Airway Hyperresponsiveness in Allergically Inflamed Mice: the Role of Airway Closure

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2007 Jan 27

PMID 17255559

Citations 54

Authors

Lennart K A Lundblad

John Thompson-Figueroa

Gilman B Allen

Lisa Rinaldi

Ryan J Norton

Charles G Irvin

Jason H T Bates

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

A current review on animal models of anti-asthmatic drugs screening.

Singh S, Kularia S, Shukla S, Singh M, Kumar M, Sharma A Front Pharmacol. 2025; 16:1508460.

PMID: 39981184 PMC: 11841448. DOI: 10.3389/fphar.2025.1508460.

More airway smooth muscle in males versus females in a mouse model of asthma: A blessing in disguise?.

Gill R, Rojas-Ruiz A, Boucher M, Henry C, Bosse Y Exp Physiol. 2023; 108(8):1080-1091.

PMID: 37341687 PMC: 10988431. DOI: 10.1113/EP091236.

Application-specific approaches to MicroCT for evaluation of mouse models of pulmonary disease.

Redente E, Kopf K, Bahadur A, Robichaud A, Lundblad L, McDonald L PLoS One. 2023; 18(2):e0281452.

PMID: 36757935 PMC: 9910664. DOI: 10.1371/journal.pone.0281452.

Oscillometry of the respiratory system: a translational opportunity not to be missed.

Lundblad L, Robichaud A Am J Physiol Lung Cell Mol Physiol. 2021; 320(6):L1038-L1056.

PMID: 33822645 PMC: 8203417. DOI: 10.1152/ajplung.00222.2020.

Forced expiratory time: a composite of airway narrowing and airway closure.

Skloot G, OConnor-Chapman K, Schechter C, Markley D, Bates J J Appl Physiol (1985). 2020; 130(1):80-86.

PMID: 33090909 PMC: 7944929. DOI: 10.1152/japplphysiol.00556.2020.

References

Laurent F, Latrabe V, Raherison C, Marthan R, Tunon-de-Lara J . Functional significance of air trapping detected in moderate asthma. Eur Radiol. 2000; 10(9):1404-10. DOI: 10.1007/s003300000504. View

Lauzon A, Bates J . Kinetics of respiratory system elastance after airway challenge in dogs. J Appl Physiol (1985). 2000; 89(5):2023-9. DOI: 10.1152/jappl.2000.89.5.2023. View

Petak F, Habre W, Donati Y, Hantos Z, Barazzone-Argiroffo C . Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography. J Appl Physiol (1985). 2001; 90(6):2221-30. DOI: 10.1152/jappl.2001.90.6.2221. View

Wagers S, Lundblad L, Moriya H, Bates J, Irvin C . Nonlinearity of respiratory mechanics during bronchoconstriction in mice with airway inflammation. J Appl Physiol (1985). 2002; 92(5):1802-7. DOI: 10.1152/japplphysiol.00883.2001. View

Ricciardolo F . Multiple roles of nitric oxide in the airways. Thorax. 2003; 58(2):175-82. PMC: 1746564. DOI: 10.1136/thorax.58.2.175. View

Belik J, Jankov R, Pan J, Tanswell A . Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat. J Appl Physiol (1985). 2003; 94(6):2303-12. DOI: 10.1152/japplphysiol.00820.2002. View

Brusasco V, Pellegrino R . Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness. J Appl Physiol (1985). 2003; 95(3):1305-13. DOI: 10.1152/japplphysiol.00001.2003. View

Niimi A, Matsumoto H, Takemura M, Ueda T, Chin K, Mishima M . Relationship of airway wall thickness to airway sensitivity and airway reactivity in asthma. Am J Respir Crit Care Med. 2003; 168(8):983-8. DOI: 10.1164/rccm.200211-1268OC. View

Pare P . Airway hyperresponsiveness in asthma: geometry is not everything!. Am J Respir Crit Care Med. 2003; 168(8):913-4. DOI: 10.1164/rccm.2307005. View

10.

Fredberg J . Bronchospasm and its biophysical basis in airway smooth muscle. Respir Res. 2004; 5:2. PMC: 387531. DOI: 10.1186/1465-9921-5-2. View

11.

Wagers S, Lundblad L, Ekman M, Irvin C, Bates J . The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?. J Appl Physiol (1985). 2003; 96(6):2019-27. DOI: 10.1152/japplphysiol.00924.2003. View

12.

Wagers S, Norton R, Rinaldi L, Bates J, Sobel B, Irvin C . Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness. J Clin Invest. 2004; 114(1):104-11. PMC: 437962. DOI: 10.1172/JCI19569. View

13.

Morgan J, Franz G, Frazer D . Regional differences in gas trapping (airway closure) between apex and base of excised rat lungs. Respir Physiol. 1984; 55(3):309-16. DOI: 10.1016/0034-5687(84)90053-7. View

14.

Beckett W, Wong N . Effect of normobaric hyperoxia on airways of normal subjects. J Appl Physiol (1985). 1988; 64(4):1683-7. DOI: 10.1152/jappl.1988.64.4.1683. View

15.

Domino K, Hlastala M, Eisenstein B, Cheney F . Effect of regional alveolar hypoxia on gas exchange in dogs. J Appl Physiol (1985). 1989; 67(2):730-5. DOI: 10.1152/jappl.1989.67.2.730. View

16.

Wollner A, Bar-Yishay E . Effect of hyperoxia on bronchial response to inhaled methacholine. Allergy. 1991; 46(1):35-9. DOI: 10.1111/j.1398-9995.1991.tb00540.x. View

17.

Mitzner W, Blosser S, Yager D, Wagner E . Effect of bronchial smooth muscle contraction on lung compliance. J Appl Physiol (1985). 1992; 72(1):158-67. DOI: 10.1152/jappl.1992.72.1.158. View

18.

Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg J . Input impedance and peripheral inhomogeneity of dog lungs. J Appl Physiol (1985). 1992; 72(1):168-78. DOI: 10.1152/jappl.1992.72.1.168. View

19.

Bates J, Lauzon A, Dechman G, Maksym G, Schuessler T . Temporal dynamics of pulmonary response to intravenous histamine in dogs: effects of dose and lung volume. J Appl Physiol (1985). 1994; 76(2):616-26. DOI: 10.1152/jappl.1994.76.2.616. View

20.

Bates J, Schuessler T, Dolman C, Eidelman D . Temporal dynamics of acute isovolume bronchoconstriction in the rat. J Appl Physiol (1985). 1997; 82(1):55-62. DOI: 10.1152/jappl.1997.82.1.55. View