Could Olfactory Dysfunction Help Us Diagnose Acute Mountain Sickness?

To the Editor:

From a clinician’s point of view, the principal limitation of the current methods of acute mountain sickness (AMS) assessment is reliance on self-reporting of AMS symptoms, which can be heavily influenced by multiple factors, including psychological factors. ¹ Objective measurement of maladaptation to hypobaric hypoxia at high altitude would be clearly preferred. Heart rate and oxygen saturation values, albeit measured on most expeditions, are not diagnostic criteria for AMS. Their usability to detect or predict the occurrence of AMS by nonmedical personnel is, at best, limited. High-altitude medicine is still searching for a reliable, objective way to assess AMS that is easy to use even without medical training, inexpensive, and lightweight.

Olfactory dysfunction is found in patients affected by various medical conditions. Recently, both quantitative ^{1 -}3 and qualitative^2,3 impairment of the sense of smell caused by ascending altitude was found in high-altitude mountaineers. Experimental studies have already established the connection between olfactory dysfunction and normobaric hypoxia ⁴ and hypobaric conditions. ⁵ The olfactory bulb is a part of the brain that is predominantly affected by hypoxia-related microscopic damage, including capillary leak ⁶ and microhemorrhages. ⁷ At the molecular level, the importance of olfactory receptor-78 in the regulation of erythropoietin and cardiorespiratory responses to hypobaric hypoxia, both critical for acute adaptation to high altitudes, was demonstrated. ⁸ Hypoxia-inducible factor-1α in the olfactory mucosa mesenchymal stem cells has a pivotal role in the adaptation of the brain to hypoxia. ⁹

Given that both AMS and olfactory dysfunction have causal relations with hypoxic and hypobaric conditions, we hypothesized an association between AMS and olfactory dysfunction. In practical terms, persons with a propensity for maladaptive response to hypobaric hypoxia recognized as more severe AMS might be prone to a more severe loss of smell. The relevance of detecting olfactory dysfunction associated with AMS could potentially extend to patients with normobaric hypoxia, usually found in patients with critical illness or heart or lung disease. This could help identify patients with poor adaptation to normobaric hypoxia, thus allowing better phenotype-based risk stratification and more efficient healthcare resource allocation.

Unlike the current AMS criteria, diagnosing olfactory dysfunction is a matter of objective measurement, but it could be challenging to measure in remote areas if standardized methods are used. Both quantitative ¹ and qualitative ² commercially available tests were used for that purpose. However, they represent an additional weight that must be carried and require personnel with formal medical training and significant financial commitment, making them less suitable for remote expeditions. Our goal was, instead, to assess olfactory function in a manner relevant to real-world conditions using inexpensive items that are readily available in remote areas but chosen according to a standardized commercially available test. ¹⁰

We approached a team of mountaineers on an Island Peak (6160 m) expedition in Nepal. We evaluated their olfactory function using a 3-item odor identification test developed by Hummel et al. ¹⁰ Bags containing fresh garlic cloves and coffee and a bottle of rose water were held 5 cm below the subject’s nose. The subjects were asked to identify the odor with their eyes closed. The olfactory function was intact in all subjects up to 3900 m. As the ascent progressed, the number of identified odors per subject decreased, suggesting altitude-related hyposmia.

Our results suggest that a qualitative test consisting of everyday items could potentially be used as an objective and reliable method of olfactory dysfunction assessment at altitude in remote and resource-poor areas. However, further statistical analysis was impossible due to the small sample size. Mathematical proof of our hypothesis would require studies with a larger number of subjects to test the statistical significance of the correlation between the severity of AMS and olfactory dysfunction as well as the possible prognostic or predictive value of olfactory dysfunction in patients with acute high-altitude illness.

As a first step, we advise using standardized commercially available qualitative olfactory function tests to explore the association between AMS and olfactory dysfunction.