Per cent low attenuation volume and fractal dimension of low attenuation clusters on CT predict different long-term outcomes in COPD

Background Fractal dimension (D) characterises the size distribution of low attenuation clusters on CT and assesses the spatial heterogeneity of emphysema that per cent low attenuation volume (%LAV) cannot detect. This study tested the hypothesis that %LAV and D have different roles in predicting decline in FEV1, exacerbation and mortality in patients with COPD. Methods Chest inspiratory CT scans in the baseline and longitudinal follow-up records for FEV1, exacerbation and mortality prospectively collected over 10 years in the Hokkaido COPD Cohort Study were examined (n=96). The associations between CT measures and long-term outcomes were replicated in the Kyoto University cohort (n=130). Results In the Hokkaido COPD cohort, higher %LAV, but not D, was associated with a greater decline in FEV1 and 10-year mortality, whereas lower D, but not %LAV, was associated with shorter time to first exacerbation. Multivariable analysis for the Kyoto University cohort confirmed that lower D at baseline was independently associated with shorter time to first exacerbation and that higher LAV% was independently associated with increased mortality after adjusting for age, height, weight, FEV1 and smoking status. Conclusion These well-established cohorts clarify the different prognostic roles of %LAV and D, whereby lower D is associated with a higher risk of exacerbation and higher %LAV is associated with a rapid decline in lung function and long-term mortality. Combination of %LAV and fractal D may identify COPD subgroups at high risk of a poor clinical outcome more sensitively.