Centrilobular emphysema and coronary artery calcification: mediation analysis in the SPIROMICS cohort.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized to be mediated by systemic inflammation but this link has not been established. METHODS: We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC. RESULTS: FEV1/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p = 0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p = 0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV1/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC. CONCLUSIONS: The association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT01969344 .

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults. METHODS: We measured serum rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAAs; CT attenuation values between -600 and -250 Hounsfield units) on cardiac CT in 6736 community-dwelling US adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured interstitial lung abnormalities (ILAs) in 2907 full-lung CTs at 9.5-year median follow-up. We used generalised linear and additive models to examine associations between autoantibodies and both HAA and ILA, and tested for effect modification by smoking. RESULTS: In adjusted models, HAA increased by 0.49% (95% CI 0.11% to 0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50% to 1.40%) per RF IgA doubling. ILA prevalence increased by 11% (95% CI 3% to 20%) per RF IgA doubling. Smoking modified the associations of both RF IgM and anti-CCP with both HAA and ILA (interaction p values varied from 0.01 to 0.09). Among ever smokers, HAA increased by 0.81% (95% CI 0.33% to 1.30%) and ILA prevalence increased by 14% (95% CI 5% to 24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45% to 2.18%) and ILA prevalence increased by 13% (95% CI 2% to 24%) per anti-CCP doubling. Among never smokers, no meaningful associations were detected. CONCLUSIONS: RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Vascular abnormalities correlate with decreased soft tissue volumes in idiopathic clubfoot.

BACKGROUND: Lower extremity vascular anomalies have been described for patients with clubfoot but few imaging studies have investigated effects on soft tissues such as fat and muscle. To make these assessments we need noninvasive, noncontrast agents to more safely image children. QUESTIONS/PURPOSES: We describe a novel noninvasive imaging protocol to identify vascular and soft tissue abnormalities in the lower limbs of patients with clubfoot and determine whether these abnormalities are present in patients who had recurrent clubfoot. PATIENTS AND METHODS: Three-dimensional noncontrast-enhanced MR angiography was used to identify vascular, bone, and soft tissue abnormalities in patients with clubfoot. We determined whether these abnormalities were more common in patients who had experienced recurrent clubfoot. RESULTS: Four patients with isolated unilateral clubfoot had arterial anomalies in the clubfoot limb. All patients had less muscle volume in the affected limb, and nine of 11 patients (82%) had less subcutaneous fat, with a mean difference of 0.56 cm(3) ± 0.36 cm(3) (range, 0.08-1.12 cm(3)). Vascular anomalies and decreased fat and muscle volumes were present in all three patients with recurrent clubfoot. CONCLUSIONS: We found a high frequency of vascular and soft tissue anomalies in the affected limbs of patients with unilateral clubfoot that may correlate with response to treatment.

Luminal Plugging on Chest CT Scan: Association With Lung Function, Quality of Life, and COPD Clinical Phenotypes.

BACKGROUND: Mucous exudates occluding the lumen of small airways are associated with reduced lung function and mortality in subjects with COPD; however, luminal plugs in large airways have not been widely studied. We aimed to examine the associations of chest CT scan-identified luminal plugging with lung function, health-related quality of life, and COPD phenotypes. METHODS: We randomly selected 100 smokers without COPD and 400 smokers with COPD from the COPDGene Study. Luminal plugging was visually identified on inspiratory CT scans at baseline and 5-year follow-up. The relationships of luminal plugging to FEV1, St. George's Respiratory Questionnaire (SGRQ) score, emphysema on CT scan (defined as the percentage of low attenuation area < 950 Hounsfield units [%LAA-950]), and chronic bronchitis were assessed using linear and logistic multivariable analyses. RESULTS: Overall, 111 subjects (22%) had luminal plugging. The prevalence of luminal plugging was higher in subjects with COPD than those without COPD (25% vs 10%, respectively; P = .001). In subjects with COPD, luminal plugging was significantly associated with FEV1 % predicted (estimate, -6.1; SE, 2.1; P = .004) and SGRQ score (estimate, 4.9; SE, 2.4; P = .04) in adjusted models. Although luminal plugging was associated with log %LAA-950 (estimate, 0.43; SE, 0.16; P = .007), its relationship with chronic bronchitis did not reach statistical significance (P = .07). Seventy-three percent of subjects with COPD with luminal plugging at baseline had it 5 years later. CONCLUSIONS: In subjects with COPD, CT-identified luminal plugging is associated with airflow obstruction, worse health-related quality of life, and emphysema phenotype. This imaging feature may supplement the current clinical assessment of chronic mucus hypersecretion in COPD.

Improved identification of sternal injuries with multidetector computed tomography (MDCT): sagittal reconstructions.

Chest computed tomography is acquired in the axial plane, but sternal injuries may be missed on axial images. This study hypothesized that sagittal sternal reconstruction images improve detection of sternal injury and radiologist's confidence in diagnosis compared to axial images. Five radiologists independently reviewed first axial images and on a different day sagittal images of a retrospective set of trauma cases recording presence/absence of a sternal injury and/or adjacent hematoma. The reviewer's confidence in the presence/absence of a sternal injury was assessed on a 5-point scale. Sagittal reconstructions generally yielded higher interreader agreement and confidence indices on statistical analysis.

Short- and long-term lung cancer risk associated with noncalcified nodules observed on low-dose CT.

Chemoprevention is an important potential tool in reducing lung cancer incidence. Noncalcified nodules (NCN) observed on low-dose computed tomography (LDCT) have been proposed as intermediate endpoints in chemoprevention trials, but whether NCNs represent cancer precursors is unclear. We analyzed data from subjects in the LDCT arm of the National Lung Screening Trial (NLST) to examine short- and long-term lung cancer risks associated with NCNs and to elucidate whether some NCNs may be cancer precursors. NLST subjects received a baseline and two additional LDCT screens and were followed for a median of 6.5 years. We examined lung cancer incidence over three distinct periods from baseline-0-23 months (short-term), 24-59 months (medium-term), and 60-84 months (long-term)-in relation to baseline NCN characteristics. Spatially, lung cancer incidence was analyzed at the person, lung, and lobe levels relative to NCN location. A total of 26,272 subjects received the baseline LDCT screen, with 468, 413, and 190 lung cancers observed in the three periods. The presence of an NCN gave significantly elevated long-term lung cancer risk ratios (RR) of 1.8, 2.4, and 3.5 at the person, lung, and lobe levels; corresponding short-term RRs were 10.3, 16.8, and 38.0. Ground-glass attenuation was positively associated with long-term lung cancer risk but inversely associated with short-term risk; NCN size was positively associated with short-term risk but not significantly associated with long-term risk. That NCNs convey significantly elevated excess long-term of lung cancer lends evidence to the hypothesis that some NCNs may be cancer precursors.

Computed tomography with intravenous contrast alone: the role of intra-abdominal fat on the ability to visualize the normal appendix in children.

BACKGROUND: Computed tomography (CT) with enteric contrast is frequently used to evaluate children with suspected appendicitis. The use of CT with intravenous (IV) contrast alone (CT IV) may be sufficient, however, particularly in patients with adequate intra-abdominal fat (IAF). OBJECTIVES: The authors aimed 1) to determine the ability of radiologists to visualize the normal (nondiseased) appendix with CT IV in children and to assess whether IAF adequacy affects this ability and 2) to assess the association between IAF adequacy and patient characteristics. METHODS: This was a retrospective 16-center study using a preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV scan and measured weights and for whom appendectomy history was known from medical record review were included. The sample was chosen based on age to yield a sample with and without adequate IAF. Radiologists at each center reread their site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was categorized as "adequate" if there was any amount of fat completely surrounding the cecum and "inadequate" if otherwise. RESULTS: A total of 280 patients were included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no history of prior appendectomy; therefore, each patient had a presumed normal appendix. A total of 102 patients (36.4%) had adequate IAF. The proportion of normal appendices visualized with CT IV was 72.9% (95% confidence interval [CI] = 67.2% to 78.0%); the proportions were 89% (95% CI = 81.5% to 94.5%) and 63% (95% CI = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for difference of proportions = 16% to 36%). Greater weight and older age were strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a stronger predictor, particularly in females. Although statistically associated, there was noted overlap in the weights and ages of those with and without adequate IAF. CONCLUSIONS: Protocols using CT with IV contrast alone to visualize the appendix can reasonably include weight, age, or both as considerations for determining when this approach is appropriate. However, although IAF will more frequently be adequate in older, heavier patients, highly accurate prediction of IAF adequacy appears challenging solely based on age and weight.

Atypical tumors of the rectum with pathologic correlation.

Although the majority of rectal masses are histologically characterized as adenocarcinoma, there is a wide spectrum of rare, but specific, neoplastic processes that can involve the rectum and present with rectal bleeding. Knowledge of their existence and protean imaging features is crucial for accurate diagnosis and appropriate management. This review article describes the clinical, imaging, and histopathologic characteristics of several pathologically proven rectal lesions, including rectal carcinoid, rectal gastrointestinal stromal tumor, rectal cavernous hemangioma, primary anorectal melanoma, primary rectal lymphoma, and rectal metastases.