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Departments of 1 Respiratory Medicine and 4 Anatomy, Hannover Medical School, and 2 Fraunhofer Institute of Toxicology and Aerosol Research, Drug Research and Clinical Inhalation, 30625 Hannover, Germany; and 3 Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238
This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess bronchoconstriction in conscious rats. Using noninvasive, head-out body plethysmography and the decrease in tidal midexpiratory flow (EF50), we measured airway responsiveness (AR) to inhaled acetylcholine and allergen in conscious Brown-Norway rats, followed by invasive determination of pulmonary conductance (GL) and EF50 in anesthetized rats. Dose-response studies to acetylcholine showed that noninvasively recorded EF50 closely reflected the dose-dependent decreases observed with the invasive monitoring of simultaneously measured GL and EF50. After sensitization and intratracheal boost to ovalbumin or saline, rats were assessed for early and late AR to aerosolized ovalbumin. Ovalbumin aerosol challenge resulted in early and late AR in allergen-sensitized rats, whereas controls were unresponsive. The allergen-specific AR, as measured noninvasively by EF50, was similar in degree compared with invasively recorded EF50 and GL and was associated with enhanced IgE and airway inflammation. We conclude that EF50 is a noninvasive and physiologically valid index of bronchoconstriction in a rat model of asthma.
animal models; allergy; immunology; respiratory function test; asthma
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