Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Nonadherence 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 nonadherence 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 centers using remote monitoring technologies. Methods: Aweb-based interface with integrated remote monitoring technology was developed to deliver FENO suppression testing. We examined the utility of F-ENO suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting beta(2)-agonist treatment. Measurements and Main Results: Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (FENO and peripheral blood eosinophil count). Of 250 subjects, 201 completed the test with 130 positive suppression tests. Compared with a negative suppression test, a positive test identified a FENO-low population when adherent with ICS/long-acting beta(2)-agonist (median, 26 ppb [interquartile range, 16-36 ppb] vs. 43 ppb [interquartile range, 38-73 ppb]) with significantly greater FEV1% (mean, 88.2 +/- 616.4 vs. 74.1 +/- 620.9; P < 0.01). Asthma Control Questionnaire-5 improved significantly in both groups (positive test: mean difference, -1.2; 95% confidence interval, -0.9 to -1.5; negative test: mean difference, -0.9; 95% confidence interval, -0.4 to -1.3). Conclusions: Remote FENO suppression testing is an effective means of identifying nonadherence to ICS in subjects with difficult-tocontrol asthma and the substantial population of subjects who derive important clinical benefits from optimized ICS/long-acting beta(2)-agonist treatment.