Natl. J. Physiol. Pharm. Pharmacol. (2026), Vol. 16(1): 1-7

Original Research

10.5455/NJPPP.2026.v16.i1.1

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Effects of rapid ascent to high altitude and incidence of
high-altitude illness in third-generation Tibetan descendants

Pankaj Pande¹, Swapnil Saikhedker^1* and Aravind babu Nooney²

¹Department of Physiology, AFMC,Pune, India

²Department of ENT, INHS Asvini, Mumbai, India

*Corresponding Author: Swapnil Saikhedker, Department of Physiology, AFMC,Pune, India.
Email: realswapnil123 [at] gmail.com

Submitted: 27/09/2025 Revised: 30/11/2025 Accepted: 10/12/2025 Published: 25/01/2026

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Abstract

Background: Third-generation Tibetan descendants in the eastern Himalayas are presumed to possess genetic adaptations that confer resistance to high-altitude hypoxia. However, the impact of rapid ascent on this population, particularly among native highlanders, remains poorly documented. Anecdotal evidence and observational data indicate that highlanders ascending rapidly (e.g., >500 m/day) may experience lower incidence and milder forms of these conditions than lowlanders.

Aim: This study aimed to evaluate physiological effects and incidence of high-altitude illness (HAI) in eastern Himalayan highlanders during rapid ascent to altitudes above 14,300 feet.

Methods: A cross-sectional observational study was conducted in May 2020 at a government hospital in the Eastern Himalayas. Thirty-three male combatants of eastern Himalayan origin, who had resided at lower altitudes for over two years, were assessed using the LLSQ following acute high-altitude exposure.

Results: The prevalence of acute mountain sickness (AMS) was 27.3% (n=9), with equal distribution across mild, moderate, and severe categories (n=3 each). High-altitude pulmonary edema (HAPE) and cerebral edema (HACE) each occurred in 9.1% (n=3) and 3 % (n=1) of patients, respectively. Headache was the most frequent symptom (36.4%), whereas ataxia was the least (3.0%). Lower oxygen saturation (SpO₂ ≤ 85%) was significantly associated with AMS (χ²=15.91, p < 0.001). No fatalities were reported.

Conclusion: Third-generation Tibetan highlanders remain vulnerable to AMS, HAPE, and HACE during rapid ascent despite presumed genetic tolerance. Pharmacological prophylaxis and pulse oximetry monitoring are recommended in operational settings to mitigate risk and maintain functional capacity. This study represents the first systematic assessment of HAI incidence in Eastern Himalayan highlanders and highlights the need for high-altitude, tailored preventive strategies in primary healthcare.

Significance: This study holds multidimensional clinical, operational, and scientific importance, particularly in the context of high-altitude medicine and indigenous populations. It debunks the myth of invulnerability in Tibetan highlanders, validates pulse oximetry as a frontline tool, and drives evidence-based policy for the safety of thousands of native highlanders in military, tourism, and labour sectors at extreme altitudes.

Keywords: High altitude, LLSQ, Tibetans, Highlanders Altitude Sickness, Acute Mountain Sickness, High-Altitude Pulmonary edema, High-Altitude Cerebral edema, Hypoxia, Acclimatization.

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Introduction

High-altitude illness (HAI) comprises a spectrum of hypoxia-induced syndromes, including acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), typically precipitated by rapid ascent to elevations above 2,500 m (Basnyat, 2014; Bartsch and Swenson, 2013a,b). These conditions result from inadequate acclimatization (Cremona et al., 2002) to hypobaric hypoxia and can pose significant operational and clinical challenges in high-altitude deployments (Taylor, 2011).

Tibetan highlanders exhibit unique genetic adaptations—most notably in the EPAS1 (Bigham and Lee, 2014) and EGLN1 pathways—that confer enhanced oxygen delivery and reduce susceptibility to AMS during gradual ascent (Basnyat, 2014; Longo et al., 2024). However, prolonged residence at low altitudes may lead to de-acclimatization, (He et al., 2013; Sikri et al., 2019; Tissot Van Patot and Gassmann, (2011) diminishing these physiological advantages and potentially increasing vulnerability upon re-ascent.

The Eastern Himalayas host a population of third-generation Tibetan descendants serving in combatant forces. During periods of border conflict, these individuals are rapidly mobilized from lowland garrisons (<1,500 m) to high-altitude posts exceeding 4,350 m (14,300 ft) via road transport, often within hours. This abrupt ascent (Bigham and Lee, 2014) bypasses standard acclimatization protocols and may increase the risk of HAI—even among genetically predisposed highlanders. Despite their ethnic lineage and ancestral altitude exposure, systematic data on their risk of HAI during rapid re-ascent are scarce (Zhang et al., 2021).

This pilot study addresses this gap by investigating HAI outcomes in combatants of Tibetan origin stationed in the Eastern Himalayas.

Specifically, the study aims to:

1. The incidence and severity of AMS following rapid ascent were estimated.
2. Identifying clinical and physiological predictors of AMS using field-deployable tools such as pulse oximetry, Lake Louis Scoring Questionnaire (LLSQ), (Roach et al., 2018; Roach and Auerbach, 2017) and detailed clinical examination (Taylor, 2011).
3. Assess the progression to HAPE (Cremona et al., 2002) and HACE under the operational conditions.
4. To generate evidence to inform context-specific primary health care and operational protocols for high-altitude deployments.

This study offers novel insights into altitude re-exposure physiology and contributes to the development of targeted mitigation strategies for HAI in military and humanitarian contexts by focusing on a genetically predisposed yet operationally vulnerable cohort.

Aim

To estimate the prevalence of acute mountain sickness (AMS) among native Eastern Himalayan highlanders (third-generation Tibetans) following rapid ascent to high altitude, using the Lake Louise Scoring Questionnaire (LLSQ) as the diagnostic tool.

Objectives

To study the effects of rapid ascent to high altitude on native Eastern Himalayan highlanders.

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Materials and Methods

Study design and setting

This observational cross-sectional study was conducted in May 2020 at a government peripheral hospital in a high-altitude area of East Eastern Himalayas, India. This study assessed to assess the incidence of HAI among deacclimatized high-altitude natives undergoing rapid ascent.

Sampling method and participants

A purposive sampling technique was used to recruit 33 male combatants of Tibetan descent. All participants were third-generation highlanders native to the Eastern Himalayas who had resided at low altitudes (<1,500 m) for more than two years and had not travelled to high-altitude areas (>4,000 m) during that period. Due to operational requirements, these individuals were rapidly deployed by road from 1,525 m (5,000 ft) to 4,360 m (14,300 ft) within approximately four hours.

Inclusion and exclusion criteria

Inclusion criteria comprised all 33 ascenders who presented to the hospital and provided informed consent after being briefed on the study objectives. Exclusion criteria included individuals with conditions that could mimic AMS, such as carbon monoxide poisoning, dehydration, exhaustion, hypoglycemia, hypothermia, and motion sickness (Wu et al., 2009).

Clinical assessment and data collection

Upon arrival at high altitude, participants underwent a basic clinical evaluation (Taylor, 2011), including measurement of resting heart rate, systolic and diastolic blood pressure, mean arterial pressure, respiratory rate, and peripheral oxygen saturation (SpO₂). All baseline parameters were within the normal limits. No laboratory investigations were performed due to logistical constraints.

Diagnosis of HAI

The diagnosis of AMS was based on the LLSQ (André et al., 2021) administered within 24 hours of arrival at the high-altitude site. AMS was defined as the presence of headache (mandatory) in an unacclimatized individual with recent altitude gain, accompanied by at least one additional symptom (gastrointestinal disturbance, dizziness, or fatigue), and an Lake Louise Score (LLS) ≥ 3 (Hackett and Roach, 2011). Scores >5 were classified as moderate to severe AMS. Of the 33 participants, 9 (27.3%) met the AMS criteria (André et al., 2021).

Cases of HAPE (Cremona et al., 2002) and HACE were identified based on clinical signs, including respiratory distress, altered mental status, and poor response to initial treatment. Three participants (9.1%) were diagnosed with HAPE, and one participant (3.0%) was diagnosed with HACE. Severe cases were referred to tertiary care facilities at lower altitudes for further management.

Data management and analysis

Detailed histories, including symptom onset, physical activity, sleep duration, pre-induction medical evaluations, and awareness of acclimatization protocols (Sikri et al., 2019), were obtained from all participants. The data were recorded in Microsoft Excel and analyzed using descriptive statistics to determine the prevalence of AMS, HAPE, and HACE (Honigman et al., 1993; Mairer et al., 2009; Cremona et al., 2002).

Ethical approval

This study qualified as minimal-risk observational research conducted during a humanitarian emergency in accordance with the Indian Council of Medical Research National Ethical Guidelines (2017). All participants provided informed consent, and confidentiality was maintained throughout the study.

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Results

This observational cross-sectional study, conducted in May 2020 at a government hospital in the Eastern Himalayas, evaluated 33 male combatants of Tibetan descent who underwent rapid road ascent from 1,525 m (5,000 ft) to 4,360 m (14,300 ft) within 4 hours. All participants were native highlanders residing at low altitudes for more than two years, rendering them unacclimatized.

Table 1. Distribution of subjects according to effects (Complication).

Table 2. Mean distribution of vital parameters among study subjects.

Table 3. Anthropological data.

The baseline clinical parameters, including pulse, blood pressure, and SpO₂ were within normal limits (Tables 1–3, 5). No laboratory investigations were performed (Hackett and Roach, 2011). AMS was assessed using the LLS at a (LLS) at the deployment altitude of 4,270 m. AMS was diagnosed in 9 participants (27.3%) with LLS ≥ 3, including moderate to severe cases (LLS > 5) (Tables 4 and 6). Three cases (9.1%) of HAPE and one case (3.0%) of HACE, (Table 6) were identified and referred for tertiary care (Hackett and Roach, 2011).

Table 4. Maximum symptom score.

Table 5. Association of acute mountain sickness and SPO2 in study subjects.

Table 6. Physiological and AMS data.

Fig. 1. Prevalence of acute mountain illness (AMS) among Sikkim highlanders using LLSQ. During acute ascent 3 mild AMS and 3 moderate and 3 severe AMS cases were diagnosed based on LLSQ.

The exclusion criteria ruled out alternate diagnoses such as dehydration, hypoglycemia, hypothermia, and motion sickness. Detailed histories and physiological (Gilbert-Kawai et al., 2014) assessments were recorded, and descriptive statistics were used to analyze the data.

These findings highlight the substantial burden of HAI among high-altitude natives following rapid reascent, which is comparable to or exceeds the AMS rates reported in lowlanders after acute ascent. The results underscore the need for acclimatization protocols and early screening in operational deployments.

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Discussion

In this pilot study of 33 Tibetan-descendant (Gao, 2024) combatants undergoing rapid road ascent to altitudes exceeding 4,350 m in the Eastern Himalayas, the prevalence (Honigman et al., 1993) of AMS was 27.3%, with HAPE and HACE observed in 9.1% and 3.0% of participants, respectively (Fig. 1 and Table 6). These findings are clinically significant, particularly given the high-altitude ancestry of the participants, which is often assumed to confer protection against hypoxia-related illness.

Tibetan highlanders Gao, (2024), Petousi et al., (2014) are known to possess genetic adaptations—most notably in EPAS1 and EGLN1— (Bigham and Lee, 2014) that enhance oxygen delivery and reduce erythropoietic stress under hypobaric hypoxia (Longo et al., 2025). However, de-acclimatization following prolonged low-altitude residence may diminish these protective effects, as demonstrated in studies of Tibetan (Gao, 2024; Petousi et al., 2014) students returning to Lhasa after years at sea level (Longo et al., 2025). This study confirms that genetic predisposition alone does not eliminate the risk of HAI , especially under conditions of rapid ascent (Longo et al., 2025).

The use of the Lake Louise Scoring System (LLSS) (André et al., 2021) enabled a standardized diagnosis of AMS, which typically presents within 6–12 hours of ascent and is characterized by headache, fatigue, dizziness, and gastrointestinal symptoms. While AMS is often self-limiting, progression to HAPE and HACE can be life-threatening (Bartsch and Swenson, 2013a,b). HAPE results from exaggerated hypoxic pulmonary vasoconstriction leading to noncardiogenic pulmonary edema and has been reported at altitudes as low as 2,000–2,500 m in susceptible individuals. HACE, a severe form of AMS involving cerebral edema, requires immediate intervention with descent and corticosteroids.

In this study, the ascent profile exceeded 2,800 m/day, with sleeping altitudes above 3,000 m, placing participants in the high-risk category for AMS according to wilderness medicine guidelines (Luks et al., 2024; Bartsch and Swenson, 2013a). Ideally, ascent should be limited to <300 m/day above 2,500 m, with rest days every 3–4 days (Bartsch and Swenson, 2013a,b). However, operational constraints during border mobilization often preclude such protocols, necessitating alternative mitigation strategies.

Pharmacologic prophylaxis with acetazolamide (Leaf and Goldfarb, 2007) and dexamethasone has been shown to reduce the incidence of AMS and HACE, while dexamethasone may also benefit HAPE by Cremona et al., (2002) reducing pulmonary inflammation. In this study, limited access to prophylaxis and lack of acclimatization likely contributed to the observed HAI rates.

This study is among the first to document HAI prevalence in combatants of Tibetan descent undergoing rapid terrestrial reascent. This study challenges the assumption of complete genetic protection and highlights the need for field-based screening, structured acclimatization planning, and emergency preparedness protocols in high-risk deployments. Limitations include the small sample size, absence of female participants, and lack of a comparison group. Nonetheless, the findings provide valuable insights for operational medicine and high-altitude public health.

This study has several important limitations that affect how its findings should be interpreted. The small sample size of only 33 participants reduces statistical power and limits generalizability. Since the cohort included only males, gender-based differences in susceptibility and symptom presentation could not be assessed. The absence of a control group, such as lowlanders or acclimatized highlanders, restricts contextual comparisons. Data collection was limited to a short observation window without follow-up, preventing evaluation of symptom progression or delayed onset. Reliance on clinical evaluation and pulse oximetry without laboratory diagnostics may have led to underdiagnosis or misclassification. Additionally, operational constraints in conflict zones and the single-center design limit standardization and broader applicability. Despite these challenges, the study offers preliminary insights into HAI risk among de-acclimatized Tibetan highlanders and underscores the need for larger, multi-center studies with extended monitoring and advanced diagnostic tools (Bigham and Lee, 2014).

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Conclusion

Despite well-documented genetic adaptations, (Gilbert-Kawai et al., 2014) third-generation Tibetan highlanders remain vulnerable to HAIs—including AMS, HAPE, and HACE—following rapid ascent after prolonged low-altitude residence. The observed incidence of AMS (27.3%), HAPE (9.1%), and HACE (3.0%) among previously de-acclimatized combatants highlights the physiological strain imposed by abrupt elevation gain, even in ancestrally adapted populations.

The findings are particularly relevant in the context of military and emergency deployments, where rapid terrestrial ascent (Basnyat, 2014) is often required without adequate acclimatization. This study is among the first to document HAI outcomes in combatants of Tibetan descent in the Eastern Himalayas, offering critical insights into the interplay between genetic predisposition, environmental stress, and gaps in reacclimatization. Although resource-limited, primary health centers (PHCs), serve as frontline responders in such high-altitude settings. Their role in early detection, triage, and referral is vital. Incorporating structured screening protocols, preascent (Basnyat, 2014) medical evaluations, and pharmacologic prophylaxis (e.g., acetazolamide (Berger et al., 2022) and dexamethasone) can mitigate risk. Given the association between AMS and reduced SpO₂, ensuring access to pulse oximetry and supplemental oxygen at high-altitude posts is essential. To reduce morbidity and preserve operational performance, ascent (Basnyat, 2014) profiles should ideally not exceed 500 m/day above 2,500 m, with rest days every 1,000 m. In scenarios where this is not feasible, tailored interventions—including education, medication, and monitoring—must be prioritized. Further research is warranted to develop context-specific guidelines for high-altitude reexposure in native populations, particularly within the constraints of PHC-based care.

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Acknowledgments

All staff of PHC and tertiary centre of eastern Himalayas.’

Conflict of interest

The authors declare no conflict of interest.

Funding

This research received no external funding.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Author contributions

Pankaj Pande: Conception and design of the work, Acquisition, analysis, and interpretation of data for the work, literature search, manuscript preparation and editing. Swapnil Saikhedker: Role-Acquisition, analysis, interpretation of data for the work and drafting, literature search, manuscript preparation, and editing. Aravind Nooney Babu: Role-Acquisition, analysis, and interpretation of data for the work, drafting, data collection, and editing.

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