Table 4.
Marginal and Interaction Analyses of the Composite Events in the ICS Withdrawal Dataset
| Variables | Marginal Analysis | Interaction Analysis | |||
|---|---|---|---|---|---|
| HR (95% CI) | P-value | HR (95% CI) | P-value | P-value for Interaction | |
| COPD treatment | |||||
| Triple therapy | Reference | ||||
| Dual bronchodilators | 1.23 (1.11–1.38) | <0.001 | |||
| Age | 0.265 | ||||
| <65 years | Reference | 1.153 (0.979–1.356) | 0.088 | ||
| ≥65 years | 0.99 (0.89–1.11) | 0.886 | 1.305 (1.128–1.510) | <0.001 | |
| Sex | 0.111 | ||||
| Female | Reference | 1.385 (1.160–1.653) | <0.001 | ||
| Male | 0.74 (0.66–0.83) | <0.001 | 1.154 (1.007–1.324) | 0.040 | |
| Race | 0.014 | ||||
| Other | Reference | 0.922 (0.712–1.195) | 0.541 | ||
| White | 1.16 (1.01–1.34) | 0.037 | 1.318 (1.170–1.485) | <0.001 | |
| Smoking history | 0.903 | ||||
| Current smoker | Reference | 1.222 (1.007–1.483) | 0.043 | ||
| Former smoker | 1.07 (0.95–1.20) | 0.270 | 1.240 (1.088–1.413) | 0.001 | |
| COPD duration | 0.251 | ||||
| <1 year | Reference | 0.850 (0.446–1.623) | 0.623 | ||
| ≥1 year | 1.49 (1.09–2.04) | 0.013 | 1.248 (1.118–1.394) | <0.001 | |
| Exacerbation in the previous year | 0.147 | ||||
| <3 | Reference | 1.190 (1.056–1.341) | 0.004 | ||
| ≥3 | 1.47 (1.27–1.71) | <0.001 | 1.469 (1.135–1.901) | 0.003 | |
| Exacerbation requiring systemic steroid in the previous year | 0.371 | ||||
| 0 | Reference | 1.192 (0.866–1.640) | 0.281 | ||
| 1 | 1.22 (1.03–1.45) | 0.021 | 1.153 (0.988–1.347) | 0.071 | |
| 2 or more | 1.40 (1.17–1.67) | <0.001 | 1.360 (1.144–1.616) | <0.001 | |
| FEV1 (%) predicted | 0.835 | ||||
| <30 | Reference | 1.226 (0.972–1.548) | 0.086 | ||
| ≥30 to <50 | 0.75 (0.66–0.85) | <0.001 | 1.269 (1.093–1.474) | 0.002 | |
| ≥50 | 0.58 (0.50–0.68) | <0.001 | 1.172 (0.945–1.453) | 0.148 | |
| CAT score | 0.969 | ||||
| <20 | Reference | 1.237 (1.056–1.449) | 0.008 | ||
| ≥20 | 1.02 (0.92–1.14) | 0.716 | 1.232 (1.061–1.430) | 0.006 | |
| Blood eosinophil count (109 cells per L) | 0.017 | ||||
| <0.1 | Reference | 1.009 (0.806–1.262) | 0.940 | ||
| ≥0.1 to <0.3 | 1.04 (0.91–1.18) | 0.585 | 1.211 (1.041–1.408) | 0.013 | |
| ≥0.3 | 1.42 (1.22–1.65) | <0.001 | 1.586 (1.274–1.975) | <0.001 | |
Notes: Marginal and interaction analyses were performed using Cox proportional hazards regression models to investigate clinical factors that would modify the effect of inhaled corticosteroid use on the composite events. For simplicity, predictive factors with P-value >0.2 (age, smoking, and COPD assessment test score) in the multivariable marginal analysis were further excluded from the final model.
Abbreviations: CAT, chronic obstructive pulmonary disease assessment test; CI, confidence interval; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 sec; HR, hazard ratio.