It Is High Time: Rationale for Inclusion of Quantitative Markers for Acute Mountain Sickness Screening

Dear Editor,

Acute mountain sickness (AMS) is a combination of nonspecific symptoms upon ascent to high-altitude (≥2,500 m) in unacclimatized lowlanders without prophylactic medications. The symptoms generally appear with a usual delay of 4−12 hours post ascent within a span of 1–5 days after arrival. The severity of symptoms depends on individual susceptibility, rate of ascent, altitude attained, preacclimatization, previous history of high-altitude illness and gender (Luks et al. 2024).

AMS diagnosis is based solely on reported symptoms and self-assessment questionnaire like Lake Louise score (LLS), Chinese AMS Score (CAS), and the Environmental Symptoms Questionnaire are used to diagnose the severity. LLS is the most popular questionnaire that considers headache as a cardinal symptom with other symptoms including gastrointestinal symptoms, fatigue and/or weakness, dizziness/light-headedness and an optional AMS functional score for assessing severity both in clinical and research settings (no discomfort = 0; mild symptoms = 1; moderate symptoms = 2; severe symptoms = 3) (Roach et al., 2018). Despite widespread use, the nonspecificity of the symptoms often results in erroneous LLS scores and concerns have been raised in recent studies (Yang et al., 2022; Luks et al., 2024)

The ‘‘Chinese AMS score’’ for screening AMS considers headache and vomiting as major nonspecific symptoms. It also considers several other nonspecific symptoms like dizziness/light-headedness, short breath, chest distress, nausea, palpitation, dazzling/blurred vision, insomnia, diarrhea, anorexia, constipation, cyanosis of the lips, lethargy, and numbness of the extremities with equal weightage (Wu et al., 2016). Several bottlenecks like too many nonspecific symptoms, complicated scoring system and poor correlation with LLS has limited the use of CAS.

There exists neither diagnostic gold standard nor fixed threshold for defining severity of the symptoms (Luks et al., 2024). Currently, AMS scoring is solely based on voluntary disclosures. Inadequate and improper disclosure of symptom severity by the assessee is a bottleneck for researchers. This warrants inclusion of reliable and validated biomarkers in the existing scoring systems to asses AMS severity.

A number of studies investigating AMS susceptibility have reported higher levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and CRP) in AMS positive volunteers (Pham et al., 2021) while a handful of studies have reported no changes. Significant higher levels of vascular endothelial growth factor, ret proto-oncogene phosphoglycerate dehydrogenase ADAM metallopeptidase domain 15 (ADAM15), and TNF receptor associated factor 2 (TRAF2) has been implicated for AMS severity (Yang et al., 2022). Inclusion of these biochemical markers with definite threshold range will increase both sensitivity and specificity of the existing AMS screening methods.

Majority of the AMS screening is performed at high-altitude with limited resources. Sensitive detection of biochemical markers at field conditions will pose technical challenges. However, this screening will assist in lowering numbers of false negative individuals at high-altitude who are in persistent danger of developing further life threating complications. In addition, this will also help researchers in case identification as well as benefit healthcare professionals in monitoring traveler well-being at high-altitude.