Airway hyperresponsiveness in allergically inflamed mice: the role of airway closure

Am J Respir Crit Care Med. 2007 Apr 15;175(8):768-74. doi: 10.1164/rccm.200610-1410OC. Epub 2007 Jan 25.


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% O(2) during this procedure and another group was ventilated with air. After the procedure, the mice were killed and ventilated with pure N(2), 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 O(2) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bronchial Hyperreactivity / diagnostic imaging
  • Bronchial Hyperreactivity / etiology
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Female
  • Lung Volume Measurements
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Atelectasis / complications
  • Pulmonary Atelectasis / diagnostic imaging
  • Pulmonary Atelectasis / physiopathology*
  • Respiration, Artificial
  • Respiratory Hypersensitivity / complications
  • Respiratory Hypersensitivity / diagnostic imaging
  • Respiratory Hypersensitivity / physiopathology*
  • Tomography, X-Ray Computed