Cysteinyl leukotriene blockade does not prevent acute mountain sickness

Area of Science:

• Altitude sickness research
• Pulmonary and respiratory medicine
• Pharmacology

Background:

• Acute Mountain Sickness (AMS) is a common, multi-system illness affecting individuals ascending rapidly to high altitudes.
• AMS pathogenesis may involve hypoxia-induced cerebral edema and increased capillary permeability.
• Cysteinyl leukotrienes (CysLTs) are implicated due to their known effects on endothelial permeability.

Purpose of the Study:

• To investigate the potential role of CysLTs in AMS development.
• To determine if a CysLTs type-1 receptor antagonist (montelukast) can prevent or reduce AMS symptoms.
• To assess the relationship between CysLTs levels and AMS severity.

Main Methods:

• A randomized, placebo-controlled, crossover study involving 11 subjects exposed to 4,300 m in a hypobaric chamber.
• Oral administration of montelukast or placebo before and during high-altitude exposure.
• Measurement of AMS prevalence and severity, plasma CysLTs, urinary LTE4, and physiological parameters.

Main Results:

• Montelukast significantly reduced AMS prevalence and severity at 12 hours but not at 22 hours of exposure.
• Plasma CysLTs and urinary LTE4 levels did not significantly increase with altitude exposure.
• No correlation was found between CysLTs levels and AMS severity; montelukast did not alter physiological measures.

Conclusions:

• The study does not support a role for CysLTs in mediating the early development of AMS via the CysLT-1 receptor.
• Montelukast's early protective effect may not be linked to CysLT pathway modulation.
• Further research is needed to fully elucidate AMS pathophysiology.