10 research outputs found
Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
Background Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (nâ=â156) and independently on data from a subset of U-BIOPRED asthma participants (nâ=â82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (nâ=â397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was âmild, good lung function, early onsetâ, with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a âmoderate, hyper-responsive, eosinophilicâ phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a âmixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilicâ phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a âsevere uncontrolled, severe reversible obstruction, mixed granulocyticâ phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies