Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study.

Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; P = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; P = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; P < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; P < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; P = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; P < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Im in this issue.

One size does not fit all: Factors associated with increased frequency of radiation overexposure alerts based on fixed-alert thresholds.

OBJECTIVES: Quantify the expected rate of CT radiation dose alerts for three body regions using accepted radiation dose benchmarks and assess key determinants of alert frequency. METHODS: This IRB-approved retrospective cohort study evaluated consecutive CT examinations performed between July and December 2013 within an academic medical system. CTDIvol x-ray tube output metrics were compared to the body-region-specific benchmark levels, Achievable Doses (AD), Diagnostic Reference Levels (DRL), and Dose Notification Values (DNV). A logistic regression model for the simulated alerts was fit as a function of the independent predictors: scanner, body region, gender, weight, and age. RESULTS: For 17,000 exams, the proportion of events triggering alerts increased with patient weight. Significant covariates were scanner, body region, patient weight and patient age (all p < 0.0001). Odds of alert generation for the AD, DRL, and DNV benchmarks increased by 7.6%, 6.6% and 2.9% per kilogram, respectively, and by 0.8%, 1.1% and -2.7% per year of age (all p < 0.0001). Compared to the most highly optimized scanner, odds of alert generation varied by a factor of 595 for AD, 1126 for DRL, and 13 for DNV. CONCLUSION: Alert frequency was significantly correlated with weight, age, body region and scanner. Controllable factors include scanner functionality and associated protocol optimization. Patient factors driving alert frequency are predominantly weight, and to a lesser degree, age. Size-agnostic fixed dose thresholds can frequently produce false positive alerts in appropriately performed exams of large patients, while missing opportunities to identify outlier scans of higher-than-expected dose in small patients.

Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study.

BACKGROUND: Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort. METHODS: Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables. RESULTS: ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 - not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment. CONCLUSIONS: ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.

Traction Bronchiectasis/Bronchiolectasis is Associated with Interstitial Lung Abnormality Mortality.

PURPOSE: To investigate if the presence and severity of traction bronchiectasis/bronchiolectasis are associated with poorer survival in subjects with ILA. METHOD: The study included 3,594 subjects (378 subjects with ILA and 3,216 subjects without ILA) in AGES-Reykjavik Study. Chest CT scans of 378 subjects with ILA were evaluated for traction bronchiectasis/bronchiolectasis, defined as dilatation of bronchi/bronchioles within areas demonstrating ILA. Traction bronchiectasis/bronchiolectasis Index (TBI) was assigned as: TBI = 0, ILA without traction bronchiectasis/bronchiolectasis: TBI = 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion: TBI = 2, ILA with mild to moderate traction bronchiectasis: TBI = 3, ILA and severe traction bronchiectasis and/or honeycombing. Overall survival (OS) was compared among the subjects in different TBI groups and those without ILA. RESULTS: The median OS was 12.93 years (95%CI; 12.67 - 13.43) in the subjects without ILA; 11.95 years (10.03 - not reached) in TBI-0 group; 8.52 years (7.57 - 9.30) in TBI-1 group; 7.63 years (6.09 - 9.10) in TBI-2 group; 5.40 years (1.85 - 5.98) in TBI-3 group. The multivariable Cox models demonstrated significantly shorter OS of TBI-1, TBI-2, and TBI-3 groups compared to subjects without ILA (P < 0.0001), whereas TBI-0 group had no significant OS difference compared to subjects without ILA, after adjusting for age, sex, and smoking status. CONCLUSIONS: The presence and severity of traction bronchiectasis/bronchiolectasis are associated with shorter survival. The traction bronchiectasis/bronchiolectasis is an important contributor to increased mortality among subjects with ILA.

Concordance between gene expression in peripheral whole blood and colonic tissue in children with inflammatory bowel disease.

BACKGROUND: Presenting features of inflammatory bowel disease (IBD) are non-specific. We hypothesized that mRNA profiles could (1) identify genes and pathways involved in disease pathogenesis; (2) identify a molecular signature that differentiates IBD from other conditions; (3) provide insight into systemic and colon-specific dysregulation through study of the concordance of the gene expression. METHODS: Children (8-18 years) were prospectively recruited at the time of diagnostic colonoscopy for possible IBD. We used transcriptome-wide mRNA profiling to study gene expression in colon biopsies and paired whole blood samples. Using blood mRNA measurements, we fit a regression model for disease state prediction that was validated in an independent test set of adult subjects (GSE3365). RESULTS: Ninety-eight children were recruited [39 Crohn's disease, 18 ulcerative colitis, 2 IBDU, 39 non-IBD]. There were 1,118 significantly differentially (IBD vs non-IBD) expressed genes in colon tissue, and 880 in blood. The direction of relative change in expression was concordant for 106/112 genes differentially expressed in both tissue types. The regression model from the blood mRNA measurements distinguished IBD vs non-IBD disease status in the independent test set with 80% accuracy using only 6 genes. The overlap of 5 immune and metabolic pathways in the two tissue types was significant (p<0.001). CONCLUSIONS: Blood and colon tissue from patients with IBD share a common transcriptional profile dominated by immune and metabolic pathways. Our results suggest that peripheral blood expression levels of as few as 6 genes (IL7R, UBB, TXNIP, S100A8, ALAS2, and SLC2A3) may distinguish patients with IBD from non-IBD.

Detection of unwarranted CT radiation exposure from patient and imaging protocol meta-data using regularized regression.

BACKGROUND: Variability in radiation exposure from CT scans can be appropriate and driven by patient features such as body habitus. Quantitative analysis may be performed to discover instances of unwarranted radiation exposure and to reduce the probability of such occurrences in future patient visits. No universal process to perform identification of outliers is widely available, and access to expertise and resources is variable. OBJECTIVE: The goal of this study is to develop an automated outlier detection procedure to identify all scans with an unanticipated high radiation exposure, given the characteristics of the patient and the type of the exam. MATERIALS AND METHODS: This Institutional Review Board-approved retrospective cohort study was conducted from June 30, 2012 - December 31, 2013 in a quaternary academic medical center. The de-identified dataset contained 28 fields for 189,959 CT exams. We applied the variable selection method Least Absolute Shrinkage and Selection Operator (LASSO) to select important variables for predicting CT radiation dose. We then employed a regression approach that is robust to outliers, to learn from data a predictive model of CT radiation doses given important variables identified by LASSO. Patient visits whose predicted radiation dose was statistically different from the radiation dose actually received were identified as outliers. RESULTS: Our methodology identified 1% of CT exams as outliers. The top-5 predictors discovered by LASSO and strongly correlated with radiation dose were Tube Current, kVp, Weight, Width of collimator, and Reference milliampere-seconds. A human expert validation of the outlier detection algorithm has yielded specificity of 0.85 [95% CI 0.78-0.92] and sensitivity of 0.91 [95% CI 0.85-0.97] (PPV = 0.84, NPV = 0.92). These values substantially outperform alternative methods we tested (F1 score 0.88 for our method against 0.51 for the alternatives). CONCLUSION: The study developed and tested a novel, automated method for processing CT scanner meta-data to identify CT exams where patients received an unwarranted amount of radiation. Radiation safety and protocol review committees may use this technique to uncover systemic issues and reduce future incidents.

Quantifying the white blood cell transcriptome as an accessible window to the multiorgan transcriptome.

MOTIVATION: We investigate and quantify the generalizability of the white blood cell (WBC) transcriptome to the general, multiorgan transcriptome. We use data from the NCBI's Gene Expression Omnibus (GEO) public repository to define two datasets for comparison, WBC and OO (Other Organ) sets. RESULTS: Comprehensive pair-wise correlation and expression level profiles are calculated for both datasets (with sizes of 81 and 1463, respectively). We have used mapping and ranking across the Gene Ontology (GO) categories to quantify similarity between the two sets. GO mappings of the most correlated and highly expressed genes from the two datasets tightly match, with the notable exceptions of components of the ribosome, cell adhesion and immune response. That is, 10 877 or 48.8% of all measured genes do not change >10% of rank range between WBC and OO; only 878 (3.9%) change rank >50%. Two trans-tissue gene lists are defined, the most changing and the least changing genes in expression rank. We also provide a general, quantitative measure of the probability of expression rank and correlation profile in the OO system given the expression rank and correlation profile in the WBC dataset.