LATE-BREAKING ABSTRACT: Transcriptomic fingerprinting in severe adult-onset asthma shows type2-high and inflammatory-cell gene signatures in the U-BIOPRED cohort

Hekking, Pieter Paul; Loza, Matthew J.; Pavlidis, Stelios; Meulder, Bertrand De; Baribaud, Fred; Auffray, Charles; Wagener, Ariane H.; Bansal, Aruna T.; Corfield, Julie; Bel, EH; Adcock, Ian M.; Chung, Kian Fan; Djukanović, Ratko; Sterk, Peter J.

doi:10.1183/13993003.congress-2015.oa291

Cited by 3 publications

(4 citation statements)

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“…11 One sophisticated study based on gene set variation analysis revealed that LOA was characterized by enriched gene signatures of eosinophils. 10 Note that their findings are complementary to those in the current study. Post-hoc analysis in trials of anti-IL-5 biologics for severe eosinophilic asthma revealed variations in responses as a function of the age of onset.…”

Section: Discussionsupporting

confidence: 80%

“…6 Early-onset asthma (EOA) and late-onset asthma (LOA) are recognized as distinct phenotypes, in terms of risk factors, remission rate, co-morbidities, eosinophilic inflammation, and gene signatures. [9][10][11][12] One study reported that airway eosinophils in patients with LOA were less strongly associated with type 2 inflammation than were eosinophils in patients with EOA. 11 In cases of LOA, blood eosinophilia levels were also associated with disease severity.…”

Section: Introductionmentioning

confidence: 99%

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High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma

Lin,

Lo,

Chang

et al. 2023

JAA

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Background The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Methods Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed. Results The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. Conclusion This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma

Lin,

Lo,

Chang

et al. 2023

JAA

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“…Future clinical trials are needed to validate genotype‐guided treatment in patients carrying the risk variants. In contrast to genomics, epigenomics, and transcriptomics profiles are tissue‐specific and in complex diseases such as asthma, several types of tissues and cells are involved in the disease pathology . Hence, to gain a better understanding of the disease, samples from different tissues must be collected.…”

Section: Discussionmentioning

confidence: 99%

“…Findings of the U‐BIOPRED project, show a marginal overlap between conventional definition of severe asthma based solely on clinical manifestations and definitions of disease based on unbiased molecular mechanisms. In a recent study by Hekking et al significant difference between gene expression profiles of childhood‐onset severe asthma (onset before 18 years of age) and adult‐onset severe asthma indicated distinct underlying mechanisms of the disease in these two age groups of patients. Differences in gene signatures between adult‐onset and childhood‐onset severe asthma treated with ICS indicate an age dependent difference in response to this medication.…”

Section: Introductionmentioning

confidence: 98%

The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand?

Farzan

Vijverberg

Kabesch

et al. 2018

Pediatric Pulmonology

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Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals. However, biologicals are recommended only for patients with specific asthma phenotypes who remain uncontrolled despite high dosages of conventional asthma treatment. One of the main unmet needs in their application is lack of clinically available biomarkers to individualize pediatric asthma management and guide treatment. Pharmacogenomics, epigenomics, and transcriptomics are three omics fields that are rapidly advancing and can provide tools to identify novel asthma mechanisms and biomarkers to guide treatment. Pharmacogenomics focuses on variants in the DNA, epigenomics studies heritable changes that do not involve changes in the DNA sequence but lead to alteration of gene expression, and transcriptomics investigates gene expression by studying the complete set of mRNA transcripts in a cell or a population of cells. Advances in high-throughput technologies and statistical tools together with well-phenotyped patient inclusion and collaborations between different centers will expand our knowledge of underlying molecular mechanisms involved in disease onset and progress. Furthermore, it could help to select and stratify appropriate therapeutic strategies for subgroups of patients and hopefully bring precision medicine to daily practice.

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Severe asthma phenotypes and targeted therapy: news from the 25th European Respiratory Society international congress, 26–30 September, Amsterdam

McNab

2016

Drugs Ther Perspect

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LATE-BREAKING ABSTRACT: Transcriptomic fingerprinting in severe adult-onset asthma shows type2-high and inflammatory-cell gene signatures in the U-BIOPRED cohort

Cited by 3 publications

References 0 publications

High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma

High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma

The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand?

Severe asthma phenotypes and targeted therapy: news from the 25th European Respiratory Society international congress, 26–30 September, Amsterdam

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