Related Experiment Video
Updated: Nov 2, 2025
02:09
Multi-modal Pulmonary Imaging: Using Complementary Information from CT and Hyperpolarized 129Xe MRI to Evaluate Lung Structure-Function
Published on: April 12, 2024
784
Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled
Malcolm Begg1, J Nicole Hamblin1, Emily Jarvis2
1Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
Summary
Inhaled nemiralisib improved neutrophil migration in stable chronic obstructive pulmonary disease (COPD) patients but not those with acute exacerbations. Induced sputum analysis revealed treatment effects in stable COPD, while lung function improved in acute exacerbations.
Area of Science:
- Pulmonology
- Immunology
- Pharmacology
Background:
- Neutrophil migration is dysregulated in chronic obstructive pulmonary disease (COPD).
- Phosphoinositide 3-kinase delta (PI3Kδ) inhibition shows potential for correcting neutrophil migration.
- Nemiralisib is a potent, inhaled PI3Kδ inhibitor.
Purpose of the Study:
- To evaluate nemiralisib's effect on neutrophil phenotype in stable COPD and acute exacerbation of COPD (AECOPD) using induced sputum.
- To establish induced sputum as a biomarker for treatment response in COPD.
Main Methods:
- Two randomized, double-blind, placebo-controlled trials in stable COPD (N=28) and AECOPD (N=44).
- Patients received inhaled nemiralisib (1mg).
- Primary endpoint: sputum transcriptomics; secondary endpoints: inflammatory mediators, functional respiratory imaging (FRI), spirometry.
Main Results:
- Nemiralisib altered sputum neutrophil transcriptomics in stable COPD, suggesting improved migration.
- No similar transcriptomic changes were observed in AECOPD.
- Sputum inflammatory mediators decreased in stable COPD but not AECOPD.
- AECOPD patients showed a placebo-corrected improvement in FEV1 (136 mL).
- FRI endpoints did not change.
Conclusions:
- Nemiralisib induces changes in neutrophil migration phenotype in stable COPD.
- Induced sputum can measure neutrophil phenotype alterations in stable COPD.
- Nemiralisib improved lung function in AECOPD, but not neutrophil phenotype.
- The study provides sputum transcriptomic data during AECOPD recovery.
More Related Videos
Related Concept Videos
01:20COPD: Pathogenesis and Clinical Features
1.5K
Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
1.5K
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
3.5K
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
3.5K
01:26COPD: Management Using Bronchodilators and Corticosteroids
504
Chronic obstructive pulmonary isease (COPD) involves a group of progressive lung disorders characterized by persistent airflow limitation and chronic respiratory symptoms. Asthma-COPD Overlap Syndrome (ACOS), encompassing features of both asthma and Chronic obstructive pulmonary disease (COPD), is a group of progressive lung disorders that includes chronic bronchitis, emphysema, and refractory (non-reversible) asthma. ACOS leads to complex clinical presentations that combine the inflammatory...
504
01:27Chronic Obstructive Pulmonary Disease-IV: Assessement and Diagnostic Studies
2.7K
Assessing and diagnosing Chronic Obstructive Pulmonary Disease (COPD) involves a detailed approach that includes a comprehensive review of medical history, physical examination, and a variety of diagnostic tests. This thorough evaluation is essential to ensure an accurate diagnosis and guide effective management strategies.
Medical History
Medical History
2.7K
01:29Chronic Obstructive Pulmonary Disease-V: Management
2.8K
Managing Chronic Obstructive Pulmonary Disease (COPD) involves a multifaceted approach to reduce symptoms, prevent exacerbations, improve overall health status, and slow disease progression. Key strategies include lifestyle modifications, pharmacotherapy, supportive therapies, and, in some cases, surgery. Here is an overview of the primary COPD management strategies:
Smoking Cessation
Smoking Cessation
2.8K
01:20Chronic Obstructive Pulmonary Disease-I: Introduction
3.1K
Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting respiratory condition requiring continuous attention and care. It is a progressive lung disease that leads to breathing challenges due to airflow obstruction. It manifests as persistent respiratory symptoms and restricted airflow resulting from abnormalities in the airways and alveoli, usually due to long-term exposure to harmful particles or gases. COPD mainly consists of two primary conditions: emphysema and chronic bronchitis.
3.1K