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1 Department of Respiratory Medicine, Hannover Medical School, 30625 Hannover; 2 Institute of Laboratory Medicine and Pathobiochemistry, Charité Campus Virchow Clinic, Humboldt University, 13353 Berlin; 3 Institute of Clinical Chemistry and Molecular Diagnostics, Philipps-University, 35043 Marburg, Germany; and 4 Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238
A method for the noninvasive measurement of
airway responsiveness was validated in allergic BALB/c mice. With
head-out body plethysmography and the decrease in tidal
midexpiratory flow (EF50) as an indicator of airway
obstruction, responses to inhaled methacholine (MCh) and the allergen
ovalbumin were measured in conscious mice. Allergen-sensitized and
-challenged mice developed airway hyperresponsiveness as measured by
EF50 to aerosolized MCh compared with that in control animals. This response was associated with increased allergen-specific IgE and IgG1 production, increased levels of interleukin-4 and interleukin-5 in bronchoalveolar lavage fluid and eosinophilic lung
inflammation. Ovalbumin aerosol challenge elicited no acute bronchoconstriction but resulted in a significant decline in
EF50 baseline values 24 h after challenge in allergic
mice. The decline in EF50 to MCh challenge correlated
closely with simultaneous decreases in pulmonary conductance and
dynamic compliance. The decrease in EF50 was partly
inhibited by pretreatment with the inhaled 
2-agonist
salbutamol. We conclude that measurement of EF50 to inhaled
bronchoconstrictors by head-out body plethysmography is a valid measure
of airway hyperresponsiveness in mice.
body plethysmography; allergy; lung function method
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