Lung volume reduction procedures are an established evidence-based aspect of chronic obstructive pulmonary disease (COPD) care. We conducted a research prioritisation exercise involving people with COPD and healthcare professionals across a range of disciplines, to identify a clear set of 10 questions to guide the development of research proposals in this area. Priorities were identified using an iterative approach based on the James Lind Alliance methodology. The final set of 10 priorities address the identification, assessment and optimisation of patients with COPD prior to any procedure, how lung volume reduction procedures are conducted and how care after the procedure has taken place should be organised.

Background Epithelial–immune cell interactions are crucial in the regulation of pulmonary immune responses. Emerging evidence suggests that cell populations lining the airways may play a pivotal role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a disease characterised by progressive scarring of the lung parenchyma. We profiled the cellular landscape of the airway mucosal niche in incident cases of IPF to understand early-stage events contributing to disease development. Methods Single-cell RNA-sequencing was used to explore cellular heterogeneity in proximal airway brushings from seven healthy controls and nine patients with newly diagnosed IPF. In-depth bioinformatics analysis was used to interrogate changes in cell populations and cell–cell communication in IPF patients compared to controls. Results We show a relative increase in the abundance of airway macrophage subsets in IPF compared to healthy controls, and disease-specific changes in their transcriptional profile. Increased frequency of airway macrophages and proliferating macrophages was associated with more extensive disease at baseline quantified by the composite physiological index and radiological severity of traction bronchiectasis. Monocyte-derived macrophages were significantly enriched at baseline in IPF patients who had disease progression at 12 months. Using CellChat we exposed differences in cell–cell communication between airway epithelial cells, airway macrophages and T-cells in IPF. We identified dysregulation in signalling pathways such as SEMA3, ANXA1 and DESMOSOME, which modulate airway epithelial–macrophage interactions, potentially driving disease pathology. Conclusions Airway epithelial cells and macrophages may play a key role in orchestrating the early immunopathology of IPF, and these data support further exploration of novel, airway-focused therapeutic targets in IPF.

Focal consolidation on CT may be inflammatory or malignant, and PET-CT imaging is rarely discriminatory. Furthermore, consolidation may demonstrate spontaneous resolution obviating the need for PET-CT imaging. This retrospective study sought to assess the safety and cost-effectiveness of short-interval 6-week follow-up CT for consolidation in a lung cancer screening programme. Between January 2019 and January 2024, participants in a regional lung cancer screening programme with focal indeterminate consolidation underwent a 6-week repeat CT rather than immediate PET-CT and invasive investigation. The proportion of participants with non-resolving consolidation, the risk of malignancy in consolidation at a 6-week follow-up, and the risk of upstaging over a 6-week delay were determined. Cost savings were estimated from National Health Service reference costs. In 10,247 CT studies, focal indeterminate consolidation was detected in 113 participants (1.1

Rationale: Recovery from chronic obstructive pulmonary disease (COPD) exacerbations is heterogeneous and has a profound impact on disease trajectories. Resolution of airway inflammation is an active process that may be driven by specialized proresolving mediators (SPMs). Objectives: We sought to characterize the temporal change in SPMs in the sputum of patients with COPD during exacerbations, their association with exacerbation triggers, and exacerbation recovery. Methods: Participants were recruited from the London COPD Exacerbation Cohort between January 11, 2016, and April 30, 2018. Participants were reviewed at baseline, exacerbation onset, 1 week, 2 weeks, and 6 weeks during their exacerbation recovery. Sputum collection, nasopharyngeal swabs, phlebotomy, quality-of-life questionnaires, and spirometry were performed at each visit. SPMs were measured in sputum by liquid chromatography-tandem mass spectrometry. Respiratory viruses were measured by quantitative PCR and bacteria by microbiological culture. Measurements and Main Results: There were 68 exacerbations during the study period. Median time to symptomatic recovery was 21 days for viral exacerbations, compared with 13 days in nonviral exacerbations (P < 0.001). There was a significant increase in resolvin D1 (RvD1) at exacerbation onset in bacterial exacerbations but not in viral exacerbations. Lower levels of RvD1 were associated with prolonged respiratory symptoms during the 1-week and 2-week recovery time points. Exogenous RvD1 significantly reduced IL-6 and CXCL8 response to rhinovirus infection in COPD bronchial epithelial cells. Conclusions: There is a dynamic temporal change in airway SPMs during COPD exacerbations. Reduced levels of RvD1 were associated with prolonged respiratory symptoms. SPMs may be a potential therapeutic approach to promote exacerbation recovery.

Introduction Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK.Methods Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023.Results Data on 541 patients from 14 participating centres were analysed. Baseline disease severity was similar in patients who had surgery n=244 (44.9%), or EBV placement n=219 (40.9%), for example, forced expiratory volume in 1 s (FEV1) 32.1 (12.1)% vs 31.2 (11.6)%. 89% of cases had discussion at a multidisciplinary meeting recorded. Median (IQR) length of stay postprocedure for LVRS and EBVs was 12 (13) vs 4 (4) days(p=0.01). Increasing age, male gender and lower FEV1%predicted were associated with mortality risk, but survival did not differ between the two procedures, with 50 (10.8%) deaths during follow-up in the LVRS group vs 45 (9.7%) following EBVs (adjusted HR 1.10 (95% CI 0.72 to 1.67) p=0.661)Conclusion Based on data entered in the UKLVR registry, LVRS and EBV procedures for emphysema are being performed in people with similar disease severity and long-term survival is similar in both groups.

Respiratory viruses cause chronic obstructive pulmonary disease (COPD) exacerbations. Rhinoviruses (RVs) are the most frequently detected. Some patients with COPD experience frequent exacerbations (≥2 exacerbations/yr). The relationship between exacerbation frequency and antiviral immunity remains poorly understood. The objective of this study was to investigate the relationship between exacerbation frequency and antiviral immunity in COPD. Alveolar macrophages and bronchial epithelial cells (BECs) were obtained from patients with COPD and healthy participants. Alveolar macrophages were infected with RV-A16 multiplicity of infection (MOI) 5 and BECs infected with RV-A16 MOI 1 for 24. Interferons (IFNs) and proinflammatory cytokines IL-1β, IL-6, C-X-C motif chemokine ligand (CXCL)-8, and TNF were measured in cell supernatants using a mesoscale discovery platform. Viral load and interferon-stimulated genes were measured in cell lysates using quantitative PCR. Spontaneous and RV-induced IFN-β, IFN-γ, and CXCL-11 release were significantly reduced in alveolar macrophages from patients with COPD compared with healthy subjects. IFN-β was further impaired in uninfected alveolar macrophages from patients with COPD with frequent exacerbations 82.0 pg/mL versus infrequent exacerbators 234.7 pg/mL, P = 0.008 and RV-infected alveolar macrophages from frequent exacerbators 158.1 pg/mL versus infrequent exacerbators 279.5 pg/mL, P = 0.022. Release of proinflammatory cytokines CXCL-8, IL-6, TNF, and IL-1β was higher in uninfected BECs from patients with COPD compared with healthy subjects but there was no difference in proinflammatory response to RV between groups. IFN responses to RV were impaired in alveolar macrophages from patients with COPD and further reduced in patients with frequent exacerbations.NEW & NOTEWORTHY COPD exacerbations are commonly triggered by viral infections. Some patients with COPD have frequent exacerbations leading to rapid lung function decline and increased mortality. In this study, antiviral responses (interferons) from bronchial epithelial cells and alveolar macrophages were reduced in patients with COPD compared with healthy participants and further reduced in patients with COPD with frequent exacerbations. Impaired antiviral immunity may lead to frequent COPD exacerbations. Targeted vaccinations and antiviral therapy may reduce exacerbations in COPD.

Background Immediate smoking cessation interventions delivered alongside targeted lung health checks (TLHCs) to screen for lung cancer increase self-reported abstinence at 3 months. The impact on longer term, objectively confirmed quit rates remains to be established. Methods We followed up participants from two clinical trials in people aged 55–75 years who smoked and took part in a TLHC. These randomised participants in the TLHC by day of attendance to either usual care (UC) (signposting to smoking cessation services) or an offer of immediate smoking cessation support including pharmacotherapy. In the QuLIT1 trial, this was delivered face to face and in QuLIT2, it was delivered remotely. Follow-up was conducted 12 months after the TLHC by telephone interview with subsequent biochemical verification of smoking cessation using exhaled CO. Results 430 people were enrolled initially (115 in QuLIT1 and 315 in QuLIT2), with 4 deaths before 12 months leaving 426 (62.1±5.27 years old and 48% women) participants for analysis. At 12 months, those randomised to attend on smoking cessation support intervention days had higher quit rates compared with UC adjusted for age, gender, deprivation, and which trial they had been in; self-reported 7-day point prevalence (20.0% vs 12.8%; adjusted OR (AOR)=1.78; 95% CI 1.04 to 2.89) and CO-verified quits (12.1% vs 4.7%; AOR=2.97; 95% CI 1.38 to 6.90). Those in the intervention arm were also more likely to report having made a quit attempt (30.2% vs UC 18.5%; AOR 1.90; 95% CI 1.15 to 3.15). Conclusion Providing immediate smoking cessation support alongside TLHC increases long term, biochemically confirmed smoking abstinence. Trial registration number ISRCTN12455871 .

Background Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. Methods This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. Results 88 participants (48% female, mean± sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS −1.10±1.44 versus BLVR −0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS −36.1% (95% CI −54.6– −10%) versus BLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm. Conclusion Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

BACKGROUND: Lung cancer screening programs provide an opportunity to support people who smoke to quit, but the most appropriate model for delivery remains to be determined. Immediate face-to-face smoking cessation support for people undergoing screening can in-crease quit rates, but it is not known whether remote delivery of immediate smoking cessation counselling and pharmacotherapy in this context also is effective.RESEARCH QUESTION: Does an immediate telephone smoking cessation intervention increase quit rates compared with usual care among a population enrolled in a targeted lung health check (TLHC)?STUDY DESIGN AND METHODS: In a single-masked randomized controlled trial, people 55 to 75 years of age who smoke and attended a TLHC were allocated by day of attendance to receive either immediate telephone smoking cessation intervention (TSI) support (starting imme-diately and lasting for 6 weeks) with appropriate pharmacotherapy or usual care (UC; very brief advice to quit and signposting to smoking cessation services). The primary outcome was self-reported 7-day point prevalence smoking abstinence at 3 months. Differences between groups were assessed using logistic regression.RESULTS: Three hundred fifteen people taking part in the screening program who reported current smoking with a mean +/- SD age of 63 +/- 5.4 years, 48% of whom were women, were randomized to TSI (n = 152) or UC (n = 163). The two groups were well matched at baseline. Self-reported quit rates were higher in the intervention arm, 21.1% vs 8.9% (OR, 2.83; 95% CI, 1.44-5.61; P = .002). Controlling for participant demographics, neither baseline smoking characteristics nor the discovery of abnormalities on low-dose CT imaging modified the effect of the intervention.INTERPRETATION: Immediate provision of an intensive telephone-based smoking cessation intervention including pharmacotherapy, delivered within a targeted lung screening context, is associated with increased smoking abstinence at 3 months.TRIAL REGISTRY: ISRCTN registry; No.: ISRCTN12455871; URL: www.IRSCN.com

Background Methods to improve stratification of small (≤15 mm) lung nodules are needed. We aimed to develop a radiomics model to assist lung cancer diagnosis. Methods Patients were retrospectively identified using health records from January 2007 to December 2018. The external test set was obtained from the national LIBRA study and a prospective Lung Cancer Screening programme. Radiomics features were extracted from multi-region CT segmentations using TexLab2.0. LASSO regression generated the 5-feature small nodule radiomics-predictive-vector (SN-RPV). K-means clustering was used to split patients into risk groups according to SN-RPV. Model performance was compared to 6 thoracic radiologists. SN-RPV and radiologist risk groups were combined to generate “Safety-Net” and “Early Diagnosis” decision-support tools. Results In total, 810 patients with 990 nodules were included. The AUC for malignancy prediction was 0.85 (95% CI: 0.82–0.87), 0.78 (95% CI: 0.70–0.85) and 0.78 (95% CI: 0.59–0.92) for the training, test and external test datasets, respectively. The test set accuracy was 73% (95% CI: 65–81%) and resulted in 66.67% improvements in potentially missed [8/12] or delayed [6/9] cancers, compared to the radiologist with performance closest to the mean of six readers. Conclusions SN-RPV may provide net-benefit in terms of earlier cancer diagnosis.

Background Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. Methods This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. Results 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS −1.10±1.44 versus BLVR −0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS −36.1% (95% CI −54.6– −10%) versus BLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm. Conclusion Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments. In this first randomised study to compare lung volume reduction surgery and endobronchial valve placement in people who are suitable for both treatments, surgery did not produce substantially superior outcomes at 1 year post-procedure http://bit.ly/3D0DjoN

Background: EBVs are an effective treatment for hyperinflation in COPD. Microbial colonisation can occur in COPD, and may affect clinician and multidisciplinary team decision whether to offer patients EBVs. However, little is known about the prevalence or significance of bacterial, fungal or mycobacterial presence in patients undergoing EBV treatment. Aim: To assess the prevalence of bacteria, fungi and mycobacteria in patients undergoing EBV treatment for COPD. Methods: We performed a single-centre retrospective analysis of almost 4 years reviewing bronchoalveolar lavage (BAL) fluid culture results for bacteria, fungi and mycobacteria in patients undergoing EBV treatment for COPD between January 2017 – October 2020 at the Royal Brompton Hospital. Patients who had a baseline BAL (immediately prior to EBV insertion or at chartis bronchoscopy) were included. Results: 32 patients meeting the inclusion criteria were identified. 12 patients (37.5%) had positive BAL cultures for at least 1 organism. 9 patients (28%) had positive cultures for bacteria, 4 patients (12.5%) for fungi, and 2 (6%) for mycobacteria. Conclusion: There is a high prevalence of positive BAL cultures in patients with COPD undergoing EBV treatment. This warrants evaluation of its significance and whether positive cultures correlate with worse clinical outcomes post EBV treatment. Table 1

Aberrant expansion of KRT5 + basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5 + cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5 + cells migrate within the fibrotic lung, navigating regional differences in collagen topography. In vitro, KRT5 + cell migratory characteristics and expression of remodelling genes are modulated by extracellular matrix (ECM) composition and organisation. Mass spectrometry- based proteomics revealed compositional differences in ECM components secreted by primary human lung fibroblasts (HLF) from IPF patients compared to controls. Over-expression of ECM glycoprotein, Secreted Protein Acidic and Cysteine Rich (SPARC) in the IPF HLF matrix restricts KRT5 + cell migration in vitro. Together, our findings demonstrate how changes to the ECM in IPF directly influence KRT5 + cell behaviour and function contributing to remodelling events in the fibrotic niche.

Introduction Although lung volume reduction surgery and bronchoscopic lung volume reduction with endobronchial valves have both been shown to improve lung function, exercise capacity and quality of life in appropriately selected patients with emphysema, there are no direct comparison data between the two procedures to inform clinical decision-making. Methods and analysis We describe the protocol of the CELEB study, a randomised controlled trial which will compare outcomes at 1 year between the two procedures, using a composite disease severity measure, the iBODE score, which includes body mass index, airflow obstruction, dyspnoeaand exercise capacity (incremental shuttle walk test). Ethics and dissemination Ethical approval to conduct the study has been obtained from the Fulham Research Ethics Committee, London (16/LO/0286). The outcome of this trial will provide information to guide treatment choices in this population and will be presented at national and international meetings and published in peer-reviewed journals. We will also disseminate the main results to all participants in a letter. Trial registration number ISRCTN19684749 ; Pre-results.

Interstitial lung abnormalities (ILA) can be incidentally detected in patients undergoing low-dose CT screening for lung cancer. In this retrospective study, we explore the downstream impact of ILA detection on interstitial lung disease (ILD) diagnosis and treatment. Using a targeted approach in a lung cancer screening programme, the rate of de novo ILD diagnosis was 1.5%. The extent of abnormality on CT and severity of lung function impairment, but not symptoms were the most important factors in differentiating ILA from ILD. Disease modifying therapies were commenced in 39% of ILD cases, the majority being antifibrotic therapy for idiopathic pulmonary fibrosis.

IntroductionWe aim to investigate clinicopathological characteristics of our surgical lung cancer population presenting during the 1st wave of pandemic, describe the key service parameters, and to identify pathological upstaging compared to a pre-pandemic cohort.MethodsThis is part of an ongoing observational study including all primary lung cancer patients who underwent resection at our centre. Data were collected as part of an institutional lung cancer database. COVID vulnerability status was derived from Department of Health (UK) guidelines. Clinically significant pathological upstaging was defined as migration between clinical and pathological final TNM stage, either major (between stages) or minor (between substages except IA). Logistic regression was employed to identify independent predictors of upstaging, and a 3-tier risk stratification system was developed.ResultsWe included 242 cases from 1st wave and 456 cases from a 2019 cohort. Radiological lesion size, nodal status, Maximum Standard Unit Value (SUVmax) and histological risk group were independent predictors of upstaging. The 3-tier system stratified such risk into low (8.3%), intermediate (26.1%) and high (48.4%), with AUC of 0.683. There was 20.4% reduction in caseload, and significant drop in all-purpose frozen section usage. No significant difference was seen regarding patients classified as clinically extremely vulnerable (CEV), clinically vulnerable (CV) as well as multimorbidity. No significant changes were observed for surgical waiting time, histological subtypes, final pathological stage, R0 resection or clinically significant upstaging (30.1% vs 30.2%), but there was minor impact on pathology reporting times.ConclusionsView Large Image Figure ViewerDownload Hi-res image Download (PPT)KeywordsLung cancer, Pathological upstaging, COVID-19 IntroductionWe aim to investigate clinicopathological characteristics of our surgical lung cancer population presenting during the 1st wave of pandemic, describe the key service parameters, and to identify pathological upstaging compared to a pre-pandemic cohort.

Background: Lung cancer screening programs provide an opportunity to support smokers to quit, but the most appropriate model for delivery remains to be determined. Immediate face to face smoking cessation support for people undergoing screening can increase quit rates, but it is not known whether remote delivery of immediate smoking cessation counselling and pharmacotherapy in this context is also effective. Methods: In a single-blind randomised controlled trial, smokers aged 55-75 years attending a Targeted Lung Health Check (TLHC) were allocated by day of attendance to receive either telephone smoking cessation support (TSI) (starting immediately and lasting for 6 weeks) with appropriate pharmacotherapy, or usual care (very brief advice to quit and signposting to smoking cessation services) (UC). The primary outcome was self-reported 7-day point prevalence smoking abstinence at three months. Differences between groups were assessed using logistic regression. Results: 315 current smokers taking part in the screening programme, mean (SD) age 63(5.4) years, 48% female, were randomised to TSI (n=152) or UC (n=163). Quit rates were higher in the intervention arm, 21.1% vs 8.9% ([OR]: 2.88, 95% CI 1.44-5.77, p=0.003), as were quit attempts (TSI: 37.5% vs UC: 22.0%), (OR: 2.11, 95% CI 1.29- 3.47 p=0.003 (figure 1). Controlling for participant demographics, baseline smoking characteristics or CT scan results did not influence these associations. Conclusion: Immediate provision of an intensive telephone-based smoking cessation intervention, delivered within a lung screening context, is associated with increased smoking abstinence at three months.