Rationale and Objectives
The progressive changes in lung morphology observed in cystic fibrosis (CF) can potentially affect the statistical distribution of computed tomography (CT) density values. This study aimed to characterize the lung CT density distributions by quantifying indices of the kurtosis and skewness of the lung density distribution and to compare these indices to radiologic scores and lung function parameters in children and young adults with CF.
Materials and Methods
CT scans and lung function of 26 patients with CF were retrospectively examined. The Bhalla radiologic scoring was performed separately, in random order, by two expert radiologists, blinded to the patient’s identity, age, clinical status, results of lung function tests, and the other paired observer’s score.
Results
Positive relations were evidenced between the log indices of lung density distribution kurtosis (iKurtosis) and the overall radiologic scores (RS) of both observers (R = 0.58; P < .001 vs RS1 and R = 0.71; P < .001 vs RS2). A similar relationship was evidenced with the log index of the degree of distribution asymmetry (iSkewness; R = 0.62; P < .001 vs RS1 and R = 0.62; P < .001 vs RS2). Log-iKurtosis and log-iSkewness were related to FEV1 (R = −0.56; P < 10 −5 and R = −0.55; P < 10 −5 ) and to residual volume (R = 0.40; P < .001 and R = 0.45; P < .001, respectively). Both radiologic scores showed significant relation with lung function. The correlation between RS1 and RS2 was excellent (R = 0.93), with a Cohen weighted kappa of 0.43.
Conclusions
Characteristic indices of lung CT density distribution are correlated to lung function and radiologic scores in patients with CF and merit further evaluation as part of more comprehensive automated methods for quantifying CF lung CT data.
Advances in Knowledge
Automatically calculated indices used to quantify the sharpness of the lung computed tomography density distribution peak (kurtosis) and the degree of distribution asymmetry (skewness) show significant relations with both lung function and the radiologic score of Bhalla et al. (eg, log kurtosis index: R = 0.56; P < 10 −5 vs 1-second forced expiratory volume; R = 0.58; P < .001 vs total score of observer 1; R = 0.71; P < .001 vs observer 2) in patients with cystic fibrosis.
Introduction
Cystic fibrosis (CF), the most frequent autosomal recessive disease in Caucasians, leads to inflammatory changes in the airways and lung parenchyma due to chronic bacterial infection. Life expectancy in this disease remains severely compromised due to respiratory complications. Lung function tests (LFTs) remain the gold standard for monitoring the progression of respiratory disease in children with CF. High-resolution computed tomography (CT) is also used on a periodic basis in some centers to follow-up the progression of structural changes due to CF lung disease. Previous investigations have demonstrated that radiologic scores allowing semiquantitative assessment of various structural lung changes are significantly correlated to lung functional parameters . Some studies have suggested that changes in CT radiologic scores may be detected earlier than those in LFTs as they provide a more sensitive outcome measurement in patients with CF . However, the routine use of CT scoring has some drawbacks as it is time consuming and observer dependent . Moreover, interobserver agreement is often poor and, at best, moderate .
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Subjects and methods
Study Population
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Table 1
Patient Characteristics, Mean Values of Lung Function, and Radiologic Parameters and Scores
CT1 CT2 CT3 CT4P Value age (mean), years 9.9 10.6 12.3 12.9 range (minimum–maximum) 4.0–16.5 5.0–17.5 6.6–18.5 6.9–19.5 N 19 26 23 23 Gender (M/F) (7/14) (11/15) (11/13) (10/13) Time from CT1, years 0 1.0 ± 0.2 1.9 ± 0.4 2.9 ± 0.4 FEV1 (% pred) 88.3 ± 28.7 88.9 ± 28.1 83.9 ± 27.1 81.8 ± 26.8 .040 FVC (% pred) 89.6 ± 24.0 91.3 ± 23.5 90.6 ± 21.9 89.4 ± 22.5 .869 FEV1/FVC (% pred) 98.1 ± 10.3 95.9 ± 10.8 91.7 ± 12.1 89.7 ± 13.8 .011 PEF (% pred) 89.8 ± 22.6 86.4 ± 23.3 82.4 ± 30.1 82.4 ± 27.6 .253 FEF25–75 (% pred) 77.7 ± 38.1 74.7 ± 40.8 64.3 ± 42.3 63.2 ± 38.1 .003 Raw (% pred) 178.4 ± 63.7 225.3 ± 89.1 232.0 ± 123.9 230.2 ± 119.8 .005 RV (% pred) 123.0 ± 60.4 154.3 ± 62.1 164.7 ± 61.4 137.8 ± 64.0 .001 TLC (% pred) 99.3 ± 23.1 101.2 ± 18.9 99.9 ± 20.3 98.4 ± 15.3 .714 TcSaO 2 (%) 97.0 ± 1.6 97.0 ± 1.3 97.6 ± 1.5 97.6 ± 1.3 .062 RS1 6.8 ± 5.4 7.2 ± 6.7 7.8 ± 6.63 8.2 ± 6.5 .036 RS2 7.8 ± 6.2 8.0 ± 6.6 8.8 ± 7.03 9.2 ± 6.67 .030 MLA (HU) −787.7 ± 95.7 −808.4 ± 70.8 −818.6 ± 57.8 −809.2 ± 71.4 .326 iSkewness 0.79 ± 0.19 0.83 ± 0.27 0.83 ± 0.26 0.79 ± 0.18 .403 iKurtosis 1.21 ± 0.67 1.42 ± 1.37 1.41 ± 1.27 1.20 ± 0.66 .135
CT, computed tomography; FEF25–75, mean forced expiratory flow between 25% and 75% of forced vital capacity; FEV1, forced expiratory volume in 1 second (expressed as percent predicted value [% pred]); FVC, forced vital capacity; HU, Hounsfield units; iKurtosis, index of the lung density distribution kurtosis; iSkewness, index of the lung density distribution skewness; MLA, mean lung attenuation in Hounsfield units; PEF, peak expiratory flow; Raw, airway resistance; RS1, RS2, total radiologic scores provided by each observer; RV, residual volume; TcSaO 2 , transcutaneous oxygen saturation; TLC, total lung capacity.
Data are mean ± standard deviation.
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CT Imaging
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Radiologic Evaluation
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CT Density Distribution Analysis
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Lung Function
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Statistical Analysis
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Results
Study Population
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Lung Function, Radiologic Score, and Indices of Lung Density Distribution Skewness and Kurtosis
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Table 2
Correlation Between Total Radiologic Scores and Indices of the Lung Density Distribution Versus Lung Function Parameters
FEV1 FVC FEV1/FVC PEF FEF25–75 RV TLC TcSaO 2 RS1 R −0.64 −0.56 −0.52 −0.36 −0.50 0.31 −0.24 −0.44 CI (−0.75 to −0.48) (−0.69 to −0.39) (−0.66 to −0.33) (−0.54 to −0.15) (−0.65 to −0.32) (0.08 to 0.50) (−0.45 to −0.01) (−0.62 to −0.21)P value <10 −5 <10 −5 <10 −5 <0.01 <10 −5 .009 .039 <.001 RS2 R −0.70 −0.64 −0.52 −0.41 −0.57 0.39 −0.28 −0.44 CI (−0.80 to −0.57) (−0.75 to −0.48) (−0.67 to −0.34) (−0.58 to −0.21) (−0.70 to −0.40) (0.18 to 0.57) (−0.48 to −0.06) (−0.62 to −0.21)P value <10 −12 <10 −8 <10 −5 <.001 <10 −5 <.001 .016 <.001 Log (iSkewness) R −0.55 −0.53 −0.43 −0.49 −0.46 0.45 −0.21 −0.33 CI (−0.69 to −0.37) (−0.67 to −0.35) (−0.60 to −0.23) (−0.64 to −0.30) (−0.61 to −0.26) (0.24 to 0.62) (−0.42 to 0.03) (−0.54 to −0.08)P value <10 −5 <10 −5 <.001 <10 −4 <10 −4 <.001 .081 .01 Log (iKurtosis) R −0.56 −0.55 −0.42 −0.46 −0.45 0.40 −0.24 −0.46 CI (−0.70 to −0.39) (−0.68 to −0.37) (−0.59 to −0.22) (−0.62 to −0.27) (−0.61 to −0.26) (0.18 to 0.58) (−0.45 to 0.01) (−0.62 to −0.25)P value <10 −5 <10 −5 <.001 <10 −4 <10 −4 <.001 .044 <.001
CI, confidence interval; FEF25–75, mean forced expiratory flow between 25% and 75% of forced vital capacity; FEV1, forced expiratory volume in 1 second (expressed as percent predicted value [% pred]); FVC, forced vital capacity; iKurtosis, index of the lung density distribution kurtosis; iSkewness, index of the lung density distribution skewness; PEF, peak expiratory flow; R, Pearson correlation coefficient; RS1, RS2, overall radiologic scores provided by each observer; RV, residual volume; TcSaO 2 , transcutaneous oxygen saturation; TLC, total lung capacity.
Pearson correlation coefficients and significance ( P value) between overall radiologic scores from each observer (RS1, RS2, respectively), log-transformed indices of the lung density distribution skewness and kurtosis (iSkewness and iKurtosis, respectively) versus lung function parameters.
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Interobserver Agreement
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Table 3
Cohen Weighted Kappa of Individual Score Criteria and of the Overall Score
Individual Score Criteria Cohen Weighted Kappa_n_ 94 Severity of bronchiectasis 0.66 Extent of bronchiectasis 0.74 Peribronchial thickening 0.34 Extent of mucous plugging 0.68 Sacculation or abscesses 0.41 Generations of bronchial divisions involved 0.87 Number of bullae 0.51 Air trapping 0.43 Collapse/consolidation 0.56 Total score 0.45
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Discussion
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Acknowledgments
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