Dynamics of inhaled corticosteroid use are associated with asthma attacks

Inhaled corticosteroids (ICS) suppress eosinophilic airway inflammation in asthma, but patients may not adhere to prescribed use. Mean adherence-averaging total doses taken over prescribed-fails to capture many aspects of adherence. Patients with difficult-to-treat asthma underwent electronic monitoring of ICS, with data collected over 50 days. These were used to calculate entropy (H) a measure of irregular inhaler use over this period, defined in terms of transitional probabilities between different levels of adherence, further partitioned into increasing (H-inc) or decreasing (H-dec) adherence. Mean adherence, time between actuations (Gap(max)), and cumulative time- and dose-based variability (area-under-the-curve) were measured. Associations between adherence metrics and 6-month asthma status and attacks were assessed. Only H and H-dec were associated with poor baseline status and 6-month outcomes: H and H-dec correlated negatively with baseline quality of life (H:Spearman r(S)=-0.330, p=0.019, H(dec:)r(S)=-0.385, p=0.006) and symptom control (H:r(S)=-0.288, p=0.041, H-dec: r(S)=-0.351, p=0.012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic=-2.34, p=0.019), and H-dec with subsequent asthma attacks of other severities. Significant associations were maintained in multivariable analyses, except when adjusted for blood eosinophils. Entropy analysis may provide insight into adherence behavior, and guide assessment and improvement of adherence in uncontrolled asthma.