The detection, assessment and clinical evolution of interstitial lung abnormalities identified through lung cancer screening

Introduction Interstitial lung abnormalities (ILAs) are common incidental findings in lung cancer screening; however, their clinical evolution and longer-term outcomes are less clear. The aim of this cohort study was to report 5-year outcomes of individuals with ILAs identified through a lung cancer screening programme. In addition, we compared patient-reported outcome measures (PROMs) in patients with screen-detected ILAs to newly diagnosed interstitial lung disease (ILD) to assess symptoms and health-related quality of life (HRQoL). Methods Individuals with screen-detected ILAs were identified, and 5-year outcomes, including ILD diagnoses, progression-free survival and mortality, were recorded. Risk factors associated with ILD diagnosis were assessed using logistic regression and survival using Cox proportional hazard analysis. PROMs were compared between a subset of patients with ILAs and a group of ILD patients. Results 1384 individuals underwent baseline low-dose computed tomography screening, with 54 (3.9%) identified as having ILAs. 22 (40.7%) were subsequently diagnosed with ILD. 14 (25.9%) individuals died, and 28 (53.8%) suffered disease progression within 5 years. Fibrotic ILA was an independent risk factor for ILD diagnosis, mortality and reduced progression-free survival. Patients with ILAs had lower symptom burden and better HRQoL in comparison to the ILD group. Breathlessness visual analogue scale (VAS) score was associated with mortality on multivariate analysis. Conclusions Fibrotic ILA was a significant risk factor for adverse outcomes including subsequent ILD diagnosis. While screen-detected ILA patients were less symptomatic, breathlessness VAS score was associated with adverse outcomes. These results could inform risk stratification in ILA

Clinical expert guidelines for the management of cough in lung cancer: report of a UK task group on cough

Background Cough is a common and distressing symptom in lung cancer patients. The clinical management of cough in lung cancer patients is suboptimal with limited high quality research evidence available. The aim of the present paper is to present a clinical guideline developed in the UK through scrutiny of the literature and expert opinion, in order to aid decision making in clinicians and highlight good practice. Methods Two systematic reviews, one focusing on the management of cough in respiratory illness and one Cochrane review specifically on cancer, were conducted. Also, data from reviews, phase II trials and case studies were synthesized. A panel of experts in the field was also convened in an expert consensus meeting to make sense of the data and make clinical propositions. Results A pyramid of cough management was developed, starting with the treatment of reversible causes of cough/specific pathology. Initial cough management should focus on peripherally acting and intermittent treatment; more resistant symptoms require the addition of (or replacement by) centrally acting and continuous treatment. The pyramid for the symptomatic management starts from the simpler and most practical regimens (demulcents, simple linctus) to weak opioids to morphine and methadone before considering less well-researched and experimental approaches. Conclusion The clinical guidelines presented aim to provide a sensible clinical approach to the management of cough in lung cancer. High quality research in this field is urgently required to provide more evidence-based recommendations

Measuring spirometry in a lung cancer screening cohort highlights possible underdiagnosis and misdiagnosis of Chronic Obstructive Pulmonary Disease

Introduction: Chronic Obstructive Pulmonary Disease (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 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. Multivariable logistic regression analysis identified factors associated with possible underdiagnosis and misdiagnosis of COPD in this population, with airflow obstruction (AO) defined as FEV1/FVC ratio <0.70. // Results: Of 3,920 LHC attendees undergoing spirometry, 17% had undiagnosed AO with respiratory symptoms, representing potentially undiagnosed COPD. Compared to those with a primary care COPD code, this population had milder symptoms, better lung function, and were more likely to be current smokers (p≤0.001 for all comparisons). Of 836 attendees with a primary care COPD code who underwent spirometry, 19% did not have AO, potentially representing misdiagnosed COPD, although symptom burden was high. // Discussion: Spirometry offered alongside LDCT screening can potentially identify cases of undiagnosed and misdiagnosed COPD. Future research should assess the downstream impact of these findings to determine if any meaningful changes to treatment and outcomes occurs, and also to assess the impact on co-delivering spirometry on other parameters of LDCT screening performance such as participation and adherence. Additionally, work is needed to better understand the aetiology of respiratory symptoms in those with misdiagnosed COPD, to ensure this highly symptomatic group receive evidence-based interventions

The Cost-Effectiveness Of The Manchester ‘Lung Health Checks’, A Community-Based Lung Cancer Low-Dose CT Screening Pilot

Background: Previous evaluations of low-dose CT (LDCT) lung cancer screening programmes have taken very different approaches in the design of the informative trials and the methods applied to determine cost-effectiveness. Therefore, it has not been possible to determine if differences in cost-effectiveness are due to different screening approaches or the evaluation methodology. This study reports the findings of an evaluation of the first round of a community-based, LDCT screening pilot Manchester, applying previously published methodology to ensure consistency. Methods: Using the economic evaluation method reported in the UKLS trial, applying Manchester specific evidence where possible, we estimate the cost-effectiveness of LDCT for lung cancer. Estimates of the total costs and quality adjusted life years (QALYs) were calculated. Results: The Manchester programme cost £663,076, diagnosed 42 patients with lung cancer resulting in a gain in population health of 88.13 discounted life years, equivalent to 65.85 QALYs. This implied an incremental cost-effectiveness ratio of £10,069/QALY. Conclusions: We found the Manchester programme to be a cost-effective use of limited NHS resources. The findings suggest that further research is now needed not as to whether LDCT screening is cost-effective but under what conditions can it improve patient health by the most while remaining cost-effective

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. METHODS AND ANALYSIS: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. ETHICS AND DISSEMINATION: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110

A large-scale genomic snapshot of Klebsiella spp. isolates in Northern Italy reveals limited transmission between clinical and non-clinical settings

Genomic analyses of Klebsiella isolates sampled from multiple human, animal and environmental sources in Northern Italy explore Klebsiella population diversity and show that transmission of multidrug-resistant clones between clinical and environmental settings is scarce.The Klebsiella group, found in humans, livestock, plants, soil, water and wild animals, is genetically and ecologically diverse. Many species are opportunistic pathogens and can harbour diverse classes of antimicrobial resistance genes. Healthcare-associated Klebsiella pneumoniae clones that are non-susceptible to carbapenems can spread rapidly, representing a high public health burden. Here we report an analysis of 3,482 genome sequences representing 15 Klebsiella species sampled over a 17-month period from a wide range of clinical, community, animal and environmental settings in and around the Italian city of Pavia. Northern Italy is a hotspot for hospital-acquired carbapenem non-susceptible Klebsiella and thus a pertinent setting to examine the overlap between isolates in clinical and non-clinical settings. We found no genotypic or phenotypic evidence for non-susceptibility to carbapenems outside the clinical environment. Although we noted occasional transmission between clinical and non-clinical settings, our data point to a limited role of animal and environmental reservoirs in the human acquisition of Klebsiella spp. We also provide a detailed genus-wide view of genomic diversity and population structure, including the identification of new groups.Peer reviewe

How should performance in EBUS mediastinal staging in lung cancer be measured?

There has been a paradigm shift in mediastinal staging algorithms in non-small cell lung cancer over the last decade in the United Kingdom (UK). This has seen endoscopic nodal staging (predominantly endobronchial ultrasound, EBUS) almost replace surgical staging (predominantly mediastinoscopy) as the pathological staging procedure of first choic