RT info:eu-repo/semantics/article T1 The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment A1 González Carracedo, Mario Andrés A1 Pérez García, Javier A1 Espuela Ortiz, Antonio A1 Hernández Pérez, Jose M. A1 González Pérez, Ruperto A1 Sardón Prado, Olaia A1 Martín González, Elena A1 Mederos Luis, Elena A1 Poza Guedes, Paloma A1 Corcuera Elosegui, Paula A1 Callero, Ariel A1 Sánchez Machín, Inmaculada A1 Korta Murua, Javier A1 Pérez Pérez, José A. A1 Villar, Jesús A1 Del Pino Yanes, María del Mar A1 Lorenzo Díaz, Fabián A2 BioquímicaMicrobiología, Biología Celular y Genética AB Background: The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. Methods: Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. Results: In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 < _ P < _.037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 < _ P <_.046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 3 10212 < _ FDR < _ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUCtraining: 0.82 and AUCvalidation: 0.77). Conclusion: The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS. (J Allergy Clin Immunol 2023;151:706-15.) YR 2023 FD 2023 LK http://riull.ull.es/xmlui/handle/915/41760 UL http://riull.ull.es/xmlui/handle/915/41760 LA en DS Repositorio institucional de la Universidad de La Laguna RD 26-abr-2025