Background
Methods
Human data and QCT imaging
Stratum 1 (Healthy) | Stratum 2 | Stratum 3 | Stratum 4 | P value | |
---|---|---|---|---|---|
N = 130 | N = 114 | N = 131 | N = 39 | ||
Demography | |||||
Age, yrs | 47.8 (16.9) | 53.7 (8.1) | 62 (8.1) | 62.6 (7.7) | < 0.0001 |
BMI, kg/m2 | 27.4 (5.5) | 28.4 (5.3) | 26.3 (4.8) | 23.8 (4.9) | < 0.0001 |
Gender, (Male/Female %) | 41.5/58.5 | 49.1/50.9 | 61.8/38.2 | 69.2/30.8 | 0.039 |
Race, Caucasian/ African American/ Other (%) | 71.5/16.2/12.3 | 45.6/48.2/6.1 | 77.1/19.1/3.8 | 71.8/20.5/7.7 | < 0.0001 |
Baseline lung functiona | |||||
FEV1% predicted | 100 (13) | 93 (14) | 64 (18) | 34 (7) | < 0.0001 |
FVC % predicted | 99 (11) | 98 (14) | 87 (19) | 67 (16) | < 0.0001 |
FEV1/FVC × 100 | 80 (7) | 75 (6) | 56 (8) | 40 (11) | < 0.0001 |
Maximal lung functionb | |||||
FEV1% predicted | 102 (11) | 99 (14) | 73 (16) | 40 (7) | < 0.0001 |
FVC % predicted | 99 (10) | 100 (13) | 96 (18) | 78 (17) | < 0.0001 |
FEV1/FVC × 100 | 82 (6) | 78 (5) | 58 (8) | 41 (11) | < 0.0001 |
Multiscale imaging-based variables
Clustering and statistical analysis
Results
Four clusters and imaging-based characteristics
Variable | Region | Wilk’s λ value | Cluster 1 (N = 96) | Cluster 2 (N = 45) | Cluster 3 (N = 88) | Cluster 4 (N = 55) | P value | Healthy subjects (N = 130) |
---|---|---|---|---|---|---|---|---|
fSAD% | Total | 0.28 | 4.6 (5.4) | 8.4 (8.2) | 12.3 (6.9) | 34.9 (7.9) | < 0.0001 | 4.4 (5.2) |
Jacobian | Total | 0.145 | 2.09 (0.266) | 1.496 (0.218) | 1.671 (0.168) | 1.353 (0.136) | < 0.0001 | 2.082 (0.41) |
βtissue | Total | 0.107 | 0.127 (0.02) | 0.162 (0.031) | 0.117 (0.017) | 0.095 (0.019) | < 0.0001 | 0.119 (0.027) |
WT* | sRML | 0.086 | 0.599 (0.036) | 0.615 (0.047) | 0.557 (0.035) | 0.563 (0.043) | < 0.0001 | 0.588 (0.047) |
ADI | RUL | 0.072 | 0.406 (0.078) | 0.314 (0.101) | 0.309 (0.079) | 0.22 (0.074) | < 0.0001 | 0.35 (0.093) |
Dh* | sLLL | 0.064 | 0.349 (0.034) | 0.322 (0.048) | 0.307 (0.036) | 0.289 (0.04) | < 0.0005 | 0.339 (0.041) |
Emph% | Total | 0.058 | 2.8 (3) | 2.4 (3) | 4.2 (4.5) | 13.5 (8.7) | < 0.0001 | 2.8 (3.8) |
ADI | Total | 0.054 | 0.467 (0.066) | 0.332 (0.086) | 0.378 (0.07) | 0.269 (0.073) | < 0.0001 | 0.429 (0.101) |
ΔVairF | LLL | 0.051 | 0.245 (0.031) | 0.207 (0.062) | 0.254 (0.041) | 0.273 (0.045) | < 0.0001 | 0.263 (0.037) |
Cr | LMB | 0.049 | 0.976 (0.009) | 0.965 (0.016) | 0.973 (0.012) | 0.962 (0.015) | < 0.0001 | 0.977 (0.011) |
Associations with demography and PFT
Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | P value | |
---|---|---|---|---|---|
N = 96 | N = 45 | N = 88 | N = 55 | ||
Demography | |||||
GOLD stages (%) (0/1/2/3/4) | 68/22/10/0/0 | 47/11/33/9/0 | 27/15/51/7/0 | 4/2/40/47/7 | < 0.0001 |
ABCD assessment (%) (A/B/C/D) | 37/47/1/14 | 25/52/0/22 | 35/49/0/16 | 10/51/0/39 | = 0.0005 |
Strata (%) (2/3/4) | 68/32/0 | 51/40/9 | 27/66/7 | 4/44/52 | < 0.0001 |
Gender (Female %) | 44 | 49 | 44 | 31 | 0.26 |
Race (White/Black/Others) | 60/32/7 | 36/58/7 | 72/26/2 | 80/15/5 | 0.0001 |
Age (yrs.) | 54.44 (8.01) | 56.76 (8.51) | 61.01 (8.24) | 64.47 (8.14) | < 0.0001 |
BMI (kg/m2) | 27.63 (4.7) | 31.1 (5.04) | 25.58 (4.76) | 23.65 (4.26) | < 0.0001 |
BODE index | 0.48 (0.9) | 1.4 (1.9) | 0.98 (1.1) | 2.94 (1.7) | < 0.0001 |
Pre-bronchodilator valuesa | |||||
FEV1% predicted | 0.91 (0.17) | 0.73 (0.22) | 0.68 (0.2) | 0.42 (0.17) | < 0.0001 |
FVC % predicted | 1.01 (0.15) | 0.86 (0.17) | 0.86 (0.18) | 0.74 (0.16) | < 0.0001 |
FEV1/FVC | 0.71 (0.09) | 0.66 (0.14) | 0.61 (0.1) | 0.43 (0.11) | < 0.0001 |
Post-bronchodilator valuesb | |||||
FEV1% predicted | 0.97 (0.16) | 0.8 (0.2) | 0.76 (0.18) | 0.49 (0.17) | < 0.0001 |
FVC % predicted | 1.04 (0.15) | 0.92 (0.16) | 0.93 (0.17) | 0.85 (0.16) | < 0.0001 |
FEV1/FVC | 0.74 (0.09) | 0.68 (0.13) | 0.63 (0.11) | 0.44 (0.12) | < 0.0001 |
Associations with symptoms and disease histories
Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | P value | |
---|---|---|---|---|---|
N = 96 | N = 45 | N = 88 | N = 55 | ||
Symptoms and disease History | |||||
History of pulmonary/vascular condition (%) | 19 | 13 | 24 | 23 | 0.53 |
Smoking pack-years at baseline | 41.79 (22.05) | 42.89 (18.7) | 47.06 (19.36) | 54.95 (21.03) | 0.0016 |
Chronic Bronchitis (%) | 16 | 20 | 20 | 39 | 0.016 |
Emphysema (%) | 17 | 20 | 25 | 55 | < 0.0001 |
COPD diagnosed at baseline (%) | 29 | 51 | 58 | 83 | < 0.0001 |
Chronic bronchitis diagnosed at baseline (%) | 21 | 33 | 28 | 41 | 0.079 |
Asthma (%) | 20 | 36 | 22 | 21 | 0.19 |
Wheezing and whistling in chest (%) | 60 | 62 | 66 | 89 | 0.002 |
Wheezing age (yrs.) (%) | 60 | 86 | 84 | 92 | 0.0003 |
Sleep Apnea at baseline (%) | 6 | 21 | 7 | 6 | 0.02 |
Shortness of breath during sleep (%) | 18 | 29 | 14 | 29 | 0.06 |
Coronary artery disease | 2 | 4 | 9 | 6 | 0.19 |
Diabetes (%) | 6 | 18 | 9 | 9 | 0.2 |
Heart attack (%) | 3 | 4 | 6 | 2 | 0.65 |
Congestive heart failure (%) | 3 | 0 | 1 | 0 | 0.33 |
Genetic effect | |||||
Father had COPD (%) | 19 | 13 | 23 | 22 | 0.61 |
Mother had COPD (%) | 17 | 13 | 19 | 9 | 0.39 |
CAT score, activity limitation and exacerbation histories
Cluster 1 | Cluster 2 | Cluster 3 | Cluster 4 | P value | |
---|---|---|---|---|---|
N = 92 | N = 45 | N = 87 | N = 55 | ||
Blood/serum biomarkers | |||||
RBC distribution width (%) | 14.25 (1.17) | 14.04 (0.87) | 13.63 (0.84) | 14.13 (1.19) | 0.0016 |
Total WBC count (N/μl) | 7153.15 (2290.62) | 7352.89 (2527.31) | 7109.77 (1954.51) | 7073.09 (2122.85) | 0.924 |
Neutrophils% (%) | 58.06 (9.52) | 58.24 (11.78) | 58.06 (9.65) | 61.14 (10.22) | 0.26 |
Lymphocyte% (%) | 31.35 (8.09) | 31.39 (10.45) | 30.81 (8.58) | 27.74 (9.53) | 0.088 |
Monocyte% (%) | 7.3 (2.5) | 7.46 (2.12) | 7.67 (2.18) | 7.85 (2.2) | 0.512 |
Eosinophils% (%) | 2.63 (1.64) | 2.29 (1.74) | 2.72 (1.75) | 2.61 (1.9) | 0.6 |
Basophils% (%) | 0.71 (0.61) | 0.52 (0.36) | 0.62 (0.54) | 0.68 (0.64) | 0.278 |
Baseline CAT scorea | |||||
13.17 (7.95) | 16.45 (9.54) | 13.78 (7.86) | 20.06 (7.86) | < 0.0001 | |
Exacerbations | |||||
Severeb | 0.2 (0.6) | 0.44 (1.62) | 0.31 (0.82) | 1.25 (2.27) | < 0.0001 |
Totalc | 0.49 (1.19) | 1.09 (3.39) | 0.92 (2.14) | 2.09 (2.91) | < 0.0001 |
Total at baselined | 0.25 (0.68) | 0.58 (1.39) | 0.22 (0.63) | 0.62 (0.99) | 0.011 |
Activity limitation | |||||
6-min walk distance (m) | 445.66 (91.31) | 386.64 (136.27) | 420.38 (71.19) | 385.16 (94.09) | 0.0003 |
Oxygen desaturation with 6-min walk (%) | 14 | 36 | 14 | 41 | < 0.0001 |
Cluster characteristics
Cluster 1: Relatively resistant smokers with preserved pulmonary function
Cluster 2: Airway-wall-thickening fSAD-dominant subjects with obesity and activity limitation
Cluster 3: Airway-wall-thinning fSAD-dominant subjects
Cluster 4: Severe emphysema-fSAD-mixed subjects with severe airway luminal narrowing and wall thinning
Discussion
Variable | Cluster 1 (N = 96) | Cluster 2 (N = 45) | Cluster 3 (N = 88) | Cluster 4 (N = 55) | P value |
---|---|---|---|---|---|
fSAD (U/L ratio) | 9.54 (14.04) | 5.1 (6.06) | 5.92 (6.64) | 1.63 (1.42) | < 0.0001 |
Emph (U/L ratio) | 2.14 (3.15) | 2.21 (2.36) | 2.52 (3.42) | 1.6 (1.85) | 0.389 |
fSAD/Emph (% Total) | 1.75 (1.67) | 5.91 (7.44) | 5.15 (4.16) | 4.60 (4.72) | < 0.0001 |