3.1 Study Population and Patient Characteristics
Of the total 26,301 newly diagnosed asthma patients, 14,207 (54.01%) patients received treatment of one or more controller medications and the remaining 12,094 (45.98%) patients did not receive any controllers during the study period. Following the initial diagnosis, 9,166 patients had at least 3-month follow-up visits and 7,996 patients had continuous care by the end of 12 months (Figure 2). Table 1 displays number of patients entered into the study cohort by year from 2001 to March 2019. Vast majority of patients were diagnosed in secondary (71.8%) or tertiary (25.2%) hospitals on the index date. Patient demographic characteristics are presented in Table 2.
Table 1. Distribution of Index date (year)
Table 2. Patient characteristics
Table 1. Patient characteristics
|
|
Total
|
With controller medication prescriptions over the study period
|
With 12-month follow-up
|
|
N=26,301
|
N=14,207
|
N=7,996
|
Gender, n (%)
|
|
|
|
|
|
|
males
|
11,651
|
44.30%
|
6,269
|
44.13%
|
3,621
|
45.29%
|
females
|
14,397
|
54.74%
|
7,776
|
54.73%
|
4,281
|
53.54%
|
Unidentified
|
253
|
0.96%
|
162
|
1.14%
|
94
|
1.18%
|
Age, years, mean (SD)
|
48(17.05)
|
49(16.51)
|
52(17.08)
|
14-39
|
8,699
|
33.07%
|
4,352
|
30.63%
|
2,110
|
26.39%
|
40-60
|
10,016
|
38.08%
|
5,644
|
39.73%
|
2,875
|
35.96%
|
>60
|
7,586
|
28.84%
|
4,211
|
29.64%
|
3,011
|
37.66%
|
Hospital, n (%)
|
|
|
|
|
|
|
Tertiary
|
6,639
|
25.24%
|
4,457
|
31.37%
|
2,019
|
25.25%
|
Secondary
|
18,893
|
71.83%
|
9,435
|
66.41%
|
5,635
|
70.47%
|
Primary
|
769
|
2.92%
|
315
|
2.22%
|
342
|
4.28%
|
3.2 Treatment
3.2.1 Initial Treatment
On the index date, a total of 26,301 patients were diagnosed with asthma from various departments, in descending order, respiratory (26.54%), internal medicine (24.39%), emergency (16.62%), general medicine (14.21%), Chinese medicine (8.74%), etc (Table 3). There were significant differences in department distribution between tertiary and secondary hospitals.
At the initial diagnosis, 11,965 (45.49%) patients received controller medications, 6,249 (23.76%) received anti-asthmatic reliver only, 3,825 (14.54%) received symptomatic medications, e.g. antitussives, mucolytics or antibiotics, and 4,262 (16.2%) received no prescription of medications. In patients receiving controller therapies, corticosteroid-containing and leukotriene receptor antagonist (LTRA) were most commonly prescribed with 4,564 (38.14%) and 3,359 (28.07%) patients, respectively. Other less frequently used controller medications included xanthine derivatives (15.8%) and others (17.98%), e.g., mast cell stabilizers (MCS), etc. Among 4,433 (18.0%) patients with LTRA prescriptions, LTRA only, combination of corticosteroid and combination of other controllers were 2,225 (47.01%), 1,374 (29.3%) and 1,134 (23.96%), respectively. Among 4,359 (16.57%) patients with short-acting β2-agonist (SABA) treatment, 2,327 (53.28%) were in combination use with the controllers. There were significant differences in all prescriptions, including LTRA and SABA between tertiary and secondary hospitals at the initial asthma diagnosis.
Table 3. Treatment received at the initial asthma diagnosis
|
All Hospitals
N=26301 (100%)
|
Tertiary Hospitals
N=6,639 (25.24%)
|
Secondary Hospitals
N=18,893 (71.83%)
|
Primary Hospitals
N=769 (2.92%)
|
Tertiary
vs. Secondary
P value
|
Department, n, %
|
|
|
|
|
|
|
|
|
|
Respiratory
|
6979
|
26.54%
|
3558
|
53.59%
|
3340
|
17.68%
|
|
|
<0.001
|
Internal medicine
|
6416
|
24.39%
|
1112
|
16.75%
|
5426
|
28.72%
|
|
|
Emergency
|
4370
|
16.62%
|
445
|
6.70%
|
3925
|
20.77%
|
|
|
General medicine
|
3737
|
14.21%
|
590
|
8.89%
|
2329
|
12.33%
|
752
|
97.79%
|
Chinese medicine
|
2300
|
8.74%
|
375
|
5.65%
|
1950
|
10.32%
|
|
|
Otolaryngology
|
1421
|
5.40%
|
146
|
2.20%
|
1275
|
6.75%
|
|
|
Surgical
|
405
|
1.54%
|
139
|
2.09%
|
266
|
1.41%
|
|
|
Pediatric
|
365
|
1.39%
|
204
|
3.07%
|
162
|
0.86%
|
|
|
Obstetrics and Gynecology
|
74
|
0.28%
|
32
|
0.48%
|
41
|
0.22%
|
|
|
Unidentified
|
234
|
0.89%
|
38
|
0.57%
|
179
|
0.95%
|
17
|
2.21%
|
All prescriptions N=26,301
|
Controller, n, %
|
11,965
|
45.49%
|
4,032
|
60.73%
|
7,717
|
40.85%
|
216
|
28.09%
|
|
OCS containing
|
908
|
3.5%
|
211
|
3.18%
|
671
|
3.55%
|
26
|
3.38%
|
<0.001
|
ICS-LABA containing
|
3,148
|
12.0%
|
1,585
|
23.87%
|
1,563
|
8.27%
|
|
|
ICS containing
|
508
|
1.9%
|
149
|
2.24%
|
359
|
1.90%
|
|
|
LTRA containing
|
3,359
|
12.8%
|
1,309
|
19.72%
|
2,049
|
10.85%
|
1
|
0.13%
|
Theophylline containing
|
1,891
|
7.2%
|
411
|
6.19%
|
1,380
|
7.30%
|
100
|
13.00%
|
Others (MCS etc.)
|
2,151
|
8.2%
|
367
|
5.53%
|
1,695
|
8.97%
|
89
|
11.57%
|
Anti-asthmatic relivers, n, %
|
6,249
|
23.76%
|
837
|
12.61%
|
5113
|
27.06%
|
299
|
38.88%
|
SABA containing
|
2,032
|
7.7%
|
327
|
4.93%
|
1,633
|
8.64%
|
72
|
9.36%
|
Other anti-asthmatic relivers
|
4,217
|
16.0%
|
510
|
7.68%
|
3,480
|
18.42%
|
227
|
29.52%
|
Symptomatic medications, n, %
|
3,825
|
14.54%
|
861
|
12.97%
|
2,826
|
14.96%
|
138
|
17.95%
|
No prescription, n, %
|
4,262
|
16.20%
|
909
|
13.69%
|
3,237
|
17.13%
|
116
|
15.08%
|
LTRA Prescription N=4,733 (18.00%)
|
Corticosteroid, n, %
|
1,374
|
29.03%
|
541
|
11.43%
|
833
|
17.6%
|
-
|
-
|
<0.001
|
OCS combination
|
324
|
6.85%
|
64
|
1.35%
|
260
|
5.49%
|
-
|
-
|
ICS-LABA combination
|
925
|
19.54%
|
462
|
9.76%
|
463
|
9.78%
|
-
|
-
|
ICS combination
|
125
|
2.64%
|
15
|
0.32%
|
110
|
2.32%
|
-
|
-
|
Other controllers, n, %
|
1,134
|
23.96%
|
366
|
7.73%
|
768
|
16.23%
|
-
|
-
|
Theophylline combination
|
556
|
11.75%
|
145
|
3.06%
|
411
|
8.68%
|
-
|
-
|
Others (MCS etc.)
|
578
|
12.21%
|
221
|
4.67%
|
357
|
7.54%
|
-
|
-
|
LTRA only, n, %
|
508
|
10.73%
|
227
|
4.80%
|
280
|
5.92%
|
1
|
0.02%
|
Other anti-asthmatic relivers, n, %
|
887
|
18.74%
|
309
|
6.53%
|
578
|
12.21%
|
-
|
-
|
Symptomatic medications, n, %
|
830
|
17.54%
|
407
|
8.60%
|
423
|
8.94%
|
-
|
-
|
SABA Prescription N=4,359 (16.57%)
|
Controller, n, %
|
2,327
|
53.38%
|
648
|
14.87%
|
1,664
|
38.17%
|
15
|
0.34%
|
<0.001
|
OCS combination
|
50
|
1.15%
|
6
|
0.14%
|
41
|
0.94%
|
3
|
0.07%
|
ICS-LABA combination
|
564
|
12.94%
|
239
|
5.48%
|
325
|
7.46%
|
-
|
-
|
ICS combination
|
161
|
3.69%
|
24
|
0.55%
|
137
|
3.14%
|
-
|
-
|
LTRA combination
|
741
|
17.00%
|
275
|
6.31%
|
466
|
10.69%
|
-
|
-
|
Theophylline combination
|
365
|
8.37%
|
54
|
1.24%
|
306
|
7.02%
|
5
|
0.11%
|
Others (MCS etc.)
|
446
|
10.23%
|
50
|
1.15%
|
389
|
8.92%
|
7
|
0.16%
|
SABA only, n, %
|
367
|
8.42%
|
68
|
1.56%
|
296
|
6.79%
|
3
|
0.07%
|
Other anti-asthmatic relivers, n, %
|
1,395
|
32.00%
|
235
|
5.39%
|
1110
|
25.46%
|
50
|
1.15%
|
Symptomatic medications, n, %
|
270
|
6.19%
|
24
|
0.55%
|
227
|
5.21%
|
19
|
0.44%
|
Note:
1. Patient was categorized by the highest preferred treatment of each step from GINA 2018, e.g. categorized as OCS if use combination of OCS and ICS-LABA, without overlapping counting in every category.
2. Other anti-asthmatic relivers included SAMA, SABA/SAMA combination, short-acting xanthine derivatives, short course (≤7 days) injective/oral/nebulized corticosteroids
3. Symptomatic medications included TCM, antitussive, mucolytics, cough-mucolytics combination, anti-histamine, antibiotics
OCS: Oral corticosteroid; ICS-LABA: Inhaled corticosteroid and long-acting β2-agonist combination; ICS: Inhaled corticosteroid; LTRA: Leukotriene receptor antagonist; MCS: Mast cell stabilizers; SABA: short-acting β2-agonist; TCM: Traditional Chinese medicine
|
3.2.2 Changes in Asthma Treatment
3.2.2.1 Adherence to Follow-up Hospital Visits
Overall, 7,996 (30.4%) of 26,301 newly diagnosed asthma patients received continuous care for 12 months. Among them, 5,109 (63.89%) had at least one controller medication prescription over the follow-up period and 2,887 (36.11%) patients were not treated with any controller medication.
Among 14,207 patients with controller medication prescriptions, it’s appeared to be similar proportions of patients who lost to follow-up by end of each 3-month OWU (Figure 3 A1). The trends in tertiary, secondary and primary hospitals were similar (Figure 3 B1, C1, D1).
3.2.2.1 Controller Medication Pattern
Among 14,207 patients receiving treatment of controller medications during the study period, treatment pattern of controllers was examined in each 3-month OWU by different tiers of hospitals (Figure 3).
On index date and over 1st 3-month OWU, respectively, the most common prescriptions were ICS-containing, including ICS and ICS-LABA (25.73% and 32.08%), LTRA-containing (23.64% and 23.01%), others (15.14% and 15.40%) and theophylline-containing (13.31% and 13.63%). Over 2nd to 4th 3-month OWUs, respectively, the most common options were no controller prescription (77.35%, 79.86% and 79.04%), ICS-containing (10.17%, 9.8% and 9.81%) and LTRA-containing (4.21%, 3.62% and 3.44%) (Figure 3 A2).
Among patients treated in tertiary hospitals, on the index date and over 1st 3-month OWU, ICS-containing medications were prescribed in 38.91% and 46.26% patients, respectively; LTRA-containing were used in 29.37% and 27.32% patients, respectively. Over 2nd to 4th 3-month OWUs, no controller were prescribed in 79.76%, 81.46% and 80.04% of patients, respectively and ICS-containing was used in 13.16%, 12.07% and 12.75%, respectively. (Figure 3 B2). Among patients treated in secondary hospitals, the most common prescriptions were LTRA-containing (21.72%), ICS-containing (20.37%), no controller use (18.21%) at diagnosis; ICS-containing (26.9%), LTRA-containing (22.19%), others (17.02%) over 1st 3-month OWU; and no controller prescriptions (76.15%, 79.06% and 78.47%), ICS-containing (9.16%, 8.82% and 8.86%) over 2nd to 4th 3-month OWUs, respectively (Figure 3 C2). Among patients treated in primary hospitals, the most common prescriptions were no controller use, theophylline-containing and MCS-containing treatment (Figure 3 D2).
Many patients discontinued controller prescriptions over the follow-up visits and discontinuation of controller medication was most common in patients with mild asthma and occurred within first 6 months of the initial diagnosis. Among 7,315 patients having at least two OWUs follow-up visits, 64.17%, 28.14% and 7.68% patients with mild, moderate and severe asthma in 1st 3-month OWU discontinued controller prescription in 2nd OWU, respectively. Among 6,074 patients having at least three 3-month OWUs follow-up visits, 57.5%, 33.33% and 9.17% patients with mild, moderate and severe asthma in 2nd 3-month OWU discontinued controller prescriptions in 3rd 3-month OWU, respectively.
For all prescriptions, there were significant differences in prescription types between tertiary and secondary hospitals (Table 4).
Table 4 Treatment pattern in patients received controller medications during the study period
|
|
ALL
|
Tertiary Hospitals
|
Secondary Hospitals
|
Primary Hospitals
|
Tertiary vs. Secondary
|
Index date
|
|
N=14,207 (100%)
|
N=4,457 (31.37%)
|
N=9,435 (66.41%)
|
N=315 (2.22%)
|
P value
|
Controller, n, %
|
11,965
|
84.22%
|
4,032
|
90.46%
|
7,717
|
81.79%
|
216
|
68.57%
|
<0.001
|
OCS containing
|
908
|
6.39%
|
211
|
4.73%
|
671
|
7.11%
|
26
|
8.25%
|
ICS-LABA containing
|
3,148
|
22.16%
|
1,585
|
35.56%
|
1,563
|
16.57%
|
0
|
0.00%
|
ICS containing
|
508
|
3.58%
|
149
|
3.34%
|
359
|
3.80%
|
0
|
0.00%
|
LTRA containing
|
3,359
|
23.64%
|
1,309
|
29.37%
|
2,049
|
21.72%
|
1
|
0.32%
|
Theophylline containing
|
1,891
|
13.31%
|
411
|
9.22%
|
1,380
|
14.63%
|
100
|
31.75%
|
Others (MCS etc.)
|
2,151
|
15.14%
|
367
|
8.23%
|
1,695
|
17.97%
|
89
|
28.25%
|
No Controller, n, %
|
2,242
|
15.78%
|
425
|
9.54%
|
1,718
|
18.21%
|
99
|
31.43%
|
OWU1
|
|
N=9,166 (100%)
|
N=2,914 (34.79%)
|
N=5,918 (64.56%)
|
N=234 (2.55%)
|
|
|
Controller, n, %
|
8,605
|
93.88%
|
2,821
|
96.81%
|
5,501
|
92.95%
|
183
|
78.21%
|
<0.001
|
OCS containing
|
895
|
9.76%
|
191
|
6.55%
|
672
|
11.36%
|
32
|
13.68%
|
ICS-LABA containing
|
2,519
|
27.48%
|
1,238
|
42.48%
|
1,281
|
21.65%
|
0
|
0.00%
|
ICS containing
|
421
|
4.59%
|
110
|
3.77%
|
311
|
5.26%
|
0
|
0.00%
|
LTRA containing
|
2,109
|
23.01%
|
796
|
27.32%
|
1,313
|
22.19%
|
0
|
0.00%
|
Theophylline containing
|
1,249
|
13.63%
|
253
|
8.68%
|
917
|
15.50%
|
79
|
33.76%
|
Others (MCS etc.)
|
1,412
|
15.40%
|
233
|
8.00%
|
1,007
|
17.02%
|
72
|
30.77%
|
No Controller, n, %
|
561
|
6.12%
|
93
|
3.19%
|
417
|
7.05%
|
51
|
21.79%
|
OWU2
|
|
N=7,315 (100%)
|
N=2,302 (31.47%)
|
N=4,813 (65.80%)
|
N=200(2.73%)
|
|
With Controller, n, %
|
1,657
|
22.65%
|
466
|
20.24%
|
1,148
|
23.85%
|
43
|
21.50%
|
<0.001
|
OCS containing
|
206
|
2.82%
|
36
|
1.56%
|
162
|
3.37%
|
8
|
4.00%
|
ICS-LABA containing
|
648
|
8.86%
|
283
|
12.29%
|
365
|
7.58%
|
0
|
0.00%
|
ICS containing
|
96
|
1.31%
|
20
|
0.87%
|
76
|
1.58%
|
0
|
0.00%
|
LTRA containing
|
308
|
4.21%
|
81
|
3.52%
|
227
|
4.72%
|
0
|
0.00%
|
Theophylline containing
|
209
|
2.86%
|
26
|
1.13%
|
162
|
3.37%
|
21
|
10.50%
|
Others (MCS etc.)
|
190
|
2.60%
|
20
|
0.87%
|
156
|
3.24%
|
14
|
7.00%
|
No Controller, n, %
|
5,658
|
77.35%
|
1,836
|
79.76%
|
3,665
|
76.15%
|
157
|
78.50%
|
OWU3
|
|
N=6,074 (100%)
|
N=1,872 (30.82%)
|
N=4,002 (65.89%)
|
N=184 (3.03%)
|
|
|
Controller, n, %
|
1,223
|
20.14%
|
347
|
18.54%
|
838
|
20.94%
|
22
|
11.96%
|
<0.001
|
OCS containing
|
127
|
2.09%
|
25
|
1.34%
|
98
|
2.45%
|
4
|
2.17%
|
ICS-LABA containing
|
514
|
8.46%
|
226
|
12.07%
|
288
|
7.20%
|
0
|
0.00%
|
ICS containing
|
81
|
1.33%
|
0
|
0.00%
|
65
|
1.62%
|
0
|
0.00%
|
LTRA containing
|
220
|
3.62%
|
61
|
3.26%
|
159
|
3.97%
|
0
|
0.00%
|
Theophylline containing
|
147
|
2.42%
|
17
|
0.91%
|
121
|
3.02%
|
9
|
4.89%
|
Others (MCS etc.)
|
134
|
2.21%
|
18
|
0.96%
|
107
|
2.67%
|
9
|
4.89%
|
No Controller, n, %
|
4,851
|
79.86%
|
1,525
|
81.46%
|
3,164
|
79.06%
|
162
|
88.04%
|
OWU4
|
|
N=5109 (100%)
|
N=1,608 (31.47%)
|
N=3,339 (65.36%)
|
N=162 (3.17%)
|
|
|
Controller, n, %
|
1,071
|
20.96%
|
321
|
19.96%
|
719
|
21.53%
|
31
|
19.14%
|
<0.001
|
OCS containing
|
119
|
2.33%
|
22
|
1.37%
|
90
|
2.70%
|
7
|
4.32%
|
ICS-LABA containing
|
441
|
8.63%
|
193
|
12.00%
|
248
|
7.43%
|
0
|
0.00%
|
ICS containing
|
60
|
1.17%
|
12
|
0.75%
|
48
|
1.44%
|
0
|
0.00%
|
LTRA containing
|
176
|
3.44%
|
53
|
3.30%
|
123
|
3.68%
|
0
|
0.00%
|
Theophylline containing
|
138
|
2.70%
|
21
|
1.31%
|
104
|
3.11%
|
13
|
8.02%
|
Others (MCS etc.)
|
137
|
2.68%
|
20
|
1.24%
|
106
|
3.17%
|
11
|
6.79%
|
No Controller, n, %
|
4,038
|
79.04%
|
1,287
|
80.04%
|
2,620
|
78.47%
|
131
|
80.86%
|
3.2.2.3 Non-controller Medications Pattern
Of the 12,094 (45.98%) patients who did not receive treatment with any controller medications, 70.16% used relivers or other medications (including antibiotics, Traditional Chinese medicine (TCM), anti-histamine, cough, mucolytic and cough mucolytic combination) during follow-up visits with 60.92% receiving relivers plus other medications and 39.08% receiving relivers prescription only. The most common prescriptions were short-acting xanthine derivatives (22.09%), SABA (12.72%) and short course (≤7 days) use of oral corticosteroids (10.91%) in anti-asthmatic relivers, and antibiotics (29.5%), TCM (26.93%), anti-histamine (23.07%), antitussive (22.44%), and mucolytics (14.52%) in symptomatic medications.
3.3 Asthma Severities
A total of 7,996 (30.4%) patients had continuous care by end of 12-month follow-up. The distributions of asthma severity in each 3-month OWU are presented in Figure 4. The proportion of mild, moderate and severe patients were 76.86%, 17.88% and 5.25%, respectively, in 1st 3-month OWU. The proportions of both moderate and severe asthma patients decreased by about half from 1st 3-month OWU to 2nd 3-month OWU and then remained stable from 2nd to 4th 3-month OWUs.