Erratum: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

An erratum was issued for: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion. The Authors section was updated from: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation to: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Nick Maskell4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation.

Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Surveillance of pneumococcal serotypes in adults hospitalised with acute lower respiratory tract infection in Bristol, UK.

INTRODUCTION: Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. METHODS: A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). RESULTS: Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DISCUSSION: Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

A chylothorax in a young woman: The difficulties of medical management.

Lymphangioleiomyomatosis is a rare pulmonary disease affecting women of childbearing age. Whilst chylothorax is a well-recognized complication of the condition, management strategies aren't well-defined, have low success rates and are often only available at tertiary or specialist centres. We describe a case of a young woman referred to pleural clinic with a chylous effusion found to be secondary to lymphangioleiomyomatosis. Initial medical management was unsuccessful and recurrent drainages caused significant complications. Remission was ultimately achieved with a combination of mTOR inhibitors and interventional radiology techniques.

Association of ABO and Rhesus blood groups with severe outcomes from non-SARS-CoV-2 respiratory infection: A prospective observational cohort study in Bristol, UK 2020-2022.

Despite significant global morbidity associated with respiratory infection, there is a paucity of data examining the association between severity of non-SARS-CoV-2 respiratory infection and blood group. We analysed a prospective cohort of adults hospitalised in Bristol, UK, from 1 August 2020 to 31 July 2022, including patients with acute respiratory infection (pneumonia [n = 1934] and non-pneumonic lower respiratory tract infection [NP-LRTI] [n = 1184]), a negative SARS-CoV-2 test and known blood group status. The likelihood of cardiovascular complication, survival and hospital admission length was assessed using regression models with group O and RhD-negative status as reference groups. Group A and RhD-positive were over-represented in both pneumonia and NP-LRTI compared to a first-time donor population (p < 0.05 in all); contrastingly, group O was under-represented. ABO group did not influence cardiovascular complication risk; however, RhD-positive patients with pneumonia had a reduced odds ratio (OR) for cardiovascular complications (OR = 0.77 [95% CI = 0.59-0.98]). Compared to group O, group A individuals with NP-LRTI were more likely to be discharged within 60 days (hazard ratio [HR] = 1.17 [95% CI = 1.03-1.33]), while group B with pneumonia was less likely (HR = 0.8 [95% CI = 0.66-0.96]). This analysis provides some evidence that blood group status may influence clinical outcome following respiratory infection, with group A having increased risk of hospitalisation and RhD-positive patients having reduced cardiovascular complications.

The impact of outpatient versus inpatient management on health-related quality of life outcomes for patients with malignant pleural effusion: the OPTIMUM randomised clinical trial.

BACKGROUND: The principal aim of malignant pleural effusion (MPE) management is to improve health-related quality of life (HRQoL) and symptoms. METHODS: In this open-label randomised controlled trial, patients with symptomatic MPE were randomly assigned to either indwelling pleural catheter (IPC) insertion with the option of talc pleurodesis or chest drain and talc pleurodesis. The primary end-point was global health status, measured with the 30-item European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) at 30 days post-intervention. 142 participants were enrolled from July 2015 to December 2019. RESULTS: Of participants randomly assigned to the IPC (n=70) and chest drain (n=72) groups, primary outcome data were available in 58 and 56 patients, respectively. Global health status improved in both groups at day 30 compared with baseline: IPC (mean difference 13.11; p=0.001) and chest drain (mean difference 10.11; p=0.001). However, there was no significant between-group difference at day 30 (mean intergroup difference in baseline-adjusted global health status 2.06, 95% CI -5.86-9.99; p=0.61), day 60 or day 90. No significant differences were identified between groups in breathlessness and chest pain scores. All chest drain arm patients were admitted (median length of stay 4 days); seven patients in the IPC arm required intervention-related hospitalisation. CONCLUSIONS: While HRQoL significantly improved in both groups, there were no differences in patient-reported global health status at 30 days. The outpatient pathway using an IPC was not superior to inpatient treatment with a chest drain.

PET-CT-guided versus CT-guided biopsy in suspected malignant pleural thickening: a randomised trial.

BACKGROUND: Pleural biopsy is the gold standard for diagnosis of pleural malignancy but a significant proportion will have an inconclusive biopsy despite ongoing clinical suspicion of malignancy. We investigated whether positron emission tomography-computed tomography (PET-CT) targeted pleural biopsy is superior to standard CT-guided pleural biopsy following an initial non-diagnostic biopsy. METHODS: The TARGET trial was a multicentre, parallel group randomised trial. Patients with a previous inconclusive pleural biopsy but an ongoing suspicion of pleural malignancy were randomised (1:1) to receive either CT-guided biopsy (standard care) or PET-CT followed by a targeted CT biopsy (intervention). The primary outcome was pleural malignancy correctly identified from the trial biopsy. RESULTS: Between September 2015 and September 2018, 59 participants were randomised from eight UK hospital sites: 29 to CT-only followed by targeted biopsy and 30 to PET-CT followed by targeted biopsy. The proportion of pleural malignancy correctly identified was similar between the groups (risk ratio 1.03 (95% CI 0.83-1.29); p=0.77). The sensitivity of the trial biopsy to identify pleural malignancy was 79% (95% CI 54-94%) in the CT-only group versus 81% (95% CI 54-96%) in the PET-CT group. CONCLUSIONS: The results do not support the practice of PET-CT to guide pleural biopsies in patients with a previous non-diagnostic biopsy. The diagnostic sensitivity in the CT-only group was higher than anticipated and supports the practice of repeating a CT-guided biopsy following an inconclusive result if clinical suspicion of malignancy persists.

Relative vaccine effectiveness of mRNA COVID-19 boosters in people aged at least 75 years during the spring-summer (monovalent vaccine) and autumn-winter (bivalent vaccine) booster campaigns: a prospective test negative case-control study, United Kingdom, 2022.

BackgroundUnderstanding the relative vaccine effectiveness (rVE) of new COVID-19 vaccine formulations against SARS-CoV-2 infection is a public health priority. A precise analysis of the rVE of monovalent and bivalent boosters given during the 2022 spring-summer and autumn-winter campaigns, respectively, in a defined population remains of interest.AimWe assessed rVE against hospitalisation for the spring-summer (fourth vs third monovalent mRNA vaccine doses) and autumn-winter (fifth BA.1/ancestral bivalent vs fourth monovalent mRNA vaccine dose) boosters.MethodsWe performed a prospective single-centre test-negative design case-control study in ≥ 75-year-old people hospitalised with COVID-19 or other acute respiratory disease. We conducted regression analyses controlling for age, sex, socioeconomic status, patient comorbidities, community SARS-CoV-2 prevalence, vaccine brand and time between baseline dose and hospitalisation.ResultsWe included 682 controls and 182 cases in the spring-summer booster analysis and 572 controls and 152 cases in the autumn-winter booster analysis. A monovalent mRNA COVID-19 vaccine as fourth dose showed 46.6% rVE (95% confidence interval (CI): 13.9-67.1) vs those not fully boosted. A bivalent mRNA COVID-19 vaccine as fifth dose had 46.7% rVE (95% CI: 18.0-65.1), compared with a fourth monovalent mRNA COVID-19 vaccine dose.ConclusionsBoth fourth monovalent and fifth BA.1/ancestral mRNA bivalent COVID-19 vaccine doses demonstrated benefit as a booster in older adults. Bivalent mRNA boosters offered similar protection against hospitalisation with Omicron infection to monovalent mRNA boosters given earlier in the year. These findings support immunisation programmes in several European countries that advised the use of BA.1/ancestral bivalent booster doses.

Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study.

INTRODUCTION: Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time. METHODS AND ANALYSIS: STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I-III lung cancer, (2) mini-PE, (3) Performance Status 0-2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023. ETHICS AND DISSEMINATION: Protocol approved by the West of Scotland Research Ethics Committee (Ref: 19/WS/0093). Results will be published in peer-reviewed journals and presented at international meetings. TRIAL REGISTRATION NUMBER: ISRCTN13584097.

Clinical characteristics of chylothorax: results from the International Collaborative Effusion database.

Background: Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features. Methods: The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed. Descriptive and inferential statistics were performed. Results: 77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL-1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL-1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase <500 U·L-1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL-1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival. Conclusion: Chylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed.

The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol.

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. Methods: RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Discussion: Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN Registration: ISRCTN14813929 (22/04/2021).

BACKGROUND AND AIMS: Patches containing a numbing medication (lidocaine), put on the skin over broken ribs, may help to improve outcomes in older people. We will carry out a clinical trial of these patches, to see whether this research would work in Accident and Emergency (A&E) and whether patients will take part. DESIGN: We will ask 100 older people who need to stay in hospital with broken ribs to take part in this research. We will ask permission from relatives to include people with dementia. We will put those who agree to take part into one of two groups by chance. One group will have the patch put over their broken ribs in A&E for up to 3 days, along with usual pain killers if needed. We will treat people in the other group in the normal way, without a patch. We will track how many people are willing to take part. We will collect information on patient recovery in the 30 days after going to A&E and ask people to complete questionnaires about their health. We will interview patients and clinicians to get feedback. Patient and Public Involvement: Patient volunteers helped us design this research and will provide advice throughout. They agreed that including older people was appropriate, people with dementia and their carers should take part, and side-effects of strong pain killers are important to patients. FINDINGS: We will use the research findings to develop a larger trial to see if lidocaine patches help patients with broken ribs. We will write up results for scientific journals, speak at conferences and to our patient group.

Diathermy and bone sawing are high aerosol yield procedures.

Aims: Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians' health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations. Methods: The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 µm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures. Results: Diathermy (electrocautery) and oscillating bone saw use had a high aerosol yield (> 100 particles detected per s) consistent with high exposure to aerosol in the respirable range (< 5 µm) for the lead surgeon. Pulsed lavage, reaming, osteotome use, and jig application/removal were medium aerosol yield (10 to 100 particles s-1). However, pulsed lavage aerosol was largely attributed to the saline jet, osteotome use was always brief, and jig application/removal had a large variability in the associated aerosol yield. Suctioning (with/without saline irrigation) had a low aerosol yield (< 10 particles s-1). Most surprisingly, other high-speed procedures, such as drilling and screwing, had low aerosol yields. Conclusion: This work suggests that additional precautions should be recommended for diathermy and bone sawing, such as enhanced personal protective equipment or the use of suction devices to reduce exposure.

Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3.

Rationale: Assessing the early use of video-assisted thoracoscopic surgery (VATS) or intrapleural enzyme therapy (IET) in pleural infection requires a phase III randomized controlled trial (RCT). Objectives: To establish the feasibility of randomization in a surgery-versus-nonsurgery trial as well as the key outcome measures that are important to identify relevant patient-centered outcomes in a subsequent RCT. Methods: The MIST-3 (third Multicenter Intrapleural Sepsis Trial) was a prospective multicenter RCT involving eight U.K. centers combining on-site and off-site surgical services. The study enrolled all patients with a confirmed diagnosis of pleural infection and randomized those with ongoing pleural sepsis after an initial period (as long as 24 h) of standard care to one of three treatment arms: continued standard care, early IET, or a surgical opinion with regard to early VATS. The primary outcome was feasibility based on >50% of eligible patients being successfully randomized, >95% of randomized participants retained to discharge, and >80% of randomized participants retained to 2 weeks of follow-up. The analysis was performed per intention to treat. Measurements and Main Results: Of 97 eligible patients, 60 (62%) were randomized, with 100% retained to discharge and 84% retained to 2 weeks. Baseline demographic, clinical, and microbiological characteristics of the patients were similar across groups. Median times to intervention were 1.0 and 3.5 days in the IET and surgery groups, respectively (P = 0.02). Despite the difference in time to intervention, length of stay (from randomization to discharge) was similar in both intervention arms (7 d) compared with standard care (10 d) (P = 0.70). There were no significant intergroup differences in 2-month readmission and further intervention, although the study was not adequately powered for this outcome. Compared with VATS, IET demonstrated a larger improvement in mean EuroQol five-dimension health utility index (five-level edition) from baseline (0.35) to 2 months (0.83) (P = 0.023). One serious adverse event was reported in the VATS arm. Conclusions: This is the first multicenter RCT of early IET versus early surgery in pleural infection. Despite the logistical challenges posed by the coronavirus disease (COVID-19) pandemic, the study met its predefined feasibility criteria, demonstrated potential shortening of length of stay with early surgery, and signals toward earlier resolution of pain and a shortened recovery with IET. The study findings suggest that a definitive phase III study is feasible but highlights important considerations and significant modifications to the design that would be required to adequately assess optimal initial management in pleural infection.The trial was registered on ISRCTN (number 18,192,121).

Frailty and its influence on mortality and morbidity in COPD: A Systematic Review and Meta-Analysis.

Frailty increases vulnerability to adverse outcomes. Long-term conditions increase the risk of frailty. We searched PubMed, Web of Science, The Cochrane Library, EMBASE from inception to March 2022. Quality assessment was conducted using the NOS. Data was analysed in a pooled a random-effects meta-analysis. Our primary outcome was the impact of frailty on mortality in adults with Chronic Obstructive Pulmonary Disease (COPD) diagnosis according to the guidelines. Secondary outcomes were: frailty and association with readmissions, hospitalisations, exacerbation rates, and prevalence of frailty in COPD. We identified 25 studies, with 5882 participants. The median prevalence of frailty was 47% (IQR, 39.3-66.3%, range 6.4-72%). There was an association between COPD patients living with frailty and increased risk of mortality versus COPD patients without frailty (pooled OR, 4.21 (95% CI 2.99-5.93, I2 55%). A descriptive analysis of relationship between frailty and hospital readmission and all cause hospitalization showed positive associations. The relationship between frailty and the risk of exacerbation showed a pooled OR, 1.45 (95% CI 0.37-5.70, I2 80%). Frailty is significantly associated with higher mortality risk in COPD. Frailty is common in patients with COPD and its measurement should be considered in clinical practice to better characterise COPD.

Frailty Prevalence and Association with Clinical Outcomes in Interstitial Lung Disease, Asthma, and Pleural Disease.

BACKGROUND: Frailty is a syndrome characterised by increased vulnerability to negative outcomes. Interstitial lung disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. METHODS: We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including interstitial lung disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, systemic sclerosis-associated ILD, connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough contextually homogeneous studies were included, a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. RESULTS: The review found three studies relating to frailty in asthma. No studies relating to pleural disease and frailty were identified. The median prevalence in asthma was 9.5% (IQR, 7.8-11.3). Six relevant studies incorporating 1471 ILD patients (age 68.3 ± SD2.38; 50% male) were identified, which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR, 25-50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31-4.15, I2 9%). One study reported a hospitalization rate of HR = 1.97(1.32-3.06) within 6 months in frail ILD patients. CONCLUSIONS: Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population.

Does previous asbestos exposure increase the risk of a post coronary artery bypass graft (CABG) pleural effusion - a routine data study?

BACKGROUND: Development of pleural effusion (PE) following CABG is common. Post-CABG PE are divided into early- (within 30 days of surgery) and delayed-onset (30 days-1 year) which are likely due to distinct pathological processes. Some experts suggest asbestos exposure may confer an independent risk for late-onset post-CABG PE, however no large studies have explored this potential association. RESEARCH QUESTION: To explore possible association between asbestos exposure and post-CABG PE using routine data. METHODS: All patients who underwent CABG 01/04/2013-31/03/2018 were identified from the Hospital Episode Statistics (HES) Database. This England-wide population was evaluated for evidence of asbestos exposure, pleural plaques or asbestosis and a diagnosis of PE or PE-related procedure from 30 days to 1 year post-CABG. Patients with evidence of PE three months prior to CABG were excluded, as were patients with a new mesothelioma diagnosis. RESULTS: 68,150 patients were identified, of whom 1,003 (1%) were asbestos exposed and 2,377 (3%) developed late-onset PE. After adjusting for demographic data, Index of Multiple Deprivation and Charlson Co-morbidity Index, asbestos exposed patients had increased odds of PE diagnosis or related procedure such as thoracentesis or drainage (OR 1.35, 95% CI 1.03-1.76, p = 0.04). In those with evidence of PE requiring procedure alone, the adjusted OR was 1.66 (95% CI 1.14-2.40, p = 0.01). Additional subgroup analysis of the 518 patients coded for pleural plaques and asbestosis alone revealed an adjusted OR of post-CABG PE requiring a procedure of 2.16 (95% CI 1.38-3.37, p = 0.002). INTERPRETATION: This large-scale study demonstrates prior asbestos exposure is associated with modestly increased risk of post-CABG PE development. The risk association appears higher in patients with assigned clinical codes indicative of radiological evidence of asbestos exposure (pleural plaques or asbestosis). This association may fit with a possible inflammatory co-pathogenesis, with asbestos exposure 'priming' the pleura resulting in greater propensity for PE evolution following the physiological insult of CABG surgery. Further work, including prospective studies and clinicopathological correlation are suggested to explore this further.

Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance.

OBJECTIVES: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI). DESIGN: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size. SETTING: 4 UK pleural disease centres (February 2019-January 2020). PARTICIPANTS: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up. OUTCOME MEASURES: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression. RESULTS: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)). CONCLUSIONS: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500. TRIAL REGISTRATION NUMBER: ISRCTN12840870.