Journal article
Inflammation as a Regulator of the Airway Surface Liquid pH in Cystic Fibrosis
Cells (Basel, Switzerland), Vol.12(8), 1104
04/07/2023
DOI: 10.3390/cells12081104
PMCID: PMC10137218
PMID: 37190013
Abstract
The airway surface liquid (ASL) is a thin sheet of fluid that covers the luminal aspect of the airway epithelium. The ASL is a site of several first-line host defenses, and its composition is a key factor that determines respiratory fitness. Specifically, the acid–base balance of ASL has a major influence on the vital respiratory defense processes of mucociliary clearance and antimicrobial peptide activity against inhaled pathogens. In the inherited disorder cystic fibrosis (CF), loss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function reduces HCO
3
−
secretion, lowers the pH of ASL (pH
ASL
), and impairs host defenses. These abnormalities initiate a pathologic process whose hallmarks are chronic infection, inflammation, mucus obstruction, and bronchiectasis. Inflammation is particularly relevant as it develops early in CF and persists despite highly effective CFTR modulator therapy. Recent studies show that inflammation may alter HCO
3
−
and H
+
secretion across the airway epithelia and thus regulate pH
ASL
. Moreover, inflammation may enhance the restoration of CFTR channel function in CF epithelia exposed to clinically approved modulators. This review focuses on the complex relationships between acid–base secretion, airway inflammation, pH
ASL
regulation, and therapeutic responses to CFTR modulators. These factors have important implications for defining optimal ways of tackling CF airway inflammation in the post-modulator era.
Details
- Title: Subtitle
- Inflammation as a Regulator of the Airway Surface Liquid pH in Cystic Fibrosis
- Creators
- Tayyab Rehman - University of MichiganMichael J. Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cells (Basel, Switzerland), Vol.12(8), 1104
- DOI
- 10.3390/cells12081104
- PMID
- 37190013
- PMCID
- PMC10137218
- NLM abbreviation
- Cells
- eISSN
- 2073-4409
- Publisher
- MDPI
- Grant note
- HL091842; HL152960 / NIH research Cystic Fibrosis Foundation Harry Shwachman Clinical Investigator Award
- Language
- English
- Date published
- 04/07/2023
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984399498002771
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