – 34.0)		0.0001
Moderate CMS	4.5 (3.1 – 6.4)	0.8 (0.1 – 2.7)	6.7 (4.6 – 9.6)
Severe CMS	0.4 (0.1 – 1.4)	0.4 (0.0 – 2.5)	0.5 (0.1 – 1.8)		NS
Erythrocythemia (>21 gm% in males and >19 gm% infemales)	10.5 (8.4 – 13.1)	7.7 (4.7 – 11.6)	12.3 (9.4 – 15.8)	0.95 (0.90 – 0.99)	0.055
SPO₂<85%	7.5 (5.7 – 9.8)	6.1 (4.7 – 11.6)	8.3 (9.4 – 15.8)	0.97 (0.93 – 1.01)	0.35
HAPH
TR gradient >50 mmHg	6.2 (1.7 – 15.0)	11.8 (1.5 – 36.4)	4.2 (0.5 – 14.3)	1.08 (0.90 – 1.3)	0.27
PFAT (<90 msec)	12.1 (9.6 – 15.5)	12.4 (8.4 – 17.5)	11.8 (8.8 – 15.7)	1.00 (0.94 – 1.07)	0.9
ECG R/S >1 in V1.	6.2 (4.6 – 8.4)	4.3 (2.2 – 7.6)	7.3 (5.1 – 10.3)	0.96 (0.93 – 1.00)	0.16
T wave inversion in V1 – V2	1.6 (0.9 – 3.0)	0.8 (0.1 – 2.8)	2.1 (1 – 4.1)	0.98 (0.96 – 1.00)	0.3
Right axis deviation	11.9 (9.4 – 15.1)	17.0 (12.2 – 22.7)	8 (5.8 – 12.3)	1.10 (1.02 – 1.18)	0.003

Table 3.

Distribution Characteristics of CMS in Study Population

Characteristics	Group with CMS (N=199) N (%)	Group without CMS (N=495) N (%)	R. R. (95% C.I.)	P value
Sex (Male)	41 (20.6%)	220 (44.5%)	0.76 (0.69 – 0.83)	<0.0001
Literacy status (Illiterates) N=653	75 (40.1%)	329 (70.6%)	0.676 (0.59 – 0.76)	<0.0001
Occupation N=591
Farmers	130 (69.1%)	285 (60.5%)		0.01
Employed	28 (14.9%)	101 (21.4%)
Retired	0 (0%)	3 (0.6%)
Student	6 (3.2%)	38 (8.1%)
Altitude group N=694
I	72 (36.2%)	162 (32.7%)	1.01 (0.91 – 1.12)	0.69
II	99 (49.7%)	183 (37.0%)	1.07 (1.04 – 1.12)	0.02
III	28 (14.1%)	150 (30.3%)	0.79 (0.72 – 0.86)	0.001
Behavioral
Tobacco consumers (N=656)	9 (4.8%)	38 (8.1%)	0.89 (0.76 – 1.04)	0.18
Alcohol Consumers (N=649)	9 (4.8%)	38 (8.1%)	0.94 (0.90 – 0.98)	0.04
Salt tea consumers (N=644)	124 (66.3%)	308 (67.4%)	0.96 (0.76 – 1.23)	0.86
Clinical Characteristics
Obesity (N=685)	49 (24.9%)	123 (25.2%)	0.99 (0.90 – 1.10)	0.99
Truncal obesity (N=674)	123 (62.7%)	165 (34.6%)	1.74 (1.43 – 2.18)	<0.00001
Hypertension (N=693)	84 (42.4%)	138 (27.9%)	1.25 (1.08 – 1.42)	0.0002
Diabetes (N=632)	2 (1.2%)	16 (3.5%)	0.97 (0.95 – 1.00)	0.20

Table 4.

Comparison of Descriptive Statistics Between Group With CMS and Without CMS

Characteristics	Group with CMS (n=199) N (Mean±SD)	Group without CMS (n=495) N (Mean±SD)	P value
Age	198 (47.1±14.87)	493 (37.1±12.46)	0.0001
BMI	197 (20.9±2.97)	488 (21.1±3.3)	0.71
Waist circumference	197 (84.2±7.6)	476 (80.8±8.8)	0.001
Physical Activity Index	166 (1881.1±578.3)	454 (2011.6±576.1)	0.02
SBP	198 (134.1±24.9)	495 (124.5±17.0)	0.001
DBP	198 (87.2±15.4)	495 (82.4±13.3)	0.001
HR	195 (72.3±13.2)	485 (70.4±12.1)	0.06
HB	199 (16.4±3.9)	495 (15.2±2.8)	0.001
Arterial saturation	199 (88.00±4.9)	495 (89.9±2.9)	0.001
PFAT	164 (118.3±27.2)	425 (122.05±24.5)	0.09
TR gradient	22 (29.9±11.0)	43 (27.4±9.3)	0.34
PFT
% predicted FEV1	141 (92.2±26.9)	421 (88.8±24.3)	0.15
% predicted FVC	141 (85.2±29.3)	421 (82.5±25.2)	0.2
% predicted FEV1/FVC	141 (107.7±23.1)	421 (107.2±23.2)	0.84
FEV1	142 (2.2±0.8)	419 (2.53±0.72)	0.001
FVC	142 (2.4±0.86)	419 (2.72±0.80)	0.001
FEV1/FVC	141 (91.9±7.3)	420 (93.2±6.9)	0.001

Table 5.

Multivariable Logistic Regression Model for Independent Predictors of CMS

Variable	Odds Ratio	95%	C.I.	Coefficient	S.E.	Z-Statistic	P Value
Age	1.0492	1.0260	1.0730	0.0480	0.0114	4.2044	0.0000
Altitude group I	1.4151	1.1141	1.7973	0.3472	0.1220	2.8460	0.0044
Central obesity	1.8087	1.0915	2.9972	0.5926	0.2577	2.2996	0.0215
FEV1/FVC	1.0014	0.9503	1.0551	0.0014	0.0267	0.0508	0.9595
FEV1	0.8964	0.2235	3.5951	−0.1093	0.7086	−0.1543	0.8774
FVC	1.3922	0.3781	5.1265	0.3309	0.6651	0.4975	0.6189
Physical Activity Index	0.9994	0.9989	0.9998	−0.0006	0.0002	−2.8350	0.0046
HT	0.9669	0.5641	1.6573	−0.0337	0.2749	−0.1225	0.9025
Sex (Male)	0.2887	0.1509	0.5525	−1.2423	0.3311	−3.7520	0.0002
CONSTANT	^*	^*	^*	−2.7240	2.8947	−0.9410	0.3467

There were 65 subjects with TR Doppler signals recorded for estimation of pulmonary hypertension out of which 22 subjects were in CMS group and 43 subjects were from group without CMS. Three (13.6%) subjects in the CMS group had PAH (TR gradient >50 mmHg), while only 1 (2.3%) subject in the group without CMS had PAH. Pulmonary flow Doppler signals from RVOT were recorded in 589 subjects (164 in CMS group and 425 subjects in population without CMS) for recording PFAT. 28 (17.1%) in the CMS group and 43 (10.1%) in the population without CMS had PAH (PFAT <90 msec). ECG features of RV overload were evaluated by recording QRS right axis deviation > +90° in 527 subjects, R/S >1 in V1, and T wave inversion in lead V1 and V2 in 694 subjects. 10.2% in the CMS group and 12.7% in the group without CMS had RAD (p – NS). 3.1% in the CMS group and 1% in the group without CMS had T wave inversions in V1 and V2 (p=0.06). 6.7% in the CMS group and 6.0% in the population without CMS had R/S >1 in V1 (p – NS).

Gender comparison of indices of oxygen transport system among group with and without CMS

The mean Hb value was significantly higher in CMS group compared to group without CMS both in men and women 17.0 vs. 16.0 gm%, p<0.05, and 16.1 vs. 14.6 gm%, p<0.001, respectively (Table 7). A similar difference in the mean level of Sao2 in group with CMS was significantly lower compared to group without CMS both in men and women 87.0 vs. 89.8%, p<0.006, and 88.2 vs. 89.9%, p<0.0001, respectively. However, indices of PFT was significantly compromised in women with CMS than women without CMS FEV1: 2.1 vs. 2.3, p<0.002, FVC: 2.2 vs. 2.4, p<0.02, and FEV1/FVC: 81.4 vs. 89.1, p<0.005 in women. There were no significant differences in the indices of PFT among men with and without CMS; FEV1 2.8 vs. 2.8, p<0.8; FVC; 3.0 vs. 3.0, p<0.8; and FEV1/FVC ratio of 83.5 vs. 91.0, p<0.35, respectively.

Table 7.

Gender Comparison of Indices of Oxygen Transport System Amongst Group With and Without CMS.

	Female			Male
Feature	CMS group N (Mean±SD)	Without CMS group N (Mean±SD)	Sig. (2 tailed)	CMS group N (Mean±SD)	Without CMS group N (Mean±SD)	Sig. (2 tailed)
Hb	158 (16.1±3.8)	274 (14.6±2.6)	0.001	41 (17.4±4.2)	220 (16.0±2.8)	0.05
SPO₂	158 (88.2±4.3)	274 (89.9±3.1)	0.0001	41 (87.0±6.6)	220 (89.8±2.6)	0.006
FEV1	111 (2.1±0.6)	230 (2.3±0.6)	0.002	31 (2.8±0.9)	189 (2.8±0.7)	0.8
FVC	111 (2.2 0.8)	231 (2.4±0.7)	0.02	31 (3.0±0.9)	188 (3.0±0.8)	0.8
FEV1/FVC	110 (81.4±30.1)	230 (89.1±20.6)	0.005	31 (83.5±28.4)	190 (91.0±14.9)	0.35

Discussion

This epidemiological study of CMS in natives of Spiti residing at an altitude of 3000–4200 meters in greater Himalayas revealed 28.7% (95% C.I. of 25.9–32.8%) of the population were affected with CMS and was more prevalent amongst women (36.6% vs. 15.7%, p<0.001) contrary to the observation reported by other investigators (Moore, 2001; Wu et al., 1998a). Erythrocythemia and hypoxemia was observed in 10.5% and 7.5% of the natives, respectively. There was a trend of higher prevalence of erythrocythemia (12.3% vs. 7.7%, p<0.055) and hypoxemia (8.3% vs. 6.1%, p<0.35) in women but was statistically not significant. Prevalence of CMS observed in the present study is the highest ever reported. Wu et al (1998a) reported prevalence of 1.26% in native Tibetans and 5.56% in Han Chinese, and Monge et al., (1992) reported 15.6% in Quechua Andeans. 6.2% and 12.1% had HAPH diagnosed based on TR gradient >50 mmHg and PFAT of <90 msec, respectively. Prevalence of HAPH was not significantly different in men and women (11.8% vs. 4.2%) p<0.27 based on TR gradient of more than 50 mmHg.

Analysis of association of demographics, and behavioral and biological CV risk factors with CMS revealed CMS had significant association with elderly population, female gender, people engaged in farming, illiterates, people residing at higher altitude, with central obesity, physical inactivity, hypertensives, and lower indices of pulmonary functions (e.g., FEV1, FVC, and FEV1/FVC). However, a multivariable logistic regression analysis revealed; age (Z-statistics 4.2, p<0.0001), women (Z statistics −3.7, p<0.0002), central obesity (Z statistics 2.2, p<0.02), higher altitude of residence (Z statistics 2.8, p<0.004), and lower physical activity index (Z statistics −2.8, p<0.04) were independent predictors of CMS. Premenopausal women have been found to have a lower prevalence of CMS (Leon-Velarde et al., 1997). Premenopausal women are believed to be less vulnerable for CMS due to respiratory stimulant effect of progesterone and cyclic menstrual flow, thus protecting against excessive erythrocytosis (Leon-Velarde et al., 2001; Moore, 2001). Risk of CMS in Tibetan men is about 3 times higher than Tibetan women (Wu et al., 1998a). A reason for higher prevalence in women in the present study is not clear. Comparison of indices of pulmonary functions FEV1, FVC, and ratio of FEV1/FVC among group with and without CMS in men and women revealed significantly compromised lung functions amongst women with CMS compared to women without CMS (p<0.001). There was no significant different in lung functions in men with and without CMS, suggesting that compromised lung function could be one of the contributory factors for higher prevalence of CMS observed in women. Since the majority of the women were engaged in farming occupations and have a role in cooking meals for family, and are exposed to both indoor and outdoor pollution in fields, they are more vulnerable to developing chronic bronchitis and compromised lung function. Exposure to biomass smoke has been associated with obstructive lung disease in women (Ekici et al., 2005; Regalado et al., 2006). The mean symptom score of CMS, without including the scores for erythrocythemia and hypoxemia, was significantly higher in women than in men (4.1±2.8 vs. 2.8±2.3, p<0.001). The higher CMS symptom score recorded in women than in men could also be partly attributed to HAPH, however there was no significant difference in prevalence of HAPH between men and women (11.8% vs. 4.2%, p<0.27). The prevalence of erythrocythemia and hypoxemia in women was higher than men but was statistically not significant (12.3% vs. 7.7%, p<0.055) and (8.3% vs. 6.1%, p<0.97), respectively. Thus these observations do indicate that higher prevalence of symptom complexes related to CMS in women is not necessarily related to hypoxemia and or polycythemia. This may point out the lack of specificity of contemporary symptoms based diagnostic criteria in women for diagnosis of CMS or may be that the threshold for symptoms related to hypoxemia and polycythemia in females is lower than in males.

Increasing age (Sime et al., 1974) and altitude of residence (Wu et al., 1998a) are well established risk factors for CMS. Urbanization and associated changes in lifestyle also could have role in development of CMS (Winslow et al., 1987; Xie et al., 1981). Tobacco consumption has been reported to be a predisposing factor (Heath et al., 1981; Monge et al., 1992). However, no significant association was observed in natives of Spiti Valley. Failure to observe association between tobacco consumption and CMS could be that the number of tobacco consumers in the study population was low (7.2%). Central obesity and lower physical activity had independent significant association with CMS, but the exact underlying mechanisms would be conjectural at this point. Certainly the observation has an important implication for public health interventions in prevention of CMS. CMS may be associated with HAPH related to increase PVR as a result of erythrocytosis and associated alveolar hypoxia induced pulmonary vasoconstrictions. Some of the patients of CMS could have severe HAPH leading to RHF (HAHD) (Leon Velarde et al., 2005; Penaloza et al.,1971a, 1971b). Prevalence of HAPH is more common in Andean population and Han immigrant Chinese than in native Tibetan population (Yang et al., 1985, Wu et al., 1998b, 1999). In the present study, no case of subacute mountain sickness with severe PAH with right heart failure was recorded, although prevalence of HAPH was higher among CMS group compared to group without CMS (TR gradient of >50 mmHg in 13.6% vs. 2.3%, respectively, p<0.18, and PFAT <90 msec. was 17.1% vs. 10.1%, p<0.02.), respectively.

Age-related trends of changes in Hb, Sao₂ and indices of pulmonary function was analyzed in men and women to gain mechanistic insights about causes of CMS and revealed there was no significant change in the level of Hb with age in men, but a significant increase in levels of Hb was observed in women across age groups of 10 years interval. Increase in levels of Hb with age has also been reported amongst Andeans (Leon Velarde et al., 1993). However, age-related change in Hb level was not observed in Tibetan natives (Beall, 2000; Wu et al., 1998). Increase in Hb levels with age may be due to attenuation of hypoxic ventilatory response with age. Spo₂ levels declined significantly with age both in men and women (p<0.001), but no significant change in the value of percentage predicted FEV1/FVC with age both in men and women, (p=0.3) thus suggesting that age-related significant decline in Sao₂ is probably related to impaired hypoxic ventilatory response with age and may also be due to impaired lung diffusion. Attenuation of hypoxic ventilatory response with age has been documented by various investigators in high land natives that is more severe in patients with CMS; older CMS more than young CMS and similarly older healthy natives more than young healthy natives and is genetically regulated (Enrique Vargas et al., 2006). The mean level of Hb was 15.5±3.2 and is similar to Tibetan population but lower than the values reported in Andean population (Beall, 2000; Monge et al., 1992, Wu et al 1998a, 1998b, 1998c). The mean Spo₂ of the study population of 89.2±3.7% is higher than the values reported from Andean populations and are similar to Tibetan population (Beall, 2000; Monge et al., 1992; Weitz et al., 2007).

Study limitations

Intra and inter observer variability of symptoms and signs based scoring for diagnosis of CMS was not tested to estimate the reproducibility of the score results. Chest X-ray for CMS did not exclude pathologies related to lungs. Only data of 41.7% of the study population were analyzed to estimate the prevalence of CMS, although population excluded was not selective but was based on presence of cardiorespiratory diseases and due to lack of data related to CMS diagnosis. There was no difference in gender distribution and CMS symptom based score levels between the group included and the group excluded. The group excluded was younger than the group included and as prevalence of CMS is known to increase with age, there is possibility of overestimation of the prevalence of CMS.

Conclusion

Prevalence of CMS amongst natives of Spiti Valley residing at an altitude of 3000–4200 meters was 28.7% (95% C.I. 25.9–32.8%) and moderate to severe CMS was observed in 4.9% (95% C.I. 3.2–7.8%). CMS was significantly higher amongst women than in men. Age, central obesity, and female gender, altitude of residence, and physical inactivity were independent predictors for CMS. Hypertension, tobacco consumption, and indices of pulmonary function did not have any significant association with CMS. The urbanized lifestyle seems to be an important predisposing factor. Observations made in the present study have important implications for health policy makers and public health providers for creating awareness among the natives of Spiti about CMS predisposing factors and appropriate preventive measures and creating infrastructures and capacity building in the health system for diagnosis, treatment, and for preventive measures in order to reduce morbidity and mortality.

Footnotes

Acknowledgments

We would like to acknowledge valuable help extended by the medical officers posted in Spiti Valley, Dr. Sonam Negi, Dr. Dolker, Dr. J.C. Negi, Dr. Bhavesh Thakur, Dr. Arvind Chopra, Dr. B.K Negi, Dr. Dinesh, Dr. Shiv Prakash Block Medical Officer in charge of Kaza Hospital Spiti, Health Workers Devi Dekid, Vidhya Sagar, Ghabar,Nursing staff of Kaza Hospital Palmo, Shallu and Lab Technician Mr. Yadav during survey period of 2009 to 2011.

We express our gratitude and thank Dr. Fabiola Leon- Velarde for reading our manuscript and making her valuable observations and comments that have been incorporated in the manuscript as appropriate.

Author Disclosure Statement

The study was funded by the Defense Research and Development Organization, Government of India. The authors have no conflicts of interest or financial ties to disclose.

Abbreviations Used

References

*Chinese Medical Association for high altitude medicine. 1996. Recommendations for the classification and diagnostic criteria for high altitude disease in China. Chin High Alt Med J (Chin), 6:2–5.

**Consensus Statement by ad hoc committee of the international society for mountain medicine on chronic high altitude diseases. 2004 Sixth world congress on mountain medicine and high altitude physiology, Aug 12–15 Xining, Qinghai, China, 5–10.

Beall

. 2000. Tibetan and Andean patterns of adaptation to high altitude hypoxia. Hum Biol, 72:201–228.

Ekici

, Ekici

, Kurtipek

et al. 2005. Obstructive airway diseases in women exposed to biomass smoke. Environ Res, 99:93–98.

Enrique Vargas

, Spielvogel

. 2006. Chronic mountain sickness, optimal hemoglobin, and heart disease. High Alt Med Biol, 7:138–149.

, Shai

, Chen

. 1995. Changes of red cell 2,3-diphosphoglycerate and oxygen affinity of blood in subjects with high altitude polycythemia. Chin J Appl Physiol (Chin), 11:205–208.

Heath

, Williams

. 1981. Man at High Altitude. Churchill Livingston: London and New York.

Kryger

, Grover

. 1983. Chronic mountain sickness. Semin Respir Med, 5:164–168.

Leon Velarde

, Arregui

, Monge

, Ruiz

. 1993. Aging at high altitude and the risk of chronic mountain sickness. J Wild Med, 4:183–188.

10.

Leon-Velarde

, Ramos

, Hernandez

et al. 1997. The role of menopause in the development of chronic mountain sickness. Am J Physiol Reg Integ Comp Physiol, 272:R90–R94.

11.

Leon-Velarde

, Maria

Rivera-Ch

, Tapia

, Huicho , Monge

. 2001. Relationship of ovarian hormones to hypoxemia in women residents of 4,300 m. Am J Physiol Reg Integ Comp Physiol, 280:R488–R493.

12.

Leon-Velarde

, Maggiorini

, Reeves

et al. 2005. Consensus statement on chronic and subacute high altitude disease. High Alt Med Biol, 6:147–157.

13.

Maria

Rivera-Ch

, Leon-Velarde

, Luis

Huicho

. 2007. Treatment of chronic mountain sickness: Critical reappraisal of an old problem. Resp Physiol Neurobiol, 158:251–265.

14.

Monge

, Arregui

, Leon Velarde

. 1992. Pathophysiology and epidemiology of chronic mountain sickness. Int J Sports Med, 13:S79–S81.

15.

Moore

. 2001. Human genetic adaptation to high altitude. High Alt Med Biol, 2:257–279.

16.

Pei

, Cheng

, Si Ren

et al. 1989. Chronic mountain sickness in Tibet. Q J Med, 71:555–574.

17.

Penaloza

, Sime

. 1971. Chronic cor pulmonale due to loss of altitude acclimatization (chronic mountain sickness) Am J Med, 50:728–743.

18.

Penaloza

, Sime

, Ruiz

. 1971. Cor pulmonale in chronic mountain sickness. Present concept of Monge's disease. High Altitude Physiology: Cardiac and Respiratory Aspects. Porter

, Knight

. Churchill Livingstone: Edinburgh and London, 41–60.

19.

Regalado

, Perez-Padilla

, Sansores

et al. 2006. The effect of biomass burning on respiratory symptoms and lung function in rural Mexican women. Am J Respir Crit Care Med, 174:901–905.

20.

Richalet

, Rivera

, Bouchet

et al. 2005. Acetazolamide: A treatment of chronic mountain sickness. Am J Respir Crit Care Med, 172:1427–1433.

21.

Richalet

, Rivera Chira

, Maignan

et al. 2008. Acetazolamide for Monge's disease. Efficiency and tolerance of a 6 month treatment. Am J Respir Crit Care Med, 177:1370–1376.

22.

Sime

, Monge

, Whittembury

. 1975. Age as a cause of chronic mountain sickness (Monge's disease) Int J Biometerol, 19:93–98.

23.

Weitz

, Ralph

. 2007. A comparative analysis of arterial oxygen saturation among Tibetans and Han born and raised at high altitude. High Alt Med Biol, 8:13–26.

24.

Winslow

, Monge

. 1987. Hypoxia, Polycythemia, and Chronic Mountain Sickness. The Johns Hopkins University Press: Baltimore and London, 17–18.

25.

, Zhang

, Die

, Jin

. 1987. Chronic mountain sickness occurring in Tibetan Natives [in Chinese] Natl Med J China (Chin), 67:167–168.

26.

, Zhang

, Jin

, Xu

, Cheng

, Wang

. 1992. Chronic mountain sickness (Monge's disease). An observation in Qinghai – Tibet plateau. High Altitude Medicine. Ueda

, Reeves

J.T.

, Sekiguchi

. Shinshu University Press: Matsumoto, 314–324.

27.

, Li

, Ge

et al. 1998a. Epidemiology of chronic mountain sickness. Ten years study in Qinghai,Tibet. Progress in Mountain Medicine and High Altitude Physiology. Ohno

, Kobayashi

, Masuyama

, Nakashima

Press committee of the 3rd world congress on mountain medicine and high altitude physiology, Matsumoto, Japan, Matsumoto, Japan, 120–125.

28.

, Tu

, Zha

et al. 1998b. The physiologic difference between the Tibetans and the Andeans. Progress in Mountain Medicine and High Altitude Physiology. Ohno

, Kobayashi

, Masuyama

, Nakashima

Press committee of the 3rd world congress on mountain medicine and high altitude physiology, Matsumoto, Japan, 190–194.

29.

, Li

, Wei

et al. 1998c. A preliminary study on the diagnosis of chronic mountain sickness in Tibetan populations. Progress in Mountain Medicine and High Altitude Physiology. Ohno

, Kobayashi

, Masuyama

, Nakashima

. Press committee of the 3rd world congress on mountain medicine and high altitude physiology, Matsumoto, Japan, 337–342.

30.

, Miao

, Li

et al. 1999. Determination of pulmonary arterial pressure in high altitude residents [in Chinese] Chin J High Alt Med, 9:8.

31.

. 2000. Relationship between erythrocyte rheological properties and RBC superoxide dismutase and plasma malondialdehyde in patients with high altitude polycythemia. Chin J Pathophysiol (Chin), 16:412–414.

32.

Xie

, Pei

. 1981. Some physiological data on sojourners and indigenous highlanders at 3 different altitudes in Xizang. Geological and Ecological Studies of Qinghai–Xizang (Tibet) Plateau. Proc Symp Qinghai – Xizang (Tibet) plateau, Beijing, China. 2 Liu

. Gordon and Breach Press: New York, 1449–1452.

33.

Zhang

, Cui

, Cheng

. 1999. A comparative study of free radical metabolism of youths in indigenous Tibetans and migrated Hans at 4300m. Chin J High Alt Med (Chin), 10:9–11.

34.

Zhou

, Yang

, Liu

. 1983. A clinical observation on high altitude polycythemia treated with medroxyprogesterone [in Chinese] Chin J Hematol, 4:132–133.

Epidemiological Study of Chronic Mountain Sickness in Natives of Spiti Valley in the Greater Himalayas

Abstract

Abstract

Introduction

Materials and Methods

Study population and sampling methods

Stage I

Stage II

Statistical analysis

Results

Clinical characteristics of study population

Hb, arterial oxygen saturations levels and indices of pulmonary function (Table 1)

Prevalence of polycythemia, hypoxemia, and HAPH

ECG changes of RV overload

Age-related trends in changes in indices of oxygen transport system in women and men

Prevalence of CMS and its predisposing factors (Tables 2–5)

Gender comparison of indices of oxygen transport system among group with and without CMS

Discussion

Study limitations

Conclusion

Footnotes

Acknowledgments

Author Disclosure Statement

Abbreviations Used

References

Prevalence of CMS and its predisposing factors (Tables 2 –5)