The effect of exacerbations on lung density in α1-antitrypsin deficiency.

Background: Acute exacerbations of COPD (AECOPD) have unclear impacts on emphysema measurement using computed tomography (CT)-derived 15th percentile lung density (PD15). The aim of this study was to assess the influence of AECOPD on PD15 lung density in α1-antitrypsin deficiency. Methods: In a post hoc analysis of the RAPID (Randomised Trial of Augmentation Therapy in α1-Proteinase Inhibitor Deficiency) trial, raw marginal residuals of PD15 (measured - predicted) were determined by fitting a regression line to individual patient CT data. These deviations from the expected slope were compared by age, sex, baseline forced expiratory volume in 1 s, diffusing capacity of the lungs for carbon monoxide % predicted and PD15, inhaled corticosteroid use and treatment group. Results: Positive and negative residuals (reflecting higher or lower lung density than predicted from regression) were observed, which declined in magnitude over time following AECOPD events. Logistic regression confirmed a limited effect of patient characteristics on the absolute size of residuals, whereas AECOPD within 6 weeks of CT had a notable effect versus no AECOPD within 6 weeks (OR 5.707, 95% CI 3.375-9.652; p<0.0001). Conclusion: AECOPD result in higher or lower CT lung density estimates; the effect is greatest in the 2 weeks immediately after an AECOPD and persists for <6 weeks. Patient characteristics were less relevant than AECOPD within 6 weeks, supporting the reliability of PD15 as a measure of lung density. An exacerbation-free period prior to CT scan is advisable to reduce signal-to-noise ratio in future clinical trials.