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

Charlie Strange; N Gerard McElvaney; Claus F Vogelmeier; Marcos Marin-Galiano; Michaela Buch-Haensel; Xiang Zhang; Younan Chen; Oliver Vit; Marion Wencker; Kenneth R Chapman

doi:10.1183/23120541.00457-2022

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

ERJ Open Res. 2023 Mar 13;9(2):00457-2022. doi: 10.1183/23120541.00457-2022. eCollection 2023 Mar.

Authors

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA.
² Irish Centre for Genetic Lung Disease, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.
³ Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany.
⁴ M.A.R.C.O. GmbH & Co. KG Institute for Clinical Research and Statistics, Düsseldorf, Germany.
⁵ Global Medical Affairs Respiratory, CSL Behring, Marburg, Germany.
⁶ Biostatistics, CSL Behring, King of Prussia, PA, USA.
⁷ Clinical Research and Development, CSL Behring, Bern, Switzerland.
⁸ Conresp, Loerzweiler, Germany.
⁹ Department of Medicine, University of Toronto, Toronto, ON, Canada.

Abstract

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.