Mechanisms of FeNO Non-Suppression in Severe Asthma: Analysis of Sputum Type 2 Cytokines and Chemokines

Background: Non-suppression of fractional exhaled nitric oxide (FeNO) during remotely monitored inhaled corticosteroid (ICS) therapy is associated with persistent symptoms and blood eosinophilia. To provide mechanistic insight, we assessed sputum type 2 cytokines and chemokines before and after a FeNO suppression test. Methods: FeNO suppression was performed in 44 patients with severe asthma and FeNO > 40 ppb. FeNO was monitored for 7 days of 1000μg of fluticasone propionate delivered via an INCATM device, with clinical and sputum sampling on days 0 and 7. FeNO suppression was defined as a 42% reduction in FeNO. Sputum supernatant was analyzed in 15 paired samples by ELISA (Prostaglandin D2, Leukotriene E4) and MSD assays (IL-4,-5,-13,-25,-33, CCL26, TSLP). Results: Suppressors (n=21) vs non-suppressors had a greater drop in ACQ-5 (mean∆: -1.2 vs -0.3, p Conclusion: Failure to suppress FeNO during ICS treatment was associated with steroid-unresponsive sputum PGD2 and LTE4 levels.