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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

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


Harm Maarsingh

C�cile M. Bidan

Professor of Mathematical Medicine and Biology

Annet B. Zuidhof

Carolina R.S. Elzinga

Marieke Smit

Anouk Oldenburger

Reinoud Gosens

Wim Timens

Herman Meurs


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 ?m) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (

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
Keywords airway constriction; airway remodeling; biomechanical modeling; emphysema; human lung
Public URL
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