Relating Type 2 status to steroid exposure, cytokine expression and symptoms

T2 low asthma remains poorly understood even though it may account for up to 50% of patients.

We aimed to characterise the inflammatory signature and symptom burden in T2 low patients and relate T2 status to corticosteroid exposure.

We evaluated 200 patients? T2 status from the INCA-SUN RCT over 6 visits. Four groups were identified based on frequency of T2 inflammation: Consistently T2 low (n=40), Usually T2 low (n=48), Usually T2 high (n=64) and Consistently T2 high (n=48). Inhaled (ICS) and oral corticosteroid burden (OCS) were measured by digital inhaler monitors and pharmacy records. Multiplex assays of inflammatory pathways (Th-1, T2, Th-17 and TRegs) were performed in these patients and healthy controls. Symptom burden was assessed using the Asthma Control Test (ACT).

Low T2 biomarkers were independently associated with higher ICS and OCS exposure, OR 1.03 per mg fluticasone propionate (p=.011), OR 1.44 per course of OCS, p=.018. The Consistently T2 high group had higher periostin (p<.0001), IgE (p<.0001), IL-4 (p=.0061) and IL-5 (p<.0001) compared to the other cohorts. Increasing prevalence of T2 high status was associated with worse and more unstable lung function. The Consistently T2 low patients showed no evidence of alternate inflammatory pathways. Their cytokine results most closely resembled healthy controls but their symptom burden was similar to other groups. ACT scores related poorly to objective markers of asthma. Persistently low ACT scores were associated with co-morbidities such as GORD (p=.006) and anxiety/depression (p=.028)

T2 low asthma may be explained by steroid exposure and co-morbid conditions.