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

Harm Maarsingh1,2,3,4, Cécile M Bidan5,6, Bindi S Brook7

  • 1Department of Molecular Pharmacology, University of Groningen , Groningen , The Netherlands.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|January 11, 2019
PubMed
Summary

This study reveals that small airway hyperresponsiveness in chronic obstructive pulmonary disease (COPD) is linked to structural lung changes. These findings in guinea pigs and COPD patients highlight potential biomechanical alterations in the airways.

Keywords:
airway constrictionairway remodelingbiomechanical modelingemphysemahuman lung

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Area of Science:

  • Pulmonary Medicine
  • Respiratory Physiology
  • Biomedical Engineering

Background:

  • The link between structural lung changes and airway hyperresponsiveness (AHR) in chronic obstructive pulmonary disease (COPD) remains unclear.
  • Investigating AHR in relation to airway and parenchymal structural changes is crucial for understanding COPD.
  • Current models lack detailed insights into the biomechanical underpinnings of AHR in COPD.

Purpose of the Study:

  • To investigate airway hyperresponsiveness (AHR) in relation to airway and parenchymal structural changes in a guinea pig model of COPD and in human COPD patients.
  • To determine the role of airway smooth muscle mass and alveolar airspace size in AHR.
  • To identify potential biomechanical changes contributing to AHR using a mathematical model.

Main Methods:

  • Preparation of precision-cut lung slices (PCLS) from guinea pigs and human COPD patients.
  • Measurement of AHR to methacholine in large and small airways using video-assisted microscopy.
  • Quantification of airway smooth muscle mass, alveolar airspace size, and biomechanical properties using a mathematical model.

Main Results:

  • Lipopolysaccharide-challenged guinea pigs exhibited increased large airway sensitivity and small airway constriction to methacholine.
  • COPD patients showed similarly increased small airway responsiveness.
  • Increased alveolar airspace correlated with small airway hyperresponsiveness in guinea pigs, while airway smooth muscle mass remained unaltered.
  • Mathematical modeling indicated weakened matrix mechanical properties and altered stiffness differences between airway and parenchyma in COPD.

Conclusions:

  • This study demonstrates small airway hyperresponsiveness in precision-cut lung slices from COPD patients.
  • These changes may be associated with reduced parenchymal retraction forces and biomechanical alterations in the airway wall.
  • Precision-cut lung slices from lipopolysaccharide-exposed guinea pigs serve as a valuable model for studying small airway hyperresponsiveness mechanisms in COPD.