PI3K Pathway Activation in Severe Asthma is Linked to Steroid Insensitivity and Adverse Outcomes

What is it about?

Steroid-resistant asthma is a severe form of asthma associated with worse clinical outcomes. This study shows that patients with severe asthma have decreased steroid sensitivity, as evidenced by lower dexamethasone-induced FKBP5 expression in peripheral blood mononuclear cells (PBMCs). This decreased sensitivity correlates with a higher risk of exacerbations and difficulty reaching remission, lasting at least one year. Additionally, activation of the phosphoinositide 3-kinase delta/gamma (PI3Kδ/γ) pathway is linked to reduced steroid sensitivity, indicating a possible mechanism for adverse clinical outcomes. Overall, these findings emphasize the clinical significance and underlying mechanisms of steroid resistance in severe asthma.

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Photo by CNordic Nordic on Unsplash

Photo by CNordic Nordic on Unsplash

Why is it important?

Patients with severe asthma have reduced steroid sensitivity, which leads to unfavorable clinical outcomes, including exacerbations and an inability to achieve clinical remission. Conversely, inhibition of the PI3K pathway significantly improves steroid sensitivity.