@article { , title = {Small airway hyperresponsiveness in COPD: relationship between structure and function in lung slices}, 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 ?m) airways toward methacholine by 4.4-fold and the maximal constriction of small airways (}, doi = {10.1152/ajplung.00325.2018}, eissn = {1522-1504}, issn = {1040-0605}, issue = {3}, journal = {American Journal of Physiology-Lung Cellular and Molecular Physiology}, pages = {L537-L546}, publicationstatus = {Published}, publisher = {American Physiological Society}, url = {https://nottingham-repository.worktribe.com/output/1491678}, volume = {316}, keyword = {airway constriction, airway remodeling, biomechanical modeling, emphysema, human lung}, year = {2019}, author = {Maarsingh, Harm and Bidan, Cécile M. and Brook, Bindi Shah and Zuidhof, Annet B. and Elzinga, Carolina R.S. and Smit, Marieke and Oldenburger, Anouk and Gosens, Reinoud and Timens, Wim and Meurs, Herman} }