Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.

RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.

Clinically Relevant Biomarkers in Connective Tissue Disease-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) complicates connective tissue disease (CTD) with variable incidence and is a leading cause of death in these patients. To improve CTD-ILD outcomes, early recognition and management of ILD is critical. Blood-based and radiologic biomarkers that assist in the diagnosis CTD-ILD have long been studied. Recent studies, including -omic investigations, have also begun to identify biomarkers that may help prognosticate such patients. This review provides an overview of clinically relevant biomarkers in patients with CTD-ILD, highlighting recent advances to assist in the diagnosis and prognostication of CTD-ILD.

Enhancing Early Lung Cancer Diagnosis: Predicting Lung Nodule Progression in Follow-Up Low-Dose CT Scan with Deep Generative Model.

Early diagnosis of lung cancer can significantly improve patient outcomes. We developed a Growth Predictive model based on the Wasserstein Generative Adversarial Network framework (GP-WGAN) to predict the nodule growth patterns in the follow-up LDCT scans. The GP-WGAN was trained with a training set (N = 776) containing 1121 pairs of nodule images with about 1-year intervals and deployed to an independent test set of 450 nodules on baseline LDCT scans to predict nodule images (GP-nodules) in their 1-year follow-up scans. The 450 GP-nodules were finally classified as malignant or benign by a lung cancer risk prediction (LCRP) model, achieving a test AUC of 0.827 ± 0.028, which was comparable to the AUC of 0.862 ± 0.028 achieved by the same LCRP model classifying real follow-up nodule images (p = 0.071). The net reclassification index yielded consistent outcomes (NRI = 0.04; p = 0.62). Other baseline methods, including Lung-RADS and the Brock model, achieved significantly lower performance (p < 0.05). The results demonstrated that the GP-nodules predicted by our GP-WGAN model achieved comparable performance with the nodules in the real follow-up scans for lung cancer diagnosis, indicating the potential to detect lung cancer earlier when coupled with accelerated clinical management versus the current approach of waiting until the next screening exam.

Leveraging Serial Low-Dose CT Scans in Radiomics-based Reinforcement Learning to Improve Early Diagnosis of Lung Cancer at Baseline Screening.

Purpose To evaluate the feasibility of leveraging serial low-dose CT (LDCT) scans to develop a radiomics-based reinforcement learning (RRL) model for improving early diagnosis of lung cancer at baseline screening. Materials and Methods In this retrospective study, 1951 participants (female patients, 822; median age, 61 years [range, 55-74 years]) (male patients, 1129; median age, 62 years [range, 55-74 years]) were randomly selected from the National Lung Screening Trial between August 2002 and April 2004. An RRL model using serial LDCT scans (S-RRL) was trained and validated using data from 1404 participants (372 with lung cancer) containing 2525 available serial LDCT scans up to 3 years. A baseline RRL (B-RRL) model was trained with only LDCT scans acquired at baseline screening for comparison. The 547 held-out individuals (150 with lung cancer) were used as an independent test set for performance evaluation. The area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI) were used to assess the performances of the models in the classification of screen-detected nodules. Results Deployment to the held-out baseline scans showed that the S-RRL model achieved a significantly higher test AUC (0.88 [95% CI: 0.85, 0.91]) than both the Brock model (AUC, 0.84 [95% CI: 0.81, 0.88]; P = .02) and the B-RRL model (AUC, 0.86 [95% CI: 0.83, 0.90]; P = .02). Lung cancer risk stratification was significantly improved by the S-RRL model as compared with Lung CT Screening Reporting and Data System (NRI, 0.29; P < .001) and the Brock model (NRI, 0.12; P = .008). Conclusion The S-RRL model demonstrated the potential to improve early diagnosis and risk stratification for lung cancer at baseline screening as compared with the B-RRL model and clinical models. Keywords: Radiomics-based Reinforcement Learning, Lung Cancer Screening, Low-Dose CT, Machine Learning © RSNA, 2024 Supplemental material is available for this article.

Progressive Pulmonary Fibrosis and Interstitial Lung Abnormalities: AJR Expert Panel Narrative Review.

Progressive pulmonary fibrosis (PPF) and interstitial lung abnormalities (ILA) are relatively new concepts in interstitial lung disease (ILD) imaging and clinical management. Recognition of signs of PPF, as well as identification and classification of ILA, are important tasks during chest high-resolution CT interpretation, to optimize management of patients with ILD and those at risk of developing ILD. However, following professional society guidance, the role of imaging surveillance remains unclear in stable patients with ILD, asymptomatic patients with ILA who are at risk of progression, and asymptomatic patients at risk of developing ILD without imaging abnormalities. In this AJR Expert Panel Narrative Review, we summarize the current knowledge regarding PPF and ILA and describe the range of clinical practice with respect to imaging patients with ILD, those with ILA, and those at risk of developing ILD. In addition, we offer suggestions to help guide surveillance imaging in areas with an absence of published guidelines, where such decisions are currently driven primarily by local pulmonologists' preference.

Local heterogeneity of normal lung parenchyma and small airways disease are associated with COPD severity and progression.

BACKGROUND: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline. METHODS: PRM metrics of normal lung (PRMNorm) and functional SAD (PRMfSAD) were generated from CT scans collected as part of the COPDGene study (n = 8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRMNorm and PRMfSAD. Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV1 decline using a machine learning model. RESULTS: Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRMfSAD and PRMNorm were independently associated with the amount of emphysema. Readouts χfSAD (ß of 0.106, p < 0.001) and VfSAD (ß of 0.065, p = 0.004) were also independently associated with FEV1% predicted. The machine learning model using PRM topologies as inputs predicted FEV1 decline over five years with an AUC of 0.69. CONCLUSIONS: We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRMfSAD and PRMNorm may show promise as an early indicator of emphysema onset and COPD progression.

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.

Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer.

Low-dose computed tomography (LDCT) screening for lung cancer substantially reduces mortality from lung cancer, as revealed in randomized controlled trials and meta-analyses. This review is based on the ninth CT screening symposium of the International Association for the Study of Lung Cancer, which focuses on the major themes pertinent to the successful global implementation of LDCT screening and develops a strategy to further the implementation of lung cancer screening globally. These recommendations provide a 5-year roadmap to advance the implementation of LDCT screening globally, including the following: (1) establish universal screening program quality indicators; (2) establish evidence-based criteria to identify individuals who have never smoked but are at high-risk of developing lung cancer; (3) develop recommendations for incidentally detected lung nodule tracking and management protocols to complement programmatic lung cancer screening; (4) Integrate artificial intelligence and biomarkers to increase the prediction of malignancy in suspicious CT screen-detected lesions; and (5) standardize high-quality performance artificial intelligence protocols that lead to substantial reductions in costs, resource utilization and radiologist reporting time; (6) personalize CT screening intervals on the basis of an individual's lung cancer risk; (7) develop evidence to support clinical management and cost-effectiveness of other identified abnormalities on a lung cancer screening CT; (8) develop publicly accessible, easy-to-use geospatial tools to plan and monitor equitable access to screening services; and (9) establish a global shared education resource for lung cancer screening CT to ensure high-quality reading and reporting.

Topologic Parametric Response Mapping Identifies Tissue Subtypes Associated with Emphysema Progression.

RATIONALE AND OBJECTIVES: Small airways disease (SAD) and emphysema are significant components of chronic obstructive pulmonary disease (COPD), a heterogenous disease where predicting progression is difficult. SAD, a principal cause of airflow obstruction in mild COPD, has been identified as a precursor to emphysema. Parametric Response Mapping (PRM) of chest computed tomography (CT) can help distinguish SAD from emphysema. Specifically, topologic PRM can define local patterns of both diseases to characterize how and in whom COPD progresses. We aimed to determine if distribution of CT-based PRM of functional SAD (fSAD) is associated with emphysema progression. MATERIALS AND METHODS: We analyzed paired inspiratory-expiratory chest CT scans at baseline and 5-year follow up in 1495 COPDGene subjects using topological analyses of PRM classifications. By spatially aligning temporal scans, we mapped local emphysema at year five to baseline lobar PRM-derived topological readouts. K-means clustering was applied to all observations. Subjects were subtyped based on predominant PRM cluster assignments and assessed using non-parametric statistical tests to determine differences in PRM values, pulmonary function metrics, and clinical measures. RESULTS: We identified distinct lobar imaging patterns and classified subjects into three radiologic subtypes: emphysema-dominant (ED), fSAD-dominant (FD), and fSAD-transition (FT: transition from healthy lung to fSAD). Relative to year five emphysema, FT showed rapid local emphysema progression (-57.5% ± 1.1) compared to FD (-49.9% ± 0.5) and ED (-33.1% ± 0.4). FT consisted primarily of at-risk subjects (roughly 60%) with normal spirometry. CONCLUSION: The FT subtype of COPD may allow earlier identification of individuals without spirometrically-defined COPD at-risk for developing emphysema.

Measuring the Impact of AI in the Diagnosis of Hospitalized Patients: A Randomized Clinical Vignette Survey Study.

Importance: Artificial intelligence (AI) could support clinicians when diagnosing hospitalized patients; however, systematic bias in AI models could worsen clinician diagnostic accuracy. Recent regulatory guidance has called for AI models to include explanations to mitigate errors made by models, but the effectiveness of this strategy has not been established. Objectives: To evaluate the impact of systematically biased AI on clinician diagnostic accuracy and to determine if image-based AI model explanations can mitigate model errors. Design, Setting, and Participants: Randomized clinical vignette survey study administered between April 2022 and January 2023 across 13 US states involving hospitalist physicians, nurse practitioners, and physician assistants. Interventions: Clinicians were shown 9 clinical vignettes of patients hospitalized with acute respiratory failure, including their presenting symptoms, physical examination, laboratory results, and chest radiographs. Clinicians were then asked to determine the likelihood of pneumonia, heart failure, or chronic obstructive pulmonary disease as the underlying cause(s) of each patient's acute respiratory failure. To establish baseline diagnostic accuracy, clinicians were shown 2 vignettes without AI model input. Clinicians were then randomized to see 6 vignettes with AI model input with or without AI model explanations. Among these 6 vignettes, 3 vignettes included standard-model predictions, and 3 vignettes included systematically biased model predictions. Main Outcomes and Measures: Clinician diagnostic accuracy for pneumonia, heart failure, and chronic obstructive pulmonary disease. Results: Median participant age was 34 years (IQR, 31-39) and 241 (57.7%) were female. Four hundred fifty-seven clinicians were randomized and completed at least 1 vignette, with 231 randomized to AI model predictions without explanations, and 226 randomized to AI model predictions with explanations. Clinicians' baseline diagnostic accuracy was 73.0% (95% CI, 68.3% to 77.8%) for the 3 diagnoses. When shown a standard AI model without explanations, clinician accuracy increased over baseline by 2.9 percentage points (95% CI, 0.5 to 5.2) and by 4.4 percentage points (95% CI, 2.0 to 6.9) when clinicians were also shown AI model explanations. Systematically biased AI model predictions decreased clinician accuracy by 11.3 percentage points (95% CI, 7.2 to 15.5) compared with baseline and providing biased AI model predictions with explanations decreased clinician accuracy by 9.1 percentage points (95% CI, 4.9 to 13.2) compared with baseline, representing a nonsignificant improvement of 2.3 percentage points (95% CI, -2.7 to 7.2) compared with the systematically biased AI model. Conclusions and Relevance: Although standard AI models improve diagnostic accuracy, systematically biased AI models reduced diagnostic accuracy, and commonly used image-based AI model explanations did not mitigate this harmful effect. Trial Registration: ClinicalTrials.gov Identifier: NCT06098950.

RadioGraphics Update: Lung-RADS 2022.

Editor's Note.-RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics. These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.

Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression.

Objectives: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline. Materials and Methods: PRM metrics of normal lung (PRMNorm) and functional SAD (PRMfSAD) were generated from CT scans collected as part of the COPDGene study (n=8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRMNorm and PRMfSAD. Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV1 decline using a machine learning model. Results: Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRMfSAD and PRMNorm were independently associated with the amount of emphysema. Readouts χfSAD (ß of 0.106, p<0.001) and VfSAD (ß of 0.065, p=0.004) were also independently associated with FEV1% predicted. The machine learning model using PRM topologies as inputs predicted FEV1 decline over five years with an AUC of 0.69. Conclusions: We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRMfSAD and PRMNorm may show promise as an early indicator of emphysema onset and COPD progression.

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment.

Rationale: Cigarette smoking contributes to the risk of death through different mechanisms. Objectives: To determine how causes of and clinical features associated with death vary in tobacco cigarette users by lung function impairment. Methods: We stratified current and former tobacco cigarette users enrolled in Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) into normal spirometry, PRISm (Preserved Ratio Impaired Spirometry), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 COPD, and GOLD 3-4 COPD. Deaths were identified via longitudinal follow-up and Social Security Death Index search. Causes of death were adjudicated after a review of death certificates, medical records, and next-of-kin interviews. We tested associations between baseline clinical variables and all-cause mortality using multivariable Cox proportional hazards models. Measurements and Main Results: Over a 10.1-year median follow-up, 2,200 deaths occurred among 10,132 participants (age 59.5 ± 9.0 yr; 46.6% women). Death from cardiovascular disease was most frequent in PRISm (31% of deaths). Lung cancer deaths were most frequent in GOLD 1-2 (18% of deaths vs. 9-11% in other groups). Respiratory deaths outpaced competing causes of death in GOLD 3-4, particularly when BODE index ⩾7. St. George's Respiratory Questionnaire score ⩾25 was associated with higher mortality in all groups: Hazard ratio (HR), 1.48 (1.20-1.84) normal spirometry; HR, 1.40 (1.05-1.87) PRISm; HR, 1.80 (1.49-2.17) GOLD 1-2; HR, 1.65 (1.26-2.17) GOLD 3-4. History of respiratory exacerbations was associated with higher mortality in GOLD 1-2 and GOLD 3-4, quantitative emphysema in GOLD 1-2, and airway wall thickness in PRISm and GOLD 3-4. Conclusions: Leading causes of death vary by lung function impairment in tobacco cigarette users. Worse respiratory-related quality of life is associated with all-cause mortality regardless of lung function.

Clinically Relevant Biomarkers in Connective Tissue Disease-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) complicates connective tissue disease (CTD) with variable incidence and is a leading cause of death in these patients. To improve CTD-ILD outcomes, early recognition and management of ILD is critical. Blood-based and radiologic biomarkers that assist in the diagnosis CTD-ILD have long been studied. Recent studies, including -omic investigations, have also begun to identify biomarkers that may help prognosticate such patients. This review provides an overview of clinically relevant biomarkers in patients with CTD-ILD, highlighting recent advances to assist in the diagnosis and prognostication of CTD-ILD.

Outcomes From More Than 1 Million People Screened for Lung Cancer With Low-Dose CT Imaging.

BACKGROUND: Lung cancer screening (LCS) with low-dose CT (LDCT) imaging was recommended in 2013, making approximately 8 million Americans eligible for LCS. The demographic characteristics and outcomes of individuals screened in the United States have not been reported at the population level. RESEARCH QUESTION: What are the outcomes among people screened and entered in the American College of Radiology's Lung Cancer Screening Registry compared with those of trial participants? STUDY DESIGN AND METHODS: This was a cohort study of individuals undergoing baseline LDCT imaging for LCS between 2015 and 2019. Predictors of adherence to annual screening were computed. LDCT scan interpretations by Lung Imaging Reporting and Data System (Lung-RADS) score, cancer detection rates (CDRs), and stage at diagnosis were compared with National Lung Cancer Screening Trial data. RESULTS: Adherence was 22.3%, and predictors of poor adherence included current smoking status and Hispanic or Black race. On baseline screening, 83% of patients showed negative results and 17% showed positive screening results. The overall CDR was 0.56%. The percentage of people with cancer detected at baseline was higher in the positive Lung-RADS categories at 0.4% for Lung-RADS category 3, 2.6% for Lung-RADS category 4A, 11.1% for Lung-RADS category 4B, and 19.9% for Lung-RADS category 4X. The cancer stage distribution was similar to that observed in the National Lung Cancer Screening Trial, with 53.5% of patients receiving a diagnosis of stage I cancer and 14.3% with stage IV cancer. Underreporting into the registry may have occurred. INTERPRETATION: This study revealed both the positive aspects of CT scan screening for lung cancer and the challenges that remain. Findings on CT imaging were correlated accurately with lung cancer detection using the Lung-RADS system. A significant stage shift toward early-stage lung cancer was present. Adherence to LCS was poor and likely contributes to the lower than expected cancer detection rate, all of which will impact the outcomes of patients undergoing screening for lung cancer.

Predicting severe chronic obstructive pulmonary disease exacerbations using quantitative CT: a retrospective model development and external validation study.

BACKGROUND: Quantitative CT is becoming increasingly common for the characterisation of lung disease; however, its added potential as a clinical tool for predicting severe exacerbations remains understudied. We aimed to develop and validate quantitative CT-based models for predicting severe chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: We analysed the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS) cohort, a multicentre study done at 12 clinical sites across the USA, of individuals aged 40-80 years from four strata: individuals who never smoked, individuals who smoked but had normal spirometry, individuals who smoked and had mild to moderate COPD, and individuals who smoked and had severe COPD. We used 3-year follow-up data to develop logistic regression classifiers for predicting severe exacerbations. Predictors included age, sex, race, BMI, pulmonary function, exacerbation history, smoking status, respiratory quality of life, and CT-based measures of density gradient texture and airway structure. We externally validated our models in a subset from the Genetic Epidemiology of COPD (COPDGene) cohort. Discriminative model performance was assessed using the area under the receiver operating characteristic curve (AUC), which was also compared with other predictors, including exacerbation history and the BMI, airflow obstruction, dyspnoea, and exercise capacity (BODE) index. We evaluated model calibration using calibration plots and Brier scores. FINDINGS: Participants in SPIROMICS were enrolled between Nov 12, 2010, and July 31, 2015. Participants in COPDGene were enrolled between Jan 10, 2008, and April 15, 2011. We included 1956 participants from the SPIROMICS cohort who had complete 3-year follow-up data: the mean age of the cohort was 63·1 years (SD 9·2) and 1017 (52%) were men and 939 (48%) were women. Among the 1956 participants, 434 (22%) had a history of at least one severe exacerbation. For the CT-based models, the AUC was 0·854 (95% CI 0·852-0·855) for at least one severe exacerbation within 3 years and 0·931 (0·930-0·933) for consistent exacerbations (defined as ≥1 acute episode in each of the 3 years). Models were well calibrated with low Brier scores (0·121 for at least one severe exacerbation; 0·039 for consistent exacerbations). For the prediction of at least one severe event during 3-year follow-up, AUCs were significantly higher with CT biomarkers (0·854 [0·852-0·855]) than exacerbation history (0·823 [0·822-0·825]) and BODE index 0·812 [0·811-0·814]). 6965 participants were included in the external validation cohort, with a mean age of 60·5 years (SD 8·9). In this cohort, AUC for at least one severe exacerbation was 0·768 (0·767-0·769; Brier score 0·088). INTERPRETATION: CT-based prediction models can be used for identification of patients with COPD who are at high risk of severe exacerbations. The newly identified CT biomarkers could potentially enable investigation into underlying disease mechanisms responsible for exacerbations. FUNDING: National Institutes of Health and the National Heart, Lung, and Blood Institute.

A Quick Reference Guide for Incidental Findings on Lung Cancer Screening CT Examinations.

PURPOSE: The US Preventive Services Task Force has recommended lung cancer screening (LCS) with low-dose CT (LDCT) in high-risk individuals since 2013. Because LDCT encompasses the lower neck, chest, and upper abdomen, many incidental findings (IFs) are detected. The authors created a quick reference guide to describe common IFs in LCS to assist LCS program navigators and ordering providers in managing the care continuum in LCS. METHODS: The ACR IF white papers were reviewed for findings on LDCT that were age appropriate for LCS. A draft guide was created on the basis of recommendations in the IF white papers, the medical literature, and input from subspecialty content experts. The draft was piloted with LCS program navigators recruited through contacts by the ACR LCS Steering Committee. The navigators completed a survey on overall usefulness, clarity, adequacy of content, and user experience with the guide. RESULTS: Seven anatomic regions including 15 discrete organs with 45 management recommendations were identified as relevant to the age of individuals eligible for LCS. The draft was piloted by 49 LCS program navigators from 32 facilities. The guide was rated as useful and clear by 95% of users. No unexpected or adverse experiences were reported in using the guide. On the basis of feedback, relevant sections were reviewed and edited. CONCLUSIONS: The ACR Lung Cancer Screening CT Incidental Findings Quick Reference Guide outlines the common IFs in LCS and can serve as an easy-to-use resource for ordering providers and LCS program navigators to help guide management.