Beyond type 2 asthma biomarkers: risk stratification for NSAID-exacerbated respiratory disease.

Autor:	Pérez-Pazos J; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Hospital Universitario de Salamanca, Pharmacogenetics and Precision Medicine Unit, Clinical Biochemistry Department, Salamanca, Spain., García-Sánchez A; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias - RICORS, Madrid, Spain.; Universidad de Salamanca, Biomedical and Diagnostics Sciences Department, Salamanca, Spain., Estravís M; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias - RICORS, Madrid, Spain., Moreno-Jimenez E; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Universidad de Salamanca, Microbiology and Genetics Department, Salamanca, Spain., Morgado N; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Universidad de Salamanca, Biomedical and Diagnostics Sciences Department, Salamanca, Spain., Gómez-García M; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Hospital Universitario de Salamanca, Pharmacogenetics and Precision Medicine Unit, Clinical Biochemistry Department, Salamanca, Spain., Ramos-González J; Hospital Universitario de Salamanca, Pneumology Department, Salamanca, Spain., Gil-Melcón M; Hospital Universitario de Salamanca, Otorhinolaryngology and Head and Neck Surgery Department, Salamanca, Spain., Martín-García C; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Hospital Universitario de Salamanca, Allergy Department, Salamanca, Spain., Muñoz-Bellido F; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias - RICORS, Madrid, Spain.; Hospital Universitario de Salamanca, Allergy Department, Salamanca, Spain., Sanz C; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias - RICORS, Madrid, Spain.; Universidad de Salamanca, Microbiology and Genetics Department, Salamanca, Spain., Isidoro-García M; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias - RICORS, Madrid, Spain.; Universidad de Salamanca, Medicine Department, Salamanca, Spain.; Hospital Universitario de Salamanca, Clinical Biochemistry Department, Salamanca, Spain.; These authors shared senior authorship., Dávila I; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain.; Instituto de Salud Carlos III, Red de Enfermedades Inflamatorias - RICORS, Madrid, Spain.; Universidad de Salamanca, Biomedical and Diagnostics Sciences Department, Salamanca, Spain.; Hospital Universitario de Salamanca, Allergy Department, Salamanca, Spain.; These authors shared senior authorship.
Jazyk:	angličtina
Zdroj:	ERJ open research [ERJ Open Res] 2024 Aug 05; Vol. 10 (4). Date of Electronic Publication: 2024 Aug 05 (Print Publication: 2024).
DOI:	10.1183/23120541.00909-2023
Abstrakt:	Introduction: Type 2 (T2) asthma is often associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Additionally, nonsteroidal anti-inflammatory drug (NSAID) intolerance leads to NSAID-exacerbated respiratory disease (N-ERD). Previous transcriptomic data in non-CRSwNP T2 asthma patients showed differentially expressed genes. We focused on ALOX15 , CLC , CYSLTR2 , HRH4 and SMPD3 to investigate their role in T2 asthma. Methods: The study included 100 healthy controls and 103 T2 asthma patients, divided into patients with asthma (n=54), patients with asthma and CRSwNP (n=29) and patients with N-ERD (n=20). Quantitative PCR analysis was performed on blood-derived RNA samples first to validate the five differentially expressed genes. The data were further analysed to find potential associations and biomarkers. Results: Patients, regardless of stratification, exhibited significantly higher gene expression than healthy controls. The patterns of association revealed that ALOX15 was exclusively present in the non-comorbidity group, SMPD3 and CLC in the comorbidity groups, and HRH4 in all patient groups. ALOX15 , CYSLTR2 and SMPD3 expression showed potential as biomarkers to confirm the diagnosis of T2 asthma using peripheral blood eosinophils as the initial criterion. Peripheral blood eosinophils combined with gene expression, especially SMPD3 , may improve the diagnosis. CLC and CYSLTR2 expression play a specific role in discriminating N-ERD. Discussion: We validated the transcriptomic data of five differentially expressed genes in T2 asthma. Different patterns of association were identified in patient stratification, suggesting that different molecular mechanisms underlie the spectrum of T2 asthma. Potential biomarkers were also found and used to design an algorithm with practical diagnostic utility for T2 asthma, including risk stratification for N-ERD. Competing Interests: Conflict of interest: A. García-Sánchez has received payment for lectures from Leti. Conflict of interest: M. Estravís has received payment for lectures from Sanofi in the last 3 years. Conflict of interest: J. Ramos-González has received payments for lectures from AstraZeneca, Chiesi, GSK, Novartis, Sanofi, Menarini and Boehringer; and for consultancy from AstraZeneca, GSK, Novartis and Sanofi. Conflict of interest: M. Gil-Melcón has received payment for lectures from AstraZeneca, GSK and Sanofi. Conflict of interest: I. Dávila has received payment for lectures, including service on speaker's bureaus, from Allergy Therapeutics, AstraZeneca, Chiesi, Diater, GSK, Leti, Novartis and Sanofi; for consultancy from Allergy Therapeutics, ALK-Abello, AstraZeneca, GSK, Merck, MSD, Novartis and Sanofi; and grants from Thermofisher Diagnostics. Conflict of interest: The rest of the authors declare no conflict of interest. The funders had no role in the study's design, in the collection, analyses or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
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