The Risk of Sepsis with Inhaled and Oral Corticosteroids in Patients with COPD

Figures & data

Table 1. Quasi-cohort characteristics based on inhaled corticosteroid exposure.

	Current users^*	Discontinued	Non-users
Number of subjects	3,735	2,881	9,902
Age (years), mean ± SD	79.2 ± 7.9	78.3 ± 8.1	79.4 ± 8.1
Follow-up (years), mean ± SD	4.7 ± 3.7	4.3 ± 3.6	4.7 ± 3.7
Sex, % men	48.2	43.9	45.4
Hospitalization for pneumonia in the year prior to index date, %	4.6	3.5	2.1
Hospitalization for COPD in the year prior to index date, %	24.7	19.3	10.7
Number of hospitalizations for COPD in the year prior to index date (mean ± SD)	0.1 ± 0.5	0.1 ± 0.4	0.0 ± 0.2
Respiratory medication use in the year prior to index date
Antibiotics (no. of prescriptions), mean ± SD	1.0 ± 3.4	0.7 ± 2.7	0.4 ± 2.6
Oral corticosteroids (no. of prescriptions), mean ± SD	1.1 ± 3.7	0.7 ± 2.9	0.4 ± 2.9
Oral corticosteroids in the month prior index date, %	7.1	4.1	2.8
Other respiratory drugs (no. of prescriptions), mean ± SD	17.9 ± 12.2	8.8 ± 8.6	4.4 ± 7.3
Short-acting B agonists, %	87.2	81.8	41.6
Short-acting anticholinergics, %	51.4	38.2	24.7
Long-acting B agonists, %	25.8	22.7	12.4
Long-acting anticholinergics, %	3.0	2.2	1.7
Theophylline, %	10.5	9.9	10.0
Other medication use in the year prior to index date
Cardiac drugs, %	79.8	79.0	77.3
ACE, %	29.7	28.5	26.9
Statins, %	25.4	26.3	23.9
Other cardiac drugs, %	74.6	73.2	72.1
Diabetes drugs, %	13.8	16.0	15.9
Antidepressants, %	18.8	21.3	17.9
Central nervous system drugs, %	55.8	55.2	54.3
Osteoporosis drugs, %	18.9	18.2	16.7
NSAIDs, %	26.5	30.9	28.6
Narcotics, %	16.9	19.0	15.9
Antirheumatic drugs, %	1.0	0.8	1.1
Acid suppressant drugs, %	41.1	38.4	34.3
Proton pump inhibitors, %	32.7	30.5	26.2

^* Subjects were considered current inhaled corticosteroid users if their index date was preceded by a prescription for inhaled corticosteroid by 60 days or less. Non-use was defined as the index date preceded by no such prescription during the entire prior year. Subjects who were not current users but whose index date was preceded by a prescription dispensed between 61 and 365 days previously were classified as discontinued users.

Table 2. Quasi-rates, crude and adjusted rate ratios of sepsis associated with exposure to inhaled corticosteroids.

	No. with sepsis	No. Quasi-cohort person-days	Quasi-rates (per 1000 person-years)	Crude quasi-rate ratio	Adjusted^† quasi-rate ratio	95% CI
Number	1,704	16,518
Inhaled corticosteroid use
No use	942	9,902	1.79	1.00	1.00	Reference
Current use	433	3,735	2.18	1.22	0.98	0.84 to 1.14
Low dose	34	377	1.69	0.95	0.93	0.64 to 1.36
Medium dose	194	1,818	2.00	1.12	0.93	0.77 to 1.13
High dose	205	1,540	2.50	1.40	1.06	0.89 to 1.27
Discontinued	329	2,881	2.15	1.20	0.97	0.83 to 1.12
Time since discontinuation:
61-180 days	211	1,665	2.38	1.33	1.06	0.89 to 1.27
181-270 days	68	701	1.82	1.02	0.82	0.62 to 1.08
271-365 days	50	515	1.82	1.02	0.86	0.63 to 1.18

^† Adjusted for all the variables in Table 1.

Table 3. Quasi-cohort characteristics based on oral corticosteroid exposure.

	Current users^*	Discontinued	Non-users
Number of subjects	959	1,777	13,782
Age (years), mean ± SD	79.2 ± 7.9	78.8 ± 7.6	79.2 ± 8.1
Follow-up (years), mean ± SD	5.2 ± 3.9	4.7 ± 3.9	4.6 ± 3.6
Sex, % men	49.0	47.7	45.3
Hospitalization for pneumonia in the year prior to index date, %	8.4	8.8	1.7
Hospitalization for COPD in the year prior to index date, %	39.0	36.0	11.1
Number of hospitalizations for COPD in the year prior to index date (mean ± SD)	0.3 ± 0.8	0.2 ± 0.6	0.0 ± 0.1
Respiratory medication use in the year prior to index date
Antibiotics (no. of prescriptions), mean ± SD	6.5 ± 9.4	1.8 ± 2.1	0.0 ± 0.0
Inhaled corticosteroids, %	61.3	68.5	34.9
Other respiratory drugs (no. of prescriptions), mean ± SD	16.2 ± 15.4	14.9 ± 12.8	6.8 ± 9.0
Short-acting B agonists, %	80.0	86.4	53.9
Short-acting anticholinergics, %	56.8	59.2	28.1
Long-acting B agonists, %	32.2	34.3	14.0
Long-acting anticholinergics, %	7.4	5.1	1.3
Theophylline, %	14.6	12.3	9.5
Other medication use in the year prior to index date
Cardiac drugs, %	79.2	79.1	78.0
ACE, %	29.6	28.8	27.6
Statins, %	22.1	24.6	24.8
Other cardiac drugs, %	74.9	73.4	72.7
Diabetes drugs, %	14.6	12.9	15.8
Antidepressants, %	21.8	21.4	18.1
Central nervous system drugs, %	62.4	58.2	53.8
Osteoporosis drugs, %	33.9	21.1	15.9
NSAIDs, %	30.7	29.4	28.2
Narcotics, %	27.5	23.1	15.1
Antirheumatic drugs, %	8.1	1.5	0.5
Acid suppressant drugs, %	51.1	45.1	34.5
Proton pump inhibitors, %	42.2	36.0	26.5

* Subjects were considered current oral corticosteroid users if their index date was preceded by a prescription for oral corticosteroid by 60 days or less. Non-use was defined as the index date preceded by no such prescription during the entire prior year. Subjects who were not current users but whose index date was preceded by a prescription dispensed between 61 and 365 days previously were classified as discontinued users.

Table 4. Quasi-rates, crude and adjusted rate ratios of sepsis associated with exposure to oral corticosteroids.

	No. with sepsis	No. Quasi-cohort person-days	Quasi-rates (per 1000 person-years)	Crude quasi-rate ratio	Adjusted^† quasi-rate ratio	95% CI
Number	1,704	16,518
Oral corticosteroid use
No use	1,226	13,782	1.67	1.00	1.00	Reference
Current use	238	959	4.66	2.79	1.66	1.35 to 2.05
Discontinued	240	1,777	2.54	1.52	1.10	0.93 to 1.30
Time since discontinuation:
61-180 days	134	790	3.19	1.91	1.39	1.12 to 1.72
181-270 days	59	521	2.13	1.27	0.91	0.68 to 1.23
271-365 days	47	466	1.89	1.13	0.84	0.61 to 1.15

^† Adjusted for all the variables in Table 3.

Figure 1. Rate ratio for sepsis with 95% confidence interval according to time since the last oral corticosteroid (OCS) prescription.