Quantitative Emphysema on Low-Dose CT Imaging of the Chest and Risk of Lung Cancer and Airflow Obstruction: An Analysis of the National Lung Screening Trial.

BACKGROUND: Lung cancer risk prediction models do not routinely incorporate imaging metrics available on low-dose CT (LDCT) imaging of the chest ordered for lung cancer screening. RESEARCH QUESTION: What is the association between quantitative emphysema measured on LDCT imaging and lung cancer incidence and mortality, all-cause mortality, and airflow obstruction in individuals who currently or formerly smoked and are undergoing lung cancer screening? STUDY DESIGN AND METHODS: In 7,262 participants in the CT arm of the National Lung Screening Trial, percent low attenuation area (%LAA) was defined as the percentage of lung volume with voxels less than -950 Hounsfield units on the baseline examination. Multivariable Cox proportional hazards models, adjusting for competing risks where appropriate, were built to test for association between %LAA and lung cancer incidence, lung cancer mortality, and all-cause mortality with censoring at 6 years. In addition, multivariable logistic regression models were built to test the cross-sectional association between %LAA and airflow obstruction on spirometry, which was available in 2,700 participants. RESULTS: The median %LAA was 0.8% (interquartile range, 0.2%-2.7%). Every 1% increase in %LAA was independently associated with higher hazards of lung cancer incidence (hazard ratio [HR], 1.02; 95% CI, 1.01-1.03; P = .004), lung cancer mortality (HR, 1.02; 95% CI, 1.00-1.05; P = .045), and all-cause mortality (HR, 1.01; 95% CI, 1.00-1.03; P = .042). Among participants with spirometry, 892 had airflow obstruction. The likelihood of airflow obstruction increased with every 1% increase in %LAA (odds ratio, 1.07; 95% CI, 1.06-1.09; P < .001). A %LAA cutoff of 1% had the best discriminative accuracy for airflow obstruction in participants aged > 65 years. INTERPRETATION: Quantitative emphysema measured on LDCT imaging of the chest can be leveraged to improve lung cancer risk prediction and help diagnose COPD in individuals who currently or formerly smoked and are undergoing lung cancer screening.

Acute Late-Stage Myocarditis in the Crab-Eating Macaque Model of Hemorrhagic Smallpox.

Hemorrhagic smallpox, caused by variola virus (VARV), was a rare but nearly 100% lethal human disease manifestation. Hemorrhagic smallpox is frequently characterized by secondary bacterial infection, coagulopathy, and myocardial and subendocardial hemorrhages. Previous experiments have demonstrated that intravenous (IV) cowpox virus (CPXV) exposure of macaques mimics human hemorrhagic smallpox. The goal of this experiment was to further understand the onset, nature, and severity of cardiac pathology and how it may contribute to disease. The findings support an acute late-stage myocarditis with lymphohistiocytic infiltrates in the CPXV model of hemorrhagic smallpox.