Table 3. The association between ACOS and drug day (per year) and average dose (per year) of ICSs, OSs, and antibiotic therapy for the risk of stroke, Parkinson’s disease, dementia.
| Variables | N | Event | Rate | Crude HR (95% CI) | Adjusted HR (95% CI)† |
|---|---|---|---|---|---|
| Stroke | |||||
| Non-ACOS cohort | 20513 | 2008 | 15.1 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without ICSs | 7538 | 984 | 21.7 | 1.44 (1.34, 1.56)*** | 1.43 (1.31, 1.55)*** |
| With ICSs (gram), per year | |||||
| ≤ 0.12 | 910 | 105 | 14.4 | 0.95 (0.78,1 .16) | 1.08 (0.89, 1.32) |
| 0.13–0.43 | 869 | 52 | 8.60 | 0.57 (0.43, 0.75)*** | 0.64 (0.48, 0.85)** |
| > 0.43 | 1853 | 46 | 8.55 | 0.57 (0.42, 0.76)*** | 0.57 (0.43, 0.77)*** |
| Non-ACOS cohort | 20513 | 2008 | 15.1 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without OSs | 2319 | 326 | 24.3 | 1.61 (1.43, 1.81)*** | 1.64 (1.46, 1.85)*** |
| With OSs (gram), per year | |||||
| ≤0.07 | 2573 | 619 | 33.0 | 2.19 (2.00, 2.40)*** | 2.05 (1.87, 2.26)*** |
| 0.08–0.26 | 2650 | 109 | 5.97 | 0.40 (0.33, 0.48)*** | 0.42 (0.34, 0.50)*** |
| > 0.26 | 2718 | 133 | 9.80 | 0.65 (0.55, 0.77)*** | 0.63 (0.52, 0.75)*** |
| Non-ACOS cohort | 20513 | 2008 | 15.1 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without ICSs | 7538 | 984 | 21.7 | 1.44 (1.34, 1.56)*** | 1.42 (1.30, 1.54)*** |
| ICSs (fluticasone equivalent) | |||||
| Low dose (< 250 ug/d) | 451 | 24 | 6.65 | 0.44 (0.30, 0.66)*** | 0.53 (0.35, 0.79)** |
| Middle dose (250–500 ug/d) | 375 | 25 | 9.72 | 0.64 (0.43, 0.96)* | 0.70 (0.47, 1.04) |
| High dose (>500 ug/d) | 1896 | 154 | 12.3 | 0.82 (0.69, 0.96)* | 0.86 (0.73,1 .02) |
| Parkinson’s disease | |||||
| Non-ACOS cohort | 20513 | 532 | 3.87 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without ICSs | 7538 | 309 | 6.52 | 1.69 (1.47, 1.94)*** | 1.59 (1.37, 1.85)*** |
| With ICSs (gram), per year | |||||
| ≤ 0.12 | 910 | 47 | 6.28 | 1.61 (1.19, 2.17)** | 1.81 (1.33, 2.46)*** |
| 0.13–0.43 | 869 | 11 | 1.80 | 0.46 (0.26, 0.84)* | 0.53 (0.29, 0.97)* |
| > 0.43 | 1853 | 13 | 2.40 | 0.62 (0.36, 1.08) | 0.65 (0.37, 1.13) |
| Non-ACOS cohort | 20513 | 532 | 3.87 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without OSs | 20513 | 532 | 3.87 | 2.12 (1.74, 2.60)*** | 1.98 (1.61, 2.43)*** |
| With OSs (gram), per year | |||||
| ≤ 0.07 | 2573 | 218 | 10.8 | 2.77 (2.36, 3.24)*** | 2.31 (1.96, 2.73)*** |
| 0.08–0.26 | 2650 | 23 | 1.25 | 0.32 (0.21, 0.49)*** | 0.30 (0.20, 0.47)*** |
| > 0.26 | 2718 | 23 | 1.68 | 0.44 (0.29, 0.67)*** | 0.35 (0.23, 0.55)*** |
| Non-ACOS cohort | 20513 | 532 | 3.87 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without ICSs | 7538 | 309 | 6.52 | 1.69 (1.47, 1.94)*** | 1.59 (1.36, 1.85)*** |
| ICSs (fluticasone equivalent) | |||||
| Low dose (< 250 ug/d) | 451 | 10 | 2.75 | 0.71 (0.38, 1.32) | 0.83 (0.44, 1.55) |
| Middle dose (250–500 ug/d) | 375 | 11 | 4.22 | 1.09 (0.60, 1.98) | 1.21 (0.66, 2.20) |
| High dose (>500 ug/d) | 1896 | 50 | 3.91 | 1.01 (0.76, 1.35) | 1.09 (0.81, 1.48) |
| Dementia | |||||
| Non-ACOS cohort | 20513 | 1194 | 8.81 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without ICSs | 7538 | 619 | 13.3 | 1.52 (1.38, 1.67)*** | 1.49 (1.34, 1.66)*** |
| With ICSs (gram), per year | |||||
| ≤ 0.12 | 910 | 59 | 7.93 | 0.88 (0.68, 1.15) | 1.05 (0.80, 1.36) |
| 0.13–0.43 | 869 | 25 | 4.10 | 0.47 (0.31, 0.69)*** | 0.58 (0.39, 0.87)** |
| > 0.43 | 1853 | 23 | 4.25 | 0.49 (0.32, 0.74)*** | 0.55 (0.36, 0.83)** |
| Non-ACOS cohort | 20513 | 1194 | 8.81 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without OSs | 2319 | 213 | 15.3 | 1.76 (1.52, 2.04)*** | 1.78 (1.54, 2.07)*** |
| With OSs (gram), per year | |||||
| ≤ 0.07 | 2573 | 383 | 19.4 | 2.17 (1.93, 2.43)*** | 1.97 (1.75, 2.23)*** |
| 0.08–0.26 | 2650 | 67 | 3.65 | 0.42 (0.33, 0.53)*** | 0.44 (0.34, 0.56)*** |
| > 0.26 | 2718 | 63 | 4.62 | 0.54 (0.42, 0.69)*** | 0.51 (0.39, 0.66)*** |
| Non-ACOS cohort | 20513 | 1194 | 8.81 | 1.00 | 1.00 |
| ACOS cohort | |||||
| Without ICSs | 7538 | 619 | 13.3 | 1.52 (1.38, 1.67)*** | 1.48 (1.33, 1.65)*** |
| ICSs (fluticasone equivalent) | |||||
| Low dose (< 250 ug/d) | 451 | 14 | 3.86 | 0.43 (0.25, 0.73)** | 0.53 (0.31, 0.90)* |
| Middle dose (250–500 ug/d) | 375 | 11 | 4.20 | 0.48 (0.26, 0.86)* | 0.55 (0.31, 1.01) |
| High dose (>500 ug/d) | 1896 | 82 | 6.45 | 0.73 (0.59, 0.92)** | 0.85 (0.67, 1.07) |
ACOS, asthma–COPD overlap syndrome; the average use day on median use is partitioned in to 2 segments by median; the average dose on median use is partitioned in to 3 segments by tertile; Rate, incidence rate (per 1,000 person-years); IRR, incidence rate ratio; Adjusted HR†: multiple cox model analysis including age, sex, each comorbidity, inhaled corticosteroid (ICSs), oral steroid(OSs); *p < 0.05, **p < 0.01, ***p < 0.001.