Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Nonadherence in Severe Asthma

• Published in: American journal of respiratory and critical care medicine Vol. 199; no. 4; pp. 454 - 464
• Main Authors: Heaney, Liam G., Busby, John, Bradding, Peter, Chaudhuri, Rekha, Mansur, Adel H., Niven, Robert, Pavord, Ian D., Lindsay, John T., Costello, Richard W.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 15.02.2019
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Anti-Asthmatic Agents - therapeutic use; Assessment of Medication Adherence; Asthma; Asthma - drug therapy; Asthma - psychology; Biomarkers; Clinical outcomes; Clinical trials; Confidence intervals; Data compression; Female; Humans; Male; Medication Adherence - psychology; Middle Aged; Nitric oxide; Nitric Oxide - metabolism; Patients; Questionnaires; Remote Sensing Technology - methods; Spirometry; Surveys and Questionnaires; Systematic review; Thorax; United Kingdom > UK; inhaler monitoring; asthma; technology
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201806-1182OC

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. Suppression of fractional exhaled nitric oxide (Fe ) 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 suppression testing in routine clinical care within UK severe asthma centers using remote monitoring technologies. A web-based interface with integrated remote monitoring technology was developed to deliver Fe suppression testing. We examined the utility of Fe suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting β -agonist treatment. Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (Fe 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 -low population when adherent with ICS/long-acting β -agonist (median, 26 ppb [interquartile range, 16-36 ppb] vs. 43 ppb [interquartile range, 38-73 ppb]) with significantly greater FEV % (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). Remote Fe 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 β -agonist treatment.