ArticleInternational journal of chronic obstructive pulmonary disease2021
Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials.
Article in International journal of chronic obstructive pulmonary disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02522299 (A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 for 12 Weeks in Adult Subjects Diagnosed With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease), which is not on this map. Cited by 11 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.
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 for 12 Weeks in Adult Subjects Diagnosed With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)
Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- CHF6523 data suggest that the phosphoinositide 3-kinase delta isoform is not a suitable target for the management of COPD.Respiratory research · 2024Trial
- Decoding serum C-reactive protein-associated molecular patterns in aging and secondhand smoke exposure chronic obstructive pulmonary disease male patients: evidence from cross-sectional, multi-omic and clinical studies.Frontiers in medicine · 2026Article
- SPG7-Mediated Regulation of mPTP and Mitochondrial Flickering in COPD: A Bioinformatics-Based Prediction of Mechanistic Framework.International journal of chronic obstructive pulmonary disease · 2026Article
- PI3K Inhibitors as Potential Therapeutic Agents for the Treatment of COPD with Associated Atherosclerosis.Drugs · 2025Review
- Emerging Anti-Inflammatory COPD Treatments: Potential Cardiovascular Impacts.International journal of chronic obstructive pulmonary disease · 2024Review
- 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
- Novel Anti-Inflammatory Approaches to COPD.International journal of chronic obstructive pulmonary disease · 2023Review
- An inhibitor of RORγ for chronic pulmonary obstructive disease treatment.Scientific reports · 2022Article
- Pathological Mechanism and Targeted Drugs of COPD.International journal of chronic obstructive pulmonary disease · 2022Review
- The future of inhalation therapy in chronic obstructive pulmonary disease.Current research in pharmacology and drug discovery · 2022Review
- Our evolving view of neutrophils in defining the pathology of chronic lung disease.Immunology · 2021Review
Corrections and comments
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Authors and funding
25 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD). Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD. Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg). Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry. Results: In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD. Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients. In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals -46, 315mL) with a probability that the true treatment ratio was >0% (Pr(θ>0)) of 93% was observed in AECOPD. However, FRI endpoints remained unchanged. Conclusion: We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group. We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD.
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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.