The Bronchial Response, but not the Pulmonary Response to Inhaled Methacholine Is Dependent on the Aerosol Deposition Pattern: Conclusion
Theoretically, differences in regional deposition of a vasoactive drug might then elicit different responses or time courses of effects, dependent on the deposition pattern. Experimental studies have suggested that a compound may be rapidly redistributed throughout the lung by bronchial blood flow This ability may have a role in airway homeostasis by enhancing the clearance of inhaled agents. In accordance, impairment of the bronchial perfusion prolonged the recovery of airway responses in sheep as well as in an isolated canine lung preparation in contrast to an intact preparation, with unaltered airway blood supply. The time to eliminate high local concentrations of a compound to the level when the receptors—which are situated mainly in the central airways—do not respond, would theoretically be longer than the time to eliminate a low concentration of the same compound. Our findings contrasted to this assumption, and although the intervals between the physiologic measurements in our experiments were not evenly distributed throughout the trial, we judged that the duration of bronchoconstriction was not longer, but rather tended to be shorter after the central airway deposition than after the peripheral airway deposition. The results are, therefore, compatible with a selective enhancement of the bronchial perfusion in the central airways by higher local doses of methacholine, potentially giving a faster clearance of the inhaled drug from the target area. natural inhalers for asthma
In conclusion, we state that the process induced by bronchoconstrictor agents is complex and may involve a variety of prereceptor and postreceptor determinants, as well as bronchial and pulmonary vascular responses, and differences in receptor localization, density, and sensitivity. Also, the response to second messengers by the target organs may vary along the bronchial tree. The end organs may respond independently of each other, as suggested by the differences in time courses of disturbances of gas exchange and bronchial constriction, and this appears to occur independently of the aerosol deposition pattern. The suggested difference in magnitude and duration of airway contraction, as measured by sGaw, after central or peripheral airway deposition of methacholine, may be consistent with the conception of a major difference in patency of the bronchial circulation in the two experiments performed in our patients. The relative contribution of the bronchial circulation to the magnitude and time courses of airway responses to inhaled methacholine thus emphasizes the need for highly standardized procedures for formation of aerosols, mode of inhalation, and recording of the physiologic responses to inhaled methacholine. Studies on bronchial responsiveness in various physiologic conditions and the potential variability in responses due to differences in bronchial and pulmonary circulation are, therefore, warranted.