Disease Studies

Non-T2 (Non-Eosinophilic) Asthma

Asthma is a broad diagnostic label given to a range of conditions that exhibit similar clinical features – chronic airway inflammation, reversible airflow obstruction, wheezing, shortness of breath, chest tightness etc. While it’s understood that several pathophysiological processes can lead to asthma, most asthma patients continue to be treated using a one-size-fits-all approach, including new biologic approaches.

Treatment-refractory asthmatics form a relatively large group of patients suffering from frequent, severe asthma exacerbations, which remain challenging to control. There is a high level of unmet need in severe, refractory asthma, especially in Th2-low or non-Th2 asthma patients.

We identified clear differences in the SNPs, genes and pathways associated with Th2 and non-Th2 asthma, creating opportunities for development of new treatment options and better patient stratification biomarkers for clinical decision support.



Methodology

Our goal was to study the differences between Th2-mediated and non-Th2 asthma at a genetic level. We used PrecisionLife® to perform combinatorial analysis on UK Biobank cohorts of 7,500 Th2-mediated and 15,000 non-Th2 asthma patients, against a common set of age and sex matched non-asthmatic controls.

The SNPs, genes and pathways associated with Th2 and non-Th2 disease were identified and compared to evaluate the similarity (or lack of it) between disease causing factors for Th2 and non-Th2 patients.


Results/Findings

PrecisionLife identified clear differences in the SNPs, genes and pathways associated with Th2 and non-Th2 disease.

We observed key differences in pathway enrichment between the two asthma subtypes. This clear segregation of pathways demonstrates that they are two distinct diseases, with different underlying mechanisms of action. Our findings confirm the common understanding that cytokine regulation (especially IL-5 and IL-13) plays a key role in Th2 asthma, and provide some promising novel indications of the mechanisms underpinning the pathogenesis of non-Th2 asthma.

We have identified over 20 novel genes that are significant only in the non-Th2 population with strong, testable hypotheses for their mechanism of action. These include multiple promising novel drug targets for the development of personalized therapies for non-allergic asthma patients.


Pathway enrichment results for Th2 vs. non-Th2 asthma


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