The effect of exacerbations on lung density in alpha-1 antitrypsin deficiency

Acute exacerbations of chronic obstructive pulmonary disease (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 alpha-1 antitrypsin deficiency.In apost hocanalysisof the RAPID 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.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 effectversusno AECOPD within 6 weeks (odds ratio: 5.707; 95% confidence interval: 3.375–9.652, p<0.0001).AECOPD result in higher or lower CT lung density estimates; the effect is greatest in the two weeks immediately after an AECOPD and persists for less than 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.