Introduction
Methods
Data sources
Study populations
Outcome and prognostic predictors
Multivariable prognostic scores
Modelling the putative prognostic predictors
Validation of the risk model
Comparing observed and predicted mortality probability
Comparing the risk model with established multivariable prognostic scores
Results
Characteristics of the COPD populations
Characteristic | Training set | Test set | Died | Not died | ||||
---|---|---|---|---|---|---|---|---|
N
| % |
N
| % |
N
| % |
N
| % | |
Total | 27,472 | 50.0 | 27,518 | 50.0 | 11,775 | 21.4 | 43,215 | 78.6 |
Mean age, years (SD) | 69.9 (10.7) | 70.0 (10.6) | 76.6 (9.2) | 68.1 (10.3) | ||||
Gender (males) | 14,869 | 54.1 | 12,603 | 45.9 | 4933 | 41.9 | 20,353 | 47.1 |
IMD quartiles | ||||||||
1 (least deprived) | 5251 | 19.2 | 5254 | 19.1 | 2237 | 19.0 | 8268 | 19.1 |
2 | 6926 | 25.3 | 6910 | 25.2 | 3021 | 25.7 | 10,815 | 25.0 |
3 | 7314 | 26.7 | 7341 | 26.8 | 3176 | 27.0 | 11,479 | 26.6 |
4 | 7891 | 28.8 | 7937 | 28.9 | 3327 | 28.3 | 12,501 | 28.9 |
Mean BMI, kg/m2 (SD) | 27.5 (6.2) | 27.5 (6.2) | 26.0 (6.3) | 28.0 (6.1) | ||||
Mean FEV1, L (SD) | 1.59 (0.7) | 1.59 (0.7) | 1.27 (0.60) | 1.67 (0.69) | ||||
GOLD stage | ||||||||
1 | 10,117 | 43.1 | 10,231 | 43.5 | 3205 | 27.2 | 17,143 | 39.7 |
2 | 7850 | 33.5 | 7883 | 33.5 | 2776 | 23.6 | 12,957 | 30.0 |
3 | 4459 | 19.0 | 4407 | 18.8 | 2545 | 21.6 | 6321 | 14.6 |
4 | 1031 | 4.4 | 987 | 4.2 | 886 | 7.5 | 1132 | 2.6 |
MRC score | ||||||||
1 | 14,553 | 53.5 | 14,524 | 53.5 | 3793 | 32.2 | 25,284 | 58.5 |
2 | 7011 | 25.8 | 7025 | 25.9 | 3262 | 27.7 | 10,774 | 24.9 |
3 | 4497 | 16.5 | 4482 | 16.5 | 3185 | 27.0 | 5794 | 13.4 |
4 | 1144 | 4.2 | 1118 | 4.1 | 1349 | 11.5 | 913 | 2.1 |
Smoking status | ||||||||
Current | 16,006 | 58.2 | 15,829 | 57.6 | 7272 | 61.8 | 24,563 | 56.8 |
Ex-smoker | 11,512 | 41.8 | 11,643 | 42.4 | 4503 | 38.2 | 18,652 | 43.2 |
GP treated exacerbations | ||||||||
1–2 | 7885 | 28.7 | 7738 | 28.2 | 3483 | 29.6 | 12,140 | 28.1 |
> 2 | 2230 | 8.1 | 2272 | 8.3 | 1291 | 11.0 | 3211 | 7.4 |
Hospitalised exacerbations | ||||||||
1–2 | 1548 | 5.6 | 1609 | 5.9 | 1399 | 11.9 | 1758 | 4.1 |
> 2 | 149 | 0.5 | 118 | 0.4 | 181 | 1.5 | 86 | 0.2 |
Medications | ||||||||
ICS | 19,252 | 70.0 | 18,932 | 68.9 | 8937 | 75.9 | 29,247 | 67.7 |
LABA | 17,638 | 64.1 | 17,456 | 63.5 | 8330 | 70.7 | 26,764 | 61.9 |
LAMA | 13,522 | 49.1 | 13,585 | 49.5 | 6636 | 56.4 | 20,471 | 47.4 |
Influenza vaccination | 22,663 | 82.4 | 22,649 | 82.4 | 9984 | 84.8 | 35,328 | 81.7 |
Pneumococcal vaccination | 2195 | 27.5 | 1983 | 25.5 | 1059 | 9.0 | 3119 | 7.2 |
Comorbidities | ||||||||
Myocardial infarction | 2310 | 8.4 | 2162 | 7.8 | 1501 | 12.8 | 2971 | 6.7 |
Stroke | 1393 | 5.1 | 1387 | 5.1 | 947 | 8.0 | 1833 | 15.6 |
Asthma | 13,442 | 48.9 | 13,198 | 48.0 | 5937 | 50.4 | 20,703 | 175.8 |
Hypertension | 13,263 | 48.3 | 13,130 | 47.7 | 6550 | 55.6 | 19,843 | 168.5 |
Atrial fibrillation (COTE) | 2157 | 7.9 | 2222 | 8.1 | 1176 | 10.0 | 2663 | 22.6 |
Chronic kidney disease | 2403 | 8.7 | 2391 | 8.7 | 2805 | 23.8 | 1989 | 16.9 |
Dementia | 428 | 1.6 | 418 | 1.5 | 424 | 3.6 | 422 | 3.6 |
Anxiety (COTE) | 6689 | 24.3 | 6715 | 24.4 | 2729 | 23.2 | 10,675 | 90.7 |
Depression | 7941 | 28.9 | 8027 | 29.2 | 3004 | 25.5 | 12,964 | 110.1 |
Lung cancer (COTE) | 1109 | 4.0 | 1055 | 3.8 | 1282 | 10.9 | 882 | 7.5 |
Cirrhosis (COTE) | 119 | 0.4 | 118 | 0.4 | 76 | 0.6 | 161 | 1.4 |
Oesophageal cancer (COTE) | 41 | 0.1 | 35 | 0.1 | 41 | 0.3 | 35 | 0.3 |
Diabetes | 4599 | 16.7 | 4742 | 17.2 | 2408 | 20.5 | 6933 | 58.9 |
Pulmonary embolism | 642 | 2.3 | 680 | 2.5 | 374 | 3.2 | 948 | 8.1 |
Heart failure (COTE) | 1825 | 6.6 | 1775 | 6.5 | 1566 | 13.3 | 2034 | 17.3 |
Osteoporosis | 2421 | 8.8 | 2392 | 8.7 | 11,480 | 97.5 | 3333 | 28.3 |
Coronary artery disease (COTE) | 5620 | 20.5 | 5469 | 19.9 | 3361 | 28.5 | 7728 | 65.6 |
Pancreatic cancer (COTE) | 5 | 0.0 | 5 | 0.0 | < 5 | < 0.1 | 6 | 0.1 |
Pulmonary fibrosis (COTE) | 183 | 0.7 | 177 | 0.6 | 144 | 1.2 | 216 | 1.8 |
Breast cancer (COTE) | 425 | 1.5 | 443 | 1.6 | 213 | 1.8 | 655 | 5.6 |
Gastric/duodenal ulcers (COTE) | 230 | 0.8 | 229 | 0.8 | 121 | 1.0 | 338 | 2.9 |
Diabetes with neuropathy (COTE) | 3894 | 14.2 | 4021 | 14.6 | 2073 | 17.6 | 5842 | 49.6 |
Blood tests | ||||||||
CRP, mg/L mean (SD) | 13.5 (29.5) | 13.2 (29.6) | 19.4 (36.8) | 11.5 (24.5) | ||||
Low albumin, g/L | 1185 | 4.3 | 1176 | 4.3 | 1039 | 8.8 | 1322 | 11.2 |
Hb, g/dL mean (SD) | 138.5 (41.4) | 138.3 (37.5) | 133.7 (40.0) | 139.8 (39.2) | ||||
Low platelets, × 109/L | 655 | 3.6 | 690 | 3.8 | 431 | 3.7 | 914 | 7.8 |
High platelets, × 109/L | 1374 | 7.5 | 1368 | 7.5 | 783 | 6.6 | 1959 | 16.6 |
Creatinine, μmol/L mean (SD) | 88.9 (37.7) | 88.2 (34.1) | 98.1 (48.5) | 85.7 (30.6) | ||||
Bereavement | 1337 | 4.9 | 1354 | 4.9 | 611 | 5.2 | 2080 | 17.7 |
Characteristic | External set | Died | Not died | |||
---|---|---|---|---|---|---|
N
| % |
N
| % |
N
| % | |
Total | 4931 | 100 | 1424 | 28.9 | 3507 | 71.1 |
Mean age, years (SD) | 71.1 (11.0) | 75.0 (9.0) | 68.3 (11.1) | |||
Gender (males) | 2718 | 55.1 | 912 | 64 | 1806 | 51.5 |
Mean BMI, kg/m2 (SD) | 26.9 (6.5) | 25.2 (6.2) | 27.7 (6.4) | |||
Mean FEV1, L (SD) | 1.52 (0.70) | 1.34 (0.61) | 1.73 (0.70) | |||
MRC score | ||||||
1 | 2433 | 49.3 | 478 | 33.6 | 1955 | 55.8 |
2 | 1224 | 24.8 | 373 | 26.2 | 851 | 24.3 |
3 | 926 | 18.8 | 387 | 27.2 | 539 | 15.4 |
4 | 348 | 7.1 | 186 | 13.1 | 162 | 4.6 |
Smoking status | ||||||
Ex-smoker | 2657 | 53.9 | 793 | 55.7 | 1864 | 53.1 |
Current | 2274 | 46.1 | 631 | 44.3 | 1643 | 46.9 |
Hospitalised exacerbations | ||||||
1–2 | 224 | 4.5 | 102 | 1.2 | 122 | 3.5 |
> 2 | 9 | 0.2 | 7 | 0.5 | < 5 | . |
Comorbidities | ||||||
Stroke | 368 | 7.5 | 144 | 10.1 | 224 | 6.4 |
Asthma | 2452 | 49.7 | 736 | 51.7 | 1716 | 48.9 |
Hypertension | ||||||
Atrial fibrillation (COTE) | 731 | 14.8 | 330 | 23.2 | 401 | 11.4 |
Chronic kidney disease | 733 | 14.9 | 340 | 23.9 | 393 | 11.2 |
Dementia | 210 | 4.3 | 76 | 5.3 | 134 | 3.8 |
Lung cancer (COTE) | 80 | 1.6 | 50 | 3.5 | 30 | 0.9 |
Pulmonary fibrosis (COTE) | 80 | 1.6 | 33 | 2.3 | 47 | 1.3 |
Blood tests | ||||||
Low albumin, g/L | 369 | 7.5 | 153 | 10.7 | 216 | 6.2 |
Hb, g/dL mean (SD) | 141.1 (67.7) | 143.6 (102.0) | 140.0 (47.1) | |||
Low platelets, × 109/L | 211 | 4.3 | 142 | 4.1 | 69 | 4.9 |
High platelets, × 109/L | 398 | 8.1 | 138 | 9.7 | 260 | 7.4 |
Creatinine, μmol/L mean (SD) | 94.1 (45.4) | 105 (52.5) | 89.4 (41.3) |
Prevalence of prognostic predictors
Identification of the risk model
Coefficient | SE | p value | |
---|---|---|---|
Continuous variables | |||
Age | 0.040 | 0.004 | < 0.0001 |
BMI | − 0.047 | 0.006 | < 0.0001 |
Creatinine | 0.001 | 0.001 | < 0.05 |
Haemoglobin | − 0.006 | 0.001 | < 0.0001 |
FEV1 | − 0.433 | 0.078 | < 0.0001 |
Categorical variables | |||
Asthma | − 0.155 | 0.057 | < 0.01 |
Atrial fibrillation | 0.450 | 0.077 | < 0.0001 |
No CKD | − 0.314 | 0.143 | < 0.05 |
Current smoker | 0.179 | 0.061 | < 0.05 |
Dementia | 0.391 | 0.137 | < 0.01 |
Female | − 0.331 | 0.069 | < 0.0001 |
Hospitalisations | |||
1–2/year | 0.517 | 0.081 | < 0.0001 |
> 2/year | 0.980 | 0.181 | < 0.0001 |
Low albumin | 0.531 | 0.089 | < 0.0001 |
Lung cancer | 1.063 | 0.135 | < 0.0001 |
Lung fibrosis | 0.794 | 0.219 | < 0.0001 |
MRC | |||
2 | 0.577 | 0.130 | < 0.0001 |
3 | 0.890 | 0.133 | < 0.0001 |
4 | 1.599 | 0.142 | < 0.0001 |
Platelets | |||
Normal | − 0.394 | 0.131 | < 0.01 |
High | − 0.208 | 0.161 | > 0.05 |
Stroke | 0.235 | 0.097 | < 0.05 |
Validation of the risk model
Mean | SE | 95% CI | Mean | SE | 95% CI | |
---|---|---|---|---|---|---|
Test set | External validation | |||||
Harrell’s C-index | 0.794 | 0.006 | 0.782–0.807 | 0.671 | 0.012 | 0.647–0.695 |
D-statistic | 1.865 | 0.048 | 1.770–1.959 | 0.983 | 0.080 | 0.826–1.141 |
Calibration slope | 0.947 | 0.024 | 0.900–0.993 | 0.544 | 0.046 | 0.454–0.635 |
Comparing mortality between that observed and predicted
Comparing the BARC to ADO, BODEx and DOSE
AUC | SE | 95% CI | AUC | SE | 95% CI | |
---|---|---|---|---|---|---|
Prognostic index | First cohort | External validation | ||||
ADO | 0.675 | 0.010 | 0.655–0.694 | 0.568 | 0.014 | 0.541–0.595 |
BODEx | 0.483 | 0.015 | 0.453–0.512 | 0.413 | 0.017 | 0.379–0.447 |
DOSE | 0.591 | 0.012 | 0.568–0.614 | 0.515 | 0.015 | 0.485–0.546 |
BARC | 0.781 | 0.009 | 0.764–0.792 | 0.695 | 0.012 | 0.671–0.719 |