ArticleAmerican journal of respiratory cell and molecular biology2017
The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.
Article in American journal of respiratory cell and molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Pooled it
- Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2025Trial
- Icenticaftor, a CFTR Potentiator, in COPD: A Multicenter, Parallel-Group, Double-Blind Clinical Trial.American journal of respiratory and critical care medicine · 2023Trial
- Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.Respiratory research · 2021Trial
- Efficacy and Safety of the CFTR Potentiator Icenticaftor (QBW251) in COPD: Results from a Phase 2 Randomized Trial.International journal of chronic obstructive pulmonary disease · 2020Trial
- Mucoactive Agents in Muco-Obstructive Lung Diseases: A Critical Reappraisal of Pharmacological Effects and Clinical Outcomes.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities.Nature reviews. Drug discovery · 2026Review
- ACE-2 blockade and TMPRSS2 inhibition mitigate SARS-CoV-2 severity following cigarette smoke exposure in airway epithelial cellsMolecular therapy. Nucleic acids · 2025Article
- Development and Characterization of a Primary Ciliated Porcine Airway Model for the Evaluation of In Vitro Mucociliary Clearance and Mucosal Drug Delivery.Pharmaceutics · 2025Article
- Optical Imaging of Cilia in the Head and Neck.Journal of clinical medicine · 2025Review
- Secondhand vape exposure regulation of CFTR and immune function in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Association between biomarkers of tobacco smoke exposure and clinical efficacy of ivacaftor in the G551D observational trial (GOAL).Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2024Observational
- Comparison of a novel potentiator of CFTR channel activity to ivacaftor in ameliorating mucostasis caused by cigarette smoke in primary human bronchial airway epithelial cells.Respiratory research · 2024Article
- Therapeutic Targets and Precision Medicine in COPD: Inflammation, Ion Channels, Both, or Neither?International journal of molecular sciences · 2023Review
- Article
- 30-Min Exposure to Tobacco Smoke Influences Airway Ion Transport-An In Vitro Study.Current oncology (Toronto, Ont.) · 2023Article
- Animal models and mechanisms of tobacco smoke-induced chronic obstructive pulmonary disease (COPD).Journal of toxicology and environmental health. Part B, Critical reviews · 2023Review
- Furin as a therapeutic target in cystic fibrosis airways disease.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Nicotine aerosols diminish airway CFTR function and mucociliary clearance.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Mucociliary clearance augmenting drugs block SARS-CoV-2 replication in human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-μm resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.
Indexed as
Identifiers
What OpenQuestion holds
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.