Transient Airway Cooling Modulates Dry-Air-induced and Hypertonic Aerosol-induced Bronchoconstriction

Abstract

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.

Dry air- and hypertonic aerosol-induced bronchoconstriction and cellular responses in the canine lung periphery

“…When canine peripheral airways are artificially cooled and simultaneously exposed to a hypertonic aerosol, the onset of HIB is delayed in a manner similar to AIB [8]. This is consistent with the hypothesis that dry air and hypertonic aerosol activate portions of the same regulatory pathway.…”

“…Airway cooling inhibited AIB and HIB in the canine lung periphery [6][7][8]. However, unlike AIB, hypertonic aerosol-induced responses normally occur in the absence of airway cooling and peak immediately after exposure [8,25]. The fact that transient airway cooling during aerosol challenge slows the development of HIB [8] is consistent with the hypothesis that during periods of hyperpnoea, airway cooling delays the onset of AIB via an inhibition of mediator release and neuronal activity.…”

“…Although these differences in the time-course of AIB and HIB appear to be unrelated to stimulus strength, they may result from differential activation or inactivation of biochemical pathways by these two stimuli. Airway cooling inhibited AIB and HIB in the canine lung periphery [6][7][8]. However, unlike AIB, hypertonic aerosol-induced responses normally occur in the absence of airway cooling and peak immediately after exposure [8,25].…”

“…The fact that hypertonicity stimulates mast cell mediator release in vitro [4], and was implicated to do so in vivo [5], is consistent with this hypothesis. However, this scenario is complicated by the fact that data from man and dog suggest that the stimulatory effects of evaporative water loss may be counterbalanced by an inhibitory pathway associated with airway cooling [6][7][8][9].…”

“…BALF cell profile data also suggest that challenge with warm, wet air [10,11,13], and pretreatment with β-agonists [14,15], attenuate AIB and significantly protect the canine mucosa from airway desiccation, when compared to untreated dry air challenged segments. In addition to β-agonists [14][15][16], methylxanthines [16,17], muscarinic receptor antagonists [13,18], cyclo-oxygenase inhibitors [11,13,19], leukotriene antagonists [20,21], and airway cooling [6][7][8][9] reduce or abolish AIB in canine peripheral airways and individuals with asthma.…”