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J Appl Physiol 97: 286-292, 2004. First published March 19, 2004; doi:10.1152/japplphysiol.00821.2003
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Unrestrained plethysmography is an unreliable measure of airway responsiveness in BALB/c and C57BL/6 mice

Andy Adler,1 Greg Cieslewicz,2 and Charles G. Irvin3

1School of Information Technology and Engineering, University of Ottawa, Ontario, Canada K1N 6N5; 2Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892; and 3Vermont Lung Center, University of Vermont, Burlington, Vermont 05405

Submitted 4 August 2003 ; accepted in final form 16 March 2004

There has been significant utilization of the technique described by Hamelmann et al. (Am J Respir Crit Care Med 156: 766–775, 1997) in which a parameter, enhanced pause (Penh), related to airways responsiveness is noninvasively measured by unrestrained plethysmography (UP). Investigating this technique, we sought to answer these questions: 1) How do changes in Penh compare with changes in traditional plethysmographic and lung mechanical parameters? 2) How do UP parameters perform in two different mouse strains? Awake immunized and control BALB/c (n = 16) and C57BL/6 (n = 14) mice were placed in the UP chamber and exposed to doses of aerosolized methacholine while the following parameters were measured at each concentration: inspiratory time (TI), expiratory time (TE), total time (Ttot), TI/Ttot, peak inspiratory pressure, peak expiratory pressure, Pause, Penh, tidal volume (VT), VT/TI, VT/TE, and VT/Ttot. The next day, lung resistance (RL) and compliance (CL) were invasively measured in the same animals. For the BALB/c, the parameters with the highest magnitude of correlation coefficient vs. RL are (in order) 1) CL, 2) Pause and Penh, 3) parameters of breathing frequency (TE, Ttot, TI), and 4) parameters related to VT (inspiratory pressure, expiratory pressure). Flow parameters (VT/Ttot, VT/TE, VT/TI) and duty cycle parameters (TI/Ttot) had insignificant correlations. This ordering is significantly different in C57BL/6 mice, in which the parameters with the largest correlations are 1) CL, 2) parameters of breathing frequency, and 3) flow parameters. Pause, Penh, VT, and duty cycle parameters had insignificant correlations. These data show that Penh is problematic in the sense that it is strain specific; it behaves very differently in BALB/c and C57BL/6 mice. We suggest that UP parameters largely originate as part of reflex control of breathing processes, rather than in the lung mechanics and conclude that it is inappropriate to use UP parameters in general, and Penh specifically, as substitute variables for invasive mechanical indexes such as RL.

enhanced pause; airway resistance; lung mechanics


Address for reprint requests and other correspondence: A. Adler, School of Information Technology and Engineering (SITE), Univ. of Ottawa, 800 King Edward Ave., Ottawa, Ontario, Canada K1N 6N5 (E-mail: aadler{at}uottawa.ca).




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