Prospective evaluation of lung cancer screening eligibility criteria and lung cancer detection in the Yorkshire Lung Screening Trial.

Introduction: Low dose CT (LDCT) screening for lung cancer reduces lung cancer mortality, but there is a lack of international consensus regarding the optimal eligibility criteria for screening. The Yorkshire Lung Screening Trial (YLST) was designed to evaluate lung cancer screening (LCS) implementation and a primary objective was prospective evaluation of 3 pre-defined eligibility criteria.

Methods: Individuals who had ever smoked, aged 55-80yrs, who responded to written invitation, underwent telephone risk assessment and if eligible by at least one criteria (PLCO≥1.

A lentiviral toolkit to monitor airway epithelial cell differentiation using bioluminescence.

Basal cells are adult stem cells in the airway epithelium and regenerate differentiated cell populations, including the mucosecretory and ciliated cells that enact mucociliary clearance. Human basal cells can proliferate and produce differentiated epithelium in vitro. However, studies of airway epithelial differentiation mostly rely on immunohistochemical or immunofluorescence-based staining approaches, meaning that a dynamic approach is lacking, and quantitative data are limited.

11β hydroxysteroid dehydrogenase type 1 transgenic mesenchymal stem cells attenuate inflammation in models of sepsis.

Background: Human bone marrow mesenchymal stem cell (MSC) administration reduces inflammation in pre-clinical models of sepsis and sepsis-related lung injury, however clinical efficacy in patients has not yet been demonstrated. We previously showed that Alveolar Macrophage (AM) 11β-hydroxysteroid dehydrogenase type-1 (HSD-1) autocrine signalling is impaired in critically ill sepsis patients, which promotes inflammatory injury. Administration of transgenic MSCs (tMSCs) which overexpress HSD-1 may enhance the anti-inflammatory effects of local glucocorticoids and be more effective at reducing inflammation in sepsis than cellular therapy alone.

Enhancing cancer prediction in challenging screen-detected incident lung nodules using time-series deep learning.

Lung cancer screening (LCS) using annual computed tomography (CT) scanning significantly reduces mortality by detecting cancerous lung nodules at an earlier stage. Deep learning algorithms can improve nodule malignancy risk stratification. However, they have typically been used to analyse single time point CT data when detecting malignant nodules on either baseline or incident CT LCS rounds.

Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models.

Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor.

Airway injury induces alveolar epithelial and mesenchymal responses mediated by macrophages.

Acute injury in the airways or the lung activates local progenitors and stimulates changes in cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted. We utilized mouse models of airway-specific epithelial injury to examine secondary tissue-wide alveolar, immune, and mesenchymal responses. Single-cell transcriptomics and validation revealed transient, tissue-wide proliferation of alveolar type 2 (AT2) progenitor cells after club cell-specific ablation.

Lentiviral expression of wild-type LAMA3A restores cell adhesion in airway basal cells from children with epidermolysis bullosa.

The hallmark of epidermolysis bullosa (EB) is fragile attachment of epithelia due to genetic variants in cell adhesion genes. We describe 16 EB patients treated in the ear, nose, and throat department of a tertiary pediatric hospital linked to the United Kingdom's national EB unit between 1992 and 2023. Patients suffered a high degree of morbidity and mortality from laryngotracheal stenosis.

Epithelial stem and progenitor cells of the upper airway.

The upper airway acts as a conduit for the passage of air to the respiratory system and is implicated in several chronic diseases. Whilst the cell biology of the distal respiratory system has been described in great detail, less is known about the proximal upper airway. In this review, we describe the relevant anatomy of the upper airway and discuss the literature detailing the identification and roles of the progenitor cells of these regions.

Factors influencing clinician and patient interaction with machine learning-based risk prediction models: a systematic review.

Machine learning (ML)-based risk prediction models hold the potential to support the health-care setting in several ways; however, use of such models is scarce. We aimed to review health-care professional (HCP) and patient perceptions of ML risk prediction models in published literature, to inform future risk prediction model development. Following database and citation searches, we identified 41 articles suitable for inclusion.

The Role of Smoking Status in Making Risk-Informed Diagnostic Decisions in the Lung Cancer Pathway: A Qualitative Study of Health Care Professionals and Patients.

Background: Lung cancer clinical guidelines and risk tools often rely on smoking history as a significant risk factor. However, never-smokers make up 14% of the lung cancer population, and this proportion is rising. Consequently, they are often perceived as low-risk and may experience diagnostic delays.

Health State Utilities Associated with False-Positive Cancer Screening Results.

Introduction: Early cancer detection can significantly improve patient outcomes and reduce mortality rates. Novel cancer screening approaches, including multi-cancer early detection tests, have been developed. Cost-utility analyses will be needed to examine their value, and these models require health state utilities.

Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study.

Introduction: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management.

Early human lung immune cell development and its role in epithelial cell fate.

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry.

Assessing eligibility for lung cancer screening using parsimonious ensemble machine learning models: A development and validation study.

Background: Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening.

Measuring spirometry in a lung cancer screening cohort highlights possible underdiagnosis and misdiagnosis of COPD.

Introduction: COPD is underdiagnosed, and measurement of spirometry alongside low-dose computed tomography (LDCT) screening for lung cancer is one strategy to increase earlier diagnosis of this disease.

Methods: Ever-smokers at high risk of lung cancer were invited to the Yorkshire Lung Screening Trial for a lung health check (LHC) comprising LDCT screening, pre-bronchodilator spirometry and a smoking cessation service. In this cross-sectional study we present data on participant demographics, respiratory symptoms, lung function, emphysema on imaging and both self-reported and primary care diagnoses of COPD.

Lung viral infection modelling in a bioengineered whole-organ.

Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

Objectives: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF).

Methods: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments.