Background
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Aim 1: We hypothesize that a distinct set of predictors are associated with PRISm status and examine the epidemiological, functional, and radiographic predictors of PRISm status relative to control and COPD subjects.
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Aim 2: We hypothesize that genetic variants may contribute to the development of PRISm among current and former smokers and explore the associations between common genetic variants and PRISm status relative to control subjects.
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Aim 3: We hypothesize that subgroups exist within the PRISm cohort and explore the utility of unbiased machine learning approaches in identifying potentially pathobiologically distinct groups within PRISm.
Materials and methods
Study population
Variable definitions
Aim 1: Epidemiological analysis
Aim 2: Genetic analysis
Aim 3: Unsupervised cluster analysis to identify potential subgroups within PRISm
Results
Aim 1: Epidemiological, functional, and radiographic predictors of PRISm status
Control subjects | PRISm | COPD | |
---|---|---|---|
n | 4388 | 1257 | 3690 |
Age | 56.7 (8.4)* | 57.2 (8.2) | 63.4 (8.5)* |
Sex (% Male) | 52.9* | 46.1 | 55.6* |
African American | 41.2 | 43.1 | 22.7* |
Current smoker | 59.7* | 63.8 | 40.7* |
Pack-years | 37.2 (20.2)* | 42.7 (24.2) | 53.0 (27.5)* |
Body Mass Index | 28.9 (5.8)* | 31.8 (7.3) | 28.1 (6.3)* |
FEV1% predicted | 97.5 (11.5)* | 70.2 (8.4) | 50.2 (18.0)* |
FVC% predicted | 96.6 (11.9)* | 71.5 (9.1) | 76.3 (17.3)* |
FEV1/FVC | 0.79 (0.05)* | 0.77 (0.05) | 0.50 (0.13)* |
Bronchodilator Responsiveness† | 10.0* | 13.7 | 36.6* |
Total Lung CapacityCT% predicted | 92.3 (14.6)* | 79.9 (13.5) | 101.5 (17.1)* |
Segmental wall area percentage | 60.1 (2.9)* | 62.5 (3.1) | 62.9 (3.1)* |
Percent emphysema (% LAA-950insp) | 2.0 (2.5)* | 1.4 (2.5) | 13.0 (12.8)* |
Percent gas trapping (% LAA-856exp) | 11.0 (9.7) | 10.4 (9.1) | 39.2 (20.8)* |
Pi10 | 3.65 (0.11)* | 3.73 (0.14) | 3.72 (0.14)* |
6 minute walk distance (feet) | 1491.5 (350.7)* | 1266.6 (366.9) | 1174.8 (397.0)* |
MMRC‡ Dyspnea score | 0.8 (1.2)* | 1.5 (1.5) | 2.1 (1.4)* |
Resting O2 saturation | 97.1 (2.0)* | 96.5 (2.5) | 94.7 (3.6)* |
Chronic bronchitis | 12.6* | 17.8 | 28.2* |
Short acting beta-agonist use | 12.0* | 28.1 | 65.7* |
Long acting beta-agonist use | 4.4* | 13.3 | 49.1* |
Inhaled corticosteroid use | 5.5* | 16.4 | 51.2* |
Oral corticosteroid use | 0.5* | 2 | 5.9* |
Congestive heart failure | 1.3* | 4.6 | 5.4 |
Coronary artery disease | 7.5* | 13.5 | 16.5* |
Diabetes mellitus | 11.6* | 21.6 | 13.1* |
Hypertension | 36.3* | 49.1 | 50.6 |
Hyperlipidemia | 34.3* | 42.5 | 41.4 |
History of blood clot | 2.8* | 5.2 | 5.7 |
Peripheral vascular disease | 1.3* | 2.7 | 3.4 |
History of stroke | 1.6* | 3.5 | 3.6 |
Gastrointestinal reflux disease | 20.3* | 25.9 | 30.3* |
History of compression fracture | 3.4* | 5.4 | 6.2 |
Currently employed | 37.3* | 28.9 | 25.3* |
Physician-diagnosed asthma | 11.4* | 21.1 | 24.6* |
Panel (a) – significant predictors in fixed threshold- defined cohorts | Panel (b) – significant predictors in LLN defined cohorts | ||
---|---|---|---|
Predictor | OR [95% CI] | Predictor | OR [95% CI] |
Pack-years | 1.008 [1.005-1.012] | Pack-years | 1.008 [1.004-1.012] |
Resting oxygen saturation | 0.907 [0.875-0.940] | Resting oxygen saturation | 0.931 [0.897-0.966] |
6 minute walk distance (per 100 feet) | 0.948 [0.926-0.971] | 6 minute walk distance (per 100 feet) | 0.953 [0.929-0.977] |
MMRC Dyspnea score | 1.226 [1.153-1.304] | MMRC Dyspnea score | 1.192 [1.116-1.273] |
Percent emphysema | 1.055 [1.020-1.091] | Percent emphysema | 1.061 [1.029-1.094] |
Total lung capacity% predicted | 0.949 [0.943-0.955] | Total lung capacity% predicted | 0.948 [0.942-0.954] |
Segmental wall area percent | 1.203 [1.168-1.238] | Segmental wall area percent | 1.190 [1.154-1.227] |
Peripheral vascular disease | 1.777 [1.038-3.043] | Peripheral vascular disease | 2.038 [1.254-3.314] |
Physician-diagnosed asthma | 1.391 [1.126-1.718] | Physician-diagnosed asthma | 1.485 [1.193-1.848] |
Age | 1.025 [1.014-1.035] | Diabetes Mellitus | 1.372 [1.111-1.695] |
Sex (male) | 0.705 [0.598-0.833] | African American race | 0.266 [0.216-0.328] |
Hyperlipidemia | 1.216 [1.031-1.433] | Body mass index | 1.026 [1.012-1.040] |
Current smoking | 1.620 [1.337-1.962] | ||
Coronary artery disease | 1.370 [1.002-1.874] |
Aim 2: Genetic associations between common genetic variants and PRISm status
Aim 3: Unsupervised cluster analysis to identify potential subgroups within PRISm subjects
(a) Non-Hispanic White subjects | (b) African American subjects | |||||
---|---|---|---|---|---|---|
Feature | Cluster 1 | Cluster 2 | Cluster 3 | Cluster 1 | Cluster 2 | Cluster 3 |
n | 227 | 291 | 137 | 171 | 167 | 142 |
Age | 57.9 (8.2) | 62.2 (8.1) | 59.2 (9.4) | 52.9 (5.8) | 54.6 (6.1) | 52.6 (5.3) |
Sex (% male) | 34.8 | 45.7 | 51.1 | 47.4 | 56.9 | 45.1 |
Body Mass Index | 30.9 (6.4) | 30.4 (6.3) | 36.2 (7.1) | 32.0 (6.8) | 27.3 (6.0) | 35.7 (8.4) |
Current smoker | 53.3 | 43.6 | 49.6 | 84.8 | 83.8 | 80.3 |
Pack-years | 42.8 (22.6) | 46.6 (24.5) | 50.9 (29.7) | 35.6 (18.5) | 39.6 (24.0) | 38.1 (21.4) |
FEV1% predicted | 74.2 (4.3) | 73.4 (5.3) | 60.5 (7.8) | 73.3 (5.1) | 72.7 (6.2) | 62.5 (8.9) |
FEV1/FVC | 0.80 (0.04) | 0.74 (0.03) | 0.74 (0.04) | 0.83 (0.04) | 0.74 (0.03) | 0.75 (0.03) |
FEF 25–75 | 2.21 (0.65) | 1.58 (0.47) | 1.41 (0.47) | 2.38 (0.71) | 1.58 (0.50) | 1.42 (0.43) |
Resting O2 saturation | 96.4(2.3) | 96.3 (2.1) | 95.2 (2.9) | 97.1 (2.2) | 97.1 (2.3) | 96.6 (2.7) |
TLCCT*% predicted | 79.4 (9.8) | 90.4 (10.7) | 74.4 (12.7) | 71.0 (11.1) | 83.6 (12.3) | 71.6 (12.3) |
Percent emphysema | 0.6 (0.7) | 2.6 (2.7) | 0.9 (1.1) | 0.5 (0.6) | 2.7 (4.5) | 0.8 (1.0) |
Segmental Wall Area% | 62.0 (2.5) | 60.6 (2.3) | 64.7 (2.6) | 62.4 (2.8) | 61.9 (2.9) | 65.7 (2.5) |
Percent Gas Trapping | 6.5 (6.0) | 13.5 (8.6) | 9.8 (7.1) | 7.2 (7.3) | 14.8 (13.5) | 9.4 (7.5) |
Diabetes Mellitus | 18.5 | 14.4 | 36.5 | 22.8 | 15.6 | 27.5 |
Hypertension | 36.6 | 47.4 | 56.2 | 53.8 | 51.5 | 54.2 |
Hyperlipidemia | 45.4 | 58.8 | 59.9 | 31.0 | 24.0 | 29.6 |
Chronic bronchitis | 16.3 | 15.8 | 32.9 | 11.1 | 19.2 | 14.8 |
Bronchodilator Response† | 11.5 | 13.5 | 22.2 | 11.4 | 9.2 | 20.1 |
MMRC‡ | 1.154 (1.32) | 1.13 (1.29) | 1.95 (1.50) | 1.63 (1.53) | 1.57 (1.47) | 1.96 (1.53) |
6 minute walk distance | 1386.5 (347.1) | 1392.2 (320.4) | 1132.6 (390.2) | 1219.9 (349.4) | 1279.5 (338.1) | 1099.2 (342.1) |