ArticleThorax2023
Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD.
Article in Thorax, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Extracellular vesicles from bronchoalveolar lavage fluid provide insights into the inhaled corticosteroids treatment response in COPD.Respiratory research · 2025Trial
- Inflammasomes in respiratory diseases: from disease pathogenesis to drug development and use of multi-omics.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Inhaled Targeted Nano-Drug Delivery Systems for COPD: Precision Solutions to Clinical Barriers.International journal of nanomedicine · 2026Review
- Chronic Obstructive Pulmonary Disease (COPD): Developments in Pharmacological Treatments.Drugs · 2025Review
- Immunohistochemical Analysis of Mastocyte Inflammation: A Comparative Study of COPD Associated with Tobacco Smoking and Wood Smoke Exposure.Biomedicines · 2025Article
- Glucocorticoid Insensitivity: Is It a Question of Time and Place?Biomedicines · 2025Review
- A Low Expression of NRF2 Enhances Oxidative Stress and Autophagy in Myofibroblasts, Promoting Progression of Chronic Obstructive Pulmonary Disease.Current medicinal chemistry · 2025Article
- Defining the Differential Corticosteroid Response Basis from Multiple Omics Approaches.International journal of molecular sciences · 2024Review
- Advances in the awareness of tuberculosis-associated chronic obstructive pulmonary disease.Chinese medical journal pulmonary and critical care medicine · 2024Review
- Type 2 inflammation in COPD: is it just asthma?Breathe (Sheffield, England) · 2024Review
- Differential expression of mast cells in the small airways and alveolar septa of current smokers and patients with small airway disease and COPD.ERJ open research · 2024Article
- Inhaled Corticosteroids in Subjects with Chronic Obstructive Pulmonary Disease: An Old, Unfinished History.Biomolecules · 2024Review
- Current smoking reduces small airway eosinophil counts in COPD.ERJ open research · 2024Article
- How inhaled corticosteroids target inflammation in COPD.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.American journal of respiratory and critical care medicine · 2023Article
- Eosinophils in chronic obstructive pulmonary disease.Therapeutic advances in respiratory diseaseReview
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16 authors at 9 institutions in 3 countries.
Funding
Abstract
rationaleSevere asthma and chronic obstructive pulmonary disease (COPD) share common pathophysiological traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort comprising one Th2-high inflammatory signature (TAC1) and two Th2-low signatures (TAC2 and TAC3).
objectiveWe examined whether gene expression signatures obtained in asthma can be used to identify the subgroup of patients with COPD with steroid sensitivity.
methodsUsing gene set variation analysis, we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment. Differential gene expression and cellular convolution were used to define key regulated genes and cell types. MEASUREMENTS AND MAIN
resultsBronchial biopsies in patients with COPD at baseline showed a wide range of expression of the 3 TAC signatures. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cell-specific genes identified by single-cell RNA-sequencing and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription correlated with the change in RV/TLC %predicted following 30-month ICS±LABA.
conclusionSputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of patients with COPD and identified a signature of airway mast cells as a predictor of corticosteroid responsiveness.
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