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Rationale: Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.e. Agatston scoring requires EKG-gated cardiac CT imaging., Objective: To determine if the assessment of CAC using non-EKG-gated chest CT and the Weston scoring system is a useful surrogate for Agatston scores in HIV-infected and HIV-uninfected individuals., Methods and Measurements: CAC was assessed by both the Weston and Agatston score in 108 men enrolled in the Multicenter AIDS Cohort Study., Results: Participants were 55.2 (IQR 50.4; 59.9) years old and 62 (57.4%) were seropositive for HIV. Inter-observer agreement (rs = 0.94, κ = 90.0%, p<0.001, n = 21) and intra-observer agreement (rs = 0.95, κ = 95.2%, p<0.001, n = 97) for category of Weston score were excellent. Weston scores were associated with similar CAD risk factors as Agatston scores (age, race, HDL cholesterol level, all p<0.05) in our cohort. There was excellent correlation (rs = 0.92, p<0.001) and agreement (κw = 0.77, p<0.001) between Weston and Agatston scores., Conclusions: This study is the first to examine calcium scoring using chest CT in HIV-infected individuals and to independently validate the Weston score as a surrogate for the Agatston score. In clinical or research settings where EKG-gated cardiac CT is not feasible for the assessment of coronary calcium, Weston scoring by using chest CT should be considered.

Background: Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals., Methods: Clinical, pulmonary function, and radiographic data were analyzed for 164 individuals from the University of Pittsburgh's HIV Lung Research Center cohort. Chest CT scans were used to quantify emphysema and compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic vertebrae. The association between mean HU attenuation values across the three vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid use, viral load, CD4 count, and forced expiratory volume in the first second (FEV1) was assessed by univariate and multivariate analyses., Results: In univariate analysis, mean HU attenuation decreased with increasing age (p<0.001), pack years (p = 0.047), and percent emphysema (p<0.001). In a multivariable model, including pack years, age, sex, ART and steroid use, greater emphysema was independently associated with this surrogate marker of BMD in HIV-infected individuals (p = 0.034)., Conclusions: The association of emphysema with thoracic bone attenuation in HIV-infected individuals is consistent with previous reports in non-HIV infected smokers. These findings suggest that emphysema should be considered a potential marker of osteoporosis risk in HIV-infected individuals.

Objectives: To investigate the association between emphysema heterogeneity in spatial distribution, pulmonary function and disease severity., Methods and Materials: We ascertained a dataset of anonymized Computed Tomography (CT) examinations acquired on 565 participants in a COPD study. Subjects with chronic bronchitis (CB) and/or bronchodilator response were excluded resulting in 190 cases without COPD and 160 cases with COPD. Low attenuations areas (LAAs) (≤ 950 Hounsfield Unit (HU)) were identified and quantified at the level of individual lobes. Emphysema heterogeneity was defined in a manner that ranged in value from -100% to 100%. The association between emphysema heterogeneity and pulmonary function measures (e.g., FEV1% predicted, RV/TLC, and DLco% predicted) adjusted for age, sex, and smoking history (pack-years) was assessed using multiple linear regression analysis., Results: The majority (128/160) of the subjects with COPD had a heterogeneity greater than zero. After adjusting for age, gender, smoking history, and extent of emphysema, heterogeneity in depicted disease in upper lobe dominant cases was positively associated with pulmonary function measures, such as FEV1 Predicted (p<.001) and FEV1/FVC (p<.001), as well as disease severity (p<0.05). We found a negative association between HI% , RV/TLC (p<0.001), and DLco% (albeit not a statistically significant one, p = 0.06) in this group of patients., Conclusion: Subjects with more homogeneous distribution of emphysema and/or lower lung dominant emphysema tend to have worse pulmonary function.

Purpose: To investigate whether the integrity (completeness) of pulmonary fissures affects pulmonary function in patients with chronic obstructive pulmonary disease (COPD)., Materials and Methods: A dataset consisting of 573 CT exams acquired on different subjects was collected from a COPD study. According to the global initiative for chronic obstructive lung disease (GOLD) criteria, these subjects (examinations) were classified into five different subgroups, namely non-COPD (222 subjects), GOLD-I (83 subjects), GOLD-II (141 subjects), GOLD-III (63 subjects), and GOLD-IV (64 subjects), in terms of disease severity. An available computer tool was used to aid in an objective and efficient quantification of fissure integrity. The correlations between fissure integrity, and pulmonary functions (e.g., FEV1, and FEV1/FVC) and COPD severity were assessed using Pearson and Spearman's correlation coefficients, respectively., Results: For the five sub-groups ranging from non-COPD to GOLD-IV, the average integrities of the right oblique fissure (ROF) were 81.8%, 82.4%, 81.8%, 82.8%, and 80.2%, respectively; the average integrities of the right horizontal fissure (RHF) were 62.6%, 61.8%, 62.1%, 62.2%, and 62.3%, respectively; the average integrities of the left oblique fissure (LOF) were 82.0%, 83.2%, 81.7%, 82.0%, and 78.4%, respectively; and the average integrities of all fissures in the entire lung were 78.0%, 78.6%, 78.1%, 78.5%, and 76.4%, respectively. Their Pearson correlation coefficients with FEV1 and FE1/FVC range from 0.027 to 0.248 with p values larger than 0.05. Their Spearman correlation coefficients with COPD severity except GOLD-IV range from -0.013 to -0.073 with p values larger than 0.08., Conclusion: There is no significant difference in fissure integrity for patients with different levels of disease severity, suggesting that the development of COPD does not change the completeness of pulmonary fissures and incomplete fissures alone may not contribute to the collateral ventilation.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD., Methodology/principal Findings: Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1%) and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status., Conclusions/significance: Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies.