Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices

Maarsingh, Harm; Bidan, C�cile M.; Brook, Bindi Shah; Zuidhof, Annet B.; Elzinga, Carolina R.S.; Smit, Marieke; Oldenburger, Anouk; Gosens, Reinoud; Timens, Wim; Meurs, Herman

Abstract

The direct relationship between pulmonary structural changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) is unclear. We investigated AHR in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in COPD patients. Precision-cut lung slices (PCLS) were prepared from guinea pigs challenged with lipopolysaccharide or saline two times weekly for 12 wk. Peripheral PCLS were obtained from patients with mild to moderate COPD and non-COPD controls. AHR to methacholine was measured in large and small airways using video-assisted microscopy. Airway smooth muscle mass and alveolar airspace size were determined in the same slices. A mathematical model was used to identify potential changes in biomechanical properties underlying AHR. In guinea pigs, lipopolysaccharide increased the sensitivity of large (>150 μm) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (

Citation

Maarsingh, H., Bidan, C. M., Brook, B. S., Zuidhof, A. B., Elzinga, C. R., Smit, M., Oldenburger, A., Gosens, R., Timens, W., & Meurs, H. (2019). Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices. AJP - Lung Cellular and Molecular Physiology, 316(3), L537-L546. https://doi.org/10.1152/ajplung.00325.2018

• Journal Article Type: Article
• Acceptance Date: Dec 30, 2018
• Online Publication Date: Jan 10, 2019
• Publication Date: Mar 1, 2019
• Deposit Date: Jan 23, 2019
• Publicly Available Date: Mar 13, 2019
• Journal: American Journal of Physiology-Lung Cellular and Molecular Physiology
• Print ISSN: 1040-0605
• Electronic ISSN: 1522-1504
• Publisher: American Physiological Society
• Peer Reviewed: Peer Reviewed
• Volume: 316
• Issue: 3
• Pages: L537-L546
• DOI: https://doi.org/10.1152/ajplung.00325.2018
• Keywords: airway constriction; airway remodeling; biomechanical modeling; emphysema; human lung
• Public URL: https://nottingham-repository.worktribe.com/output/1491678
• Publisher URL: https://www.physiology.org/doi/full/10.1152/ajplung.00325.2018
• Contract Date: Jan 23, 2019