Figures
- FIGURE 1
Pulmonary 18F-fluorodeoxyglucose positron emission tomography/computed tomography fused image of participant in the study.
- FIGURE 2
Rate of 18F-fluorodeoxyglucose uptake measured using nKi as a marker of whole lung pulmonary inflammation in COPD groups, smokers and never-smokers. Data are presented as individual values together with median, first and third quartile values (boxes). A statistical difference was observed between COPD patients, alpha-1 antitrypsin deficiency (α1ATD) patients and smokers versus never-smokers as a control group.
- FIGURE 3
Scatterplot of plasma fibrinogen and whole lung nKi values for the whole cohort. Pearson correlation between 111 cases with both fibrinogen and nKi available, r=0.391, p<0.001. α1ATD: alpha-1 antitrypsin deficiency.
- FIGURE 4
Bland–Altman plot of the rate of 18F-fluorodeoxyglucose (FDG) uptake (nKi). These data were obtained from the baseline and follow-up FDG scans of COPD participants in the placebo arm. The interval between scans was ∼4 months. Horizontal lines show the mean difference and upper and lower limits (±1.96 standard deviation) of the mean difference between paired baseline and 4-month values.
- FIGURE 5
a) nKi values at baseline and 4 months for participants without an exacerbation in between these time-points (n=22). b) nKi values at baseline and 4 months for participants that experienced an exacerbation (n=10).
Tables
- TABLE 1
Demographics, spirometry and image data
COPD α1ATD-COPD Smokers Never-smokers Subjects n 84 11 12 10 Demographics Age years 68±8 62±8* 62±6* 69±7 Male % 67 73 58 83 BMI kg·m−2 25.9±3.9 25.0±3.3 23.1±2.3* 26.6±2.6 Current smoker n (%) 11 (13)*** 2 (17)*** 12 (100)*** 0 Pack-years smoked 45±25*** 19±11*** 37±19*** 0 LABA/LAMA/ICS n (%) 68 (81) 10 (91) Lung function FEV1 L 1.37±0.6*** 1.47±0.4*** 2.84±0.56 2.88±0.6 FEV1 % predicted 51±20*** 45±16*** 95±17 100±15 FEV1/FVC 0.45±0.15 0.36±0.10 0.79±0.08 0.77±0.06 Laboratory data Fibrinogen g·L−1 3.4±0.7* 3.1±0.6 2.8±0.6 2.7±0.5 hsCRP mg·L−1 5.2±7.0* 3.3±2.3* 2.1±1.4 1.2±0.6 White cell count ×109·L−1 6.54±1.83 7.01±2.72 7.28±2.02 5.84±1.31 Neutrophils ×109·L−1 4.43±3.6 4.68±2.47 4.53±1.45 3.63±1.11 Pulmonary image data Whole lung nKi mL·cm−3·min−1 0.0037±0.001* 0.0040±0.001* 0.0040±0.001* 0.0028±0.001 Perc15 HU −889±54*** −942±28*** Upper lung nKi mL·cm−3·min−1 0.0040±0.001** 0.0038±0.001* 0.0044±0.00** 0.0027±0.001 Perc15 HU −884±61* −922±34*** Middle lung nKi mL·cm−3·min−1 0.0037±0.001** 0.0042±0.001** 0.0041±0.001** 0.0027±0.001 Perc15 HU −889±52* −943±29*** Lower lung nKi mL·cm−3·min−1 0.0036±0.001 0.0038±0.001 0.0040±0.001 0.0032±0.001 Perc15 HU −880±49** −952±26*** Data are presented as mean±sd, unless otherwise stated. α1ATD: alpha-1 antitrypsin deficiency; BMI: body mass index; LABA: inhaled long-acting β-agonist; LAMA: long-acting muscarinic antagonist; ICS: inhaled corticosteroid; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; hsCRP: high sensitivity C-reactive protein; HU: Hounsfield units. ***: p<0.001; **: p<0.01; *: p<0.05 significant difference compared to never-smokers.
- TABLE 2
Correlations between rate of 18F-fluorodeoxyglucose uptake classified by lung regions in participants with COPD
Variable (x) Upper lung Middle lung Lower lung r sig r sig r sig Fibrinogen g·L−1 0.42 <0.001 0.38 <0.001 0.16 0.16 Log10hsCRP mg·L−1 0.31 0.005 0.31 0.005 0.09 0.41 White cell count ×109·L−1 0.24 0.04 0.25 0.03 0.17 0.14 Neutrophils ×109·L−1 0.31 0.005 0.29 0.009 0.19 0.10 FEV1 L −0.33 0.003 −0.18 0.10 0.02 0.89 FEV1 % predicted −0.26 0.02 −0.16 0.17 −0.04 0.74 6MWD m 0.28 0.01 −0.25 0.03 0.08 0.51 Perc15 score HU −0.35 0.004 −0.11 0.38 −0.04 0.76 Pearson's bivariate test used. Strength of correlation determined by r and significance (sig) by p-value. hsCRP: high sensitivity C-reactive protein, FEV1: forced expiratory volume in 1 s; 6MWD: 6-min walking distance.
- TABLE 3
Variables associated with whole lung pulmonary 18F-fluorodeoxyglucose uptake in participants with COPD assessed by regression analysis
Variable (x) Standardised beta coefficient Coefficient standard error Significance Fibrinogen g·L−1 0.30 0.01 0.02 Current smoking (yes/no) 0.20 0.00 0.07 FEV1 % predicted −0.12 0.00 0.37 Neutrophils ×109·L−1 0.10 0.00 0.41 Log10hsCRP mg·L−1 0.02 0.00 0.90 Dependent variable=whole lung 18F-fluorodeoxyglucose uptake (nKi, units mL·cm−3·min−1). Multivariable model, R=0.48, R2=0.23, adjusted R2=0.17. hsCRP: high sensitivity C-reactive protein, FEV1: forced expiratory volume in 1 s.
- TABLE 4
Clinical and imaging measurements for COPD subtypes defined by computed tomography#
ADE Confluent Moderate Mild Trace p-value¶ Subjects n (%) 22 (30%) 9 (12%) 10 (14%) 15 (20%) 15 (20%) FEV1 L 0.99±0.30 1.05±0.46 1.5±0.73 1.4±0.46 1.8±0.52 <0.001 FVC L 3.1±0.78 3.1±0.70 3.0±1.2 2.7±0.75 3.1±0.74 ns Smoker % 10 11 20 11 7 Smoking years 42±6 44±13 39±12 35±11 35±13 ns 6MWD m 343±104 335±145 375±98 377±81 478±115 <0.05 Perc15 HU −949±41 −918±18 −890±35 −865±24 −833±32 <0.001 nKi ×10−3 mL·cm−3·min−1 4.0±1.1 4.0±1.1 3.9±1.1 3.5±1.1 3.5±0.9 ns Data are presented as mean±sd, unless otherwise stated. ADE: advanced destructive emphysema; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; 6MWD: 6-min walking distance; ns: nonsignificant. #: only centrilobular emphysema subtypes are analysed; n=74 high-resolution computed tomography COPD scans analysed, three (4%) scans were panlobular emphysema so were not included in analysis; no scans were identified as paraseptal emphysema, airway disease or associated features noted. ¶: overall comparison across five subtypes.
Supplementary Material
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Supplementary material 00699-2020.supplement
