The Utility of Fractional Exhaled Nitric Oxide Suppression in the Identification of Nonadherence in Difficult Asthma
RATIONALE: Non-adherence to inhaled corticosteroid therapy (ICS) is a major contributor to poor control in difficult asthma, yet it is challenging to ascertain. OBJECTIVES: Identify a test for non-adherence using fractional exhaled nitric oxide (FeNO) suppression following directly observed inhaled corticosteroid (DOICS) treatment. METHODS: Difficult asthma patients with an elevated FeNO (>45 ppb) were recruited as adherent (ICS prescription filling >80%) or non-adherent (filling <50%). They received 7 days of DOICS (budesonide 1600 μg) and a test for non-adherence based on changes in FeNO was developed. Using this test, clinic patients were prospectively classified as adherent/non-adherent and this was then validated against prescription filling records, prednisolone assay and concordance interview. MEASUREMENTS AND MAIN RESULTS: After 7 days of DOICS non-adherent (n=9) compared with adherent subjects (n=13) had a greater reduction in FeNO to 47 ± 21% vs 79 ± 26% of baseline measurement (p=0.003), which was also evident after 5 days (p=0.02) and a FeNO test for non-adherence (AUC=0.86, 95%CI: 0.68-1.00) was defined. Prospective validation in 40 subjects found the test identified 13 as non-adherent; 8 confirmed non-adherence during interview (3 of whom had excellent prescription filling but did not take medication), 5 denied non-adherence - 2 had poor inhaler technique (unintentional non-adherence), 1 also denied non-adherence to prednisolone despite non-adherent blood level. Twenty-seven participants were adherent on testing, which was confirmed in 21. Five admitted poor ICS adherence but of these, 4 were adherent with oral steroids and 1 with Omalizumab. CONCLUSIONS: FeNO suppression following DOICS provides an objective test to distinguish adherent from non-adherent patients with difficult asthma.
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