Therapeutic strategies in pulmonary medicine frequently employ bronchodilators or steroids to decrease airway resistance and improve airflow. As an alternative strategy, the viscosity and density of inspired air may be manipulated to achieve this same desired effect. Air consists of 21% oxygen, with most of the remainder being nitrogen. Oxygen and nitrogen have nearly equivalent densities, and thus altering the percentage of FIO₂ (fraction of inspired oxygen) does not appreciably change the physical properties of the gas mixture. However, replacing nitrogen with the less-dense helium can dramatically decrease the overall air density. This in turn reduces airway resistance, even without anatomical changes in airway caliber.

There are no evidence-based guidelines directing the use of heliox. However, given that heliox does not have any significant side effects, therapeutic trials may be used in patients with obstructive upper-airway conditions and respiratory compromise. Low-density gas mixtures have the greatest beneficial impact in large airways with turbulent density-dependent flow, resulting in improved alveolar emptying and reduced plateau pressures. Considering this, patients with severe asthma (requiring mechanical ventilation) may be ideal candidates for heliox therapy. Indeed, in trials of intubated patients with status asthmaticus, those treated with heliox demonstrated decreased airway pressures, decreased PaCO₂ (partial pressure of carbon dioxide, arterial), and improved acidosis. Patients with other severe upper-airway diseases such as postextubation obstruction or chronic obstructive pulmonary disease may benefit as well.