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Published ahead of print on January 25, 2007, doi:10.1164/rccm.200610-1410OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 8, April 2007, 768-774

A more recent version of this article appeared on April 15, 2007
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Submitted on October 3, 2006
Accepted on January 25, 2007

Airways Hyperresponsiveness in Allergically Inflamed Mice: The Role of Airway Closure

Lennart KA K Lundblad1*, John Thompson-Figueroa1, Gilman B Allen1, Lisa Rinaldi1, Ryan J Norton1, Charles G Irvin1, and Jason HT Bates1

1 Department of Medicine, University of Vermont, Vermont Lung Center, Burlington, VT, USA

* To whom correspondence should be addressed. E-mail: lennart.lundblad{at}uvm.edu.

Rationale: Allergically inflamed mice exhibit airways hyperresponsiveness to inhaled methacholine, which computer simulations of lung impedance suggest is due to enhanced lung derecruitment and which we sought to verify in the present study. Methods: BALB/c mice were sensitized and challenged with ovalbumin to induce allergic inflammation; the controls were sensitized but received no challenge. The mice were then challenged with inhaled methacholine and respiratory system impedance tracked for the following 10 min. Respiratory elastance (H) was estimated from each impedance measurement. One group of mice was ventilated with 100% O2 during this procedure and another group was ventilated with air. Following the procedure the mice were euthanized and ventilated with pure N2, after which, the trachea was tied off and the lungs were imaged with micro-computed tomography (micro-CT). Results: H was significantly higher in allergic mice than in controls following methacholine challenge. The ratio of H at the end of the measurement period between allergic and non-allergic mice ventilated with O2 was 1.36, indicating substantial derrecruitment in the allergic animals. The ratio between lung volumes determined by micro-CT in the controls and the allergic mice was also 1.36, indicative of a corresponding volume loss due to absorption atelectasis. Micro-CT images and histograms of Hounsfield units from the lungs also showed increased volume loss in the allergic mice compared to controls following methacholine challenge. Conclusions: These results support the conclusion that airway closure is a major component of hyperresponsiveness in allergically inflamed mice.
Key words: asthma, micro-CT, input impedance, lung derecruitment, lung volume




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