The Spatial Response of Penh as a Secondary Readout for the Airway Hyper-reactivity in Three Different Rodent Models of Airway Inflammation: A Pilot Comparison Study
Po-Chang Chiang
Genentech, South San Francisco, CA, USA
James D. Warner
OU Health Sciences Center, Oklahoma City, OK, USA
David Tung *
BioMed Valley Discoveries, Kansas City, MO, USA
*Author to whom correspondence should be addressed.
Abstract
Inflammatory cell infiltration, increase airway hyper-reactivity, and inflammatory cytokine production are all hallmarks of pulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD). While cytokine production and cellular infiltrations are relatively easy to assess in preclinical modeling for drug PK/PD, airway hyper-reactivity is more difficult to model and measure. Enhanced pause (Penh) is a non-dimensional parameter associated with the characteristic changes in the respiratory cycle. It had been used widely in the pulmonary field as a surrogate marker for airway hyper-reactivity (AHR). However, this parameter is not always suitable for measurement of the AHR response. Furthermore, the model sensitivity to Penh is not well understood and need to be further evaluated and documented. In our study, we evaluated the suitability of using Penh as measurement in three common rodent airway inflammation models as a potential secondary readout without potentially influencing the primary readout.
Keywords: Inflammation, PK/PD, Airway hyper-reactivity, Penh, secondary, marker, rodent