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Lung cancer is a leading cause of cancer death in the United States and globally with the majority of lung cancer cases attributable to cigarette smoking. Given the high societal and personal cost of a diagnosis of lung cancer including that most cases of lung cancer when diagnosed are found at a late stage, work over the past 40 years has aimed to detect lung cancer earlier when curative treatment is possible. Screening trials using chest radiography and sputum failed to show a reduction in lung cancer mortality however multiple studies using low dose CT have shown the ability to detect lung cancer early and a survival benefit to those screened. This review will discuss the history of lung cancer screening, current recommendations and screening guidelines, and implementation and components of a lung cancer screening program.

Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.

Accurate segmentation of the lung nodule in computed tomography images is a critical component of a computer-assisted lung cancer detection/diagnosis system. However, lung nodule segmentation is a challenging task due to the heterogeneity of nodules. This study is to develop a hybrid deep learning (H-DL) model for the segmentation of lung nodules with a wide variety of sizes, shapes, margins, and opacities.A dataset collected from Lung Image Database Consortium image collection containing 847 cases with lung nodules manually annotated by at least two radiologists with nodule diameters greater than 7 mm and less than 45 mm was randomly split into 683 training/validation and 164 independent test cases. The 50% consensus consolidation of radiologists' annotation was used as the reference standard for each nodule. We designed a new H-DL model combining two deep convolutional neural networks (DCNNs) with different structures as encoders to increase the learning capabilities for the segmentation of complex lung nodules. Leveraging the basic symmetric U-shaped architecture of U-Net, we redesigned two new U-shaped deep learning (U-DL) models that were expanded to six levels of convolutional layers. One U-DL model used a shallow DCNN structure containing 16 convolutional layers adapted from the VGG-19 as the encoder, and the other used a deep DCNN structure containing 200 layers adapted from DenseNet-201 as the encoder, while the same decoder with only one convolutional layer at each level was used in both U-DL models, and we referred to them as the shallow and deep U-DL models. Finally, an ensemble layer was used to combine the two U-DL models into the H-DL model. We compared the effectiveness of the H-DL, the shallow U-DL and the deep U-DL models by deploying them separately to the test set. The accuracy of volume segmentation for each nodule was evaluated by the 3D Dice coefficient and Jaccard index (JI) relative to the reference standard. For comparison, we calculated the median and minimum of the 3D Dice and JI over the individual radiologists who segmented each nodule, referred to as M-Dice, min-Dice, M-JI, and min-JI.For the 164 test cases with 327 nodules, our H-DL model achieved an average 3D Dice coefficient of 0.750 ± 0.135 and an average JI of 0.617 ± 0.159. The radiologists' average M-Dice was 0.778 ± 0.102, and the average M-JI was 0.651 ± 0.127; both were significantly higher than those achieved by the H-DL model (p 0.05). The radiologists' average min-Dice (0.685 ± 0.139) and the average min-JI (0.537 ± 0.153) were significantly lower than those achieved by the H-DL model (p 0.05). The results indicated that the H-DL model approached the average performance of radiologists and was superior to the radiologist whose manual segmentation had the min-Dice and min-JI. Moreover, the average Dice and average JI achieved by the H-DL model were significantly higher than those achieved by the individual shallow U-DL model (Dice of 0.745 ± 0.139, JI of 0.611 ± 0.161; p 0.05) or the individual deep U-DL model alone (Dice of 0.739 ± 0.145, JI of 0.604 ± 0.163; p 0.05).Our newly developed H-DL model outperformed the individual shallow or deep U-DL models. The H-DL method combining multilevel features learned by both the shallow and deep DCNNs could achieve segmentation accuracy comparable to radiologists' segmentation for nodules with wide ranges of image characteristics.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Although recommended lung cancer screening with low-dose computed tomography scanning (LDCT) reduces mortality among high-risk adults, annual screening rates remain low. This study complements a previous nationwide assessment of access to lung cancer screening within 40 miles by evaluating differences in accessibility across rural and urban settings for the population aged 50 to 80 years and a subset eligible population based on the 2021 US Preventive Services Task Force LDCT lung screening recommendations.Distances from population centers to screening facilities (American College of Radiology Lung Cancer Screening Registry) were calculated, and the number of individuals who had access within graduating distances, including 10, 20, 40, 50, and 100 miles, were estimated. Census tract results were aggregated to counties, and both geographies were classified with rural-urban schemas.Approximately 5% of the eligible population did not have access to lung cancer screening facilities within 40 miles; however, different patterns of accessibility were observed at different distances, between regions, and across rural-urban environments. Across all distances and geographies, there was a larger percentage of the population in rural geographies with no access. Although the rural population represented approximately 8% of the eligible population, the larger percentage of the rural population with no access was noteworthy and translated into a larger number of individuals with no access at longer distance thresholds (≥40 miles).Disparities in access should be examined as both percentages of the population and numbers of individuals with no access in order to tailor interventions to communities and increase access. Geospatial analysis at the census tract level is recommended to help to identify optimal focus areas and reach the most people.As annual lung cancer screening rates remain low, this study examines access to lung cancer screening nationwide and across rural and urban settings. A geographic information system network analysis of census tract-level populations is used to estimate access at different distances, including 10, 20, 40, 50, and 100 miles, and the results are aggregated to counties. Approximately 5% of the eligible population does not have access to screening facilities within 40 miles; however, different patterns of accessibility are observed at different distances, between regions, and across rural-urban environments. Across all distances and geographies, there is a larger percentage of the population in rural geographies with no access.

Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was recommended by the U.S. Preventive Services Task Force (USPSTF) in 2013, making approximately 8 million Americans eligible for screening. The demographic characteristics and adherence of persons screened in the United States have not been reported at the population level.To define sociodemographic characteristics and adherence among persons screened and entered into the American College of Radiology's Lung Cancer Screening Registry (LCSR).Cohort study.United States, 2015 to 2019.Persons receiving a baseline LDCT for LCS from 3625 facilities reporting to the LCSR.Age, sex, and smoking status distributions (percentages) were computed among persons who were screened and among respondents in the 2015 National Health Interview Survey (NHIS) who were eligible for screening. The prevalence between the LCSR and the NHIS was compared with prevalence ratios (PRs) and 95% CIs. Adherence to annual screening was defined as having a follow-up test within 11 to 15 months of an initial LDCT.Among 1 159 092 persons who were screened, 90.8% (Underreporting of LCS and missing data may skew demographic characteristics of persons reported to be screened. Underreporting of adherence may result in underestimates of follow-up.Approximately 91% of persons who had LCS met USPSTF eligibility criteria. In addition to continuing to target all eligible adults, men, those who formerly smoked, and younger eligible patients may be less likely to be screened. Adherence to annual follow-up screening was poor, potentially limiting screening effectiveness.None.

BACKGROUND: Smokers manifest varied phenotypes of pulmonary impairment. RESEARCH QUESTION: Which pulmonary phenotypes are associated with coronary artery disease (CAD) in smokers? STUDY DESIGN AND METHODS: We analyzed data from the University of Pittsburgh COPD Specialized Center for Clinically Oriented Research (SCCOR) cohort (n = 481) and the Genetic Epidemiology of COPD (COPDGene) cohort (n = 2,580). Participants were current and former smokers with > 10 pack-years of tobacco exposure. Data from the two cohorts were analyzed separately because of methodologic differences. Lung hyperinflation was assessed by plethysmography in the SCCOR cohort and by inspiratory and expiratory CT scan lung volumes in the COPDGene cohort. Subclinical CAD was assessed as the coronary artery calcium score, whereas clinical CAD was defined as a self-reported history of CAD or myocardial infarction (MI). Analyses were performed in all smokers and then repeated in those with airflow obstruction (FEV(1) to FVC ratio, < 0.70). RESULTS: Pulmonary phenotypes, including airflow limitation, emphysema, lung hyperinflation, diffusion capacity, and radiographic measures of airway remodeling, showed weak to moderate correlations (r < 0.7) with each other. In multivariate models adjusted for pulmonary phenotypes and CAD risk factors, lung hyperinflation was the only phenotype associated with calcium score, history of clinical CAD, or history of MI (per 0.2 higher expiratory and inspiratory CT scan lung volume; coronary calcium: OR, 1.2; 95% CI, 1.1-1.5; P = .02; clinical CAD: OR, 1.6; 95% CI, 1.1-2.3; P = .01; and MI in COPDGene: OR, 1.7; 95% CI, 1.0-2.8; P = .05). FEV(1) and emphysema were associated with increased risk of CAD (P < .05) in models adjusted for CAD risk factors; however, these associations were attenuated on adjusting for lung hyperinflation. Results were the same in those with airflow obstruction and were present in both cohorts. INTERPRETATION: Lung hyperinflation is associated strongly with clinical and subclinical CAD in smokers, including those with airflow obstruction. After lung hyperinflation was accounted for, FEV(1) and emphysema no longer were associated with CAD. Subsequent studies should consider measuring lung hyperinflation and examining its mechanistic role in CAD in current and former smokers.

Lung cancer screening with a low radiation dose chest CT scan is the standard of care for screening-eligible individuals. The net benefit of screening may be optimized by delivering high-quality care, capable of maximizing the benefit and minimizing the harms of screening. Valid, feasible, and relevant indicators of the quality of lung cancer screening may help programs to evaluate their current practice and to develop quality improvement plans. The purpose of this project was to develop quality indicators related to the processes and outcomes of screening. Potential quality indicators were explored through surveys of multidisciplinary lung cancer screening experts. Those that achieved predefined measures of consensus for each of the validity, feasibility, and relevance domains are proposed as quality indicators. Each of the proposed indicators is described in detail, with guidance on how to define, measure, and improve program performance within the indicator.

Differently from computed tomography (CT), well-defined terminology for chest radiography (CXR) findings and standardized reporting in the setting of known or suspected COVID-19 are still lacking. We propose a revision of CXR major imaging findings in SARS-CoV-2 pneumonia derived from the comparison of CXR and CT, suggesting a precise and standardized terminology for CXR reporting. This description will consider asymptomatic patients, symptomatic patients, and patients with SARS-CoV-2-related pulmonary complications. We suggest using terms such as ground-glass opacities, consolidation, and reticular pattern for the most common findings, and characteristic chest radiographic pattern in presence of one or more of the above-mentioned findings with peripheral and mid-to-lower lung zone distribution.

In 2014, the American College of Radiology (ACR) created Lung-RADS 1.0. The system was updated to Lung-RADS 1.1 in 2019, and further updates are anticipated as additional data become available. Lung-RADS provides a common lexicon and standardized nodule follow-up management paradigm for use when reporting lung cancer screening (LCS) low-dose CT (LDCT) chest examinations and serves as a quality assurance and outcome monitoring tool. The use of Lung-RADS is intended to improve LCS performance and lead to better patient outcomes. To date, the ACR's Lung Cancer Screening Registry is the only LCS registry approved by the Centers for Medicare & Medicaid Services and requires the use of Lung-RADS categories for reimbursement. Numerous challenges have emerged regarding the use of Lung-RADS in clinical practice, including the timing of return to LCS after planned follow-up diagnostic evaluation; potential substitution of interval diagnostic CT for future LDCT; role of volumetric analysis in assessing nodule size; assessment of nodule growth; assessment of cavitary, subpleural, and category 4X nodules; and variability in reporting of the S modifier. This article highlights the major updates between versions 1.0 and 1.1 of Lung-RADS, describes the system's ongoing challenges, and summarizes current evidence and recommendations.

Background Lung cancer risk prediction models do not routinely incorporate imaging metrics available on low-dose CT (LDCT) imaging of the chest ordered for lung cancer screening. Research Question What is the association between quantitative emphysema measured on LDCT imaging and lung cancer incidence and mortality, all-cause mortality, and airflow obstruction in individuals who currently or formerly smoked and are undergoing lung cancer screening? Study Design and Methods In 7,262 participants in the CT arm of the National Lung Screening Trial, percent low attenuation area (%LAA) was defined as the percentage of lung volume with voxels less than –950 Hounsfield units on the baseline examination. Multivariable Cox proportional hazards models, adjusting for competing risks where appropriate, were built to test for association between %LAA and lung cancer incidence, lung cancer mortality, and all-cause mortality with censoring at 6 years. In addition, multivariable logistic regression models were built to test the cross-sectional association between %LAA and airflow obstruction on spirometry, which was available in 2,700 participants. Results The median %LAA was 0.8% (interquartile range, 0.2%-2.7%). Every 1% increase in %LAA was independently associated with higher hazards of lung cancer incidence (hazard ratio [HR], 1.02; 95% CI, 1.01-1.03; P = .004), lung cancer mortality (HR, 1.02; 95% CI, 1.00-1.05; P = .045), and all-cause mortality (HR, 1.01; 95% CI, 1.00-1.03; P = .042). Among participants with spirometry, 892 had airflow obstruction. The likelihood of airflow obstruction increased with every 1% increase in %LAA (odds ratio, 1.07; 95% CI, 1.06-1.09; P 65 years. Interpretation Quantitative emphysema measured on LDCT imaging of the chest can be leveraged to improve lung cancer risk prediction and help diagnose COPD in individuals who currently or formerly smoked and are undergoing lung cancer screening.

Comprehensive biomarker testing has become the standard of care for informing the choice of the most appropriate targeted therapy for many patients with advanced cancer. Despite evidence demonstrating the need for comprehensive biomarker testing to enable the selection of appropriate targeted therapies and immunotherapy, the incorporation of biomarker testing into clinical practice lags behind recommendations in National Comprehensive Cancer Network guidelines. Coverage policy differences across insurance health plans have limited the accessibility of comprehensive biomarker testing largely to patients whose insurance covers the recommended testing or those who can pay for the testing, and this has contributed to health disparities. Furthermore, even when insurance coverage exists for recommended biomarker testing, patients may incur burdensome out-of-pocket costs depending on their insurance plan benefits, which may also create barriers to testing. Prior authorization for biomarker testing for some patients can add an administrative burden and may delay testing and thus treatment if it is not done in a timely manner. Recently, three states (Illinois, Louisiana, and California) passed laws designed to improve access to biomarker testing at the state level. However, there is variability among these laws in terms of the population affected, the stage of cancer, and whether the coverage of testing is mandated, or the legislation addresses only prior authorization. Advocacy efforts by patient advocates, health care professionals, and professional societies are imperative at the state level to further improve coverage for and access to appropriate biomarker testing.

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.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.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.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.

In chronic obstructive pulmonary disease (COPD) functional small airways disease (fSAD) has been identified as a transitional state between healthy lung and irremediable emphysema. Topological analysis of the CT-based parametric response map (PRM) spatially quantifies distribution and arrangement of fSAD and emphysema. We present a cross sectional analysis of topological PRM (tPRM) in 8,972 participants from the COPDGene study, covering a complete spectrum of COPD severity. We aimed to evaluate tPRM dynamics with respect to GOLD and test association of tPRM with pulmonary function using Spearman correlation and stepwise linear regression. Baseline CT and clinical data were included, and tPRM was computed as whole lung averages summarizing disease volume density, surface area, curvature and perforation (measured by Ⲭ). Strong correlation (ρ = -0.74, p < 0.001) was determined between degree of perforation in healthy lung (ⲬNorm) and fSAD regions (ⲬfSAD), transposing from predominantly healthy lung perforated with fSAD (GOLD 2, ⲬNorm = -0.84, ⲬfSAD = 0.47) to fSAD perforated with healthy lung (GOLD 4, ⲬNorm = 0.39, ⲬfSAD = -0.36). tPRM significantly (p < 0.05) contributed to regression modelling of FEV1/FVC (R2 = 0.71), where surface area of emphysema had the most notable effect (β = -0.49, p < 0.01). Thus, tPRM provided insight into topology of fSAD and emphysema in COPD and associated statistically with clinical lung function measures.

International audience; Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the Food and Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-ILD: nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, two generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a Phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy in the management of patients with SSc-ILD is still to be determined. The objectives of this review are two-fold: (1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and (2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical vs. clinical ILD) and associated risk of progression (low vs. high risk). The pharmacological and non-pharmacological options as first and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD.

Objectives To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). Methods A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. Results Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. Conclusions Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.

Parametric response mapping (PRM) is a novel computed tomography (CT) technology that has shown potential for assessment of bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HCT). The primary aim of this study was to evaluate whether variations in image acquisition under real-world conditions affect the PRM measurements of clinically diagnosed BOS. CT scans were obtained retrospectively from 72 HCT recipients with BOS and graft-versus-host disease from Fred Hutchinson Cancer Research Center, Karolinska Institute, and the University of Michigan. Whole lung volumetric scans were performed at inspiration and expiration using site-specific acquisition and reconstruction protocols. PRM and pulmonary function measurements were assessed. Patients with moderately severe BOS at diagnosis (median forced expiratory volume at 1 second [FEV1] 53.5% predicted) had similar characteristics between sites. Variations in site-specific CT acquisition protocols had a negligible effect on the PRM-derived small airways disease (SAD), that is, BOS measurements. PRM-derived SAD was found to correlate with FEV1% predicted and FEV1/ forced vital capacity (R = -0.236, P = .046; and R = -0.689, P < .0001, respectively), which suggests that elevated levels in the PRM measurements are primarily affected by BOS airflow obstruction and not CT scan acquisition parameters. Based on these results, PRM may be applied broadly for post-HCT diagnosis and monitoring of BOS.

Background The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. Methods An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. Results Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non–small-cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non–small-cell lung cancer. Conclusions There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

Chronic rejection of lung allografts has two major subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), which present radiologically either as air trapping with small airways disease or with persistent pleuroparenchymal opacities. Parametric response mapping (PRM), a computed tomography (CT) methodology, has been demonstrated as an objective readout of BOS and RAS and bears prognostic importance, but has yet to be correlated to biological measures. Using a topological technique, we evaluate the distribution and arrangement of PRM-derived classifications of pulmonary abnormalities from lung transplant recipients undergoing redo-transplantation for end-stage BOS (N = 6) or RAS (N = 6). Topological metrics were determined from each PRM classification and compared to structural and biological markers determined from microCT and histopathology of lung core samples. Whole-lung measurements of PRM-defined functional small airways disease (fSAD), which serves as a readout of BOS, were significantly elevated in BOS versus RAS patients (p = 0.01). At the core-level, PRM-defined parenchymal disease, a potential readout of RAS, was found to correlate to neutrophil and collagen I levels (p < 0.05). We demonstrate the relationship of structural and biological markers to the CT-based distribution and arrangement of PRM-derived readouts of BOS and RAS. ispartof: CELLS vol:11 issue:4 ispartof: location:Switzerland status: published

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas