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.

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. 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.

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.

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

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. To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. 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.

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.

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

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. To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD. We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study.

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).

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.

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

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. To phenotype patients with IPF for potential targeted therapy, we developed Cu-DOTA-ECL1i, a radiotracer to noninvasively track CCR2 monocytes and macrophages using positron emission tomography (PET).

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.

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.

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.

The breadth of the diaphragm: updates in embryogenesis and role of imaging.

The diaphragm is an unique skeletal muscle separating the thoracic and abdominal cavities with a primary function of enabling respiration. When abnormal, whether by congenital or acquired means, the consequences for patients can be severe. Abnormalities that affect the diaphragm are often first detected on chest radiographs as an alteration in position or shape.

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.

Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction.

Background: The link between mucus plugs and airflow obstruction has not been established in chronic severe asthma, and the role of eosinophils and their products in mucus plug formation is unknown.

Methods: In clinical studies, we developed and applied a bronchopulmonary segment-based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans from 146 subjects with asthma and 22 controls, and analyzed relationships among mucus plug scores, forced expiratory volume in 1 second (FEV1), and airway eosinophils. Additionally, we used airway mucus gel models to explore whether oxidants generated by eosinophil peroxidase (EPO) oxidize cysteine thiol groups to promote mucus plug formation.

Lung Cancer Risk Associated With New Solid Nodules in the National Lung Screening Trial.

Objective: As low-dose CT (LDCT) lung cancer screening moves into routine clinical practice, evaluation of nodules identified as new becomes critical. We examine the frequency and clinical outcomes of new lung nodules reported at the two postbaseline annual screening examinations (hereafter referred to as postbaseline time 1 [T1] and time 2 [T2]), compared with those detected at baseline in the National Lung Screening Trial.

Materials And Methods: Radiologists classified nodules detected at T1 and T2 as new or preexisting on the basis of comparison with findings from prior LDCT screening examinations.

Quality assurance and quantitative imaging biomarkers in low-dose CT lung cancer screening.

After years of assessment through controlled clinical trials, low-dose CT screening for lung cancer is becoming part of clinical practice. As with any cancer screening test, those undergoing lung cancer screening are not being evaluated for concerning signs or symptoms, but are generally in good health and proactively trying to prevent premature death. Given the resultant obligation to achieve the screening aim of early diagnosis while also minimizing the potential for morbidity from workup of indeterminate but ultimately benign screening abnormalities, careful implementation of screening with conformance to currently recognized best practices and a focus on quality assurance is essential.

The relationship of cancer characteristics and patient outcome with time to lung cancer diagnosis after an abnormal screening CT.

Purpose: The National Lung Screening Trial (NLST) demonstrated a reduction in lung cancer and all-cause mortality with low-dose CT (LDCT) screening. The aim of our study was to examine the time to diagnosis (TTD) of lung cancer in the LDCT arm of the NLST and assess its relationship with cancer characteristics and survival.

Methods: The subjects (N = 462) with a positive baseline screen and subsequent lung cancer diagnosis within 3 years were evaluated by data and image review to confirm the baseline abnormality.

What makes a good pediatric transplant lung: Insights from in vivo lung morphometry with hyperpolarized He magnetic resonance imaging.

Obtaining information on transplanted lung microstructure is an important part of the current care for monitoring transplant recipients. However, until now this information was only available from invasive lung biopsy. The objective of this study was to evaluate the use of an innovative non-invasive technique, in vivo lung morphometry with hyperpolarized ³He MRI-to characterize lung microstructure in the pediatric lung transplant population.

Using imaging as a biomarker for asthma.

There have been significant advancements in the various imaging techniques being used for the evaluation of asthmatic patients, both from a clinical and research perspective. Imaging characteristics can be used to identify specific asthmatic phenotypes and provide a more detailed understanding of endotypes contributing to the pathophysiology of the disease. Computed tomography, magnetic resonance imaging, and positron emission tomography can be used to assess pulmonary structure and function.

Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants.

Objectives: This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen.

Methods: The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer.