Metabo-Endotypes of Asthma Reveal Differences in Lung Function: Discovery and Validation in Two TOPMed Cohorts.
Am J Respir Crit Care Med
; 205(3): 288-299, 2022 02 01.
Article
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| MEDLINE
| ID: mdl-34767496
ABSTRACT
Rationale Current guidelines do not sufficiently capture the heterogeneous nature of asthma; a more detailed molecular classification is needed. Metabolomics represents a novel and compelling approach to derive asthma endotypes (i.e., subtypes defined by functional and/or pathobiological mechanisms). Objectives:
To validate metabolomic-driven endotypes of asthma and explore their underlying biology.Methods:
In the Genetics of Asthma in Costa Rica Study (GACRS), untargeted metabolomic profiling, similarity network fusion, and spectral clustering was used to identify metabo-endotypes of asthma, and differences in asthma-relevant phenotypes across these metabo-endotypes were explored. The metabo-endotypes were recapitulated in the Childhood Asthma Management Program (CAMP), and clinical differences were determined. Metabolomic drivers of metabo-endotype membership were investigated by meta-analyzing findings from GACRS and CAMP. Measurements and MainResults:
Five metabo-endotypes were identified in GACRS with significant differences in asthma-relevant phenotypes, including prebronchodilator (p-ANOVA = 8.3 × 10-5) and postbronchodilator (p-ANOVA = 1.8 × 10-5) FEV1/FVC. These differences were validated in the recapitulated metabo-endotypes in CAMP. Cholesterol esters, trigylcerides, and fatty acids were among the most important drivers of metabo-endotype membership. The findings suggest dysregulation of pulmonary surfactant homeostasis may play a role in asthma severity.Conclusions:
Clinically meaningful endotypes may be derived and validated using metabolomic data. Interrogating the drivers of these metabo-endotypes has the potential to help understand their pathophysiology.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Asma
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Metabolómica
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Pulmón
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Guideline
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Am J Respir Crit Care Med
Asunto de la revista:
TERAPIA INTENSIVA
Año:
2022
Tipo del documento:
Article