ArticleAmerican journal of respiratory cell and molecular biology2014
Cystic fibrosis transmembrane conductance regulator activation by roflumilast contributes to therapeutic benefit in chronic bronchitis.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respiratory research · 2014Pooled it
- Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2025Trial
- 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
- Phosphodiesterase signaling in asthma: mechanistic insights and emerging therapeutic strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Therapies for bronchiectasis: mechanisms and potential effects.Frontiers in immunology · 2026Review
- Acquired cystic fibrosis transmembrane conductance regulator dysfunction.Pflugers Archiv : European journal of physiology · 2025Review
- PDE4-Selective Inhibition in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Different Agents or Different Targets?Life (Basel, Switzerland) · 2025Review
- Transcriptional profiling of mucus production in rhesus macaque endocervical cells under hormonal regulation†.Biology of reproduction · 2024Article
- Therapeutic Targets and Precision Medicine in COPD: Inflammation, Ion Channels, Both, or Neither?International journal of molecular sciences · 2023Review
- Pharmacotherapies in Older Adults with COPD: Challenges and Opportunities.Drugs & aging · 2023Review
- Hormonal regulation of non-cystic fibrosis transmembrane conductance regulator ion channels in the endocervix.F&S science · 2023Article
- Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond.The European respiratory journal · 2023Review
- The COPD-Associated Polymorphism Impairs the CFTR Function to Suppress Excessive IL-8 Production upon Environmental Pathogen Exposure.International journal of molecular sciences · 2023Article
- Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine.Biomedicines · 2021Review
- The cAMP-phosphodiesterase 4 (PDE4) controls β-adrenoceptor- and CFTR-dependent saliva secretion in mice.The Biochemical journal · 2021Article
- Modulation of cAMP metabolism for CFTR potentiation in human airway epithelial cells.Scientific reports · 2021Article
- An Adverse Outcome Pathway for Decreased Lung Function Focusing on Mechanisms of Impaired Mucociliary Clearance Following Inhalation Exposure.Frontiers in toxicology · 2021Article
- Inhaled Dual Phosphodiesterase 3/4 Inhibitors for the Treatment of Patients with COPD: A Short Review.International journal of chronic obstructive pulmonary disease · 2021Review
- G551D mutation impairs PKA-dependent activation of CFTR channel that can be restored by novel GOF mutations.American journal of physiology. Lung cellular and molecular physiology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Cigarette smoking causes acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction and is associated with delayed mucociliary clearance and chronic bronchitis. Roflumilast is a clinically approved phosphodiesterase 4 inhibitor that improves lung function in patients with chronic bronchitis. We hypothesized that its therapeutic benefit was related in part to activation of CFTR. Primary human bronchial epithelial (HBE) cells, Calu-3, and T84 monolayers were exposed to whole cigarette smoke (WCS) or air with or without roflumilast treatment. CFTR-dependent ion transport was measured in modified Ussing chambers. Airway surface liquid (ASL) was determined by confocal microscopy. Intestinal fluid secretion of ligated murine intestine was monitored ex vivo. Roflumilast activated CFTR-dependent anion transport in normal HBE cells with a half maximal effective concentration of 2.9 nM. Roflumilast partially restored CFTR activity in WCS-exposed HBE cells (5.3 ± 1.1 μA/cm(2) vs. 1.2 ± 0.2 μA/cm(2) [control]; P < 0.05) and was additive with ivacaftor, a specific CFTR potentiator approved for the treatment of CF. Roflumilast improved the depleted ASL depth of HBE monolayers exposed to WCS (9.0 ± 3.1 μm vs. 5.6 ± 2.0 μm [control]; P < 0.05), achieving 79% of that observed in air controls. CFTR activation by roflumilast also induced CFTR-dependent fluid secretion in murine intestine, increasing the wet:dry ratio and the diameter of ligated murine segments. Roflumilast activates CFTR-mediated anion transport in airway and intestinal epithelia via a cyclic adenosine monophosphate-dependent pathway and partially reverses the deleterious effects of WCS, resulting in augmented ASL depth. Roflumilast may benefit patients with chronic obstructive pulmonary disease with chronic bronchitis by activating CFTR, which may also underlie noninfectious diarrhea caused by roflumilast.
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Registered trials
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