Transient airway cooling modulates dry-air-induced and hypertonic aerosol-induced bronchoconstriction

Airflow-induced bronchoconstriction (AIB) may be initiated in asthmatic patients by inhaling dry air during eucapnic hyperventilation or exercise. Hypertonic aerosol-induced bronchoconstriction (HIB) also occurs in these patients, but it differs from AIB by exhibiting a faster time course. Although AIB and HIB probably increase airway fluid osmolality, only AIB is associated with airway cooling. In light of the similarities between our canine model and human AIB, we examined peripheral airway responses to dry air and hypertonic aerosol challenge. Specifically, we studied the magnitude and time course of these responses in an in situ, isolated, perfused lobe in which airway temperature was independently controlled. At body temperature, HIB peaked immediately after challenge, whereas transient airway cooling during aerosol challenge delayed HIB. In contrast, airway cooling attenuated AIB but did not alter its time course. Hypocapnia- and histamine-induced responses were not affected by airway cooling, suggesting that smooth muscle function was not impaired. To the extent that the mechanisms producing AIB in dogs and in humans are similar, our results suggest that (1) changes in airway fluid osmolality initiate AIB, (2) AIB = HIB + Cooling, and (3) exercise-induced asthma results from an imbalance between an excitatory pathway stimulated by airway drying and an inhibitory pathway initiated by airway cooling.