Acute exacerbations of chronic obstructive pulmonary disease (COPD) may affect emphysema measurements obtained using computed tomography (CT)-derived 15th percentile lung density (PD15) by temporarily raising or lowering it in patients with alpha-1 antitrypsin deficiency (AATD), although this impact is minimal, according to a study published in ERJ Open Research.

AATD is characterized by early-onset emphysema; however, alpha-1 antitrypsin (AAT) supplementation may slow emphysema progression. Emphysema progression is typically measured in terms of lung density. More specifically, some scientists measure lung density using CT-derived PD15, which provides a uniform method of tracking emphysema progression. 

Importantly, this measurement method correlates with quality of life and other lung function parameters in patients with AATD. Arguably, CT-derived PD15 is superior to traditional pulmonary function tests in measuring emphysema, given that pulmonary function tests do not detect emphysema until the disease has progressed to a moderate or severe stage. 

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While CT-derived PD15 has important clinical implications, there are questions regarding whether a recent acute exacerbation of COPD might affect measurements. This is particularly pertinent among patients with AATD who also have COPD, given that acute exacerbations are common. The authors of the study hence sought to understand if acute exacerbations of COPD could induce changes in lung density estimates in the short term. 

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The research team used data from the RAPID trial program—a randomized, double-blinded, placebo-controlled clinical trial assessing lung capacity among patients who received AAT infusions compared to that of the control group. Researchers collected information regarding acute exacerbations of COPD experienced during the study period (as defined according to the Anthonisen criteria). 

The research team then sought to compare the CT-derived PD15 results of patients who experienced acute exacerbations of COPD (within 6 weeks prior to measurement) and patients who did not. Using statistical analysis, the research team was able to identify if acute exacerbations of COPD impacted lung density estimates. 

The authors of the study found that acute exacerbations of COPD did impact CT-derived PD15 estimates in that they could artificially raise or lower them. This is because acute exacerbations may increase lung density via edema/cellular infiltrate or decrease it via airway obstruction leading to hyperinflation. Nonetheless, the impact is relatively minimal. 

“A 6-week post-exacerbation period would represent a conservative approach to obtain reliable data for determining emphysema progression in future clinical trials to minimize variability in CT lung density outcomes,” the authors recommended. 


Strange C, McElvaney NG, Vogelmeier CF, et al. The effect of exacerbations on lung density in α1-antitrypsin deficiency. ERJ Open Res. 2023;9(2):00457-2022. doi:10.1183/23120541.00457-2022