TY - JOUR
T1 - Site of inflammation influences site of hyperresponsiveness in experimental asthma
AU - Collins, R.A.
AU - Sly, Peter
AU - Turner, Debra
AU - Herbert, C.
AU - Kumar, R.K.
PY - 2003
Y1 - 2003
N2 - 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. Objectives: 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 (η) 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 η indicating airway-specific hyperresponsiveness. Conclusions: Chronic inhalational exposure of sensitized mice to low-mass concentrations of OVA induces airway-specific hyperresponsiveness.
AB - 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. Objectives: 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 (η) 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 η indicating airway-specific hyperresponsiveness. Conclusions: Chronic inhalational exposure of sensitized mice to low-mass concentrations of OVA induces airway-specific hyperresponsiveness.
U2 - 10.1016/j.resp.2003.09.003
DO - 10.1016/j.resp.2003.09.003
M3 - Article
SN - 1569-9048
VL - 139
SP - 51
EP - 61
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
IS - 1
ER -