Dynamics of inhaled corticosteroid use are associated with asthma attacks

Joy Lee,Jacqueline Huvanandana,Helen K Reddel,Juliet M Foster,Mark Hew,Michael J Abramson,Cindy Thamrin

doi:10.1038/s41598-021-94219-z

Abstract

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 (Hinc) or decreasing (Hdec) adherence. Mean adherence, time between actuations (Gapmax), 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 Hdec were associated with poor baseline status and 6-month outcomes: H and Hdec correlated negatively with baseline quality of life (H:Spearman rS = − 0·330, p = 0·019, Hdec:rS = − 0·385, p = 0·006) and symptom control (H:rS = − 0·288, p = 0·041, Hdec: rS = − 0·351, p = 0·012). H was associated with subsequent asthma attacks requiring hospitalisation (Wilcoxon Z-statistic = − 2.34, p = 0·019), and Hdec 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.

Highlights

In asthma, regular inhaled corticosteroid (ICS) controller use suppresses eosinophilic airway inflammation and reduces airway hyperresponsiveness, reducing symptoms and protecting patients from potentially life-threatening
Work has focused on time-averaged metrics, typically mean adherence and it has been difficult to demonstrate a relationship between asthma outcomes and mean adherence[10,11]
This averaged metric fails to capture potentially important variations in medicationtaking behaviour, e.g. a mean adherence rate of 50% cannot distinguish between one patient consistently taking half the prescribed dose daily and another taking the full prescribed dose, but for only half the required period

Summary

Introduction

Regular inhaled corticosteroid (ICS) controller use suppresses eosinophilic airway inflammation and reduces airway hyperresponsiveness, reducing symptoms and protecting patients from potentially life-threatening. Work has focused on time-averaged metrics, typically mean adherence (total doses taken/total doses prescribed) and it has been difficult to demonstrate a relationship between asthma outcomes and mean adherence[10,11]. We designed adherence metrics to capture via EMD the extent to which patients with difficult-to-treat asthma deviate from regular controller usage, by measuring the entropy—irregularity, or disorder—with which daily medication doses are taken. Entropy has been previously applied to respiratory symptoms[13], breathing patterns, and lung function[14] We examined whether these entropy measures of adherence related to specific patient characteristics or predicted subsequent asthma-related clinical outcomes. We measured conventional mean adherence, time- and dose-based variability (using additional metrics reflecting missed days and incomplete doses respectively), and the duration of gaps in which patients completely forwent medication

Methods

Results

Discussion

Conclusion