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Airway Hyperresponsiveness in Allergically Inflamed Mice

The Role of Airway Closure

¹ Vermont Lung Center, University of Vermont, Burlington, Vermont

Correspondence and requests for reprints should be addressed to Lennart K.A. Lundblad, Ph.D., The University of Vermont College of Medicine, HSRF 230, 149 Beaumont Avenue, Burlington, VT 05405-0075. E-mail: lennart.lundblad{at}uvm.edu

Rationale: Allergically inflamed mice exhibit airway 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 control mice were sensitized but received no challenge. The mice were then challenged with inhaled methacholine and respiratory system impedance tracked for the following 10 minutes. 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. After the procedure, the mice were killed 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 control animals after methacholine challenge. The ratio of H at the end of the measurement period between allergic and nonallergic mice ventilated with O₂ was 1.36, indicating substantial derecruitment in the allergic animals. The ratio between lung volumes determined by micro-CT in the control 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 with control animals after 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-computed tomography • input impedance • lung derecruitment • lung volume

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Airway hyperresponsiveness in mouse models of asthma has traditionally been attributed to contraction of airway smooth muscle. Recent studies suggest, however, that airway closure may play a more significant role. What This Study Adds to the Field Using the forced oscillation technique and micro-computed tomography, we now show that airway hyperresponsiveness in allergic mice can be largely explained by airway closure.

 

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