Performance of database-derived severe exacerbations and asthma control measures in asthma: responsiveness and predictive utility in a UK primary care database with linked questionnaire data

Figures & data

Table 1 Patient characteristics in the Questionnaire cohort

Variables	Questionnaire cohort (n=2,366)
Age, mean (SD)	44.4 (11.1)
Male, n (%)	959 (40.5)
BMI (kg/m^2), n (%)a
<18.5	36 (1.5)
18.5–24.9	793 (34.1)
25–29.9	805 (34.7)
≥30	689 (29.7)
Smoking status, n (%)a
Nonsmoker	1,478 (62.5)
Ex-smoker	303 (12.8)
Current smoker	582 (24.6)
Year of index date, n (%)
2010	551 (23.3)
2011	450 (19)
2012	1203 (50.8)
2013	162 (6.8)
Rhinitis, n (%)
Recorded diagnosis	202 (8.5)
Patient reported	1,884 (80.8)
Events/prescriptions: observed during study period (12 months before questionnaire completion), n (%)
Asthma-related inpatient admissionb (one or more)	5 (0.2)
Asthma-related A&E attendanceb (one or more)	4 (0.2)
Asthma-related OPD attendanceb (one or more)	3 (0.1)
Acute oral corticosteroids with evidence of respiratory reviewc
0	2,135 (90.2)
1	180 (7.6)
2+	51 (2.2)
Antibiotics with evidence of respiratory reviewd
0	1,854 (78.4)
1	356 (15.0)
2+	156 (6.6)
Average SABA daily dosage (μg), mean (SD)e	213.19 (274.7)
Events/prescriptions: patient-reported for the previous 12 months, n (%)
Oral corticosteroid use
0	1,915 (80.9)
1	245 (10.4)
2+	206 (8.7)
Number of hospitalizations, mean (SD)	0.08 (0.41)

Notes:

a BMI data were missing for 1.82% of patients; smoking status was unknown in 0.1% of patients.

b Asthma-related refers to records coded with a lower respiratory code, including asthma and lower respiratory tract infection codes, or a generic hospitalization Read code which has been recorded on the same day as a Lower Respiratory Consultation (defined in the Supplementary materials).

c Defined as all courses that are definitely not maintenance therapy; and/or all courses where dosing instructions suggest exacerbation treatment (eg, 6, 5, 4, 3, 2, 1 reducing, or 30 mg as directed); and/or all courses with no dosing instructions, but unlikely to be maintenance therapy with a code for asthma or a lower respiratory event; and/or no or undefined dosing instructions but definitely not maintenance therapy, where “maintenance therapy” is defined as daily dosing instructions of ≤10 mg prednisolone or prescriptions for 1 mg prednisolone tablets.

d Evidence of respiratory review is defined in the Supplementary materials.

e Calculation is given in the Supplementary materials. The average daily dose of 213 mg salbutamol corresponds to 3.89 SABA prescriptions per year.

Abbreviations: BMI, body mass index; A&E, accident and emergency; OPD, outpatient department; SABA, short-acting beta-agonist.

Table 2 Patient characteristics in the ICS initiation and step-up cohorts

Variables	ICS initiation (n= 51,404)		ICS step-up (n=13,131)
	Baseline period	Outcome period	Baseline period	Outcome period
Age, mean (SD)	29.1 (17.0)		28.9 (18.0)
Male, n (%)	23,910 (46.5)		6,301 (48.0)
BMI (kg/m^2), n (%)a
<18.5	4,611 (12.0)		1,635 (16.1)
18.5–24.9	14,581 (37.8)		3,605 (35.6)
25–29.9	10,990 (28.5)		2,662 (26.3)
≥30	8342 (21.7)		2,222 (21.9)
Smoking status, n (%)a
Nonsmoker	30,905 (63.1)		8,360 (66.1)
Ex-smoker	11,011 (22.5)		2,433 (19.2)
Current smoker	7,027 (14.4)		1,846 (14.6)
Year of index date, median (IQR)	2001 (1996, 2004)		2001 (1997, 2005)
Events/prescriptions: observed during specified period, n (%)
Asthma-related inpatient admissionb (one or more)	88 (0.2)	78 (0.2)	40 (0.3)	24 (0.2)
Asthma-related A&E attendanceb (one or more)	177 (0.3)	122 (0.2)	86 (0.7)	43 (0.3)
Asthma-related OPD attendanceb (one or more)	28 (0.1)	45 (0.1)	16 (0.1)	18 (0.1)
Acute oral corticosteroids with evidence of respiratory reviewc
0	47,554 (92.5)	48,122 (93.6)	11,210 (85.4)	11,656 (88.8)
1	3,491 (6.8)	2,670 (5.2)	1,402 (10.7)	1,099 (8.4)
2+	359 (0.7)	612 (1.2)	519 (4.0)	376 (2.9)
Antibiotics with evidence of respiratory reviewd (one or more)	10,956 (21.3)	8,168 (15.9)	3,608 (27.5)	2,810 (21.4)
Average SABA daily dosage (μg), n (%)e
0	30,354 (59)
1–100	8,656 (16.8)
101–200	6,578 (12.8)
201+	5,816 (11.3)
0		10,197 (19.8)	2,847 (21.7)
1–100		8,956 (17.4)	1,561 (11.9)
101–200		13,579 (26.4)	2,880 (21.9)
201–400		10,814 (21.0)	2,799 (21.3)
401+		7,858 (15.3)	3,044 (23.2)
0				2,714 (20.7)
1–200				3,218 (24.5)
201–400				3,339 (25.4)
401–800				2,428 (18.5)
800+				1,432 (10.9)

Notes:

a BMI data were missing in 25.1% of patients in the ICS initiation cohort and 22.9% of patients in the ICS step-up cohort; smoking status was unknown in 4.8% of patients in the ICS initiation cohort and 3.7% of patients in the ICS step-up cohort.

b Asthma-related refers to records coded with a lower respiratory code, including asthma and lower respiratory tract infection codes, or a generic hospitalization Read code which has been recorded on the same day as a Lower Respiratory Consultation (defined in the Supplementary materials).

c Defined as all courses that are definitely not maintenance therapy; and/or all courses where dosing instructions suggest exacerbation treatment (eg, 6, 5, 4, 3, 2, 1 reducing, or 30 mg as directed); and/or all courses with no dosing instructions, but unlikely to be maintenance therapy with a code for asthma or a lower respiratory event; and/or no or undefined dosing instructions but definitely not maintenance therapy, where “maintenance therapy” is defined as daily dosing instructions of ≤10 mg prednisolone or prescriptions for 1 mg prednisolone tablets.

d Evidence of respiratory review is defined in the Supplementary materials.

e Calculation is given in the Supplementary materials. The average daily SABA use of 200 μg/day corresponds to 3.65 SABA prescriptions per year, and 800 μg/day corresponds to 14.6 prescriptions per year.

Abbreviations: ICS, inhaled corticosteroid; BMI, body mass index; IQR, interquartile range; A&E, accident and emergency; OPD, outpatient department; SABA, short-acting beta-agonist.

Figure 1 Comparison of database asthma control (RDAC and OAC) and patient-reported symptom control categories.

Note: *Patient-reported symptom control “controlled” category also includes patients whose asthma was “well-controlled” or “partly controlled” based on the 2014 GINA definition.
Abbreviations: RDAC, risk domain asthma control; OAC, overall asthma control; SABA, short-acting beta-agonist; GINA, Global Initiative for Asthma.

Figure 2 Comparison of database and patient-reported exacerbations

Table 3 Database outcomes before and after the initiation or step-up of ICS

Type of cohort and observed asthma control	Study period		P-valuea
	Baseline	Outcome
ICS initiation cohort
RDAC status, n (%)
Controlled	38,629 (75.1)	41,818 (81.4)	<0.001
Uncontrolled	12,775 (24.9)	9,586 (18.6)
Total	51,404 (100)	51,404 (100)
OAC status, n (%)b
Controlled	34,367 (66.9)	27,422 (53.3)	<0.001
Uncontrolled	17,037 (33.1)	23,982 (46.7)
Total	51,404 (100)	51,404 (100)
Number of exacerbations, mean (SD)	0.09 (0.32)	0.08 (0.35)	0.001
ICS step-up cohort
RDAC status, n (%)
Controlled	8,750 (66.6)	9,752 (74.3)	<0.001
Uncontrolled	4,381 (33.4)	3,379 (25.7)
Total	13,131 (100)	13,131 (100)
OAC status, n (%)b
Controlled	4,999 (38.1)	4,637 (35.3)	<0.001
Uncontrolled	8,132 (61.9)	8,494 (64.7)
Total	13,131 (100)	13,131 (100)
Number of exacerbations, mean (SD)	0.21 (0.60)	0.16 (0.52)	<0.001

Notes:

a P-values estimated using McNemar’s test, for OAC and RDAC, and Wilcoxon’s signed rank test, for exacerbations.

b OAC status “controlled” corresponds to RDAC “controlled” plus SABA prescriptions corresponding to an average daily SABA dose of ≤200 μg/day (ie, ≤3.65 SABA prescriptions in 12 months).

Abbreviations: ICS, inhaled corticosteroids; RDAC, risk domain asthma control; OAC, overall asthma control.

Table 4 Association between database components of asthma control and defined exacerbations in the baseline period and exacerbations observed in the outcome period

Baseline variable tested	Unadjusted rate ratio (95% CI) for exacerbations in the outcome period
	ICS initiation cohort	ICS step-up cohort
RDAC=“uncontrolled”	3.33 (3,13–3.57)	4.35 (4.00–5.00)
OAC = “uncontrolled”	2.78 (2.63–3.03)	3.23 (2.86–3.70)
Asthma-related inpatient admission	1.75 (0.87–3.53)	2.05 (1.10–3.81)
Asthma-related A&E attendance	1.85 (1.18–2.90)	2.21 (1.46–3.34)
Asthma-related OPD attendance	6.26 (3.06–12.78)	2.36 (0.77–7.24)
Acute course of oral corticosteroidsa
0	1.00	1.00
1	4.43 (4.06–4.84)	4.37 (3.87–4.93)
2+	9.00 (7.61–10.64)	9.93 (8.62–11.44)
Antibiotics prescribed with evidence of respiratory reviewb
0	1.00	1.00
1	2.39 (2.20–2.59)	2.28 (2.00–2.60)
2+	4.02 (3.62–4.46)	4.79 (4.19–5.48)
Any SABA use	1.48 (1.38–1.60)	Not analyzedc
Average SABA daily dosage (μg)d
≤200	1.00	1.00
>200	1.24 (1.11–1.38)	1.53 (1.37–1.71)
Average SABA daily dosage (μg)d
0	Not analyzedc	0.89 (0.72–1.11)
1–100		1.00
101–200		1.18 (0.96–1.44)
201–400		1.27 (1.04–1.56)
401–800		1.71 (1.38–2.13)
801+		2.05 (1.63–2.58)

Notes:

a Defined as all courses that are definitely not maintenance therapy; and/or all courses where dosing instructions suggest exacerbation treatment (eg, 6, 5, 4, 3, 2, 1 reducing, or 30 mg as directed); and/or all courses with no dosing instructions, but unlikely to be maintenance therapy with a code for asthma or a lower respiratory event; and/or no or undefined dosing instructions but definitely not maintenance therapy, where “maintenance therapy” is defined as daily dosing instructions of ≤10 mg prednisolone or prescriptions for 1 mg prednisolone tablets.

b Evidence of respiratory review is defined in the Supplementary materials.

c Calculation is given in the Supplementary materials.

d Patient numbers within SABA categories were not sufficient to fit model. An average daily SABA dosage of 200 μg/day corresponds to 3.65 SABA prescriptions in 12 months and 800 μg/day corresponds to 14.6 SABA prescriptions in 12 months.

Abbreviations: CI, confidence interval; ICS, inhaled corticosteroid; RDAC, risk domain asthma control; OAC, overall asthma control; A&E, accident and emergency; OPD, outpatient department; SABA, short-acting beta-agonist.