Can endurance exercise in cold or dry air cause airway irritation and exercise‑induced bronchoconstriction without allergy?

Endurance exercise in cold or dry environments is a potent trigger for airway dysfunction, even in individuals who do not exhibit classic allergy symptoms. High ventilatory demands during sustained activity place significant osmotic and thermal stress on the respiratory system, leading to a cascade of physiological changes that can result in exercise-induced bronchoconstriction (EIB).

Clinical and physiological evidence

The prevalence of EIB is significantly higher among endurance athletes compared to the general population, particularly those training in cold or dry conditions.

• Athlete prevalence: Research indicates that up to 24% of non-asthmatic marathon runners and between 20% and 70% of elite winter athletes, such as cross-country skiers, experience EIB.
• Epithelial markers: Studies utilizing biomarkers like Clara cell protein (CC16) demonstrate that continuous endurance exercise leads to significantly higher levels of epithelial leakage and shedding compared to intermittent exercise. This reflects the cumulative impact of sustained high ventilation rates on the airway lining.

Mechanistic explanations

The transition from healthy breathing to EIB in cold/dry air involves a well-defined mechanistic pathway centered on the airway epithelium:

• Osmotic and thermal stress: Rapid heating and humidification of cold, dry air cause significant water evaporation from the airway surface liquid (ASL). This results in a hyperosmolar state (increased salt concentration) that pulls water out of epithelial cells, causing cellular shrinkage and structural injury.
• Alarmin release: Damaged epithelial cells release "alarmins," such as IL-33 and TSLP. These molecules activate Group 2 Innate Lymphoid Cells (ILC2s), which represent a non-allergic, innate source of type-2 signaling.
• Type-2 signaling and eosinophilia: ILC2s produce IL-5, the primary cytokine responsible for the recruitment and survival of eosinophils. This leads to an eosinophilic airway inflammation endotype, characterized by elevated sputum eosinophils and fractional exhaled nitric oxide (FeNO), even in the absence of traditional IgE-mediated allergies.
• Bronchoconstriction: The resulting inflammatory environment, combined with the release of mediators like leukotrienes and prostaglandins, triggers smooth muscle contraction and airway narrowing.

Bottom line

Endurance exercise in cold or dry air causes direct epithelial damage and triggers an innate type-2 inflammatory response. This process promotes exercise-induced bronchoconstriction through osmotic and thermal stress, affecting a high percentage of athletes regardless of their allergic status.