Trial reportRespiratory research2020
Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis.
Trial report in Respiratory research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03004417 (A Randomised, Double-blind,Placebo Controlled, Repeated Dose, Three-way Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD), which is not on this map. Cited by 18 papers.
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.
A Randomised, Double-blind,Placebo Controlled, Repeated Dose, Three-way Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics and Safety of Two Doses of CHF6001 DPI in Subjects With Moderate, Severe COPD
Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Efficacy and safety of CHF6001, a novel inhaled PDE4 inhibitor in COPD: the PIONEER study.Respiratory research · 2020Trial
- Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities.Nature reviews. Drug discovery · 2026Review
- A novel drug series optimized to address cystic fibrosis and other CFTR deficiency diseases of human airways.npj drug discovery · 2025Article
- Evaluating the Impact of Hepatic or Renal Impairment on Tanimilast (CHF6001) Pharmacokinetics: Two Open-Label, Parallel-Group, Single-Center Studies.Clinical and translational science · 2025Article
- Sputum Cytokine Repeatability in COPD.International journal of chronic obstructive pulmonary disease · 2025Article
- PDE4 Inhibitors and their Potential Combinations for the Treatment of Chronic Obstructive Pulmonary Disease: A Narrative Review.The open respiratory medicine journal · 2024Review
- Serum IL-8 as a Determinant of Response to Phosphodiesterase-4 Inhibition in Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2023Article
- Severity of Lung Function Impairment Drives Transcriptional Phenotypes of COPD and Relates to Immune and Metabolic Processes.International journal of chronic obstructive pulmonary disease · 2023Article
- The PDE4 inhibitor tanimilast shows distinct immunomodulatory properties associated with a type 2 endotype and CD141 upregulation.Journal of translational medicine · 2022Article
- Inhaled Phosphodiesterase Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease.Drugs · 2021Review
- Regulatory mechanisms of neutrophil migration from the circulation to the airspace.Cellular and molecular life sciences : CMLS · 2021Review
- Tanimilast, A Novel Inhaled Pde4 Inhibitor for the Treatment of Asthma and Chronic Obstructive Pulmonary Disease.Frontiers in pharmacology · 2021Review
- COPD patients with chronic bronchitis and higher sputum eosinophil counts show increased type-2 and PDE4 gene expression in sputum.Journal of cellular and molecular medicine · 2021Article
- Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.International journal of chronic obstructive pulmonary disease · 2021Article
- A Novel Processing-Free Method for RNAseq Analysis of Spontaneous Sputum in Chronic Obstructive Pulmonary Disease.Frontiers in pharmacology · 2021Article
- Exploration of the sputum methylome and omics deconvolution by quadratic programming in molecular profiling of asthma and COPD: the road to sputum omics 2.0.Respiratory research · 2020Article
- COPD sputum eosinophils: relationship to blood eosinophils and the effect of inhaled PDE4 inhibition.The European respiratory journal · 2020Article
- Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist.Frontiers in pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundAlthough phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level. We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple therapy in sputum cells and whole blood of patients with COPD and chronic bronchitis.
methodsWhole genome gene expression analysis was carried out by microarray in 54 patients before and after 32 days treatment with CHF6001 800 and 1600 μg and placebo twice daily (BID) in a randomised crossover study.
resultsCHF6001 had a strong effect in sputum, with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-adjusted for False Discovery Rate < 0.05) with 800 and 1600 μg BID, respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (> 87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumour necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. The effect in blood was not significant.
conclusionsInhaled PDE4 inhibition by CHF6001 on top of triple therapy in patients with COPD and chronic bronchitis significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimising unwanted systemic class-effects.
trial registrationClinicalTrial.gov, EudraCT, 2015-005550-35. Registered 15 July 2016.
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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.