Abstract
Objectives
The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF).
Methods
Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores.
Results
From the most severe zones identified at baseline, QLF scores decreased by 2.6% in the cyclophosphamide group, whereas they increased by 9.1% in the placebo group, leading to ~12% difference (p = 0.0027). Between-treatment difference in whole lung QLF was ~5% (p = 0.0190). Significant associations were observed between changes in QLF and FVC (r = −0.33), dyspnea score (r = −0.29), and consensus visual score (p = 0.0001).
Conclusions
QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease.
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Acknowledgements
Supported by Public Health Service grants from the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases; cyclophosphamide (Cytoxan) was supplied by Bristol-Myers Squibb.
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Appendix
Appendix
Bland-Altman plot of quantitative lung fibrosis (QLF) score that was calculated repeatedly using a random sampling technique from 4 by 4 grid. a Mean difference was −0.008% (±0.36). The two dashed lines are 0.72% and −0.72%. For the outlying point where the difference was close to −2%, the patient had severe disease, with QLF score on the 1st run of 76.68% and 74.71% on the 2nd run. b Mean difference was 0.008% (±0.072). The two dashed lines are 0.14% and −0.14%. In Bland Altman plots, two boundaries are ±0.72% from the most severe zones and ±0.14% from the whole lung, indicating the small variation from a sampling technique from the 4 by 4 grid in the classifier model. Differences in QLF score greater than potential variation due to random sampling were demonstrated in 93% subjects (77/83) in the most severe zone at baseline and in 96% subjects (80/83) in the whole lung.
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Kim, H.J., Brown, M.S., Elashoff, R. et al. Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide. Eur Radiol 21, 2455–2465 (2011). https://doi.org/10.1007/s00330-011-2223-2
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DOI: https://doi.org/10.1007/s00330-011-2223-2