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.
Hypertonic aerosol- and dry airflow-induced bronchoconstriction were examined in the canine lung periphery by the use of a wedged bronchoscope technique. Collateral resistance was measured in anesthetized dogs before and after exposure to isotonic and hypertonic aerosols and dry airflow. Hypertonic aerosols produced significantly greater responses than isotonic aerosols, and resistance increased in an exposure-dependent manner. Atropine attenuated responses to these challenges, indicating that aerosol-induced peripheral lung constriction was, in part, muscarinic in origin. Paired hypertonic- and dry airflow-induced constriction exhibited marked differences in magnitude and time course: responses to hypertonic aerosol peaked immediately; dry air-induced responses rose slowly to a maximum 5-min postchallenge. These differences may reflect differences in stimulus strength or differences in the regulatory pathways activated by each challenge. Despite this, a significant correlation exists between aerosol- and dry air-induced responses in the canine lung periphery and suggests that changes in airway fluid osmolality have an important role in the initiation of airflow-induced bronchoconstriction.
We used a wedged bronchoscope technique in conjunction with an in situ isolated perfused left lower lobe preparation in anesthetized dogs to examine cold-associated airway modulation of peripheral lung responses to dry airflow, hypocapnia, and aerosols of histamine and hypertonic NaCl. In this preparation, airway wall temperature was rapidly lowered by decreasing the temperature of blood perfusing the wedged sublobar segment. Cooling significantly attenuated responses to dry air, hypertonic NaCl aerosol, and hypocapnic challenge. In contrast, cooling did not affect peripheral lung responses to aerosolized histamine. Thus, cooling per se does not inhibit the responsiveness of smooth muscle. We conclude that, depending on the stimulus, cooling can modulate airway reactivity. We speculate that cooling attenuates hypocapnia, hypertonic aerosol, and dry air-induced bronchospasm via a cold induced reduction in neuronal activity or mediator production and release.
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