Smoking, acute mountain sickness and altitude acclimatisation: a cohort study.

RATIONALE: The relationship between cigarette smoking and acute mountain sickness (AMS) is not clear. OBJECTIVE: To assess AMS risk and altitude acclimatisation in relation to smoking. METHODS: 200 healthy non-smokers and 182 cigarette smokers were recruited from Han lowland workers. These were men without prior altitude exposure, matched for age, health status and occupation, who were transported to an altitude of 4525 masl. MEASUREMENTS: AMS, smoking habits, arterial saturation (SpO2), haemoglobin (Hb), lung function and mean pulmonary artery pressure (PAPm) were assessed upon arrival and after 3 and 6 months. MAIN RESULTS: Compared with non-smokers, smokers had a lower incidence of AMS and lower AMS scores than non-smokers upon arrival; higher Hb and PAPm associated with lower SpO2 at 3 and 6 months at altitude; and lower forced expiratory volume in 1 s and maximal voluntary ventilation at 3 and 6 months. CONCLUSIONS: Smoking slightly decreases the risk of AMS but impairs long-term altitude acclimatisation and lung function during a prolonged stay at high altitude.

High-altitude gastrointestinal bleeding: an observation in Qinghai-Tibetan railroad construction workers on Mountain Tanggula.

AIM: To investigate the gastrointestinal bleeding (GIB) in people from lowland to high altitude and in workers on Mountain Tanggula and its causes as well as treatment and prophylaxis. METHODS: From 2001 to October 2003, we studied GIB in 13502 workers constructing the railroad on Mountain Tanggula which is 4905 m above the sea level. The incidence of GIB in workers at different altitudes was recorded. Endoscopy was performed when the workers evacuated to Golmud (2808 m) and Xining (2261 m). The available data on altitude GIB were analyzed. RESULTS: The overall incidence of GIB was 0.49% in 13502 workers. The incidence increased with increasing altitude. The onset of symptoms in most patients was within three weeks after arrival at high altitude. Bleeding manifested as hematemesis, melaena or hematochezia, and might be occult. Endoscopic examination showed that the causes of altitude GIB included hemorrhage gastritis, gastric ulcer, duodenal ulcer, and gastric erosion. Experimental studies suggested that acute gastric mucosal lesion (AGML) could be induced by hypoxic and cold stress, which might be the pathogenesis of altitude GIB. Those who consumed large amount of alcohol, aspirin or dexamethasone were at a higher risk of developing GIB. Persons who previously suffered from peptic ulcer or high-altitude polycythemia were also at risk of developing GIB. Early diagnosis, evacuation, and treatment led to early recovery. CONCLUSION: GIB is a potentially life threatening disease, if it is not treated promptly and effectively. Early diagnosis, treatment and evacuation lead to an early recovery. Death due to altitude GIB can be avoided if early symptoms and signs are recognized.

Who should not go high: chronic disease and work at altitude during construction of the Qinghai-Tibet railroad.

From 2001 to 2005, a new railroad linking Beijing with Lhasa was built by more than 100,000 workers, of whom 80% traveled from their lowland habitat to altitudes up to 5000 m to work on the railroad. We report on the medical conditions of 14,050 of these altitude workers, specifically with regard to preexisting illness. All subjects were seen at low and high altitude. Average age was 29.5 +/- 7.4 (SD) yr, range 20 to 62 yr; 98.8% of the subjects were men and 1.2% were women. Overall incidence of AMS upon first-time exposure was 51%, that of HACE 0.28%, and that of HAPE 0.49%. About 1% of the subjects were hypertensive before altitude exposure. Those with blood pressure >or=160/95 were excluded from employment at altitude. Altitude exposure led to a greater increase of blood pressure in hypertensives compared to normotensives. On prealtitude screening prevalence of cardiac arrhythmias was 0.33%. Since the majority of these were rather benign and occurring in young and otherwise healthy subjects, we allowed altitude employment. Follow-up at altitude was uneventful. Subjects with coronary heart disease and diabetes were excluded from altitude employment. Obesity was a risk factor for acute mountain sickness and for reduced work performance at altitude. Overweight subjects lost more weight during their altitude stay than subjects with normal weight. Altitude exposure was a risk factor for upper gastrointestinal tract bleeding, especially in combination with alcohol, aspirin, and dexamethasone intake. Asthmatic subjects generally did better at altitude compared to low altitude, with the exception of one subject who experienced an asthma episode from pollen exposure. In conclusion, careful evaluation of preexisting chronic illness and risk factors allowed prevention of altitude deterioration of a preexisting health condition, all the while allowing subjects with some specific conditions to work and live at altitude without problems.

[A study of high altitude environment affecting on worker's health during the constructing Qinghai-Xizang railway].

OBJECTIVE: To study high altitude environment affecting on worker's health METHODS: Using the cohort study, the altitude reaction was investigated and the WBC, RBC, Hb and oxygenation indexes were measured on workers in several periods, namely, acclimatization period, initially arrived high altitude and resident 90 days. RESULTS: The 83.3% of men had altitude reactions with different kinds at initially arrived high altitude. The headache was the most. The rate of abnormal blood pressure increased with altitude and resident time (P < 0.01). The rate of 90 day's group was 41.7%. The rise of diastole pressure was obvious (P < 0.01). As the beginning of arrived highland, the increase of WBC, RBC were significant (P < 0.01). The increase of Hb appeared only in 90 day's group. The level of malondialdehyde (MDA) obviously increased during acclimatization period and increased with altitude and resident time (P < 0.01). The activity of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) increased significantly in 90 day's group [(222.36 +/- 36.52) x 10(3) U/L, (158.49 +/- 14.42) U/L, (45.74 +/- 8.31) NU/ml respectively] (P < 0.01). CONCLUSION: The high altitude environment may result in the abnormal blood pressure, the rise of diastolic pressure was important. It lead to the increase of WBC, RBC, Hb. It initiated activity of oxygenation reaction. The symptoms of headache, dizziness, loss of appetite and insomnia appeared as working in high altitude environment.

Who are more at risk for acute mountain sickness: a prospective study in Qinghai-Tibet railroad construction workers on Mt. Tanggula.

BACKGROUND: It is important to determine the incidence of acute mountain sickness (AMS) among workers at altitudes between 3500 m and 5000 m on Mt. Tanggula during the construction of the Qinghai-Tibet railroad. This study explored the risk factors predisposing workers to developing AMS and attempted to develop more effective ways of preventing and treating AMS. METHODS: A total of 11,182 workers were surveyed by completing twice daily a Lake Louise questionnaire, and a score ≥ 3 indicated AMS. The contributing risk factors were assessed for at least 2 months for the duration of the study in the years from 2001 to 2003. A risk model was developed by multiple Logistic regression. Standard statistical methods were used to analyze data. RESULTS: AMS occurred in 56% of workers working at high altitudes on Mt. Tanggula. The incidence of AMS increased with increasing altitude. Rapid ascent to an altitude above 3500 m, sea-level or lowland newcomers, young people under 25 years of age, heavy physical exertion, obese person, and arterial oxygen saturation (SaO2) below 80% were independent AMS risk factors. No significant association was found between AMS and sex or taking Rhodiola. Medical education contributed to an early diagnosis of AMS. CONCLUSIONS: This study used the Lake Louise scoring system suggesting that it is a well-validated standard for field evaluation of AMS and for making an early diagnosis. These studies have described many variables regarding risk factors for the development of AMS. Risk factors which can be modified should be attended to, and the physicians should carry out check-ups and tests to identify subjects who are more at risk. Prevention consists in continuous gradual ascent, medical education, and prompt descent to avoid progression in patients with serious AMS. It is most important to effectively control the risk factors of AMS.

Altitude illness in Qinghai­Tibet railroad passengers.

It takes ≈24 h to travel the ≈3000-km-long Qinghai­Tibet railroad of which 85% is situated above 4000 m with a pass at 5072 m. Each year about 2 million passengers are rapidly exposed to high altitude traveling on this train. The aim of this study was to quantify the occurrence of altitude illness on the train. Three subject groups were surveyed: 160 Han lowlanders, 62 Han immigrants living at 2200 to 2500 m, and 25 Tibetans living at 3700 to 4200 m. Passengers reached 4768 m from 2808 m in less than 1.5 h, after which 78% of the passengers reported symptoms, 24% reaching the Lake Louise criterion score for AMS. AMS incidence was 31% in nonacclimatized Han compared to 16% in Han altitude residents and 0% in Tibetans. Women and older subjects had a slightly greater risk for AMS. Most cases of AMS were mild and self-limiting, resolving within days upon arrival in Lhasa. Some cases of more severe AMS necessitated medical attention. To curb the health risk of rapid travel to altitude by train, prospective travelers should be better informed, medical train personnel should be well trained, and staged travel with 1 to 2 days at intermediate altitudes should be suggested to nonacclimatized subjects.

Genetic interaction of Hsp70 family genes polymorphisms with high-altitude pulmonary edema among Chinese railway constructors at altitudes exceeding 4000 meters.

BACKGROUND: High-altitude pulmonary edema (HAPE) is thought of as an independent clinical disorder with a constitutional or genetic component in its etiology. We focused on 5 common polymorphisms within HSPA1A (rs1043618 and rs1008438), HSPA1B (rs1061581 and rs539689) and HSPA1L (rs2227956) of Hsp70 family to explore their potential interaction upon susceptibility to HAPE in Chinese. METHODS: A total of 148 HAPE patients and 483 matched controls were recruited during the construction of Qinghai-Tibet railway from 2001 to 2006. Genotyping was performed using PCR-RFLP, PCR-SSCP and PCR-direct-sequencing techniques. Promoter activity was evaluated by luciferase reporter assays. Gene-gene interaction was conducted by MDR v.2.0, and haplotype-diplotype analysis by Haplo.stats v.1.4.0. RESULTS: Significant differences were observed in the genotype (P=0.0136) and allele (P=0.0299) distributions of rs1008438, and in rs1061581 allele distribution (P=0.0421) between HAPE patients and controls. Interaction analysis indicated that 3 polymorphisms (rs1061581, rs1043618 and rs1008438) shared strong synergism with a testing accuracy of 0.792 and cross-validation consistency 10 out of 10 (P=0.001). Haplotypes Hap4 (G-C-A, in order of rs1061581, rs1043618 and rs1008438) and Hap5 (G-G-A) had an 86% reduced risk (P=0.0009) against and Hap7 (A-C-C) had a 2.43-fold increased risk for HAPE. When considered as diplotypes, significance was noted for Dip5 (Hap1-Hap7) (OR=3.39; 95% CI: 1.28-9.17; P=0.0140). Functional assessment supported the involvement of rs1008438 in the pathogenesis of HAPE. CONCLUSION: We demonstrated strong interaction of rs1061581, rs1043618 and rs1008438 polymorphisms within Hsp70 family upon susceptibility to HAPE in Chinese. Moreover, polymorphism rs1008438 might cause the development of HAPE via a change in HSPA1A promoter activity.

Reduced incidence and severity of acute mountain sickness in Qinghai-Tibet railroad construction workers after repeated 7-month exposures despite 5-month low altitude periods.

The construction of the Qinghai-Tibet railroad provided a unique opportunity to study the relation between intermittent altitude exposure and acute mountain sickness (AMS). For 5 yr, workers spent 7-month periods at altitude interspaced with 5-month periods at sea level; the incidence, severity, and risk factors of AMS were prospectively investigated. Six hundred lowlanders commuted for 5 yr between near sea level and approximately 4500 m and were compared to 600 other lowland workers, recruited each year upon their first ascent to high altitude as newcomers, and to 200 Tibetan workers native to approximately 4500 m. AMS was assessed with the Lake Louise Scoring System. The incidence and severity of AMS in commuters were lower upon each subsequent exposure, whereas they remained similar in newcomers each year. AMS susceptibility was thus lowered by repeated exposure to altitude. Repeated exposure increased resting Sao(2) and decreased resting heart rate. Tibetans had no AMS, higher Sao(2), and lower heart rates. In conclusion, repetitive 7-month exposures increasingly protect lowlanders against AMS, even when interspaced with 5-month periods spent at low altitude, but do not allow attaining the level of adaptation of altitude natives.

Endothelial nitric oxide synthase gene polymorphisms associated with susceptibility to high altitude pulmonary edema in Chinese railway construction workers at Qinghai-Tibet over 4 500 meters above sea level / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level.</p><p><b>METHODS</b>A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing.</p><p><b>RESULTS</b>The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both Pü0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both Pü0.001).</p><p><b>CONCLUSIONS</b>Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.</p>