ArticleRespiratory research2017
Roflumilast reverses CFTR-mediated ion transport dysfunction in cigarette smoke-exposed mice.
Article in Respiratory research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2025Trial
- Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials).American journal of respiratory and critical care medicine · 2023Trial
- Ensifentrine in COPD patients taking long-acting bronchodilators: A pooled post-hoc analysis of the ENHANCE-1/2 studies.Chronic respiratory diseaseTrial
- Review
- Phosphodiesterase-4 Inhibitors in Chronic Obstructive Pulmonary Disease: Molecular Mechanisms, Current Therapeutics, and Future Perspectives.Cell biochemistry and biophysics · 2026Review
- Lung Function and Safety Outcomes in Patients With Moderate-to-Severe COPD Treated With Ensifentrine: A Pooled Analysis of the ENHANCE Trials.CHEST pulmonary · 2025Article
- Targeting Non-Eosinophilic Immunological Pathways in COPD and AECOPD: Current Insights and Therapeutic Strategies.International journal of chronic obstructive pulmonary disease · 2025Review
- 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
- Aiming to Improve Equity in Pulmonary Health: Cystic Fibrosis.Clinics in chest medicine · 2023Review
- 30-Min Exposure to Tobacco Smoke Influences Airway Ion Transport-An In Vitro Study.Current oncology (Toronto, Ont.) · 2023Article
- Pharmacotherapies in Older Adults with COPD: Challenges and Opportunities.Drugs & aging · 2023Review
- Nicotine aerosols diminish airway CFTR function and mucociliary clearance.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond.The European respiratory journal · 2023Review
- Deletion of sphingosine kinase 2 attenuates cigarette smoke-mediated chronic obstructive pulmonary disease-like symptoms by reducing lung inflammation.Biomolecules & biomedicine · 2023Article
- Left behind: The potential impact of CFTR modulators on racial and ethnic disparities in cystic fibrosis.Paediatric respiratory reviews · 2022Review
- Socioeconomic determinants of respiratory health in patients with cystic fibrosis: implications for treatment strategies.Expert review of respiratory medicine · 2022Review
- Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine.Biomedicines · 2021Review
- Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2021Article
- 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
- CFTR targeted therapies: recent advances in cystic fibrosis and possibilities in other diseases of the airways.European respiratory review : an official journal of the European Respiratory Society · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDysfunction in cystic fibrosis transmembrane conductance regulator (CFTR) can be elicited by cigarette smoke and is observed in patients with chronic bronchitis. We have previously demonstrated in human airway epithelial cell monolayers that roflumilast, a clinically approved phosphodiesterase 4 inhibitor that reduces the risk of exacerbations in chronic obstructive pulmonary disease patients with chronic bronchitis and a history of exacerbations, activates CFTR-dependent chloride secretion via a cAMP-mediated pathway, partially restores the detrimental effects of cigarette smoke on CFTR-mediated ion transport, and increases CFTR-dependent gastrointestinal fluid secretion in isolated murine intestine segments. Based on these findings, we hypothesized that roflumilast could improve CFTR-mediated chloride transport and induce secretory diarrhea in mice exhibiting cigarette smoke-induced CFTR dysfunction.
methodsA/J mice expressing wild type CFTR (+/+) were exposed to cigarette smoke or air with or without roflumilast and the effect of treatment on CFTR-dependent chloride transport was quantified using nasal potential difference (NPD) measurements in vivo and short-circuit current (Isc) analysis of trachea ex vivo. Stool specimen were collected and the wet/dry ratio measured to assess the effect of roflumilast on secretory diarrhea.
resultsAcute roflumilast treatment increased CFTR-dependent chloride transport in both smoke- and air-exposed mice (smoke, -2.0 ± 0.4 mV, 131.3 ± 29.3 μA/cm
conclusionsRoflumilast effectively rescues CFTR-mediated chloride transport in vivo, further implicating CFTR activation as a mechanism through which roflumilast benefits patients with bronchitis.
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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.