Table 5. Multivariable mixed-effects Cox proportional hazards regression models in non-CPFE patients and the two CPFE subgroups in the replication IPF cohort.
| Subgroup | Baseline severity and PFTs changes models | C-index | p-value | Hazard ratio | 95% CI | |
|---|---|---|---|---|---|---|
| Lower | Upper | |||||
| Non-CPFE IPF patients (n=108, 45 deaths) |
1-year FVC relative decline | 0.823 | 8.65×10-5 | 1.086 | 1.042 | 1.132 |
| Binary 1-year FVC decline (5%) | 0.827 | 0.002 | 2.719 | 1.425 | 5.187 | |
| Binary 1-year FVC decline (10%) | 0.817 | 0.004 | 2.733 | 1.374 | 5.437 | |
| 1 -year DLco relative decline | 0.822 | 0.019 | 1.032 | 1.005 | 1.059 | |
| Binary 1-year DLco decline (10%) | 0.835 | 0.013 | 2.373 | 1.201 | 4.688 | |
| Binary 1-year DLco decline (15%) | 0.835 | 0.006 | 2.693 | 1.336 | 5.428 | |
| CPFE
patients with emphysema < 10% (n=159, 83 deaths) |
1-year FVC relative decline | 0.754 | 0.001 | 1.055 | 1.022 | 1.089 |
| Binary 1-year FVC decline (5%) | 0.763 | 0.004 | 1.960 | 1.246 | 3.083 | |
| Binary 1-year FVC decline (10%) | 0.767 | 9.27×10-5 | 2.704 | 1.642 | 4.453 | |
| 1 -year DLco relative decline | 0.776 | 2.87×10-5 | 1.032 | 1.017 | 1.047 | |
| Binary 1-year DLco decline (10%) | 0.772 | 0.0005 | 2.252 | 1.424 | 3.561 | |
| Binary 1-year DLco decline (15%) | 0.768 | 0.0001 | 2.781 | 1.659 | 4.661 | |
| CPFE
patients with emphysema ≥1% (n=115, 70 deaths) |
1-year FVC relative decline | 0.705 | 0.130 | 1.024 | 0.993 | 1.056 |
| Binary 1-year FVC decline (5%) | 0.689 | 0.707 | 1.105 | 0.656 | 1.863 | |
| Binary 1-year FVC decline (10%) | 0.706 | 0.035 | 2.028 | 1.053 | 3.906 | |
| 1 -year DLco relative decline | 0.720 | 0.001 | 1.030 | 1.012 | 1.049 | |
| Binary 1-year DLco decline (10%) | 0.716 | 0.0004 | 2.672 | 1.546 | 4.617 | |
| Binary 1-year DLco decline (15%) | 0.729 | 1.04×10-5 | 3.883 | 2.124 | 7.097 | |
Multivariable mixed-effects Cox regression models were used to investigate associations with mortality for 1-year FVC decline and 1-year DLco decline after adjusting for patient age, sex, smoking status (never versus ever), antifibrotic use (never versus ever) and baseline disease severity estimated using DLco. Binary 1-year FVC decline uses 5% and 10% relative decline as thresholds, and binary 1-year DLco decline uses 10% and 15% relative decline as thresholds. Separate centres/countries within the replication cohort were modelled as multilevel with random effects between centres/countries (a random intercept per centre/country). All models passed Schoenfeld residuals test. CPFE: combined pulmonary fibrosis and emphysema; IPF: idiopathic pulmonary fibrosis; PFT: pulmonary function test; FVC: forced vital capacity; DLco: diffusing capacity of the lung for carbon monoxide; C-index: concordance index; CI: confidence interval.