Site of inflammation influences site of hyperresponsiveness in experimental asthma.
BACKGROUND
Our recently developed murine asthma model is capable of inducing airway-specific chronic inflammatory changes and remodeling, features of human asthma commonly missing in conventional animal models.


OBJECTIVE
To validate this model by site-specific physiological evaluation of hyperresponsiveness.


METHODS
Non-sensitized and sensitized mice received either short-term uncontrolled or long-term controlled low-level exposures to aerosolized ovalbumin (OVA). Respiratory impedance (Zrs) was measured in response to increasing doses of methacholine (Mch). The constant-phase model was fitted to Zrs spectra to determine the specific site of hyperresponsiveness.


RESULTS
Sensitized acutely exposed mice had significantly increased tissue damping (G), tissue elastance (H) and hysteresivity (eta) in response to Mch, but no significant increase in airway resistance (Raw), indicating tissue-specific hyperresponsiveness. In contrast, sensitized chronically exposed mice had significantly elevated Raw at all concentrations of Mch but no increases in G, H or eta indicating airway-specific hyperresponsiveness.


CONCLUSIONS
Chronic inhalational exposure of sensitized mice to low-mass concentrations of OVA induces airway-specific hyperresponsiveness.
Collins
Rachel A
RA
Division of Clinical Sciences, TVW Telethon Institute for Child Health Research, West Perth 6872, Australia.
Sly
Peter D
PD
Turner
Debra J
DJ
Herbert
Cristan
C
Kumar
Rakesh K
RK
D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000209:etiology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000336:Aerosols; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010047:Ovalbumin