Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Non-Adherence in Severe Asthma

Rationale Poor adherence is common in difficult-to-control asthma. Distinguishing patients with difficult-to-control asthma who respond to inhaled corticosteroids (ICS) from refractory asthma is an important clinical challenge. Objectives Suppression of fractional exhaled nitric oxide (FeNO) with directly observed ICS therapy over 7 days can identify non-adherence to ICS treatment in difficult-to-control asthma. We examined the feasibility and utility of FeNO suppression testing in routine clinical care within UK severe asthma centres using remote monitoring technologies. Methods A web-based interface with integrated remote monitoring technology was developed to deliver FeNO suppression testing. We examined the utility of FeNO suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically-monitored treatment with standard high dose ICS and long-acting β2-agonist (LABA) treatment. Measurements and Main Results Clinical response was assessed using the Asthma Control Questionnaire (ACQ-5), spirometry and biomarker measurements (FeNO and peripheral blood eosinophil count). Of 250 subjects, 201 completed the test with 130 positive suppression tests. Compared to a negative suppression test, a positive test identified a FeNO-low population when adherent with ICS/LABA (median 26ppb [IQR 16-36] v 43ppb [IQR 38-73]) with significantly greater FEV1% (mean 88.2±16.4 v 74.1±20.9], p<0.01). ACQ-5 improved significantly in both groups (positive test, mean difference 1.2, 95% CI -0.9, -1.5, negative test, mean difference 0.9, 95% CI -0.4, -1.3). Conclusions Remote FeNO suppression testing is an effective means of identifying non-adherence to ICS in subjects with difficult-to-control asthma and the substantial population of subjects who derive important clinical benefits from optimised ICS/LABA treatment.