ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Linking increased airway hydration, ciliary beating, and mucociliary clearance through ENaC inhibition.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
51 citing papers in PubMed, 75 citations in OpenAlex.
- Epithelial Sodium Channel in the Respiratory System: A Bibliometric Review of Recent Studies.Biology · 2026Review
- Reflection confocal microscopy for quantitative assessment of airway surface layer dysregulation and pharmacological rescue in cystic fibrosis under near-physiological conditions.Scientific reports · 2025Article
- Exploring the pathogenesis and clinical implications of asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO): a narrative review.Frontiers in medicine · 2025Review
- BOS-318 treatment enhances elexacaftor-tezacaftor-ivacaftor-mediated improvements in airway hydration and mucociliary transport.ERJ open research · 2025Article
- Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia.American journal of physiology. Cell physiology · 2024Article
- Airway ciliated cells in adult lung homeostasis and COPD.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Mucus hypersecretion in chronic obstructive pulmonary disease: From molecular mechanisms to treatment.Journal of translational internal medicine · 2023Article
- Pathogenicity and virulence ofVirulence · 2023Review
- 30-Min Exposure to Tobacco Smoke Influences Airway Ion Transport-An In Vitro Study.Current oncology (Toronto, Ont.) · 2023Article
- Article
- Coughing Can Be Modulated by the Hydration Status in Adolescents with Asthma.Children (Basel, Switzerland) · 2022Article
- Association of genetic variants of oxidative stress responsive kinase 1 (OXSR1) with asthma exacerbations in non-smoking asthmatics.BMC pulmonary medicine · 2022Article
- Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine.Biomedicines · 2021Review
- Impaired Ciliary Beat Frequency and Ciliogenesis Alteration during Airway Epithelial Cell Differentiation in COPD.Diagnostics (Basel, Switzerland) · 2021Article
- New generation ENaC inhibitors detach cystic fibrosis airway mucus bundles via sodium/hydrogen exchanger inhibition.European journal of pharmacology · 2021Article
- Trypsin-Like Proteases and Their Role in Muco-Obstructive Lung Diseases.International journal of molecular sciences · 2021Review
- Adenine nucleotide translocase regulates airway epithelial metabolism, surface hydration and ciliary function.Journal of cell science · 2021Article
- An Adverse Outcome Pathway for Decreased Lung Function Focusing on Mechanisms of Impaired Mucociliary Clearance Following Inhalation Exposure.Frontiers in toxicology · 2021Article
- Preclinical evaluation of the epithelial sodium channel inhibitor BI 1265162 for treatment of cystic fibrosis.ERJ open research · 2020Article
- The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis and chronic bronchitis (CB). Rehydration by hypertonic saline is efficacious but suffers from a short duration of action. We tested whether epithelial sodium channel (ENaC) inhibition would rehydrate normal and dehydrated airways to increase mucociliary clearance (MCC) over a significant time frame. For this, we used a tool compound (Compound A), which displays nanomolar ENaC affinity and retention in the airway surface liquid (ASL). Using normal human bronchial epithelial cultures (HBECs) grown at an air-liquid interface, we evaluated in vitro potency and efficacy using short-circuit current (I(sc)) and ASL height measurements where it inhibited I(sc) and increased ASL height by ∼ 50% (0.052 μM at 6 h), respectively. The in vivo efficacy was investigated in a modified guinea pig tracheal potential difference model, where we observed an effective dose (ED50) of 5 μg/kg (i.t.), and by MCC measures in rats and sheep, where we demonstrated max clearance rates at 100 μg/kg (i.t.) and 75 μg/kg (i.t.), respectively. Acute cigarette smoke-induced ASL height depletion in HBECs was used to mimic the situation in patients with CB, and pretreatment prevented both cigarette smoke-induced ASL dehydration and lessened the decrease in ciliary beat frequency. Furthermore, when added after cigarette smoke exposure, Compound A increased the rate of ASL rehydration. In conclusion, Compound A demonstrated significant effects and a link between increased airway hydration, ciliary function, and MCC. These data support the hypothesis that ENaC inhibition may be efficacious in the restoration of mucus hydration and transport in patients with CB.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.