The use of β2-agonist therapy before hospital attendance for severe asthma exacerbations: a post-hoc analysis

Abstract

Background: Patterns of inhaled β2-agonist therapy use during severe asthma exacerbations before hospital attendance are poorly understood.

Aims: To assess β2-agonist use prior to hospital attendance.

Methods: We undertook an exploratory post hoc analysis of data from a 6-month clinical trial of 303 patients randomised to combination budesonide/formoterol inhaler according to a Single combination inhaler as Maintenance And Reliever Therapy regimen ('SMART') or fixed-dose budesonide/formoterol with salbutamol as reliever ('Standard'). Patterns of β2-agonist use for 14 days before hospital attendance with a severe asthma exacerbation were determined by electronic monitoring of inhaler use.

Results: There were 22 hospital attendances in 16 patients during the study. Seven and nine hospital attendances were eligible for analysis in the SMART and Standard groups, respectively. In both regimens, β2-agonist use increased before hospital attendance, with a median (range) maximum daily number of actuations of 14 (9 to 63) budesonide/formoterol in SMART and 46 (6 to 95) salbutamol in Standard with 4 (0 to 10) budesonide/formoterol actuations on the day of maximal salbutamol use. There was delay in obtaining medical review despite high β2-agonist use, in 9/16 patients. Different patterns of use were observed, including repeated days of no inhaled corticosteroid despite marked salbutamol use, which occurred in 3/9 patients in the Standard group.

Conclusions: Delay in obtaining medical review in association with high β2-agonist use is common in patients before hospital presentation with severe exacerbations of asthma. The SMART regimen reduced nonadherence with inhaled corticosteroid therapy during severe exacerbations.

Figure 1

Flow of participants through the study, showing those presenting to hospital who were eligible for analysis.

Figure 2

Individual patterns of daily budesonide/formoterol use in the 14 days before hospital attendance in the SMART group. Hospital attendances owing to Emergency Department (ED) visit or hospital admission are specified for each participant. The x axis is days preceding or following the first hospital attendance (i.e., day −1 refers to the 24 h before the first hospital attendance, and day 1 refers to the 24 h following the first hospital attendance). Data extraction was for fourteen 24-h periods before the attendance time at hospital. The y axis is the number of actuations per 24 h. Dashed horizontal lines represent the thresholds of β₂-agonist use per day above which self-management plans recommend medical review (>12 actuations of budesonide/formoterol per day for SMART patients). (d) The participant self-initiated prednisone for asthma (40 mg per day for 4 days) on day −4 (without subsequent medical review until hospital attendance). (g) The participant had four hospital attendances, identified by the solid arrows (hospital admissions occurred for the first and last attendances; ED visits occurred for the second and third attendances). Before the first ED visit, the participant who attended was seen by their general practitioner (GP). The participant was prescribed prednisone (40 mg per day for 7 days, followed by a weaning course over the next 21 days).

Figure 3

Individual patterns of daily salbutamol and budesonide/formoterol use in the 14 days before hospital attendance in the Standard group. Hospital attendances owing to Emergency Department (ED) visit or hospital admission are specified for each participant. The x axis is days preceding or following the first hospital attendance (i.e., day −1 refers to the 24 h before the first hospital attendance, day 1 refers to the 24 h following the first hospital attendance). Data extraction was for fourteen 24-h periods before the attendance time at hospital. The y axis is the number of actuations per 24 h. Horizontal dashed lines represent the thresholds of β₂-agonist use per day above which self-management plans recommend medical review (>16 actuations of salbutamol per day for Standard patients). (d) The participant self-initiated prednisone (40 mg per day for 14 days) for asthma on day −11 (with subsequent medical review by a general practitioner (GP) on day −9). (g) The participant was prescribed prednisone (40 mg per day for 7 days) for asthma by a general practitioner on day −9. (h) The participant was prescribed prednisone (40 mg per day for 4 days) for asthma by a general practitioner on day −7. (i) The participant had two ED visits, identified by the solid arrows, and there were no data before day −6, as this was the day of the first study visit (randomisation visit). The participant was prescribed prednisone (40 mg per day for 7 days). (c) and (f) refer to two episodes in the same participant, occurring 4 months apart.

Figure 4

Median daily medication use in the 14 days before hospital attendance in the SMART (n=7 attendances) (a) and Standard (n=9 attendances) (b) groups. There is a 1:2 dose bioequivalence (6 μg:200 μg) for formoterol to salbutamol, on the basis of bronchodilator studies of repeat dosing in acute asthma.^, Dashed lines represent the thresholds of β₂-agonist use per day above which self-management plans recommend medical review (>8 actuations of budesonide/formoterol per day above the four maintenance actuations (i.e., a total of 12 actuations) for SMART patients and >16 actuations of salbutamol per day for Standard patients). The x axis is days preceding the hospital attendance (i.e., day −1 refers to the 24 h before hospital attendance). Data extraction was for the fourteen 24-h periods before the attendance time at hospital for each patient. The y axis is the median number of actuations per 24 h. Error bars are the interquartile range (IQR). For one patient in the Standard group, there were no data before day −6, as this was the day of the first study visit (randomisation visit).