Tidal midexpiratory flow as a measure of airway hyperresponsiveness in allergic mice.
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 (EF(50)) 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 EF(50) 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 EF(50) baseline values 24 h after challenge in allergic mice. The decline in EF(50) to MCh challenge correlated closely with simultaneous decreases in pulmonary conductance and dynamic compliance. The decrease in EF(50) was partly inhibited by pretreatment with the inhaled beta(2)-agonist salbutamol. We conclude that measurement of EF(50) to inhaled bronchoconstrictors by head-out body plethysmography is a valid measure of airway hyperresponsiveness in mice.
Glaab
T
T
Department of Respiratory Medicine, Hannover Medical School, 30625 Hannover, Germany. thomasglaab@web.de
Daser
A
A
Braun
A
A
Neuhaus-Steinmetz
U
U
Fabel
H
H
Alarie
Y
Y
Renz
H
H
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000485:Allergens / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology*; D001991:Bronchitis / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016085:Bronchoconstrictor Agents; D016207:Cytokines / Q000032:analysis; D005260:Female; D006967:Hypersensitivity / Q000150:complications* / Q000276:immunology; D007136:Immunoglobulins / Q000097:blood; D008170:Lung Compliance; D008450:Maximal Midexpiratory Flow Rate; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D010991:Plethysmography / Q000379:methods; D011659:Pulmonary Gas Exchange; D012119:Respiration; D013990:Tidal Volume; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D000485:Allergens; D016085:Bronchoconstrictor Agents; D016207:Cytokines; D007136:Immunoglobulins; D016210:Methacholine Chloride; D000420:Albuterol