Low Levels of Emphysema Burden on Low-Dose CT Scan and Spirometry-Based Obstructive Lung Disease: Joint Effects on...

The prognostic value of low levels of CT scan-defined emphysema and their interaction with obstructive lung disease (OLD) remains unclear.

Does emphysema, as defined by low-attenuation areas (LAA_-950) on CT scan, confer differential mortality risk according to the presence of airflow limitation?

We included 5,276 adults who underwent low-dose CT scan and spirometry between 2010 and 2019. Mortality was ascertained through linkage with national death records. Cox models estimated hazard ratios (HRs) for mortality according to LAA_-950 and OLD. Dose-response relationships were assessed using restricted cubic splines, and progression was evaluated among participants with low baseline emphysema.

Among 5,276 adults in a health-screening cohort, 66.3% were male and 47.2% had a history of smoking. Over a median follow-up of 12.9 years, LAA_-950 ≥ 1.5% alone (HR, 1.32; 95% CI, 0.85-2.06) and OLD alone (HR, 0.95; 95% CI, 0.50-1.80) were not associated with mortality. Their combination increased risk (HR, 3.10; 95% CI, 1.77-5.42; P for interaction = .04). A graded association between emphysema and mortality was observed only in individuals with OLD. In stratified analyses, emphysema was associated with mortality in people who have never smoked without OLD, whereas a joint effect was observed in people with a smoking history. Among participants with LAA_-950 < 1.5%, progression to LAA_-950 ≥ 1.5% increased mortality in those with OLD (HR, 3.97; 95% CI, 1.23-12.90), but not in those without OLD.

Our results show that low-level CT scan-defined emphysema was associated with higher all-cause mortality mainly when accompanied by spirometry-defined OLD. These findings suggest that low-level LAA_-950 may have greater prognostic relevance in the presence of airflow limitation.