Feno differentiates epithelial gene expression clusters: Exploratory analysis from the MESOS randomized controlled trial - 04/10/22
Abstract |
Background |
Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis.
Objective |
This post hoc exploratory analysis of the phase II tralokinumab trial MESOS (ClinicalTrials.gov identifier NCT02449473) aimed to profile baseline airway inflammation in patients with moderate-to-severe asthma.
Methods |
The T2 and T17 gene expression signatures, 3-gene mean and 5-gene mean, were calculated through transcriptomic analysis of baseline bronchial brushing samples. Clustering analysis using these signatures identified 3 distinct inflammatory subgroups: T2LOW/T17HIGH (n = 33), T2HIGH/T17LOW (n = 10), and T2LOW/T17LOW (n = 27).
Results |
Fractional exhaled nitric oxide (Feno) levels were highest for T2HIGH/T17LOW and lowest for T2LOW/T17HIGH (median = 52.0 [range 42.5-116.3] and median = 18.8 [range 6.6-128.6] ppb, respectively; P = .003). High Feno levels were strongly correlated with high T2 gene expression (Spearman ρ = 0.5537; P < .001). Individual genes differentially expressed in patients with elevated levels of Feno, blood and bronchial submucosal eosinophil counts, and IgE level were explored, with cystatin SN (CST1) being the most upregulated gene in all subgroups (4.49- to 34.42-fold upregulation across clinically defined subgroups with high biomarker expression).
Conclusion |
Feno level may be useful to differentiate patients with T2 or T17 gene expression. Elevated Feno levels are associated with high CST1 expression.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, expression profiling
Abbreviations used : 3GM, 5GM, AMY1B, BPIFA1, CLCA1, CSF3, CST1, CXCL1, Feno, FOXA2, HSD, MUC2, MUC5B, POSTN, SCGB1A1, SERPINB2, SFTA1P, T2/17, TPSAB1
Plan
| Funded by AstraZeneca and supported by the National Institute for Health Research (NIHR), Respiratory Translational Research Collaboration and NIHR Biomedical Research Centers. Medical writing assistance, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Claire Lydon, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by AstraZeneca. |
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| Disclosure of potential conflict of interest: C. E. Brightling has received grants and/or consultancy fees paid to his institution from AstraZeneca, GlaxoSmithKline, Novartis, Chiesi, Boehringer Ingelheim, Roche, Genentech, Sanofi, Regeneron, Merck, Mologic, TEVA, and 4DPharma. C. Emson, D. Yin, S. Sridhar, J. M. Griffiths, MdlR, and G. Colice are employees of AstraZeneca and may hold company stock and/or stock options. The remaining authors declare that they have no relevant conflicts of interest. |
Vol 150 - N° 4
P. 830-840 - octobre 2022 Retour au numéro
Article précédent
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