The nasal transcriptome reflects clinically relevant disease activity in NOVELTY, with a different signal in asthma and in COPD

<bold>Background:</bold> Nasal airway sampling is a promising, easily accessible avenue to identify lower airway biology for endotyping, per the ‘united airways’ hypothesis. We aimed to assess associations of a 9-gene score, upregulated in both bronchial and upper airways in asthma, with clinical disease in patients with asthma and COPD from a sub-study of NOVELTY (<ext-link>NCT02760329</ext-link>). <bold>Methods:</bold> Nasal brushes were collected in 122 and 86 patients with physician-assigned asthma and COPD, respectively, and profiled using RNAseq. A composite 9-gene score was generated via Gene Set Variation Analysis. Group differences were assessed, adjusting for sex, age and season. <bold>Results:</bold> In asthma, higher gene scores were associated with greater airflow obstruction and type 2 inflammatory biomarkers, but not physician-assessed severity, inhaled corticosteroid (ICS) use or exacerbations (Figure A). In COPD, higher gene scores were associated with lower physician-assessed severity, less airflow obstruction, fewer exacerbations, less ICS use and elevated fractional exhaled nitric oxide, but not blood eosinophils (Figure B). <bold>Conclusion:</bold> Our findings indicate that nasal gene expression profiling has potential as a tool for airway disease biomarker development, providing insight into distinct biological patterns in asthma and in COPD. <fig><object-id>erj;64/suppl_68/PA4389/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa4389
Primary Topic
Pediatric health and respiratory diseases
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article
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article

The nasal transcriptome reflects clinically relevant disease activity in NOVELTY, with a different signal in asthma and in COPD

Maarten van den Berge, Stephanie A. Christenson, Gary P. Anderson, Kristoffer Ostridge et al.
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Pediatric health and respiratory diseases
article

The nasal transcriptome reflects clinically relevant disease activity in NOVELTY, with a different signal in asthma and in COPD

Maarten van den Berge, Stephanie A. Christenson, Gary P. Anderson, Kristoffer Ostridge, Lisa Öberg, Hana Müllerová, Martijn C. Nawijn, Adnan Azim, Greet De Baets, Daniel Muthas, Christer Janson, Rosa Faner, Arun Jayaraman, Hui Wen, Adam Platt, Machteld N. Hylkema, For The Novelty Scientific Community And The, Ian C. Scott, Rod Hughes, Zhi Lui
article en

Abstract

<bold>Background:</bold> Nasal airway sampling is a promising, easily accessible avenue to identify lower airway biology for endotyping, per the ‘united airways’ hypothesis. We aimed to assess associations of a 9-gene score, upregulated in both bronchial and upper airways in asthma, with clinical disease in patients with asthma and COPD from a sub-study of NOVELTY (<ext-link>NCT02760329</ext-link>). <bold>Methods:</bold> Nasal brushes were collected in 122 and 86 patients with physician-assigned asthma and COPD, respectively, and profiled using RNAseq. A composite 9-gene score was generated via Gene Set Variation Analysis. Group differences were assessed, adjusting for sex, age and season. <bold>Results:</bold> In asthma, higher gene scores were associated with greater airflow obstruction and type 2 inflammatory biomarkers, but not physician-assessed severity, inhaled corticosteroid (ICS) use or exacerbations (Figure A). In COPD, higher gene scores were associated with lower physician-assessed severity, less airflow obstruction, fewer exacerbations, less ICS use and elevated fractional exhaled nitric oxide, but not blood eosinophils (Figure B). <bold>Conclusion:</bold> Our findings indicate that nasal gene expression profiling has potential as a tool for airway disease biomarker development, providing insight into distinct biological patterns in asthma and in COPD. <fig><object-id>erj;64/suppl_68/PA4389/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

Uppsala University (SE), University Medical Center Groningen (NL), Uppsala University Hospital (SE), The University of Melbourne (AU), University of California, San Francisco (US), University of California System (US), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES), AstraZeneca (France) (FR), AstraZeneca (Switzerland) (CH), AstraZeneca (Finland) (FI), AstraZeneca (Spain) (ES), Melbourne Health (AU), Fundació Clínic per a la Recerca Biomèdica (ES)
Good health and well-being
Openalex Percentile: Top 65%
Pediatric health and respiratory diseases
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