The association between inhaled corticosteroid and pneumonia in COPD patients: the improvement of patients’ life quality with COPD in Taiwan (IMPACT) study

Figures & data

Figure 1 Study flowchart (nested case-control study).

Table 1 Characteristics of pneumonia cases and their matched controls selected from a cohort of patients with COPD

Characteristics	Cases n=19,838	Controls n=74,849	Crude OR (95% CI)
Male (%)	15,334 (77.3)	58,817 (78.6)	–
Days from COPD diagnosis to ICS	798.46±955.09	749.62±929.81	–
One year before the event date
Age (mean ± SD)	73.08±10.00	72.60±9.50	1.05 (1.04–1.05)*
Exacerbationa (%)	12,745 (64.2)	30,070 (40.2)	3.21 (3.10–3.33)*
Yearly rate (mean ± SD)	1.93±2.52	1.03±1.98	1.20 (1.19–1.21)*
Hospitalization for COPD (%)	7,572 (38.2)	12,494 (16.7)	3.64 (3.50–3.78)*
Yearly rate (mean ± SD)	0.63±1.03	0.23±0.61	1.99 (1.94–2.03)*
Emergency department visits (%)	5,654 (28.5)	7,957 (10.6)	3.68 (3.53–3.83)*
Yearly rate (mean ± SD)	0.46±0.95	0.15±0.52	1.96 (1.91–2.01)*
Oral steroids (%)	7,503 (37.8)	18,655 (24.9)	1.96 (1.90–2.03)*
Yearly rate (mean ± SD)	1.24±2.40	0.71±1.83	1.13 (1.12–1.14)*
Antibiotics (%)	4,671 (23.5)	9,935 (13.3)	2.12 (2.04–2.21)*
Yearly rate (mean ± SD)	0.40±1.01	0.22±0.77	1.26 (1.24–1.29)*
SABA (%)	8,234 (41.5)	22,801 (30.5)	1.74 (1.68–1.80)*
LABA (%)	1,503 (7.6)	4,649 (6.2)	1.35 (1.26–1.44)*
LAMA (%)	2,374 (12.0)	5,762 (7.7)	1.70 (1.61–1.79)*
Comorbidity (%)
DM	4,596 (23.2)	13,746 (18.4)	1.34 (1.29–1.39)*
Cancer	3,543 (17.9)	7,880 (10.5)	1.86 (1.78–1.94)*
Asthma	11,547 (58.2)	36,942 (49.4)	1.49 (1.44–1.54)*
Chronic liver disease	2,191 (11.0)	7,523 (10.1)	1.12 (1.07–1.18)*
Renal failure	2,300 (11.6)	5,726 (7.7)	1.57 (1.49–1.66)*
Hypertension	11,200 (56.5)	39,871 (53.3)	1.13 (1.10–1.17)*
Heart failure	4,119 (20.8)	8,811 (11.8)	1.99 (1.91–2.08)*
Stroke	3,571 (18.0)	9,884 (13.2)	1.44 (1.38–1.51)*
Ischemic heart disease	5,947 (30.0)	19,689 (26.3)	1.20 (1.16–1.25)*
Chronic kidney disease	2,774 (14.0)	6,989 (9.3)	1.57 (1.50–1.65)*
ESRD	250 (1.3)	409 (0.5)	2.27 (1.94–2.67)*
CCI (mean ± SD)	2.86±2.21	2.06±1.62	1.25 (1.24–1.26)*

Notes:

a Exacerbation includes use of antibiotics and oral steroids, emergency department visits, and hospitalization for COPD;

* P<0.05.

Abbreviations: DM, diabetes mellitus; ICS, inhaled corticosteroid; CCI, Charlson Comorbidity Index; CI, confidence interval; ESRD, end-stage renal disease; OR, odds ratio; LABA, long-acting β2-agonists; LAMA, long-acting anti-muscarinic antagonists; SABA, short-acting β2-agonists; SD, standard deviation.

Table 2 COPD-related health care utilization in the past year of the event

	Cases (n=19,838)	Controls (n=74,849)	Crude OR (95% CI)	Adjusted ORa (95% CI)
COPD hospitalization, n (%)
0	12,266 (61.8)	62,355 (83.3)	Reference	Reference
≥1	7,572 (38.2)	12,494 (16.7)	3.63 (3.50–3.78)*	2.58 (2.48–2.69)*
No. of days in hospital for COPD, n (%)
0	12,266 (61.8)	62,355 (83.3)	Reference	Reference
1–7	1,824 (9.2)	4,537 (6.1)	2.35 (2.21–2.50)*	1.81 (1.70–1.93)*
8–14	1,991 (10.0)	3,722 (5.0)	3.23 (3.04–3.44)*	2.38 (2.23–2.54)*
>14	3,757 (18.9)	4,235 (5.7)	5.64 (5.34–5.95)*	3.73 (3.53–3.95)*
No. of outpatient visits for COPD, n (%)
0	5,116 (25.8)	25,795 (34.5)	Reference	Reference
1–5	6,446 (32.5)	25,137 (33.6)	1.41 (1.35–1.48)*	1.06 (1.01–1.11)*
>5	8,276 (41.7)	23,917 (32.0)	2.00 (1.91–2.08)*	1.25 (1.19–1.31)*

Notes:

a The model was adjusted for age, sex, days from COPD diagnosis to ICS, oral steroid use, SABA, LABA, LAMA, DM, cancer, asthma, chronic liver disease, renal failure, hypertension, heart failure, stroke, ischemic heart disease, chronic kidney disease, ESRD, and CCI;

* P<0.05.

Abbreviations: DM, diabetes mellitus; ICS, inhaled corticosteroid; CCI, Charlson Comorbidity Index; CI, confidence interval; ESRD, end-stage renal disease; OR, odds ratio; LABA, long-acting β2-agonists; LAMA, long-acting anti-muscarinic antagonists; SABA, short-acting β2-agonists.

Table 3 Oral and inhaled corticosteroid use in pneumonia cases and control patients

	Cases (n=19,838)	Controls (n=74,849)	Crude OR (95% CI)	Adjusted ORa (95% CI)
Oral corticosteroid exposure, n (%)
Current use (within 60 days)	9,323 (47)	18,325 (24.5)	2.98 (2.88–3.09)*	2.18 (2.10–2.28)*
In the last 120 days	10,839 (54.6)	24,997 (33.4)	2.62 (2.53–2.71)*	1.85 (1.78–1.93)*
Average daily dose (DDD)b, mean (SD)	0.38 (0.62)	0.15 (0.37)	3.00 (2.89–3.11)*	2.18 (2.10–2.27)*
ICS exposure, n (%)
Current use (within 60 days)	8,260 (41.6)	25,037 (33.5)	1.55 (1.49–1.60)*	1.25 (1.20–1.30)*
In the last 120 days	10,024 (50.5)	31,482 (42.1)	1.55 (1.50–1.61)*	1.21 (1.16–1.26)*
Average daily dose (DDD)b, mean (SD)	0.43 (0.59)	0.32 (0.51)	1.55 (1.50–1.59)*	1.27 (1.23–1.31)*

Notes:

a The model was adjusted for age, sex, days from COPD diagnosis to ICS, exacerbation, hospitalization for COPD, emergency department visits, antibiotics use, oral steroids use, SABA, LABA, LAMA, DM, cancer, asthma, chronic liver disease, renal failure, hypertension, heart failure, stroke, ischemic heart disease, chronic kidney disease, ESRD, and CCI;

b doses in prednisolone equivalents;

* P<0.05.

Abbreviations: DM, diabetes mellitus; ICS, inhaled corticosteroid; CCI, Charlson Comorbidity Index; CI, confidence interval; DDD, defined daily doses; ESRD, end-stage renal disease; OR, odds ratio; LABA, long-acting β2-agonists; LAMA, long-acting anti-muscarinic antagonists; SABA, short-acting β2-agonists.

Table 4 Crude and adjusted odds ratios of pneumonia associated with inhalation steroid use

	Cases (n=19,838)	Controls (n=74,849)	Crude OR (95% CI)	Adjusted ORa (95% CI)
ICS use in the past 120 days, n (%)
No use	9,814 (49.5)	43,367 (57.9)	Reference	Reference
Current useb	8,260 (41.6)	25,037 (33.5)	1.62 (1.56–1.68)*	1.26 (1.21–1.32)*
Recent useb	1,064 (5.4)	3,754 (5.0)	1.36 (1.26–1.47)*	1.09 (1.01–1.18)*
Past useb	700 (3.5)	2,691 (3.6)	1.22 (1.12–1.34)*	0.94 (0.86–1.04)
Average daily dosage, DDDc, n (%)
No use within 60 days	11,578 (58.4)	49,812 (66.5)	Reference	Reference
>0 to 500 μg	2,798 (14.1)	9,888 (13.2)	1.31 (1.24–1.37)*	1.10 (1.04–1.16)*
>500 to 1,000 μg	4,309 (21.7)	12,659 (16.9)	1.65 (1.58–1.73)*	1.33 (1.26–1.39)*
>1,000 μg	1,153 (5.8)	2,490 (3.3)	2.31 (2.13–2.50)*	1.63 (1.50–1.78)*
Cumulative duration, years, n (%)
≤1	6,646 (33.5)	20,580 (27.5)	1.54 (1.48–1.60)*	1.24 (1.18–1.29)*
1–2	849 (4.3)	2,413 (3.2)	1.53 (1.41–1.66)*	1.25 (1.14–1.36)*
2–3	359 (1.8)	959 (1.3)	1.63 (1.44–1.85)*	1.38 (1.21–1.59)*
>3	406 (2.0)	1,085 (1.4)	1.64 (1.46–1.85)*	1.34 (1.18–1.52)*

Notes:

a The model was adjusted for age, sex, days from COPD diagnosis to ICS, exacerbation, hospitalization for COPD, emergency department visits, antibiotics use, oral steroids use, SABA, LABA, LAMA, DM, cancer, asthma, chronic liver disease, renal failure, hypertension, heart failure, stroke, ischemic heart disease, chronic kidney disease, ESRD, and CCI;

b current use with drug prescription within 60 days of the event date; recent use with drug prescription in the 60–90 days before the event date; past use with drug prescription in the 90–120 days before the event date;

c doses in fluticasone equivalents;

* P<0.05.

Abbreviations: DM, diabetes mellitus; ICS, inhaled corticosteroid; CCI, Charlson Comorbidity Index; CI, confidence interval; ESRD, end-stage renal disease; OR, odds ratio; LABA, long-acting β2-agonists; LAMA, long-acting anti-muscarinic antagonists; DDD, defined daily doses; SABA, short-acting β2-agonists.

Table 5 Risk of overall pneumonia associated with the use of any individual inhalation steroid

Inhalation steroid use, n (%)	Cases (n=19,838)	Controls (n=74,849)	Crude OR (95% CI)	Adjusted ORa (95% CI)
(1) Fluticasone/salmeterol	3,901 (19.7)	9,924 (13.3)	1.68 (1.61–1.76)*	1.35 (1.28–1.41)*
(2) Budesonide/formoterol	1,910 (9.6)	6,198 (8.3)	1.18 (1.12–1.25)*	1.02 (0.96–1.08)
(3) Fluticasone	679 (3.4)	2,041 (2.7)	1.33 (1.21–1.46)*	1.22 (1.10–1.35)*
(4) Budesonide	1,987 (10.0)	6,846 (9.1)	1.16 (1.10–1.23)*	1.06 (0.99–1.13)
(1) or (2)	5,661 (28.5)	15,915 (21.3)	1.58 (1.52–1.65)*	1.26 (1.20–1.31)*
(3) or (4)	2,632 (13.3)	8,814 (11.8)	1.23 (1.17–1.30)*	1.12 (1.05–1.18)*
(1) or (3)	4,528 (22.8)	11,879 (15.9)	1.63 (1.57–1.70)*	1.33 (1.27–1.39)*
(2) or (4)	3,815 (19.2)	12,907 (17.2)	1.17 (1.13–1.23)*	1.03 (0.99–1.08)

Notes:

a The model was adjusted for age, sex, days from COPD diagnosis to ICS, exacerbation, hospitalization for COPD, emergency department visits, antibiotics use, oral steroids use, SABA, LABA, LAMA, DM, cancer, asthma, chronic liver disease, renal failure, hypertension, heart failure, stroke, ischemic heart disease, chronic kidney disease, ESRD, and CCI;

* P<0.05.

Abbreviations: DM, diabetes mellitus; ICS, inhaled corticosteroid; CCI, Charlson Comorbidity Index; CI, confidence interval; DDD, defined daily doses; ESRD, end-stage renal disease; OR, odds ratio; LABA, long-acting β2-agonists; LAMA, long-acting anti-muscarinic antagonists; SABA, short-acting β2-agonists.