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 (Fe_NO) 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 Fe_NO suppression testing in routine clinical care within UK severe asthma centers using remote monitoring technologies.

Methods: A web-based interface with integrated remote monitoring technology was developed to deliver Fe_NO suppression testing. We examined the utility of Fe_NO suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting β₂-agonist treatment.

Measurements and main results: Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (Fe_NO 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 Fe_NO-low population when adherent with ICS/long-acting β₂-agonist (median, 26 ppb [interquartile range, 16-36 ppb] vs. 43 ppb [interquartile range, 38-73 ppb]) with significantly greater FEV₁% (mean, 88.2 ± 16.4 vs. 74.1 ± 20.9; 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 Fe_NO suppression testing is an effective means of identifying nonadherence to ICS in subjects with difficult-to-control asthma and the substantial population of subjects who derive important clinical benefits from optimized ICS/long-acting β₂-agonist treatment.