title: The bronchial response, but not the pulmonary response to inhaled methacholine is dependent on the aerosol deposition pattern.
abstract: The clinical effect of inhaled radio-labeled (Technetium-99m diethylenetriamine-pentaacetic acid) methacholine was studied in two separate experiments performed in eight symptom-free asthmatics with bronchial hyperresponsiveness. Aerosols were formed by two different nebulizers, producing either mainly small aerosol particles (2-microns mass median aerodynamic diameter [MMAD]) for peripheral, or mainly large aerosol particles (9-microns MMAD) for large airway deposition. The intended site of deposition was confirmed by gamma camera recordings. Changes in specific airway conductance (sGaw) were set as an index of central airway constriction, and functional alterations in the gas exchanging parts of the lung were estimated by multiple inert gas elimination technique (MIGET) and arterial blood gas analyses. The main finding was that the responses, as measured by the changes in arterial blood gases and by MIGET, were similar in the two experiments, while the fall in sGaw was significantly larger after deposition in the main bronchi than in the peripheral airways (p < 0.05). The time courses of the abnormalities in the gas exchanging elements were much longer than those of the responses of the central airways, and the abnormalities were recorded still at the end of the experiment 2 h after challenge in most patients. A discrepancy in dose dependency and time courses suggests differences in mechanism and/or dynamics of the responses exerted by the various target organs. Interaction in the process of clearance from the lung of inhaled methacholine by the bronchial circulation may have contributed to the observed discrepancies.
authors.affiliation: Department of Clinical Physiology, University Hospital, Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Schmekel
authors.forename: H
authors.initials: H
authors.lastname: Hedenström
authors.forename: M
authors.initials: M
authors.lastname: Kämpe
authors.forename: L
authors.initials: L
authors.lastname: Lagerstrand
authors.forename: G
authors.initials: G
authors.lastname: Stålenheim
authors.forename: P
authors.initials: P
authors.lastname: Wollmer
authors.forename: G
authors.initials: G
authors.lastname: Hedenstierna
mesh_terms: D000328:Adult; D000336:Aerosols; D000403:Airway Resistance; D001249:Asthma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D001784:Blood Gas Analysis; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D016210:Methacholine Chloride / Q000378:metabolism*; D011659:Pulmonary Gas Exchange; D011877:Radionuclide Imaging; D016284:Technetium Tc 99m Pentetate; D014692:Ventilation-Perfusion Ratio
chemical_list: D000336:Aerosols; D016210:Methacholine Chloride; D016284:Technetium Tc 99m Pentetate