Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection.

Lung cancer screening via annual low-dose computed tomography (LDCT) has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by an LDCT. Changes in genome-wide cell-free DNA (cfDNA) fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples, and then validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer, and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a five-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

Potential Role of Computed Tomography Volumetry in Size Matching in Lung Transplantation.

BACKGROUND: Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction. METHODS: Donors from the local organ procurement organization and recipients from our hospital from 2012 to 2018 were included if their CT exams were available. The CT lung volumes and plethysmography total lung capacity were measured and compared with predicted total lung capacity using Bland Altman methods. We used logistic regression to predict the need for surgical graft reduction and ordinal logistic regression to stratify the risk for primary graft dysfunction. RESULTS: A total of 315 transplant candidates with 575 CT scans and 379 donors with 379 CT scans were included. The CT lung volumes closely approximated plethysmography lung volumes and differed from the predicted total lung capacity in transplant candidates. In donors, CT lung volumes systematically underestimated predicted total lung capacity. Ninety-four donors and recipients were matched and transplanted locally. Larger donor and smaller recipient lung volumes estimated by CT predicted a need for surgical graft reduction and were associated with higher primary graft dysfunction grade. CONCLUSION: The CT lung volumes predicted the need for surgical graft reduction and primary graft dysfunction grade. Adding CT-derived lung volumes to the donor-recipient matching process may improve recipients' outcomes.

Do Biologic Therapies Decrease Mucus Plugging in Asthma?

Asthma researchers have long recognized that abnormal mucus production and clearance play a role in the pathophysiology of asthma.1 Mucus plugs are known to be common in patients with severe asthma, and mucus plug scores, for which higher scores indicate more severe plugging, are directly correlated with airflow obstruction and markers of eosinophilic airway inflammation (i.e., higher scores or marker levels are associated with more severe obstruction). Other work has shown that mucus plugs were associated with distal deficits in regional ventilation as delineated by hyperpolarized gas magnetic resonance imaging.2,3.

Treatment of Stage I Lung Cancer Detected by Computed Tomography Screening.

Introduction: Reducing lung cancer deaths through early detection by computed tomography (CT) screening requires delivery of effective treatment. We performed this retrospective study to determine the types of treatment used for screen-detected stage I lung cancer at our academic center and to compare the demographic and clinical characteristics of patients by type of treatment. Methods: All persons screened in the lung cancer screening program at our institution through June 16, 2021, were included. Those with screening CT findings needing follow-up were managed through a thoracic surgery clinic. Demographic and clinical characteristics of patients diagnosed with having stage I lung cancer through June 16, 2021, were compared by type of treatment, with follow-up through December 31, 2021. Results: Stage I NSCLC was diagnosed in 54 of 2203 persons screened (2.5%), on the basis of biopsy in 37 and on imaging findings in 17 patients in whom a tissue diagnosis could not be obtained. Treatment was by lobectomy in 18, sublobar resection in 14, and stereotactic body radiation therapy (SBRT) in 22. Patients treated with SBRT had lower forced expiratory volume in 1 second (p < 0.001) and diffusing capacity of the lung for carbon monoxide (p < 0.001) and more comorbidities (p = 0.003) than those treated with surgery. New or recurrent cancer developed in nine patients (three lobectomy, three sublobar resection, three SBRT). Conclusions: Many patients with screen-detected stage I lung cancer are medically unfit for lobectomy, and a variety of treatments are being used. Assessment of treatment-based outcomes will be critical for ensuring an optimal balance of the risks and benefits of CT screening in a medically diverse population.

Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time.

Rationale: Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. Objectives: To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. Methods: In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures. Measurements and Main Results: In 164 participants, the mean (range) mucus plug score was similar at baseline and Year 3 (3.4 [0-20] vs. 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at Year 3 than those without baseline plugs (risk ratio, 2.8; 95% confidence interval [CI], 2.0-4.1; P < 0.001; and risk ratio, 5.0; 95% CI, 4.5-5.6; P < 0.001, respectively). The change in mucus plug score from baseline to Year 3 was significantly negatively correlated with change in FEV1% predicted (rp = -0.35; P < 0.001) and with changes in CT air trapping measures (all P values < 0.05). Conclusions: Mucus plugs identify a persistent asthma phenotype, and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.

Incidental Findings on Low-Dose CT Scan Lung Cancer Screenings and Deaths From Respiratory Diseases.

BACKGROUND: Incidental respiratory disease-related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. This study analyzed data from the National Lung Screening Trial (NLST) to assess the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer. RESEARCH QUESTION: Are incidental respiratory findings on LDCT scanning associated with increased RDM? STUDY DESIGN AND METHODS: Subjects in the NLST LDCT arm received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographic characteristics, smoking history, and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM. Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT scan findings, variables included respiratory disease history (COPD/emphysema, and asthma), smoking history, and demographic factors (age, race, sex, and BMI). RESULTS: Of 26,722 subjects in the NLST LDCT arm, 25,002 received the baseline screen and a subsequent LDCT screen. Overall, 59% were male, 26.5% were aged ≥ 65 years at baseline, and 10.6% reported a history of COPD/emphysema. Emphysema on LDCT scanning was reported in 30.7% of subjects at baseline and in 44.2% at any screen. Of those with emphysema on baseline LDCT scanning, 18% reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3,639 deaths, and 708 were from respiratory diseases. Among subjects with no history of COPD/emphysema, 10-year cumulative RDM ranged from 3.9% for subjects with emphysema and reticular opacities to 1.1% for those with neither condition; the corresponding range among subjects with a COPD/emphysema history was 17.3% (both) to 3.7% (neither). Emphysema on LDCT imaging was associated with a significantly elevated RDM hazard ratio (2.27; 95% CI, 1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated hazard ratio (1.39; 95% CI, 1.19-1.62). INTERPRETATION: Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases.

Mucus Plugs in Asthma at CT Associated with Regional Ventilation Defects at 3He MRI.

Background Airway mucus plugs in asthma are associated with exacerbation frequency, increased eosinophilia, and reduced lung function. The relationship between mucus plugs and spatially overlapping ventilation abnormalities observed at hyperpolarized gas MRI has not been assessed quantitatively. Purpose To assess regional associations between CT mucus plugs scored by individual bronchopulmonary segment and corresponding measurements of segmental ventilation defect percentage (VDP) at hyperpolarized helium 3 (3He) MRI. Materials and Methods In this secondary analysis of a Health Insurance Portability and Accountability Act-compliant prospective observational cohort, participants in the Severe Asthma Research Program (SARP) III (NCT01760915) between December 2012 and August 2015 underwent hyperpolarized 3He MRI to determine segmental VDP. Segmental mucus plugs at CT were scored by two readers, with segments scored as plugged only if both readers agreed independently. A linear mixed-effects model controlling for interpatient variability was then used to assess differences in VDP in plugged versus plug-free segments. Results Forty-four participants with asthma were assessed (mean age ± standard deviation, 47 years ± 15; 29 women): 19 with mild-to-moderate asthma and 25 with severe asthma. Mucus plugs were observed in 49 total bronchopulmonary segments across eight of 44 patients. Segments containing mucus plugs had a median segmental VDP of 25.9% (25th-75th percentile, 7.3%-38.3%) versus 1.4% (25th-75th percentile, 0.1%-5.2%; P < .001) in plug-free segments. Similarly, the model estimated a segmental VDP of 18.9% (95% CI: 15.7, 22.2) for mucus-plugged segments versus 5.1% (95% CI: 3.3, 7.0) for plug-free segments (P < .001). Participants with one or more mucus plugs had a median whole-lung VDP of 11.1% (25th-75th percentile, 7.1%-18.9%) versus 3.1% (25th-75th percentile, 1.1%-4.4%) in those without plugs (P < .001). Conclusion Airway mucus plugging at CT was associated with reduced ventilation in the same bronchopulmonary segment at hyperpolarized helium 3 MRI, suggesting that mucus plugging may be an important cause of ventilation defects in asthma. © RSNA, 2021 Online supplemental material is available for this article.

QIBA guidance: Computed tomography imaging for COVID-19 quantitative imaging applications.

As the COVID-19 pandemic impacts global populations, computed tomography (CT) lung imaging is being used in many countries to help manage patient care as well as to rapidly identify potentially useful quantitative COVID-19 CT imaging biomarkers. Quantitative COVID-19 CT imaging applications, typically based on computer vision modeling and artificial intelligence algorithms, include the potential for better methods to assess COVID-19 extent and severity, assist with differential diagnosis of COVID-19 versus other respiratory conditions, and predict disease trajectory. To help accelerate the development of robust quantitative imaging algorithms and tools, it is critical that CT imaging is obtained following best practices of the quantitative lung CT imaging community. Toward this end, the Radiological Society of North America's (RSNA) Quantitative Imaging Biomarkers Alliance (QIBA) CT Lung Density Profile Committee and CT Small Lung Nodule Profile Committee developed a set of best practices to guide clinical sites using quantitative imaging solutions and to accelerate the international development of quantitative CT algorithms for COVID-19. This guidance document provides quantitative CT lung imaging recommendations for COVID-19 CT imaging, including recommended CT image acquisition settings for contemporary CT scanners. Additional best practice guidance is provided on scientific publication reporting of quantitative CT imaging methods and the importance of contributing COVID-19 CT imaging datasets to open science research databases.

Survival Following Detection of Stage I Lung Cancer by Screening in the National Lung Screening Trial.

BACKGROUND: There is limited information about survival of stage I lung cancer diagnosed by screening. RESEARCH QUESTION: What was the survival rate of screen-detected stage I lung cancer in the National Lung Screening Trial (NLST), and was it affected by screening method, patient or tumor characteristics, or treatment method? STUDY DESIGN AND METHODS: The study cohort consisted of all NLST participants with screen-detected stage I lung cancer. Lung cancer-specific survival for stage I overall and for IA and IB substages were compared in the low-dose CT and chest radiography (CXR) screening randomization arms and with an analogous cohort from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute; the cumulative incidence competing risk method was used for analysis. Cox proportional hazards models were used to evaluate the association between lung cancer-specific survival and screening arm, patient factors, primary tumor size, and treatment. RESULTS: There were 324 screen-detected stage I lung cancers in the low-dose CT arm and 125 in the CXR arm. The 10-year survival in the low-dose CT arm was greater than in the CXR arm (73.4% vs 64.6%; P = .05), and both were greater than in the Surveillance, Epidemiology, and End Results cohort (55.6%; P < .001 vs low-dose CT arm, P = .04 vs CXR arm). Proportional hazards models revealed a greater likelihood of survival in the low-dose CT arm (hazard ratio [HR], 0.69; 95% CI, 0.5-0.98) and with primary tumor size below the median of 17 mm (HR, 0.61; 95% CI, 0.42-0.88). There was no survival difference between treatment with limited resection vs full resection (HR, 1.11; 95% CI, 0.6-1.9), whereas nonsurgical treatment was associated with a reduced likelihood of survival compared with full resection (HR, 3.1; 95% CI, 1.6-6.0). INTERPRETATION: Long-term lung cancer-specific survival of stage I lung cancer was greater with low-dose CT imaging than with CXR screening or in the general population, for smaller primary tumor size, and with surgical treatment.

Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory lung disease without effective molecular markers of disease activity or treatment responses. Monocyte and interstitial macrophages that express the C-C motif CCR2 (chemokine receptor 2) are active in IPF and central to fibrosis.Objectives: To phenotype patients with IPF for potential targeted therapy, we developed 64Cu-DOTA-ECL1i, a radiotracer to noninvasively track CCR2+ monocytes and macrophages using positron emission tomography (PET).Methods: CCR2+ cells were investigated in mice with bleomycin- or radiation-induced fibrosis and in human subjects with IPF. The CCR2+ cell populations were localized relative to fibrotic regions in lung tissue and characterized using immunolocalization, single-cell mass cytometry, and Ccr2 RNA in situ hybridization and then correlated with parallel quantitation of lung uptake by 64Cu-DOTA-ECL1i PET.Measurements and Main Results: Mouse models established that increased 64Cu-DOTA-ECL1i PET uptake in the lung correlates with CCR2+ cell infiltration associated with fibrosis (n = 72). As therapeutic models, the inhibition of fibrosis by IL-1ß blockade (n = 19) or antifibrotic pirfenidone (n = 18) reduced CCR2+ macrophage accumulation and uptake of the radiotracer in mouse lungs. In lung tissues from patients with IPF, CCR2+ cells concentrated in perifibrotic regions and correlated with radiotracer localization (n = 21). Human imaging revealed little lung uptake in healthy volunteers (n = 7), whereas subjects with IPF (n = 4) exhibited intensive signals in fibrotic zones.Conclusions: These findings support a role for imaging CCR2+ cells within the fibrogenic niche in IPF to provide a molecular target for personalized therapy and monitoring.Clinical trial registered with www.clinicaltrials.gov (NCT03492762).

Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV1 and peripheral oxygen saturation (P < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P < 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) (P < 0.001).Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Improved Interobserver Agreement on Lung-RADS Classification of Solid Nodules Using Semiautomated CT Volumetry.

Background Classification of lung cancer screening CT scans depends on measurement of lung nodule size. Information about interobserver agreement is limited. Purpose To assess interobserver agreement in the measurements and American College of Radiology Lung CT Screening Reporting and Data System (Lung-RADS) classifications of solid lung nodules detected at lung cancer screening using manual measurements of average diameter and computer-aided semiautomated measurements of average diameter and volume (CT volumetry). Materials and Methods Two radiologists and one radiology resident retrospectively measured lung nodules from screening CT scans obtained between September 2016 and June 2018 with a Lung-RADS (version 1.0) classification of 2, 3, 4A, or 4B in the clinical setting. Average manual diameter and semiautomated computer-aided diameter and volume measurements were converted to the corresponding Lung-RADS categories. Interobserver agreement in raw measurements was assessed using intraclass correlation and Bland-Altman indexes, and interobserver agreement in Lung-RADS classification was assessed using bi-rater κ. Results One hundred twenty patients (mean age, 63 years ± 6 [standard deviation]; 67 women) were evaluated. All manual, semiautomated diameter, and semiautomated volume measurements were obtained by all three readers in 120 of 147 nodules (82%). Intraclass correlation coefficients were greater than or equal to 0.95 for all reader pairs using all measurement methods and were highest using volumetry. Bias and 95% limits of agreement for average diameter were smaller with semiautomated measurements than with manual measurements. κ values across all Lung-RADS classifications were greater than or equal to 0.81, with the lowest being for manual measurements and the highest being for volumetric measurements. Forty-three of 120 (36%) of the nodules were classified into a lower Lung-RADS category on the basis of volumetry compared with using manual diameter measurements by at least one reader, whereas the reverse occurred for four of 120 (3%) of the nodules. Conclusion Interobserver agreement was high with manual diameter measurements and increased with semiautomated CT volumetric measurements. Semiautomated CT volumetry enabled classification of more nodules into lower Lung CT Screening Reporting and Data System categories than manual or semiautomated diameter measurements. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Nishino in this issue.

Low-Dose CT Screening for Lung Cancer: Evidence from 2 Decades of Study.

Lung cancer remains the overwhelmingly greatest cause of cancer death in the United States, accounting for more annual deaths than breast, prostate, and colon cancer combined. Accumulated evidence since the mid to late 1990s, however, indicates that low-dose CT screening of high-risk patients enables detection of lung cancer at an early stage and can reduce the risk of dying from lung cancer. CT screening is now a recommended clinical service in the United States, subject to guidelines and reimbursement requirements intended to standardize practice and optimize the balance of benefits and risks. In this review, the evidence on the effectiveness of CT screening will be summarized and the current guidelines and standards will be described in the context of knowledge gained from lung cancer screening studies. In addition, an overview of the potential advances that may improve CT screening will be presented, and the need to better understand the performance in clinical practice outside of the research trial setting will be discussed. © RSNA, 2020.

Long-term cancer risk associated with lung nodules observed on low-dose screening CT scans.

OBJECTIVE: Non-calcified nodules (NCNs) associated with false positive low-dose CT (LDCT) lung cancer screens have been attributed to various causes. Some, however, may represent lung cancer precursors. An association of NCNs with long-term lung cancer risk would provide indirect evidence of some NCNs being cancer precursors. METHODS: LDCT arm participants in the National Lung Screening Trial (NLST) received LDCT screens at baseline and years 1-2. The relationship between NCNs found on LDCT screens and subsequent lung cancer diagnosis over different time periods was examined at the person and lobe level. For the latter, a lobe had a cancer outcome only if the cancer was located in the lobe. Separate analyses were performed on baseline and post-baseline LDCT findings; for the latter, those with baseline NCNs were excluded and only new (non-pre-existing) NCNs examined. Raw and adjusted rate-ratios (RRs) were computed for presence of NCNs and subsequent lung cancer risk; adjusted RRs controlled for demographic and smoking factors. RESULTS: 26,309 participants received the baseline LDCT screen. Over median 11.3 years follow-up, 1675 lung cancers were diagnosed. Adjusted RRs for time periods 0-4, 4-8 and 8-12 years following the baseline screen were 5.1 (95 % CI:4.4-5.9), 1.5 (95 % CI:1.3-1.9) and 1.5 (95 % CI:1.2-1.8) at the person-level and 14.7 (95 % CI:12.6-17.2), 2.6 (95 % CI: 2.0-3.4) and 2.2 (95 % CI:1.6-2.9) at the lobe-level. 18,585 participants were included in the post-baseline analysis. Adjusted RRs for periods 0-4, 4-8 and 8-11 years were 5.6 (95 % CI: 4.5-7.0), 1.9 (95 % CI: 1.3-2.7) and 1.6 (95 % CI: 0.9-2.9) at the person-level and 19.6 (95 % CI:14.9-25.3), 2.5 (95 % CI:1.3-4.7) and 3.3 (95 % CI:1.4-7.6) at the lobe-level. Raw RRs were similar. CONCLUSION: NCNs are associated with excess long-term lung cancer risk, suggesting that some may be lung cancer precursors.

Quantitative CT Analysis of Diffuse Lung Disease.

Quantitative analysis of thin-section CT of the chest has a growing role in the clinical evaluation and management of diffuse lung diseases. This heterogeneous group includes diseases with markedly different prognoses and treatment options. Quantitative tools can assist in both accurate diagnosis and longitudinal management by improving characterization and quantification of disease and increasing the reproducibility of disease severity assessment. Furthermore, a quantitative index of disease severity may serve as a useful tool or surrogate endpoint in evaluating treatment efficacy. The authors explore the role of quantitative imaging tools in the evaluation and management of diffuse lung diseases. Lung parenchymal features can be classified with threshold, histogram, morphologic, and texture-analysis-based methods. Quantitative CT analysis has been applied in obstructive, infiltrative, and restrictive pulmonary diseases including emphysema, cystic fibrosis, asthma, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue-related interstitial lung disease, and combined pulmonary fibrosis and emphysema. Some challenges limiting the development and practical application of current quantitative analysis tools include the quality of training data, lack of standard criteria to validate the accuracy of the results, and lack of real-world assessments of the impact on outcomes. Artifacts such as patient motion or metallic beam hardening, variation in inspiratory effort, differences in image acquisition and reconstruction techniques, or inaccurate preprocessing steps such as segmentation of anatomic structures may lead to inaccurate classification. Despite these challenges, as new techniques emerge, quantitative analysis is developing into a viable tool to supplement the traditional visual assessment of diffuse lung diseases and to provide decision support regarding diagnosis, prognosis, and longitudinal evaluation of disease. ©RSNA, 2019.

Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients.

BACKGROUND: Quantitative computed tomographic (QCT) biomarkers of airway morphology hold potential for understanding and monitoring regional airway remodeling in asthmatic patients. OBJECTIVE: We sought to determine whether the change in airway lumen area between total lung capacity (TLC) and functional residual capacity (FRC) lung volumes measured from CT imaging data was correlated with severe outcomes in asthmatic patients. METHODS: We studied 152 asthmatic patients (90 female and 62 male patients) and 33 healthy subjects (12 female and 21 male subjects) using QCT. Postprocessing of airways at generations 1 to 5 (1 = trachea) was performed for wall area percentage, wall thickness percentage (WT%), lumen area at baseline total lung capacity (LATLC), lumen area at baseline functional residual capacity (LAFRC), and low attenuation area at FRC. A new metric (reflecting remodeling, distal air trapping, or both), Delta Lumen, was determined as follows: Percentage difference in lumen area (LATLC - LAFRC)/LATLC × 100. RESULTS: Postprocessing of 4501 airway segments was performed (3681 segments in the 152 patients with asthma and 820 segments in the 33 healthy subjects; range, 17-28 segments per subject). Delta Lumen values were negatively correlated with WT% and low attenuation area (P < .01) in asthmatic patients. Delta Lumen values were significantly lower for airway generations 3 to 5 (segmental airways) in subjects undergoing hospitalization because of exacerbation and in patients with refractory asthma requiring treatment with systemic corticosteroids. WT% and low attenuation area were positively and Delta Lumen values were negatively associated with systemic corticosteroid treatment (P < .05), suggesting that a reduced Delta Lumen value is a potential outcome biomarker in patients with severe asthma. CONCLUSION: Reduced Delta Lumen value in the central airways measured by using QCT is a promising exploratory biomarker of unstable refractory asthma that warrants further study.