Nasal gene expression changes with inhaled corticosteroid treatment in asthma

Boudewijn, Ilse M.; Lan, Andy; Faiz, Alen; Cox, Claire A.; Brouwer, Sharon; Schokker, Siebrig; Vroegop, Sebastiaan J.; Nawijn, Martijn C.; Woodruff, Prescott G.; Christenson, Stephanie A.; Hagedoorn, Paul; Frijlink, Henderik W.; Choy, David F.; Brouwer, Uilke; Wisman, Marissa; Postma, Dirkje S.; Fingleton, James; Beasley, Richard; Berge, Maarten van den; Guryev, Victor

doi:10.1111/all.13952

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…Primary airway epithelial cells (n=6) were cultured as previously described 23 24. Following differentiation for 28 days, cells were then growth factor deprived overnight and then treated apically with/without FP (10 −8 M) for 24 hours.…”

Section: Methodsmentioning

confidence: 99%

“…Following differentiation for 28 days, cells were then growth factor deprived overnight and then treated apically with/without FP (10 −8 M) for 24 hours. RNA was then extracted and processed for RNA-seq, as previously described 24. Differential gene expression analysis was performed using the R package limma (V.3.42.0), correcting for age, gender and the first two principal components.…”

Section: Methodsmentioning

confidence: 99%

“…RNA was then extracted and processed for RNA-seq, as previously described. 24 Differential gene expression analysis was performed using the R package limma (V.3.42.0), correcting for age, gender and the first two principal components.…”

Section: Methodsmentioning

confidence: 99%

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Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD

Faiz

Pavlidis

Kuo

et al. 2022

Thorax

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Th2 high and mast cell gene signatures are associated with corticosteroid sensitivity in COPD

Faiz

Pavlidis

Kuo

et al. 2022

Thorax

Self Cite

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“…Following differentiation, for 28 days cells were then growth factor deprived overnight and then treated apically with/without Fluticasone Propionate (10 -8 M) for 24 hours. RNA was then extracted and processed for RNA-Seq as previously described (22). Differential gene expression analysis was done using the R package limma (V3.42.0) correcting age gender and the first 2 principal components.…”

Section: Air Liquid Interface Culture (Ali) and Rna-seqmentioning

confidence: 99%

Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD

Faiz

Pavlidis

Kuo

et al. 2020

Preprint

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RationaleSevere asthma and COPD share common pathophysiologic 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 U-BIOPRED cohort with one Type 2-high signature (TAC1) and 2 Type 2-low signatures. ObjectiveWe examined whether gene-expression signatures obtained in asthma can be used to identify the subgroup of COPD patients with steroid sensitivity. MethodsUsing gene set variation analysis (GSVA), 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 GLUCOLD 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. Measurements and main resultsBronchial biopsies in COPD patients at baseline showed a wide range of expression of the 3 TACs. 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 (sub)signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cellspecific genes identified by single-cell RNA-seq and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription predicted change in FEV1 %predicted following 30-month ICS±LABA. ConclusionsSputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of COPD patients and identified airway wall mast cells as a predictor of those COPD patients who will benefit from inhaled corticosteroids.Abbreviations: FEV 1 = Forced Expiratory Volume in 1second and RV/TLC= residual volume/total lung capacity .

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