THE BRONCHIAL RESPONSE, BUT NOT THE PULMONARY RESPONSE TO INHALED METHACHOLINE IS DEPENDENT ON THE AEROSOL DEPOSITION PATTERNS

The clinical effect of inhaled radio-labeled (Technetium-99m diethylen etriamine-pentaacetic acid) methacholine was studied in two separate e xperiments performed in eight symptom-free asthmatics with bronchial h yperresponsiveness. Aerosols were formed by two different nebulizers, producing either mainly small aerosol particles (2-mu m mass median ae rodynamic diameter [MMAD]) for peripheral, or mainly large aerosol par ticles (9-mu m MMAD) for large airway deposition. The intended site of deposition was confirmed by gamma camera recordings. Changes in speci fic airway conductance (sGaw) were set as an index of central airway c onstriction, 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 M IGET, 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 respons es of the central airways, and the abnormalities were recorded still a t the end of the experiment 2 h after challenge in most patients. A di screpancy in dose dependency and time courses suggests differences in mechanism and/or dynamics of the responses exerted by the various targ et organs. Interaction in the process of clearance from the lung of in haled methacholine by the bronchial circulation may have contributed t o the observed discrepancies.