Prolonged Response to HER2-Directed Therapy in Three Patients with HER2-Amplified Metastatic Carcinoma of the Biliary System: Case Study and Review of the Literature.

HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. HER2-targeting agents have been incorporated into the treatment paradigms for HER2-overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers. KEY POINTS: Current guidelines recommend molecular assessment for HER2 overexpression exclusively in breast and gastric adenocarcinoma. The focus of this report is on three cases (two biliary tract and one ampullary carcinoma) in which amplification of HER2 or overexpression of HER2 was detected and treatment with HER2-directed therapy resulted in robust responses. These cases exemplify responsiveness of non-breast/gastric histologies to HER2-directed therapies, highlighting several promising new settings for these agents. Testing for amplification of HER2 or overexpression of HER2 should be considered especially in rare diseases with limited treatment options.

Comparing RECIST 1.1 and iRECIST in advanced melanoma patients treated with pembrolizumab in a phase II clinical trial.

OBJECTIVES: To compare tumor best overall response (BOR) by RECIST 1.1 and iRECIST, to explore the incidence of pseudoprogression in melanoma treated with pembrolizumab, and to assess the impact of pseudoprogression on overall survival (OS). METHODS: A total of 221 patients with locally advanced/unresectable melanoma who received pembrolizumab as part of KEYNOTE-002 trial were included in this study. Radiological assessment of imaging was centrally reviewed to assess tumor response. Incidence of discordance in BOR between RECIST 1.1 and iRECIST as well as rate of pseudoprogression were measured. OS of patients with pseudoprogression was compared with that of those with uncontrolled disease. RESULTS: Of the 221 patients in this cohort, 136 patients developed PD as per RECIST v1.1 and 78 patients with PD continued treatment and imaging beyond initial RECIST 1.1-defined PD. Among the 78 patients who continued therapy and imaging post-progression, RECIST 1.1 and iRECIST were discordant in 10 patients (12.8%) and pseudoprogression was encountered in 14 patients (17.9%). OS of patients with pseudoprogression was longer than that of patients with uncontrolled disease/true progression (29.9 months versus 8.0 months, p value < 0.001). CONCLUSIONS: Effectiveness of immunotherapy in clinical trials depends on the criterion used to assess tumor response (RECIST 1.1 vs iRECIST) with iRECIST being more appropriate to detect pseudoprogression and potentially prevent premature termination of effective therapy. Pseudoprogression was associated with improved OS in comparison with that of patients with uncontrolled disease. KEY POINTS: • Discordance between iRECIST and RECIST 1.1 was found in 12.8% of unresectable melanoma patients on pembrolizumab who continued therapy beyond initial RECIST 1.1-defined progression. • Pseudoprogression, captured with iRECIST, occurred in 17.9% and was significantly associated with improved overall survival in comparison with uncontrolled disease.

Impact of mandated prospectively reported apparent diffusion coefficient values on the rates of positivity for clinically significant prostate cancer by PI-RADS score.

BACKGROUND: Prior research has shown that retrospectively measured apparent diffusion coefficient (ADC) of prostate magnetic resonance imaging (MRI) lesions is associated with clinically significant prostate cancer (csPCa) on targeted biopsy suggesting that ADC should be measured and reported prospectively. PURPOSE: To assess the impact of mandatory prospective measurement of ADC on the rates of positivity across PI-RADS scores for csPCa. MATERIAL AND METHODS: Consecutive patients who underwent ultrasound (US)-MRI fusion prostate biopsy from August 2018 to July 2019 and who had prospectively reported ADC were compared to control patients who did not. Rates of positivity by PI-RADS category were computed and compared using Chi-square. Multivariable regression was performed. RESULTS: In total, 126 patients (median age 65 years) with 165 prostate lesions (19, 51, 70, and 25 PI-RADS 2, 3, 4, and 5, respectively) and prospectively reported ADC values were compared to 113 control patients (median age 66 years) with 157 prostate lesions (17, 42, 64, and 34 PI-RADS 2, 3, 4, and 5, respectively). Rates of positivity across PI-RADS scores were similar between the two cohorts; 11%, 25%, 55%, and 76% and 0%, 21%, 56%, and 62% for PI-RADS 2, 3, 4, and 5 in the test and control cohorts, respectively (Chi-square P = 0.78). Multivariate logistic regression showed no significant association between the presence of prospectively measured ADC and csPCa (odds ratio 1.1, 95% confidence interval 0.7-1.7, P = 0.82). CONCLUSION: Prospective ADC measurement may not impact PI-RADS category assignments or positivity rates for csPCa under current guidelines. Future versions of PI-RADS may need to incorporate ADC into scoring rules to realize their potential.

The Negative Predictive Value of a PI-RADS Version 2 Score of 1 on Prostate MRI and the Factors Associated With a False-Negative MRI Study.

OBJECTIVE. The purpose of this study was to calculate the negative predictive value of a prostate MRI study with a Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of 1 (hereafter referred to as a PI-RADS 1 MRI study) and to explore the patient characteristics and MRI-based factors associated with an MRI study with false-negative results. MATERIALS AND METHODS. A total of 542 consecutive patients with a PI-RADS 1 MRI study obtained between January 2016 and July 2019 were retrospectively identified. Patient charts were examined to identify those patients who subsequently underwent systematic prostate biopsy within 1 year of undergoing MRI or at any later date if the biopsy was negative. Patient characteristics and MRI-specific factors were recorded. Two blinded radiologists evaluated the quality of the axial T2-weighted, DWI, and apparent diffusion coefficient sequences; measured the volume of the bladder, the prostate gland, and rectal gas; and determined whether the peripheral zone was avidly enhancing and whether low signal intensity was seen in 50% or more of the peripheral zone on T2-weighted images. Interobserver agreement was tested. Univariable and multivariable logistic regression models were built. RESULTS. A total of 150 patients (median age, 63 years; interquartile range, 56-70 years) were included. Of these patients, 19 (13%) had prostate cancer with a Gleason score of 3 + 4 or greater, yielding a negative predictive value of 87%. Both low T2 signal intensity in the peripheral zone and the prostate-specific antigen level were associated with a false-negative PI-RADS 1 assessment (odds ratio, 4.9 [95% CI, 1.6-14.9; p = 0.006] and 1.1 [95% CI, 1.0-1.2; p = 0.03], respectively). A cutoff prostate-specific antigen level of 3.97 ng/mL resulted in sensitivity and specificity of 89% and 21%, respectively. There was moderate interobserver agreement for low T2 signal intensity in the peripheral zone (κ coefficient = 0.75). CONCLUSION. Even among select patients who undergo subsequent biopsy because of a high clinical suspicion of prostate cancer, a PI-RADS 1 prostate MRI study has a high negative predictive value. A T2-hypointense peripheral zone and an elevated prostate-specific antigen level are significantly associated with a false-negative MRI study.

Active Surveillance of Small (< 4 cm) Bosniak Category 2F, 3, and 4 Renal Lesions: What Happens on Imaging Follow-Up?

OBJECTIVE. The purpose of this study was to determine the percentage of small (< 4 cm) Bosniak category 2F, 3, and 4 lesions that regress during active surveillance. MATERIALS AND METHODS. In this retrospective study, a hospital database was searched from January 1, 2005, through September 9, 2017, for small (< 4 cm) Bosniak category 2F, 3, and 4 lesions studied with initial and follow-up unenhanced and contrast-enhanced CT or MRI. Prospective Bosniak categories were recorded. Two blinded radiologists retrospectively reassigned Bosniak categories to the initial and last follow-up studies. Interreader variability was analyzed. Rates of stability, regression, and progression were calculated and stratified by size. Logistic regression was used to assess the effects of lesion size, lesion growth, and duration of follow-up on the change in Bosniak categories. RESULTS. The search identified 123 patients (85 men, 38 women) with 138 renal lesions (according to the blinded readings, 83 Bosniak category 2F, 37 category 3, and 18 category 4) and followed for 1-12.3 years (median, 2.7 years). Fifty-one percent (70/138) of the lesions were smaller than 2 cm. Eighty-eight percent (73/83) of category 2F lesions were downgraded or remained stable. Forty-five percent (25/55) of category 3 or 4 lesions were downgraded to 2F or lower. Kappa values were 0.94 between the two readers and 0.72-0.76 between the readers and the prospective Bosniak categories. There was no association between initial size, change in size, or duration of follow-up and change in Bosniak category. CONCLUSION. Approximately one-half of small (< 4 cm) Bosniak category 3 and 4 cystic renal lesions were downgraded, and the majority (88%) of small Bosniak category 2F lesions regressed or remained stable during active surveillance. Therefore, small size should be a consideration for conservative management.

Prediction of Lymph Node Maximum Standardized Uptake Value in Patients With Cancer Using a 3D Convolutional Neural Network: A Proof-of-Concept Study.

OBJECTIVE: The purpose of this study is to determine whether a convolutional neural network (CNN) can predict the maximum standardized uptake value (SUVmax) of lymph nodes in patients with cancer using the unenhanced CT images from a PET/CT examination, thus providing a proof of concept for potentially using deep learning to diagnose nodal involvement. MATERIALS AND METHODS: Consecutive initial staging PET/CT scans obtained in 2017 for patients with pathologically proven malignancy were collected. Two blinded radiologists selected one to 10 lymph nodes from the unenhanced CT portion of each PET/CT examination. The SUVmax of the lymph nodes was recorded. Lymph nodes were cropped and used with the primary tumor histology type as input for a novel 3D CNN with predicted SUVmax as the output. The CNN was trained using one cohort and tested using a separate cohort. An SUVmax of 2.5 or greater was defined as FDG avid. Two blinded radiologists separately classified lymph nodes as FDG avid or not FDG avid on the basis of unenhanced CT images and separately using a short-axis measurement cutoff of 1 cm. Logistic regression analysis was performed. RESULTS: A total of 400 lymph nodes (median SUVmax, 6.8 [interquartile range {IQR}, 2.7-11.6]; median short-axis, 1.1 cm [IQR, 0.9-1.6 cm]) in 136 patients were used for training. A total of 164 lymph nodes (median SUVmax, 3.5 [IQR, 1.9-8.6]; median short-axis, 1.0 cm [IQR, 0.7-1.4 cm]) in 49 patients were used for testing. The predicted SUVmax was associated with the real SUVmax (ß estimate = 0.83, p < 0.0001). The predicted SUVmax was associated with FDG avidity (p < 0.0001), with an ROC AUC value of 0.85, and it improved when combined with radiologist qualitative assessment and short-axis criteria. CONCLUSION: A CNN is able to predict with moderate accuracy the SUVmax of lymph nodes, as determined from the unenhanced CT images and tumor histology subtype for patients with cancer.

Ulnar Collateral Ligament Insertional Injuries in Pediatric Overhead Athletes: Are MRI Findings Predictive of Symptoms or Need for Surgery?

OBJECTIVE: The purpose of this study was to determine whether ulnar collateral ligament (UCL) insertion below the articular margin (so-called T sign) exists in the pediatric population and whether MRI features can be used to identify insertional UCL injuries in overhead athletes that are symptomatic or require surgery. MATERIALS AND METHODS: Retrospective review of elbow MR images of patients younger than 21 years from 2011 to 2017 yielded 26 control subjects who were not overhead athletes and 97 overhead athletes. According to the clinical diagnosis, 50 of the overhead athletes had symptoms. Two radiologists evaluated the UCL for thickness, abnormal insertional signal intensity, insertion distance, and adjacent marrow or soft-tissue edema. Insertion distance was defined as the coronal length of any T sign measured from the articular margin. RESULTS: Mean insertion distance was greater in overhead athletes than in control subjects (1.42 vs 0.23 mm, p = 0.001) but not significantly different in athletes with symptoms compared with those without symptoms or in those who underwent operative treatment compared with those who did not. Mean UCL thickness was greater in overhead athletes than in control subjects (2.64 vs 1.74 mm, p < 0.0001), athletes with than those without symptoms (2.84 vs 2.41 mm, p = 0.005), and athletes who did versus those who did not undergo operative treatment (3.40 vs 2.73 mm, p = 0.011). Marrow (p = 0.002) and soft-tissue (p = 0.016) edema were found more frequently in athletes with symptoms. ROC analysis of UCL thickness and insertion distance as predictors of symptoms showed AUCs of 0.69 and 0.49, respectively. CONCLUSION: The T sign is likely not an anatomic variation but is a poor predictor of symptoms and need for surgery. Soft-tissue and marrow edema are more frequently seen in overhead athletes with symptomatic injuries and can aid in the diagnosis of clinically relevant injury.

Anterior Inferior Iliac Spine Morphology: Comparison of Symptomatic Hips With Femoroacetabular Impingement and Asymptomatic Hips.

OBJECTIVE: The objective of our study was to compare anterior inferior iliac spine (AIIS) morphology in symptomatic hips with femoroacetabular impingement (FAI) and in asymptomatic hips, determine the prevalence of impingement morphology in patients with a radiographic "crossover" sign, and identify potential risk factors for having impingement morphology. MATERIALS AND METHODS: For this retrospective study, we identified consecutive symptomatic hips with FAI (n = 54) and asymptomatic hips (n = 35) in patients who underwent CT from 2015 to 2017. Two radiologists blindly and independently evaluated 3D CT images of each hip and graded the AIIS morphology according to the Hetsroni classification scheme. The prevalence of AIIS morphology types was calculated. Associations of AIIS morphology types with symptoms and the crossover sign were evaluated with a chi-square test. A multivariable logistic regression determined risk factors for abnormal AIIS morphology (i.e., type 2 or 3). RESULTS: There was no difference in the prevalence of AIIS morphology types for symptomatic hips with FAI versus asymptomatic hips (p = 0.44) or for hips with a positive versus those with a negative crossover sign (p = 0.21). There was moderate interobserver agreement (κ = 0.44) and good-to-excellent intraobserver agreement (κ = 0.67 and 0.90) for grading AIIS morphology. Age, sex, femoral version, acetabular version, alpha angle, lateral center edge angle, and the crossover sign were not significant risk factors for abnormal AIIS morphology in patients with FAI (p = 0.11-0.79). CONCLUSION: There is no difference in AIIS morphology between symptomatic hips with FAI versus asymptomatic hips or between hips with and those without the radiographic crossover sign. Age, sex, and other FAI parameters are not risk factors for developing AIIS impingement morphology.

Diffuse Peripheral Zone T2 Hypointensity: When to Worry About Prostate Cancer.

OBJECTIVE: Evaluate the accuracy of an obscured surgical capsule (OSC) for detecting diffuse prostate cancer (PCa) in the setting of diffusely T2 hypointense peripheral zones (PZs) on prostate magnetic resonance imaging. METHODS: Axial T2-weighted sequences of prostate magnetic resonance imaging performed on July 1, 2015, to August 1, 2017, were blindly assessed for diffusely T2 hypointense PZs, OSC, and focal diffusion abnormalities by 2 radiologists. Diffuse PCa was defined by the presence of bilateral PCa on at least 4 contiguous biopsy cores involving 2/3 levels. Interobserver agreement and multivariate analysis were performed. RESULTS: Seven (10%) of 70 patients had diffuse PCa. There was weak interreader agreement for OSC (κ coefficient = 0.58). Obscured surgical capsule was 57% sensitive and 89% specific for the presence of diffuse PCa and was associated with it (odds ratio, 17.6; P = 0.0008). Multivariate logistic regression demonstrated that OSC was the only significant predictor for the presence of diffuse PCa. CONCLUSION: Obscured surgical capsule is a strong independent predictor for diffuse PCa in T2 hypointense PZs.

Nonenhancing Component of Clear Cell Renal Cell Carcinoma on Computed Tomography Correlates With Tumor Necrosis and Stage and Serves as a Size-Independent Prognostic Biomarker.

OBJECTIVES: This study aimed to quantify nonenhancing tumor (NT) component in clear cell renal cell carcinoma (ccRCC) and assess its association with histologically defined tumor necrosis, stage, and survival outcomes. METHODS: Among 183 patients with ccRCC, multi-institutional changes in computed tomography attenuation of tumor voxels were used to quantify percent of NT. Associations of NT with histologic tumor necrosis and tumor stage/grade were tested using Wilcoxon signed rank test and with survival outcomes using Kaplan-Meier curves/Cox regression analysis. RESULTS: Nonenhancing tumor was higher in ccRCC with tumor necrosis (11% vs 7%; P = 0.040) and higher pathological stage (P = 0.042 and P < 0.001, respectively). Patients with greater NT had higher incidence of cancer recurrence after resection (P < 0.001) and cancer-specific mortality (P < 0.001). CONCLUSION: Nonenhancing tumor on preoperative computed tomographic scans in patients with ccRCC correlates with tumor necrosis and stage and may serve as an independent imaging prognostic biomarker for cancer recurrence and cancer-specific survival.

Stressors contributing to burnout amongst pediatric radiologists: results from a survey of the Society for Pediatric Radiology.

BACKGROUND: A recent study showed a high prevalence of burnout in pediatric radiology. OBJECTIVE: The purpose of this study is to evaluate potential stressors contributing to burnout in pediatric radiology. MATERIALS AND METHODS: Society for Pediatric Radiology members received an invitation for an anonymous survey evaluating stressors contributing to burnout. Stressors evaluated included call burden, financial stress, work-life balance, health care evolution and job market changes, and radiology as a career choice. Additional questions regarding demographics were obtained. RESULTS: The response rate was 460/1,453 (32%). The prevalence of emotional exhaustion was 66% (286/435), depersonalization was 61% (265/433) and perceived lack of personal accomplishment was 15% (67/436). In a backward selective logistic regression model, work-life imbalance and call burden were the only significant factors predicting higher emotional exhaustion (P<0.001). Using a similar model, work-life imbalance, call burden and decreased rate of reimbursement were significantly associated with higher probability of depersonalization (P=0.033, 0.0002 and 0.015, respectively). Emotional exhaustion and depersonalization were significantly associated with higher odds of a radiologist's wish to work in another medical specialty (P=0.011 and 0.002, respectively). CONCLUSION: Key stressors contributing to burnout in pediatric radiology include work-life imbalance, pediatric call burden and a decreased rate of reimbursement. Burnout in pediatric radiology is a serious issue that needs to be addressed and prioritized on the individual and departmental/institutional levels and further investigated to develop effective interventions to mitigate it.

Cerebrovascular Accidents During Mechanical Circulatory Support: New Predictors of Ischemic and Hemorrhagic Strokes and Outcome.

BACKGROUND AND PURPOSE: Left ventricular assist devices (LVADs) have emerged as an effective treatment for patients with advanced heart failure refractory to medical therapy. Post-LVAD strokes are an important cause of morbidity and reduced quality of life. Data on risks that distinguish between ischemic and hemorrhagic post-LVAD strokes are limited. The aim of this study was to determine the incidence of post-LVAD ischemic and hemorrhagic strokes, their association with stroke risk factors, and their effect on mortality. METHODS: Data are collected prospectively on all patients with LVADs implanted at Brigham and Women's Hospital. We added retrospectively collected clinical data for these analyses. RESULTS: From 2007 to 2016, 183 patients (median age, 57; 80% male) underwent implantation of HeartMate II LVAD as a bridge to transplant (52%), destination therapy (39%), or bridge to transplant candidacy (8%). A total of 48 strokes occurred in 39 patients (21%): 28 acute ischemic strokes in 24 patients (13%) and 20 intracerebral hemorrhages in 19 patients (10.3%). First events occurred at a median of 238 days from implantation (interquartile range, 93-515) among those who developed post-LVAD stroke. All but 9 patients (4.9%) were on warfarin (goal international normalized ratio, 2-3.5) and all received aspirin (81-325 mg). Patients with chronic obstructive pulmonary disease were more likely to have an ischemic stroke (odds ratio, 2.96; 95% confidence interval, 1.14-7.70). Dialysis-dependent patients showed a trend toward a higher risk of hemorrhagic stroke (odds ratio, 6.31; 95% confidence interval, 0.99-40.47). Hemorrhagic stroke was associated with higher mortality (odds ratio, 3.92; 95% confidence interval, 1.34-11.45) than ischemic stroke (odds ratio, 3.17; 95% confidence interval, 1.13-8.85). CONCLUSIONS: Stroke is a major cause of morbidity and mortality in patients on LVAD support. Chronic obstructive pulmonary disease increases the risk of ischemic stroke, whereas dialysis may increase the risk of hemorrhagic stroke. Although any stroke increases mortality, post-LVAD hemorrhagic stroke was associated with higher mortality compared with ischemic stroke.

Cholesterol, lipoproteins and subclinical interstitial lung disease: the MESA study.

We investigated associations of plasma lipoproteins with subclinical interstitial lung disease (ILD) by measuring high attenuation areas (HAA: lung voxels between -600 and -250 Hounsfield units) in 6700 adults and serum MMP-7 and SP-A in 1216 adults age 45-84 without clinical cardiovascular disease in Multi-Ethnic Study of Atherosclerosis. In cross-sectional analyses, each SD decrement in high density lipoprotein cholesterol (HDL-C) was associated with a 2.12% HAA increment (95% CI 1.44% to 2.79%), a 3.53% MMP-7 increment (95% CI 0.93% to 6.07%) and a 6.37% SP-A increment (95% CI 1.35% to 11.13%), independent of demographics, smoking and inflammatory biomarkers. These findings support a novel hypothesis that HDL-C might influence subclinical lung injury and extracellular matrix remodelling.

The Strategy of Delayed Reconstruction of the Mandible in War Injuries.

The most common causes of mandibular defects are ablative surgery of benign or malignant tumors, severe trauma, inflammatory diseases, and osteoradionecrosis. War injuries are another cause for mandibular defect. Reconstruction of the mandible is considered a challenge to the maxillofacial surgeon due to the accompanying functional and cosmetic importance. The object of this article was to show the role of nonvascularized bone graft in the reconstruction of segmental defect of the mandible resulted from projectiles and its snags. Seventeen patients underwent reconstruction of defect in the body of the mandible using non-vascularized iliac bone graft,in sixteen patients the grafts were fixed by reconstruction plate and in one by stainless-steel wire. In the emergency phase in which life-saving measures were done, in the immediate phase, treatments of associated facial and systemic injuries were carried out. The delayed phase includes the reconstruction of the residual defects and rehabilitation. A total of 17 male patients with a mean age of 34.5 years underwent reconstructive surgery, the time lapse between the injury and the delayed phase of treatment ranged from 20 days to 3 months. The size of the defects ranged from 4 to 7 cm. Treatment was considered successful in 15 patients (88.2%) in whom the grafts were incorporated to mandible with improvement of facial contour and symmetry and satisfactory occlusion of the remaining teeth. Nonvascularized bone graft is considered a feasible option for the reconstruction of a relatively small mandibular defect, especially in ascetic conditions for its role in improving facial appearance and to less extent functional benefit and more advanced method for the reconstruction needed to be introduced especially in war injuries.

APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

Plasma sphingomyelin and longitudinal change in percent emphysema on CT. The MESA lung study.

CONTEXT: Ceramide causes endothelial apoptosis and emphysema-like changes in animal models. OBJECTIVES: Test if plasma sphingomyelin, a major precursor of ceramide, would predict longitudinal increase in the percentage of emphysema-like lung on computed tomography (CT). MATERIALS AND METHODS: 3840 participants had their plasma sphingomyelin measured at baseline examination and their pulmonary emphysema measured on cardiac CT scans at baseline and on follow-up visits. Mixed effects models were used to adjust for potential confounders. RESULTS: One standard deviation increase in sphingomyelin predicted a 0.12% per year (95% CI: 0.02-0.22; p = 0.019) greater increase of percent emphysema. DISCUSSION AND CONCLUSION: Higher plasma levels of sphingomyelin predicted greater annual increase in quantitatively measured percent emphysema.

Asthma and lung structure on computed tomography: the Multi-Ethnic Study of Atherosclerosis Lung Study.

BACKGROUND: The potential consequences of asthma in childhood and young adulthood on lung structure in older adults have not been studied in a large, population-based cohort. OBJECTIVE: The authors hypothesized that a history of asthma onset in childhood (age 18 years or before) or young adulthood (age 19-45 years) was associated with altered lung structure on computed tomography in later life. METHODS: The Multi-Ethnic Study of Atherosclerosis Lung Study recruited 3965 participants and assessed asthma history by using standardized questionnaires, guideline-based spirometry, and segmental airway dimensions and percentage of low attenuation area (%LAA) on computed tomographic scans. RESULTS: Asthma with onset in childhood and young adulthood was associated with large decrements in FEV(1) among participants with a mean age of 66 years (-365 mL and -343 mL, respectively; P < .001). Asthma with onset in childhood and young adulthood was associated with increased mean airway wall thickness standardized to an internal perimeter of 10 mm (0.1 mm, P < .001 for both), predominantly from narrower segmental airway lumens (-0.39 mm and -0.34 mm, respectively; P < .001). Asthma with onset in childhood and young adulthood also was associated with a greater %LAA (1.69% and 4.30%, respectively; P < .001). Findings were similar among never smokers, except that differential %LAA in childhood-onset asthma were not seen in them. CONCLUSION: Asthma with onset in childhood or young adulthood was associated with reduced lung function, narrower airways, and among asthmatic patients who smoked, greater %LAA in later life.