Risk of tuberculosis according to inhaler medication use
| Type of use | Tuberculosis (N=4139), n (%) | Control (N=20 583), n (%) | Unadjusted | Adjusted* | ||
|---|---|---|---|---|---|---|
| OR (95% CI) | p Value | OR (95% CI) | p Value | |||
| Use of inhalers until index date | ||||||
| ICS use | ||||||
| Non-ICS users† | 3294 (79.6) | 17 007 (82.6) | 1 (ref) | 1 (ref) | ||
| ICS users‡ | 845 (20.4) | 3576 (17.4) | 1.37 (1.23 to 1.52) | <0.001 | 1.20 (1.08 to 1.34) | 0.001 |
| OCS use | ||||||
| Non-OCS users§ | 3773 (91.2) | 19 606 (95.3) | 1 (ref) | 1 (ref) | ||
| OCS users¶ | 366 (8.8) | 977 (4.7) | 2.13 (1.86 to 2.44) | <0.001 | 1.83 (1.58 to 2.12) | <0.001 |
| ICS cumulative dose (μg) | ||||||
| Median (Q1, Q3) | 25 250 (7500 to 60 000) | 15 000 (3000 to 30 000) | ||||
| p Value for trend** | <0.001 | <0.001 | ||||
| 0 dose | 2969 (71.7) | 14 345 (69.7) | 1 (ref) | 1 (ref) | ||
| 1–15 000 | 499 (12.1) | 4129 (20.1) | 0.55 (0.50 to 0.62) | <0.001 | 0.54 (0.49 to 0.61) | <0.001 |
| 15 001–45 000 | 303 (7.3) | 1299 (6.3) | 1.17 (1.01 to 1.36) | 0.035 | 1.03 (0.89 to 1.21) | 0.677 |
| 45 001–75 000 | 144 (3.5) | 378 (1.8) | 2.04 (1.66 to 2.51) | <0.001 | 1.72 (1.38 to 2.14) | <0.001 |
| 75 001+ | 224 (5.4) | 432 (2.1) | 2.92 (2.44 to 3.50) | <0.001 | 2.16 (1.77 to 2.63) | <0.001 |
| Use of inhalers until 3 months prior to index date | ||||||
| ICS use | ||||||
| Non-ICS users† | 3586 (86.6) | 18 254 (88.7) | 1 (ref) | 1 (ref) | ||
| ICS users‡ | 553 (13.4) | 2329 (11.3) | 1.35 (1.19 to 1.53) | <0.001 | 1.17 (1.03 to 1.34) | 0.016 |
| OCS use | ||||||
| Non-OCS users§ | 3910 (94.5) | 19 940 (96.9) | 1 (ref) | 1 (ref) | ||
| OCS users¶ | 229 (5.5) | 643 (3.1) | 1.97 (1.67 to 2.32) | <0.001 | 1.61 (1.34 to 1.92) | <0.001 |
| ICS cumulative dose (μg) | ||||||
| Median (Q1, Q3) | 30 000 (12 000 to 61 500) | 15 000 (7500 to 30 375) | ||||
| p Value for trend** | <0.001 | <0.001 | ||||
| 0 dose | 3421 (82.7) | 17 514 (85.1) | 1 (ref) | 1 (ref) | ||
| 1–15 000 | 265 (6.4) | 1688 (8.2) | 0.86 (0.74 to 0.99) | 0.056 | 0.81 (0.69 to 0.95) | 0.011 |
| 15 001–45 000 | 197 (4.8) | 843 (4.1) | 1.34 (1.12 to 1.61) | 0.001 | 1.23 (1.02 to 1.48) | 0.032 |
| 45 001–75 000 | 120 (2.9) | 270 (1.3) | 2.65 (2.10 to 3.35) | <0.001 | 2.15 (1.67 to 2.76) | <0.001 |
| 75 001+ | 136 (3.3) | 268 (1.3) | 3.04 (2.43 to 3.81) | <0.001 | 2.17 (1.70 to 2.77) | <0.001 |
| Use of inhalers until 6 months prior to index date | ||||||
| ICS use | ||||||
| Non-ICS users† | 3742 (90.4) | 19 065 (92.6) | 1 (ref) | 1 (ref) | ||
| ICS users‡ | 397 (9.6) | 1518 (7.4) | 1.35 (1.19 to 1.53) | <0.001 | 1.33 (1.14 to 1.54) | <0.001 |
| OCS use | ||||||
| Non-OCS users§ | 4005 (96.8) | 20 151 (97.9) | 1 (ref) | 1 (ref) | ||
| OCS users¶ | 134 (3.2) | 432 (2.1) | 1.64 (1.33 to 2.02) | <0.001 | 1.33 (1.07 to 1.66) | 0.012 |
| ICS cumulative dose (μg) | ||||||
| Median (Q1, Q3) | 29 125 (15 000 to 50 562.5) | 15 000 (7500 to 30 000) | ||||
| p Value for trend** | <0.001 | <0.001 | ||||
| 0 dose | 3631 (87.7) | 18 479 (89.9) | 1 (ref) | 1 (ref) | ||
| 1–15 000 | 192 (4.6) | 1198 (5.8) | 0.87 (0.73 to 1.05) | 0.143 | 0.82 (0.69 to 0.99) | 0.038 |
| 15 001–45 000 | 172 (4.2) | 614 (3.0) | 1.61 (1.32 to 1.95) | <0.001 | 1.45 (1.18 to 1.78) | <0.001 |
| 45 001–75 000 | 88 (2.1) | 185 (0.9) | 2.75 (2.10 to 3.60) | <0.001 | 2.18 (1.63 to 2.90) | <0.001 |
| 75 001+ | 56 (1.4) | 107 (0.5) | 3.01 (2.15 to 4.21) | <0.001 | 2.17 (1.51 to 3.11) | <0.001 |
*Adjusted for LAMA use, SABA use, SAMA use, OCS use, presence of TB sequelae, immunosuppressant use, other comorbidities (malignancy, diabetes, chronic renal failure/dialysis, silicosis, malabsorption, HIV/AIDS and transplantation), Charlson Comorbidity Index and healthcare usage.
†Defined if inhaler prescriptions shorter than 30 days during 1 year before the index date was identified.
‡Defined if inhaler prescriptions 30 days or longer during 1 year before the index date was identified.
§Defined if cumulative dose of less than 1680 mg of hydrocortisone equivalents during 1 year before the index date was identified.
¶Defined if cumulative dose of 1680 mg of hydrocortisone equivalents or more during 1 year before the index date was identified.
**Conditional logit model: used each group median.
COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LAMA, long-acting inhaled muscarinic antagonist; OCS, oral corticosteroid; SABA short-acting inhaled β2 agonists; SAMA, short-acting inhaled muscarinic antagonist.