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Phenotyping Asthma Exacerbations: One Step Further in the Management of Severe Asthma

Ojanguren I1,2,3, Quirce S3,4, Bobolea I3,5, Pérez de Llano L6, del Pozo V3,7,8

1Respiratory Department, Hospital Universitari Vall d’Hebron, Departament de Medicina, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
2Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
3CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain
4Department of Allergology, Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain
5Allergology Department, Hospital Universitario Clinic de Barcelona, Barcelona, Spain
6Pulmonology Department, Lucus Augusti University Hospital, EOXI Lugo, Monforte, Cervo, Lugo, Spain
7Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain
8Universidad Autónoma de Madrid (UAM), Madrid, Spain

J Investig Allergol Clin Immunol 2025; Vol. 35(1)
doi: 10.18176/jiaci.1043

Asthma, a prevalent chronic respiratory disease, manifests in heterogeneous phenotypes and endotypes, necessitating bespoke therapeutic approaches. Asthma exacerbations are characterized by worsening of symptoms and decline in lung function and present substantial challenges despite advances in understanding and treatment. Viral respiratory infections, notably those caused by rhinovirus, serve as primary triggers, with allergic sensitization and environmental exposures increasing susceptibility. Deficient antiviral responses in asthmatic airway epithelial cells, particularly impaired interferon production, perpetuate inflammation and hyperresponsiveness, contributing to exacerbations. Additionally, genetic polymorphisms influence host responses and susceptibility.
Recent studies underscore the association between specific inflammatory profiles, particularly eosinophil-mediated inflammation, and the frequency of exacerbations. Biologic therapies targeting inflammatory pathways show promise in reducing the frequency of exacerbations, thus underscoring the importance of understanding inflammatory phenotypes when selecting treatment. Notably, T2 inhibitors may modulate immune responses, potentially mitigating viral exacerbations.
Characterizing exacerbations is crucial for optimizing therapeutic strategies. Evidence suggests a dissociation between baseline inflammatory profiles and exacerbation phenotypes, highlighting the need for individualized management. Phenotyping exacerbations using sputum analysis helps to identify predominant inflammatory patterns and thus inform treatment decisions. The varied responses to biologic therapies further emphasize the importance of phenotyping exacerbations in refining treatment algorithms.
In conclusion, phenotyping asthma exacerbations provides valuable insights into underlying inflammatory mechanisms and enables personalized therapy. Understanding the complex interplay between viral triggers, inflammatory pathways, and responses to treatment is essential if we are to effectively manage severe asthma and reduce the burden of exacerbations. Further research into the mechanistic actions of biologic therapies in mitigating viral exacerbations is warranted to optimize asthma management strategies.

Key words: Severe asthma, Exacerbation, Phenotype, Biologic