ArticlePhysiological reports2018
Phosphodiesterase 4 inhibition reduces lung fibrosis following targeted type II alveolar epithelial cell injury.
Article in Physiological reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Safety and Efficacy of Nerandomilast in Patients With Pulmonary Fibrosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.The clinical respiratory journal · 2026Pooled it
- Pharmacokinetics and Safety of Nerandomilast in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2026Trial
- Nerandomilast is Associated With Altered Alveolar Epithelial Cell State Dynamics While Attenuating Fibrotic Remodeling in Pulmonary Fibrosis.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Nerandomilast (BI 1015550) attenuating pulmonary fibrosis in a mouse model of rheumatoid arthritis-associated interstitial lung disease by modulating the TGF-β1/PI3K/Akt signaling pathway.Journal of thoracic disease · 2026Article
- Roflumilast Inhibits Fibrogenic Activation in Human Intestinal Myofibroblasts via Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling.International journal of molecular sciences · 2026Article
- Article
- Nerandomilast in Autoimmune-Associated Interstitial Lung Diseases: Translating Evidence from Progressive Pulmonary Fibrosis Studies.Journal of clinical medicine · 2026Review
- Most Promising Emerging Therapies for Pulmonary Fibrosis: Targeting Novel Pathways.Biomedicines · 2026Review
- Antifibrotic Strategies Targeting Phosphodiesterase-4 in Idiopathic Pulmonary Fibrosis: Molecular Mechanisms and Clinical Translation.Clinical pharmacology : advances and applications · 2026Review
- Mechanistic basis for the antifibrotic actions of cAMP-based therapies.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Variable steady inflammation and inflammatory responses in precision-cut lung slices from various IPF lung Regions.Respiratory research · 2025Article
- Systemic sclerosis: pathogenic mechanisms and their implications for treatment.Seminars in immunopathology · 2025Review
- Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025Review
- Shared roles of immune and stromal cells in the pathogenesis of human bronchiolitis obliterans syndrome.JCI insight · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Inhibition of phosphodiesterases 1 and 4 prevents myofibroblast transformation in Peyronie's disease.BJU international · 2025Article
- Potential of phosphodiesterase 4B inhibitors in the treatment of interstitial lung disease associated with autoimmune diseases.Clinical and experimental rheumatology · 2025Review
- Article
- What Is on the Horizon for Treatments in Idiopathic Pulmonary Fibrosis?Journal of clinical medicine · 2024Review
- Pathological mechanisms and novel drug targets in fibrotic interstitial lung disease.Inflammation and regeneration · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Fibrosis of the lung constitutes a major clinical challenge and novel therapies are required to alleviate the associated morbidity and mortality. Investigating the antifibrotic efficacy of drugs that are already in clinical practice offers an efficient strategy to identify new therapies. The phosphodiesterase 4 (PDE4) inhibitors, approved for the treatment of chronic obstructive pulmonary disease, harbor therapeutic potential for pulmonary fibrosis by augmenting the activity of endogenous antifibrotic mediators that signal through cyclic AMP. In this study, we tested the efficacy of several PDE4 inhibitors including a novel compound (Compound 1) in a murine model of lung fibrosis that results from a targeted type II alveolar epithelial cell injury. We also compared the antifibrotic activity of PDE4 inhibition to the two therapies that are FDA-approved for idiopathic pulmonary fibrosis (pirfenidone and nintedanib). We found that both preventative (day 0-21) and therapeutic (day 11-21) dosing regimens of the PDE4 inhibitors significantly ameliorated the weight loss and lung collagen accumulation that are the sequelae of targeted epithelial cell damage. In a therapeutic protocol, the reduction in lung fibrosis with PDE4 inhibitor administration was equivalent to pirfenidone and nintedanib. Treatment with this class of drugs also resulted in a decrease in plasma surfactant protein D concentration, a reduction in the plasma levels of several chemokines implicated in lung fibrosis, and an in vitro inhibition of fibroblast profibrotic gene expression. These results motivate further investigation of PDE4 inhibition as a treatment for patients with fibrotic lung disease.
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Registered trials
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