ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure.
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 18 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
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
18 citing papers in PubMed, 29 citations in OpenAlex.
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Article
- Long-Acting βFrontiers in pharmacology · 2022Article
- Allicin Facilitates Airway Surface Liquid Hydration by Activation of CFTR.Frontiers in pharmacology · 2022Article
- Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine.Biomedicines · 2021Review
- Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance.Life (Basel, Switzerland) · 2021Review
- Purinergic receptors in airway hydration.Biochemical pharmacology · 2021Review
- Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases.Frontiers in pharmacology · 2021Review
- 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
- Functional Anatomic Imaging of the Airway Surface.Annals of the American Thoracic Society · 2018Review
- Cigarette smoke up-regulates PDE3 and PDE4 to decrease cAMP in airway cells.British journal of pharmacology · 2018Article
- Cigarette smoke modifies and inactivates SPLUNC1, leading to airway dehydration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Cigarette Smoke-Induced Acquired Dysfunction of Cystic Fibrosis Transmembrane Conductance Regulator in the Pathogenesis of Chronic Obstructive Pulmonary Disease.Oxidative medicine and cellular longevity · 2018Review
- Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- The therapeutic potential of CFTR modulators for COPD and other airway diseases.Current opinion in pharmacology · 2017Review
- Therapeutic Approaches to Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis.Annals of the American Thoracic Society · 2016Review
- Airway hydration and COPD.Cellular and molecular life sciences : CMLS · 2015Review
- Mucociliary dysfunction in HIV and smoked substance abuse.Frontiers in microbiology · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide. Recent studies have shown that cigarette smoke (CS) induces cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, which leads to airway-surface liquid (ASL) dehydration. This in turn contributes to the mucus dehydration and impaired mucociliary clearance that are seen in the chronic bronchitis form of COPD. Roflumilast is a phosphodiesterase 4 inhibitor that may improve lung function and reduce the frequency of exacerbations in patients with COPD. Although roflumilast can affect cAMP metabolism, little is known about the downstream pharmacological effects in the airways. We hypothesized that roflumilast would increase ASL rehydration in human bronchial epithelial cultures (HBECs) after chronic CS exposure. cAMP production was measured by Förster resonance energy transfer in HEK293T cells and by ELISA in HBECs. ASL height was measured by xz-confocal microscopy after air exposure or following HBEC exposure to freshly produced CS. Roflumilast had little effect on cAMP or ASL height when applied on its own; however, roflumilast significantly potentiated adenosine-induced increases in cAMP and ASL height in CS-exposed HBECs. Roflumilast increased the rate of ASL height recovery in cultures after CS exposure compared with controls. In contrast, the β2-adrenergic receptor agonists isoproterenol and salmeterol failed to increase ASL height after CS exposure. Our data suggest that roflumilast can increase ASL hydration in CS-exposed HBECs, which is predicted to be beneficial for the treatment of mucus dehydration/mucus stasis in patients with COPD chronic 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.