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Using Drugs to Probe the Variability of Trans-Epithelial Airway Resistance
Kendra Tosoni1, Diane Cassidy1, Barry Kerr2
1Division of Cardiovascular and Diabetes Medicine, University of Dundee, Medical Research Institute Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom.
Plos One
|March 2, 2016
Summary
Healthy airway epithelia exhibit significant variability in ion transport, impacting disease susceptibility. Understanding this range is crucial for developing precision medicine approaches for airway diseases.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Physiology
Background:
- Precision medicine requires understanding normal physiological variability for targeted therapies.
- Airway pathophysiology is complex due to individual differences in epithelial defense mechanisms.
- Trans-epithelial resistance in airway epithelia is a key factor in pollutant and pathogen penetration.
Purpose of the Study:
- To quantify the range of electrophysiological characteristics in healthy human airway epithelia.
- To investigate inter- and intra-subject variability in trans-epithelial resistance and ion transport.
- To establish a reference range for airway epithelial function to inform precision medicine.
Main Methods:
- Differentiated 137 human airway epithelia from 18 healthy donors at air-liquid interface.
- Measured baseline trans-epithelial resistance, voltage, and equivalent current.
- Assessed amiloride sensitivity and cAMP-stimulated chloride transport.
Main Results:
- Observed a wide, positively-skewed range for trans-epithelial resistance (309-2963 Ω·cm2), voltage (-62.3 to -1.8 mV), and current (-125.0 to -3.2 μA/cm2).
- Identified a subset of individuals with significant amiloride sensitivity.
- Demonstrated that ion transport characteristics vary significantly between healthy subjects.
Conclusions:
- Healthy airway epithelia display log-order differences in ion transport, reflecting distinct baseline set-points.
- These findings provide a reference range for airway epithelial function.
- The data will aid in selecting patient cohorts and developing precision airway medicine.
