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Data Sharing Statement: Fully anonymised data will be provided upon reasonable request to the corresponding author. Copyright © 2022 The Author(s). Background There are few evidence-based interventions for long COVID; however, holistic approaches supporting recovery are advocated. We assessed whether an online breathing and wellbeing programme improves health related quality-of-life (HRQoL) in people with persisting breathlessness following COVID-19. Methods We conducted a parallel-group, single-blind, randomised controlled trial in patients who had been referred from one of 51 UK-based collaborating long COVID clinics. Eligible participants were aged 18 years or older; were recovering from COVID-19 with ongoing breathlessness, with or without anxiety, at least 4 weeks after symptom onset; had internet access with an appropriate device; and were deemed clinically suitable for participation by one of the collaborating COVID-19 clinics. Following clinical assessment, potential participants were given a unique online portal code. Participants were randomly assigned (1:1) to either immediate participation in the English National Opera (ENO) Breathe programme or to usual care. Randomisation was done by the research team using computer-generated block randomisation lists, with block size 10. The researcher responsible for randomisation was masked to responses. Participants in the ENO Breathe group participated in a 6-week online breathing and wellbeing programme, developed for people with long COVID experiencing breathlessness, focusing on breathing retraining using singing techniques. Those in the deferred group received usual care until they exited the trial. The primary outcome, assessed in the intention-to-treat population, was change in HRQoL, assessed using the RAND 36-item short form survey instrument mental health composite (MHC) and physical health composite (PHC) scores. Secondary outcome measures were the chronic obstructive pulmonary disease assessment test score, visual analogue scales (VAS) for breathlessness, and scores on the dyspnoea-12, the generalised anxiety disorder 7-item scale, and the short form-6D. A thematic analysis exploring participant experience was also conducted using qualitative data from focus groups, survey responses, and email correspondence. This trial is registered with ClinicalTrials.gov, NCT04830033. Findings Between April 22 and May 25, 2021, 158 participants were recruited and randomly assigned. Of these, eight (5%) individuals were excluded and 150 participants were allocated to a treatment group (74 in the ENO Breathe group and 76 in the usual care group). Compared with usual care, ENO Breathe was associated with an improvement in MHC score (regression coefficient 2·42 [95% CI 0·03 to 4·80]; p=0·047), but not PHC score (0·60 [–1·33 to 2·52]; p=0·54). VAS for breathlessness (running) favoured ENO Breathe participation (−10·48 [–17·23 to –3·73]; p=0·0026). No other statistically significant between-group differences in secondary outcomes were observed. One minor self-limiting adverse event was reported by a participant in the ENO Breathe group who felt dizzy using a computer for extended periods. Thematic analysis of ENO Breathe participant experience identified three key themes: (1) improvements in symptoms; (2) feeling that the programme was complementary to standard care; and (3) the particular suitability of singing and music to address their needs. Interpretation Our findings suggest that an online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind–body and music-based approaches, including practical, enjoyable, symptom-management techniques might have a role supporting recovery. Imperial College Clinician Investigator Scholarship; National Institute for Health Research (NIHR) Biomedical Research Centre based at 506 Imperial College Healthcare NHS Trust and Imperial College London; The ENO Breathe programme is generously supported by the English National Opera’s 509 patrons and donors.

BackgroundLung 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.MethodsThis 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.Results88 participants (48% female, mean±sdage 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±1.44versusBLVR −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%)versusBLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm.ConclusionOur findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

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 (ISRCTN19684749), 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, lung function, breathlessness and exercise capacity. 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.

Aims To determine the clinical impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a) > 500 mg/L on the primary end point of quantitative myocardial perfusion, as well as secondary end points including atheroma burden, exercise capacity, symptoms, and quality of life. Methods We conducted a single-blinded randomized controlled trial in 20 patients with refractory angina and raised lipoprotein(a) > 500 mg/L, with 3 months of blinded weekly lipoprotein apheresis or sham, followed by crossover. The primary endpoint was change in quantitative myocardial perfusion reserve (MPR) assessed by cardiovascular magnetic resonance. Secondary endpoints included measures of atheroma burden, exercise capacity, symptoms and quality of life. Results The primary endpoint, namely MPR, increased following apheresis (0.47; 95% CI 0.31–0.63) compared with sham (−0.16; 95% CI − 0.33–0.02) yielding a net treatment increase of 0.63 (95% CI 0.37–0.89; P

RATIONALE: Increasing physical activity is a key therapeutic aim in COPD. Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence regarding its ability to improve physical activity levels. OBJECTIVE: To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate intensity physical activity (time ≥ 3METs) in people with COPD. METHODS: In this single-blinded randomized controlled trial, participants were assigned 1:1 to receive control (PR comprising 8 weeks, two supervised sessions/week) or intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 weeks). The randomisation process used minimisation to balance groups for age, sex, FEV1 % predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was by intention-to-treat and the trial registered with clinicaltrials.gov (Ref. NCT01719822). MEASUREMENTS: The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time ≥3METs. MAIN RESULTS: 152 participants (72% male; mean (SD) FEV1 % predicted 50.5 (21.2); median (Q1, Q3) time ≥3METS 46 (21, 92) minutes) were enrolled to intervention (n=76) or control (n=76). There was no significant difference in change in time ≥3METs between the intervention and control groups at 8 weeks (median (Q1, Q3) difference 0.5 (-1.0, 31.0) minutes; p=0.87) or at the 6 month follow-up (7.0 (-9, 27) minutes; p=0.16). CONCLUSION: Pedometer-directed step count targets during an outpatient PR program did not enhance moderate intensity physical activity levels in people with COPD. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01719822.

There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions.

Aims\ud \ud Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS.\ud \ud Methods and results\ud \ud A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting

Aims \ud Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS.\ud \ud Methods and results \ud A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting

The impact of depressive symptoms on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been thoroughly evaluated in prospective studies. We prospectively enrolled 230 consecutive patients hospitalised for AECOPD, without previous diagnosis of depression. Depressive symptoms were evaluated with Beck's depression inventory. Pulmonary function tests, arterial blood gases, COPD assessment test (CAT) and Borg dyspnoea scale were recorded on admission and on days 3, 10 and 40. Patients were evaluated monthly for 1 year. Patients with depressive symptoms required longer hospitalisation (mean±SD 11.6±3.7 versus 5.6