Beta-agonist overuse and delay in obtaining medical review in high risk asthma: a secondary analysis of data from a randomised controlled trial

Abstract

Asthma mortality surveys report delays in seeking medical review and overuse of beta-agonist therapy as factors contributing to a fatal outcome. However, the strength of these associations is limited because many asthma deaths are unwitnessed. We undertook a secondary analysis of data from a 24-week randomised controlled trial of 303 patients with high-risk asthma, randomised to combination budesonide/formoterol inhaler according to a single maintenance and reliever therapy regimen or fixed dose budesonide/formoterol with salbutamol as reliever (Standard) regimen. Medication use was measured by electronic monitors. The thresholds for high, marked and extreme beta-agonist use days were defined in the single maintenance and reliever therapy arm as: >8, >12 and >16 actuations of budesonide/formoterol in excess of four maintenance doses, respectively; and in the Standard arm as: >16, >24 and >32 actuations of salbutamol, respectively. Whether a medical review was obtained within 48 h of an overuse episode was determined by review of data collected during the study by participant report. The mean (standard deviation) proportion of days in which high, marked and extreme beta-agonist overuse occurred without medical review within 48 h was 0·94(0·20), 0·94(0·15) and 0·94(0·17), and 0·92(0·19), 0·90(0·26) and 0·94(0·15) for single maintenance and reliever therapy and Standard regimens, respectively. In at least 90% of days, in which beta-agonist overuse occurred, patients did not obtain medical review within 48 h of beta-agonist overuse, regardless of the magnitude of overuse or the inhaled corticosteroid/long-acting beta-agonist regimen.

Short-acting β2-agonist prescriptions are associated with poor clinical outcomes of asthma: the multi-country, cross-sectional SABINA III study

“…Of concern is that almost one-half of asthma deaths in the UK were among patients considered by their physicians to have asthma of mild-to-moderate severity [4]. Studies performed with inhaler dose counters confirm that much of the SABA overuse occurs during asthma worsening as patients seek relief [5]; occasionally, this may delay initiation of more effective treatment to prevent the attack or delay presentation for medical care [6]. It is salient to recognise that two-thirds of asthma deaths occur outside of medical facilities [4].…”

Detecting asthma exacerbations using daily home monitoring and machine learning

“…Validated daily outcome measures such as the Asthma Control Diary 22 and the Asthma Daily Symptom Diary 23 are available, but these instruments are subject to licencing restrictions which prevent their free use on electronic platforms. Reliever inhaler usage was self-reported in our study whereas there is now the potential to objectively monitor this using digital inhaler attachments [24][25][26][27] . There is emerging evidence that monitoring reliever inhaler usage in real time may provide important predictive information.…”

“…There is emerging evidence that monitoring reliever inhaler usage in real time may provide important predictive information. Objectively monitored reliever inhaler use has been shown to increase in the days leading up to asthma exacerbations 26 and hospital admissions 27 . It is possible that daily monitoring of additional variables such as exhaled nitric oxide would also improve the predictive power of home monitoring, albeit with the drawback of increasing cost and complexity.…”

Overuse of reliever inhalers and associated healthcare utilization of asthma patients

“…These results imply that regular and frequent use of reliever inhalers, observed in our study among more than one fourth of the study population, may be a proxy of a more comprehensive phenomenon of inappropriate use of pharmaceutical therapy for asthma management that may indicate uncontrolled asthma, which is associated with elevated HCU costs. Elevated use of relievers indicates poor asthma control and may worsen the disease symptoms due to the fact that the immediate symptomatic relief may delay or even prevent patients from seeking medical help 16 . In a qualitative study that examined guideline implementation from the patients' perspective, one interviewee described his tremendous dependence on the reliever therapy by saying that when he noticed he did not have the reliever inhaler with him, he immediately had an asthma attack 17 .…”