Introduction Pleural mesothelioma (PM) is often presaged by benign asbestos-associated pleural inflammation (AAPI), offering a unique window of opportunity for translational research. The PREDICT-Meso International Accelerator Network is leveraging this natural history to perform target identification and develop novel therapies for early-stage or pre-invasive disease. This requires assembly of a unique bioresource of longitudinal human tissue samples spanning the terminal stages of PM evolution, development of preclinical models for drug screening and reliable tools for risk prediction in patients presenting with AAPI.Methods and analysis Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS) is a prospective, multicentre observational study, comprising two arms (A and B), with a nested MRI substudy in arm A. Arm A will recruit 300 AAPI patients and perform 6-monthly surveillance for 2 years. Suspicion of PM evolution will prompt repeat biopsy and banking, delivering a primary objective of ≥38 longitudinal AAPI-PM tissue pairs. This target reflects a projected PM evolution rate of 14% (95% CI 10.5 to 19.2) derived from a prior multicentre feasibility trial. Multiomic risk profiling will be performed in arm A, using blood proteomics, exhaled breath metabolomics and perfusion MRI. Arm B will recruit 300 patients with suspected PM, permitting collection of multiregion pleural biopsies in patients spanning AAPI and PM timepoints for evaluation of anatomical heterogeneity. Where possible, patients in arm B diagnosed with AAPI will be recruited to arm A for 2-year surveillance +/− repeat biopsy in subsequent PM evolution cases. Pleural fluid will be collected in arm B for cell-line generation and diagnostic biomarker evaluation. Exhaled breath will be collected in arm B for diagnostic biomarker evaluation.Ethics and dissemination The study has ethical approval (REC Ref 21/WS/0120). Results will be disseminated via peer-reviewed journals and national/international scientific conferences. Tissues, data and derived omics will be shared via the PREDICT-Meso Research Tissue Bank (REC Ref 21/WS/0011).Trial registration number ISRCTN22929761.

Introduction: The PREDICT-Meso Accelerator Network (35 institutions, 8 countries) aims to define the biology driving malignant pleural mesothelioma (MPM) evolution and develop targeted therapies. We provide an update on Meso-ORIGINS (MO), the primary vehicle for prospective tissue collection and risk prediction. Aims: MO will generate a longitudinal cohort of patients with asbestos associated pleural inflammation (AAPI). The primary objective is to generate ≥ 63 benign-MPM tissue pairs (projected evolution rate 14% (95% CI 10.5-19.2) based on a prior feasibility trial). Secondary objectives are (a) generation of a multiomic risk prediction model (b) characterisation of intra-patient heterogeneity using multi-region thoracoscopic biopsies. Methods: Arm A will recruit 500 AAPI patients and perform 6-monthly surveillance for 2 yrs. Suspicion of MPM evolution will prompt repeat pleural biopsy and banking. Arm A includes baseline risk profiling via serum proteomics, exhaled breath metabolomics +/- perfusion MRI. Arm B will address heterogeneity by recruiting patients with suspected MPM undergoing thoracoscopy (n=39) Results: MO opened in July 2022 (planned 3.5yr recruitment). At submission, 17 UK centres are open (9 in setup). 37/500 and 26/39 patients have been recruited to Arms A and B, respectively. 2/30 Arm A cases with ≥ 1-month follow-up have evolved into MPM, making the current evolution rate 6.7% (95% CI 0.7-22.4). 5/26 Arm B cases have a confirmed MPM diagnosis with a mean (SD) of 5.2 (0.8) multi-region biopsies collected. Conclusions: MO is collecting paired tissues that are critical for downstream PREDICT-Meso work packages focused on target identification, pre-clinical models and drug development.

SummaryBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes for people with IPF.MethodWe adopted a two-stage discovery and validation design using patients from the UCL partners (UCLp) cohort. For the discovery analysis, we included 71 patients from UCLH. In the validation analysis, we included 928 people with IPF, using real-life data from UCLH and 5 other UK centres. Data were collected from patients presenting over a 13-year period with a mean follow up time of 3.7 years.FindingsIn the discovery analysis, we showed that values of NLR (<2.9 vs >/=2.9) were associated with increased risk of mortality (HR 2.04, 95% CI 1.09-3.81; p=0.025). In the validation cohort we confirmed this association of high NLR with mortality (HR 1.65, 95% CI 1.39-1.95; p<0·0001) and showed incorporation of baseline NLR in a modified GAP-stage/index (GAP/index)-plus improved predictive abilityInterpretationWe have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines clinical GAP-staging. NLR may help ILD specialist centres prioritise at risk patients in a timely way, even in the absence of lung function.

Background Cross-covering of medical and surgical specialities out-of-hours is a problem in many hospitals, leaving trainee doctors responsible out-of-hours for patients they have never met, in specialities where they do not normally work. This has implications for patient safety and doctor wellbeing. In our Trust, a historical decision resulted in trainee doctors in Trauma & Orthopaedics and Ear Nose and Throat Surgery being reallocated out-of-hours to cross-cover medical inpatients. This left one doctor cross-covering all surgical specialities, including General Surgery, Urology, Vascular, Ear, Nose and Throat surgery (ENT), Trauma & Orthopaedics (T&O) and Spinal Surgery. As the out-of-hours workload increased over time, this impacted negatively on patient safety and doctor wellbeing to a point where it became unsustainable. Methods Evidence of safety concerns relating to surgical night shifts was gathered from Exception Reporting data and anecdotally from the Postgraduate Doctor Forum. Once the scale of this problem was accepted by the hospital board, following the successful presentation of two Business Cases, 17 additional doctors were recruited. This recruitment reduced the cross-covering of specialities out-of-hours and enable adequate staffing throughout all departments. Qualitative evidence was gathered by surveying affected doctors before and after the change in order to assess its impact on doctor wellbeing, training and perceived patient safety. Quantitative analysis of Exception Reports and Immediate Safety Concerns was also performed. Results The survey results following the change were overwhelmingly positive, demonstrating a significant improvement in workload, rest breaks and quality of care for patients. Foundation doctors reported higher levels of confidence and enhanced training due to more consistent supervision. Job satisfaction improved, with 81% of surgical senior house officers reporting they would recommend their job, compared with 42% previously. Trends in out-of-hours Exception Reporting and patient safety concerns were analysed to show a moderate improvement following the intervention. Conclusion With the ever-increasing volume and complexity of patients presenting to global healthcare systems, it is key that staffing levels are safe and adequate in order to maintain patient safety and doctor wellbeing. This project has demonstrated how historic short-term fixes such as redeploying trainee doctors out of their home speciality and implementing cross-cover of multiple specialities can have detrimental long-term effects. Our preliminary data revealed multiple issues related to patient safety, junior doctor workload and lack of training opportunities. By using this data, and enlisting the help of multiple valued senior stakeholders, an acceptable Business Plan was approved by the Trust with a view to reversing these issues. The recruitment of additional Trust Grade doctors to create a third tier of the surgical out-of-hours cover has been instrumental in improving conditions within our Trust and has shown that adequate workforce planning is achievable when supported by robust evidence. This project could be used as a guide for other units seeking to make similar improvements.

The factors determining disease course and survival in fibrotic hypersensitivity pneumonitis (fHP) have not been fully elucidated.The aim of this study was to describe the characteristics of patients with fHP in a real-world cohort and investigate factors associated with worse outcomes. We aimed to explore the use of neutrophil to lymphocyte ratio (NLR) and peripheral blood monocyte levels in predicting mortality. METHODS:A retrospective, multicentre, observational UK cohort study. RESULTS:Patients with fHP were significantly younger than those with idiopathic pulmonary fibrosis (IPF) (median age fHP 73 vs IPF 75 years) and were much more likely to be woman (fHP 61% vs IPF 26%). In almost half of all fHP cases (49%, n=104/211), no causative antigen was identified from either the history or specific antigen testing. Overall, fHP was associated with a better survival than IPF, although median survival of both groups was poor (fHP 62 months vs IPF 52 months).IPF survival in patients with a high NLR was significantly lower than those with a low NLR (44 vs 83 months). A monocyte count ≥0.95 K/uL also predicted significantly poorer outcomes for patients with IPF compared with <0.95 K/uL (33 vs 57 months). In contrast, NLR and monocyte count did not predict survival in the fHP cohort. CONCLUSIONS:Although fHP has a statistically lower mortality than IPF, absolute survival time of both conditions is poor. High baseline NLR and absolute monocyte counts predict worse survival in IPF but not in fHP, highlighting the potential for divergence in their pathogenic mechanisms.

The coronavirus disease (COVID-19) pandemic has challenged healthcare systems and has resulted in complex diagnostic processes for patients with non-COVID-19 pathology. Here, we demonstrate a case of massive alveolar haemorrhage secondary to antineutrophil cytoplasmic antibody-positive vasculitis, presented to a district general hospital in the UK during the first wave of the global pandemic. This case highlights some of the difficulties clinicians may face when diagnosing life-threatening antineutrophil cytoplasmic antibody-positive vasculitis amidst the COVID-19 pandemic. The authors place emphasis on the careful interpretation of chemical biomarkers such as troponin and D-dimer when assessing patients with acute respiratory distress. They also aim to highlight the importance of CT thorax imaging when seeking an alternate diagnosis to COVID-19.

Introduction: Trainee Research Networks (TRNs) are established in other specialities, producing high quality, greater impact work by collaborating across multiple sites [1]. South West England has a population of over 5 million [2], with 39 respiratory trainee doctors across 12 hospitals. Aim: To establish a trainee led respiratory research network across SW England, with representation in all regional hospitals. Method: A constitution was drafted based on existing successful TRNs. This was presented at a regional trainee meeting with senior representation from the SW Anaesthetics TRN. Trainees were invited to read the constitution and enrol. Committee positions were advertised to all members. Results: 21 respiratory trainees signed up to PRISM (Pulmonary Research Inter Site Matrix) representing 10/12 hospitals in the South West. The network is led by a committee of five trainees. Four Consultant Directors, with links to two university research centres, provide senior guidance. Acknowledging different levels of input from contributors and data ownership rights were the most contentious issues. A project evaluating outcomes from High Flow Nasal Oxygen therapy has launched the network. Conclusion: Trainees are enthusiastic to develop research networks. We initiated our first project within four weeks and recruited patients from ten sites. This model for collaborative research is widely applicable to other regions and specialties. Future challenges include the adoption of a suitable multisite, secure IT system and maintaining momentum for collaborative work. References: [1] RAFT:uniting trainees to undertake national projects RCoA Bulletin May 2014: 52-54 [2] Office for National Statistics ; 2011 Census aggregate data. UK Data Service

Lung cancer screening is being developed to improve lung cancer care, reduce mortality and increase detection of early stage disease. The SUMMIT trial (London, UK) will assess lung cancer-screening for high-risk patients (significant smoking history, aged 50 to 77 yrs). We assessed the utility of such a programme in Somerset, a rural and largely elderly population. A review of all patients from the Somerset Lung Cancer Register was performed from 1st January- 31st December 2018. We identified 272 patients; aged 39-98 yrs (median 72); smokers 28%, ex-smokers 57%, never smokers 9%. Patients aged 50-77 yrs (n=184) accounted for 68% of the total cohort, predominantly smokers and ex-smokers (87.5%). The majority (66%) of this subgroup were PS0/1 and had adenocarcinoma (36.6%). 100% of never smokers aged 50-77 yrs (n=13) were PS0/1, which were predominantly carcinoid (30%) and adenocarcinoma (23%) and only 2 patients had stage 4 disease. Of patients aged <50 and >77 yrs (n= 88), 43% were PS0/1 with adenocarcinoma (33%), however, 51% these patients presented with stage 4 disease. In our lung cancer population, 59% of patients would be eligible for screening in current UK proposals. Depending on the results of the SUMMIT trial, non-smokers may be considered, increasing this to 68% eligibility. Non-smokers presented with early stage adenocarcinoma or carcinoid, usually with good treatment options. A small proportion (1.8%) presented <50yrs but at early stage and good PS. Older patients, who presented with more advanced disease would be picked up earlier were national screening rolled-out. Our data confirms that lung cancer screening will be beneficial to our patient cohort, particularly if non-smokers are considered.

We report a case of a 68-year-old gentleman, found to have a right hilar soft tissue mass whilst undergoing CT staging for prostate cancer. MRI imaging showed a heterogenous, enhancing solid mass without evidence of fat content. A linear probe endobronchial ultrasound-guided transbronchial needle aspiration was performed using a 19G needle. This confirmed the diagnosis of a benign chondroid hamartoma, avoiding the need for more invasive surgical biopsy.

BACKGROUND:Trainees are performing fewer bronchoscopies as a result of the increased use of endobronchial ultrasound-guided transbronchial needle aspiration. Workforce planning and changes in trainee working patterns may also have compounded this situation. We investigated current trends in endobronchial biopsy (EBB) and transbronchial biopsy (TBB) training and competency in respiratory trainees and consultants across the United Kingdom.METHODS:We performed a national survey and received 131 online responses from 58 consultants and 73 registrars across 13 United Kingdom deaneries.RESULTS:A significant proportion (31%) of consultants, more than half of which were new consultants, had performed <500 bronchoscopies. Bronchoscopic biopsy experience varies widely across trainees and consultants (9.1% of senior trainees and 14.3% of new consultants had performed <100 bronchoscopies). Most trainees and some new consultants reported performing relatively low numbers of EBB (13% <20 and 52% <50 procedures) and TBB (75% of trainees, 36% of new consultants, 12% of established consultants <10 procedures). Significant numbers of trainees do not feel competent in EBB (24%) and TBB (89% of junior trainees, 64% of senior trainees) and some consultants (24% of new and established consultants) wish for support with TBB.CONCLUSIONS:These results have implications for future specialist training, curriculum planning, and service configuration. Training and performance of EBB and TBB may become concentrated in centers with an adequate volume of these procedures. Higher volumes of EBB and TBB may well be more likely to occur paradoxically in centers without endobronchial ultrasound-guided transbronchial needle aspiration; however, this hypothesis requires further study.

Interstitial lung disease (ILD) is a common clinical problem, representing a group of diseases consisting of inflammation and progressive fibrosis of the lung. In some cases, an underlying cause is not identified; however, a significant proportion of ILD is associated with connective tissue disease (CTD). A detailed history and examination is the most important part of the assessment of patients with suspected ILD and will direct further investigation. This case illustrates the importance of identifying the symptoms and signs of CTD when assessing a patient with ILD. In addition, we describe an unusual presenting manifestation of yellow nails, which is not a recognised feature of CTD-ILD, but improved following immunomodulatory treatment for the overall condition.

OBJECTIVEMalignant pleural effusion (MPE) incidence is increasing, and prognosis remains poor. Indwelling pleural catheters (IPCs) relieve symptoms but increase the risk of pleural infection. We reviewed cases of pleural infection in patients with IPCs for MPE from six UK centers between January 1, 2005, and January 31, 2014.METHODSSurvival in patients with pleural infection was compared with 788 patients with MPE (known as the LENT [pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, serum neutrophil to lymphocyte ratio, and tumor type] cohort) and with national statistics.RESULTSOf 672 IPCs inserted, 25 (3.7%) became infected. Most patients (20 of 25) had mesothelioma or lung cancer. Median survival in the pleural infection cohort appeared longer than in the LENT cohort, although this result did not achieve significance (386 days vs 132 days; hazard ratio, 0.67; P = .07). Median survival with mesothelioma and pleural infection was twice as long as national estimates for mesothelioma survival (753 days vs < 365 days) and double the median survival of patients with mesothelioma in the LENT cohort (339 days; 95% CI, nonoverlapping). Survival with lung and breast cancer did not differ significantly between the groups. Sixty-one percent of patients experienced early infection. There was no survival difference between patients with early and late infection (P = .6).CONCLUSIONSThis small series of patients with IPCs for MPE suggests pleural infection may be associated with longer survival, particularly in patients with mesothelioma. Results did not achieve significance, and a larger study is needed to explore this relationship further and investigate whether the local immune response, triggered by infection, is able to modulate mesothelioma progression.

OBJECTIVE Malignant pleural effusion (MPE) incidence is increasing, and prognosis remains poor. Indwelling pleural catheters (IPCs) relieve symptoms but increase the risk of pleural infection. We reviewed cases of pleural infection in patients with IPCs for MPE from six UK centers between January 1, 2005, and January 31, 2014. METHODS Survival in patients with pleural infection was compared with 788 patients with MPE (known as the LENT [pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, serum neutrophil to lymphocyte ratio, and tumor type] cohort) and with national statistics. RESULTS Of 672 IPCs inserted, 25 (3.7%) became infected. Most patients (20 of 25) had mesothelioma or lung cancer. Median survival in the pleural infection cohort appeared longer than in the LENT cohort, although this result did not achieve significance (386 days vs 132 days; hazard ratio, 0.67; P = .07). Median survival with mesothelioma and pleural infection was twice as long as national estimates for mesothelioma survival (753 days vs < 365 days) and double the median survival of patients with mesothelioma in the LENT cohort (339 days; 95% CI, nonoverlapping). Survival with lung and breast cancer did not differ significantly between the groups. Sixty-one percent of patients experienced early infection. There was no survival difference between patients with early and late infection (P = .6). CONCLUSIONS This small series of patients with IPCs for MPE suggests pleural infection may be associated with longer survival, particularly in patients with mesothelioma. Results did not achieve significance, and a larger study is needed to explore this relationship further and investigate whether the local immune response, triggered by infection, is able to modulate mesothelioma progression. Malignant pleural effusion (MPE) incidence is increasing, and prognosis remains poor. Indwelling pleural catheters (IPCs) relieve symptoms but increase the risk of pleural infection. We reviewed cases of pleural infection in patients with IPCs for MPE from six UK centers between January 1, 2005, and January 31, 2014. Survival in patients with pleural infection was compared with 788 patients with MPE (known as the LENT [pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, serum neutrophil to lymphocyte ratio, and tumor type] cohort) and with national statistics. Of 672 IPCs inserted, 25 (3.7%) became infected. Most patients (20 of 25) had mesothelioma or lung cancer. Median survival in the pleural infection cohort appeared longer than in the LENT cohort, although this result did not achieve significance (386 days vs 132 days; hazard ratio, 0.67; P = .07). Median survival with mesothelioma and pleural infection was twice as long as national estimates for mesothelioma survival (753 days vs < 365 days) and double the median survival of patients with mesothelioma in the LENT cohort (339 days; 95% CI, nonoverlapping). Survival with lung and breast cancer did not differ significantly between the groups. Sixty-one percent of patients experienced early infection. There was no survival difference between patients with early and late infection (P = .6). This small series of patients with IPCs for MPE suggests pleural infection may be associated with longer survival, particularly in patients with mesothelioma. Results did not achieve significance, and a larger study is needed to explore this relationship further and investigate whether the local immune response, triggered by infection, is able to modulate mesothelioma progression.

OBJECTIVES:The aim of this study was to test the effectiveness of Provent, an expiratory nasal resistance valve, to prevent the recurrence of OSA following CPAP withdrawal.DESIGN:Randomised, partially blinded, parallel, placebo-controlled trial.SETTING:Outpatient sleep clinics in the UK (Oxford) and Switzerland (Zurich).PARTICIPANTS:67 patients with OSA receiving CPAP were randomised to one of three groups for 2 weeks: continuing CPAP, Provent or placebo Provent.MAIN OUTCOME MEASURES:Primary outcomes included for Provent versus placebo Provent, OSA severity (oxygen desaturation index (ODI), apnoea-hypopnoea index (AHI)) and Epworth Sleepiness Scale (ESS) score. Secondary outcomes for Provent versus placebo Provent included ODI from ambulatory pulse oximetry and blood pressure (BP). For CPAP versus Provent, or CPAP versus placebo Provent, secondary outcomes included ODI/AHI, ESS and BP.RESULTS:63 patients were included in the per protocol analysis. OSA recurred in the Provent (ODI 35.8, SD 17.4) and placebo Provent (ODI 28.2, SD 18.3) groups, and there was no significant difference in ODI, AHI and ESS between Provent and placebo Provent at 2 weeks (mean difference ODI -1.0, 95% CI -10.0 to +12.0, p=0.85; AHI +3.2, 95% CI -7.7 to +14.1, p=0.52; and ESS -1.4, 95% CI -4.1 to +1.4, p=0.33). ODI from ambulatory pulse-oximetry and BP at 2 weeks were not different in the Provent versus placebo Provent groups. ODI, AHI and BP, but not ESS, were significantly higher in the Provent and placebo Provent groups compared with CPAP.CONCLUSIONS:Provent cannot be recommended as an alternative short-term therapy for patients with moderate to severe OSA already on CPAP.TRIALREGNO:NCT01332175.