British Lung Foundation Research Articles

Domiciliary transcutaneous electrical stimulation in patients with obstructive sleep apnoea and limited adherence to continuous positive airway pressure therapy: a single-centre, open-label, randomised, controlled phase III trial

Hypoglossal nerve stimulation (HNS) for obstructive sleep apnoea (OSA) is a novel way to manage the condition. We hypothesised that in patients with OSA and limited adherence to continuous positive airway pressure (CPAP) therapy, domiciliary transcutaneous electrical stimulation (TESLA) would control sleep apnoea and provide health benefits. We undertook a single-centre, open-label, randomised, controlled phase III trial in patients with OSA (apnoea-hypopnoea-index [AHI] 5-35h-1), a BMI of 18.5-32kg∗m-2, and a documented lack of adherence to CPAP therapy (<4h∗night-1) at Guy's & St Thomas' NHS Foundation Trust (hospital), UK. Patients were randomly assigned (1:1) using minimisation (gender and OSA severity) to receive TESLA or usual care (CPAP) for at least 3 months; sleep study analysis was provided without knowledge of the assignment arm. The primary outcome was change in AHI at 3-months. The primary outcome and safety were analysed in the intention-to-treat population. Data are reported as median (interquartile range), unless otherwise explained. This trial is registered at ClinicalTrials.gov, NCT03160456. Between 6 June 2018 and 7 February 2023, 56 participants were enrolled and randomly assigned (29 patients in the intervention group and 27 in the usual care group). Patients were followed up for a median of 3.0 months (IQR 3.0; 10.0). The groups were similar in terms of age (55.8 (48.2; 66.0) vs 59.3 (47.8; 64.4) years), gender (male:female, 19:10 vs 18:9) and BMI (28.7 (26.4; 31.9) vs 28.4 (24.4; 31.9) kg∗m-2). The unadjusted group difference in the AHI was-11.5 (95% CI-20.7;-2.3) h-1 (p=0.016). Adjusted for the baseline value, the difference was AHI-7.0 (-15.7; 1.8) h-1 (p=0.12), in favour of the intervention. Minor adverse events were found in one of the participants who developed mild headaches related to the intervention. Domiciliary TESLA can be used safely and effectively in OSA patients with poor adherence to CPAP, with favourable impact on sleepiness and sleep fragmentation. Despite pandemic-related limitations of the amended protocol this trial provides the evidence that TESLA improves clinically meaningful outcomes over the observed follow up period, and the transcutaneous approach is likely to offer an affordable alternative for responders to electrical stimulation in clinical practice. British Lung Foundation, United Kingdom Clinical Research Collaboration-registered King's Clinical Trials Unit at King's Health Partners.

The power of music.

How music can so powerfully impact our bodies and minds defies rational explanation. Through our senses, music can mysteriously reach our deepest emotions without using language or images. Even if we do not understand it intellectually, music speaks to us, and can transform our experience. Music is often a communal experience. Anthony Storr, psychoanalyst and musician, writes that when a group of people sing together, ‘a culturally agreed upon pattern of rhythm and melody, i.e. a song, that is sung together, provides a shared form of emotion that, at least during the course of the song, carries along the participants so that they experience their bodies responding emotionally in very similar ways, sharing the emotions of the music’ (Music and the Mind, HarperCollins Publishers, 1992). But why are we talking about music here? Music is integral to healing practices in many indigenous cultures. In Western medicine, the impact of music on wellbeing is increasingly explored. The beneficial impact of music on reducing anxiety and stress responses, with possible resulting immune system modulation, has been observed in individuals with a range of nervous system conditions, from autism, depression, Parkinson's and schizophrenia. In patients with dementia, music and singing can reduce hallucinations and depression, increase social interactions and may even be associated with slower cognitive impairment. During the early phases of the COVID-19 outbreak, when most of the world was in lockdown and clinical staff were under severe psychological distress, an Italian hospital piloted a music therapy programme for healthcare staff assisting COVID-19 patients (https://doi.org/10.1016/j.aip.2020.101688). After listening to playlists prepared by trained music therapists and customized to individual preferences, clinical staff reported significantly reduced tiredness, sadness, fear and worry. Similarly, in a randomized controlled trial investigating mindfulness and music therapy in nurses caring for COVID-19 patients in Turkey, work-related strain was reduced in the intervention compared to control group. (https://doi.org/10.1097/hnp.0000000000000511). British Lung Foundation (BLF) commissioned Phoene to deliver a training programme for singing leaders entitled ‘Singing for Lung Health (SLH)’, with more than 100 groups established across the UK. Service evaluation has shown that SLH is associated with improved respiratory related quality of life and reduced health care utilization (https://journals.sagepub.com/doi/10.1177/1757913918774079). In the words of a SLH participant: ‘I feel as though my airways have really opened up and my natural breathing is more fluid. Singing has so many benefits: physical, emotional and pure enjoyment’. Group singing as a treatment for patients with chronic lung diseases is increasingly explored in Europe, North America, Australia and Africa, with research ongoing to study the physiological and psychosocial benefits for participants and how this intervention could best be implemented more widely (https://www.mdpi.com/2227-9059/10/9/2086#B14-biomedicines-10-02086). None declared.

Implementation of a primary care asthma management quality improvement programme across 68 general practice sites

Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited. It was delivered and cascaded to all relevant staff at participating practices in three Clinical Commissioning Groups. The programme focussed on improving diagnostic accuracy, management of risk and control, patient self-management and overall asthma control. Patient data were extracted by OPC for the 12 months before (baseline) and after (outcome) the intervention. In the three CCGs, 68 GP practices participated in the programme. Uptake from practices was higher in the CCG that included asthma in its incentivised quality improvement programme. Asthma outcome data were successfully extracted from 64 practices caring for 673,593 patients. Primary outcome (Royal College of Physicians Three Questions [RCP3Q]) data were available in both the baseline and outcome periods for 10,328 patients in whom good asthma control (RCP3Q = 0) increased from 36.0% to 39.2% (p < 0.001) after the intervention. The odds ratio of reporting good asthma control following the intervention was 1.15 (95% CI 1.09–1.22), p < 0.0001. This asthma management programme produced modest but highly statistically significant improvements in asthma outcomes. Key lessons learnt from this small-scale implementation will enable the methodology to be improved to maximise benefit in a larger scale role out.

OA19 Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY

Abstract Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care; 2) time to first rheumatology assessment; 3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35 days) than before (21 days; 9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic; however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic; however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely-captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection. Disclosure M.D. Russell: Honoraria; Lilly, Menarini, Biogen. Other; Lilly, Pfizer, Janssen, UCB. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB. C.D. Andrews: None. B. MacKenna: None. B. Goldacre: Grants/research support; Laura and John Arnold Foundation, NIHR, Mohn-Westlake Foundation, Wellcome Trust, Good Thinking Foundation, Health Data Research UK, Health Foundation, World Health Organisation, UKRI, Asthma UK, British Lung Foundation, and National Core Studies programme. A. Mehrkar: Other; Former employee and interim CMO of NHS Digital, and RCGP representative on GP Data Professional Advisory Group to NHS Digital. H.J. Curtis: None. B. Butler-Cole: None. T. O'Dwyer: None. S. Qureshi: Grants/research support; BMS. J.M. Ledingham: Other; Clinical director for NEIAA, Secretary for The Federation of Joint Royal Colleges of Physicians SCE Board, and trustee of the BSR. A. Mahto: Honoraria; Abbvie, Galapagos. Other; Lilly. A.I. Rutherford: Other; Lilly. M.A. Adas: None. E. Alveyn: None. S. Norton: None. A.P. Cope: Consultancies; BMS, Abbvie, GSK/Galvini. Member of speakers’ bureau; BMS, Abbvie. Grants/research support; BMS. Other; Executive committee of the EULAR research centre. K. Bechman: Grants/research support; Versus Arthritis and Pfizer Global Medical Grants.

Are we missing lifetime COPD diagnosis among people with COPD recorded death? A population-based retrospective cohort study.

The British Lung Foundation (BLF) has previously estimated that there are 2.2 million people in the UK who have symptoms, but no diagnosis, of chronic obstructive pulmonary disease (COPD). To investigate the proportion of patients with a missed COPD diagnosis among those with COPD as the cause of death on their death certificate, and how this has changed over a period of 17 years (2000-2017). Clinical Practice Research Datalink (CPRD) Aurum and GOLD primary care data were linked with Office for National Statistics (ONS) mortality data and Hospital Episode Statistics (HES) data. Adults who died between 2000 and 2017 with COPD as their main cause of death were included. Using a range of diagnostic COPD criteria, the proportion of patients with a missed COPD diagnosis was estimated, and the demographic and clinical characteristics of patients with and without prior COPD diagnosis were described, using a mixed-effect logistic regression model. Depending on the COPD definition used, between 96% and 27% of the 78 621 patients included received a diagnosis of COPD before death. Using presence of a COPD Read or SNOMED CT code and performed spirometry as a main definition, just over half of the patients (52%) had received a COPD diagnosis overall, with a proportion of those who did not decreasing from 91% in 2000 to 31% in 2017 (Ptrend <0.001). The proportion of people with COPD-recorded death and who had received a diagnosis of COPD has improved (increased) over time, and currently represents the majority of them. This suggests that few patients are now being missed.

Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.

SummaryBackgroundUncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.MethodsWe used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted.FindingsOur combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.InterpretationHospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely.FundingThis work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE – The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.

Helping you help yourself (HYHY) for people with mild breathlessness: A service evaluation in Wales

Background Pulmonary rehabilitation (PR) is an evidence-based intervention which improves exercise capacity and quality of life (QoL) for patients with chronic obstructive pulmonary disease (COPD). Commonly, outpatient rehabilitation is available for patients with significant breathlessness (Medical Research Council (MRC) &gt;3). This evaluation explored changes in exercise capacity and knowledge of condition and their relationship with the impact of COPD (CAT score) at baseline following a community exercise and education programme delivered by the British Lung Foundation (BLF) in people with mild breathlessness (MRC ≤2). Methods People with mild breathlessness, MRC ≤2, were recruited from GP surgeries, the BLF website and support groups. The 6-week Helping you help yourself (HYHY) programme included weekly exercise, education and social engagement. Participants were assessed at baseline using the COPD Assessment Tool (CAT), 6-minute walk test (6MWT), Bristol COPD Knowledge quiz (BKQ), and questions on self-management was assessed by questionnaire. After 6 weeks 6MWT, BKQ and self-management were assessed and related to CAT at baseline. The usefulness of the programme to participants was also assessed by questionnaire. Results In the 210 patients who completed assessments before and after HYHY, there was an increase in 6MWT distance, median (IQR) 60 (30–80)m and BKQ 3 (1–4) points (p &lt;0.05), and most elements of self-management improved. Almost all participants considered HYHY useful (p &lt;0.05). There was no relationship between baseline CAT score and change in outcome measures (p &gt;0.05). Conclusion The results support the provision of community rehabilitation as an alternative to hospital-based interventions to support and promote self-management in people with mild breathlessness across the severity of disease burden as measured by CAT.

Children’s charter for lung health

Every child and young person has the right to breathe clean air, with healthy lungs. Preconception, in utero and early life exposures, affect children’s lungs, their lung growth and their...

Long COVID and mental health.

Long COVID and mental health.

Research priorities for exacerbations of COPD

Research priorities for exacerbations of COPD

The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study

Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis. We did a prospective observational cohort study of patients with bronchiectasis from eastern Scotland. Patients were enrolled from Sept 11, 2012, to Dec 21, 2015, and followed until Jan 8, 2019, for long-term outcomes. Patients were included if they were aged 18 years or older, and had a high-resolution CT-confirmed diagnosis of bronchiectasis and clinical symptoms consistent with the disease. Sputum samples were obtained when patients were clinically stable. Repeat sputum samples were taken at stable and exacerbation visits during follow-up. The V3-V4 region of the bacterial 16S rRNA gene was sequenced using the Illumina MiSeq platform. The dominant bacterial genus in each sample was assigned on the basis of a previously published method. Microbiome characteristics were analysed for their association with measures of clinical disease severity and long-term outcomes using PERMANOVA, random forest, and survival analyses. Sequencing data were obtained from the sputum samples of 281 patients with bronchiectasis who were included in the stable baseline cohort. 49 (17%) of 281 patients provided more than one sample when clinically stable and were included in the longitudinal analysis. 64 (23%) patients provided both stable and exacerbation samples. In both stable bronchiectasis and during exacerbations, a sputum microbiome dominated by Proteobacteria and Firmicutes was observed. Individual patients' microbiome profiles were relatively stable over time, during exacerbations and at disease stability. Lower microbiome diversity, measured using the Shannon-Wiener diversity index, was associated with more severe bronchiectasis defined by the bronchiectasis severity index, lower FEV1, and more severe symptoms. Random forest analysis of baseline samples identified Pseudomonas, Enterobacteriaceae, and Stenotrophomonas as being associated with severe bronchiectasis (bronchiectasis severity index ≥9) and greater lung inflammation and Pseudomonas and Enterobacteriaceae with more frequent exacerbations. Patients in whom Pseudomonas was dominant (n=35) were at increased risk of all-cause mortality (hazard ratio 3·12, 95% CI 1·33-7·36; p=0·0091) and had more frequent exacerbations (incident rate ratio 1·69, 95% CI 1·07-2·67; p=0·024) during follow-up compared with patients with other dominant genera (n=246). A reduction in microbiome diversity, particularly one associated with dominance of Pseudomonas, is associated with greater disease severity, higher frequency and severity of exacerbations, and higher risk of mortality. The microbiome might therefore identify subgroups of patients at increased risk of poor outcomes who could benefit from precision treatment strategies. Further research is required to identify the mechanisms of reduced microbiome diversity and to establish whether the microbiome can be therapeutically targeted. British Lung Foundation and European Respiratory Society EMBARC2 consortium.

Neutrophil extracellular traps, disease severity, and antibiotic response in bronchiectasis: an international, observational, multicohort study

Bronchiectasis is predominantly a neutrophilic inflammatory disease. There are no established therapies that directly target neutrophilic inflammation because little is understood of the underlying mechanisms leading to severe disease. Neutrophil extracellular trap (NET) formation is a method of host defence that has been implicated in multiple inflammatory diseases. We aimed to investigate the role of NETs in disease severity and treatment response in bronchiectasis. In this observational study, we did a series of UK and international studies to investigate the role of NETs in disease severity and treatment response in bronchiectasis. First, we used liquid chromatography-tandem mass spectrometry to identify proteomic biomarkers associated with disease severity, defined using the bronchiectasis severity index, in patients with bronchiectasis (n=40) in Dundee, UK. Second, we validated these biomarkers in two cohorts of patients with bronchiectasis, the first comprising 175 patients from the TAYBRIDGE study in the UK and the second comprising 275 patients from the BRIDGE cohort study from centres in Italy, Spain, and UK, using an immunoassay to measure NETs. Third, we investigated whether pathogenic bacteria had a role in NET concentrations in patients with severe bronchiectasis. In a separate study, we enrolled patients with acute exacerbations of bronchiectasis (n=20) in Dundee, treated with intravenous antibiotics for 14 days and proteomics were used to identify proteins associated with treatment response. Findings from this cohort were validated in an independent cohort of patients who were admitted to the same hospital (n=20). Fourth, to assess the potential use of macrolides to reduce NETs in patients with bronchiectasis, we examined two studies of long-term macrolide treatment, one in patients with bronchiectasis (n=52 from the UK) in which patients were given 250 mg of azithromycin three times a week for a year, and a post-hoc analysis of the Australian AMAZES trial in patients with asthma (n=47) who were given 500 mg of azithromycin 3 times per week for a year. Sputum proteomics identified that NET-associated proteins were the most abundant and were the proteins most strongly associated with disease severity. This finding was validated in two observational cohorts, in which sputum NETs were associated with bronchiectasis severity index, quality of life, future risk of hospital admission, and mortality. In a subgroup of 20 patients with acute exacerbations, clinical response to intravenous antibiotic treatment was associated with successfully reducing NETs in sputum. Patients with Pseudomonas aeruginosa infection had a lessened proteomic and clinical response to intravenous antibiotic treatment compared with those without Pseudomonas infections, but responded to macrolide therapy. Treatment with low dose azithromycin was associated with a significant reduction in NETs in sputum over 12 months in both bronchiectasis and asthma. We identified NETs as a key marker of disease severity and treatment response in bronchiectasis. These data support the concept of targeting neutrophilic inflammation with existing and novel therapies. Scottish Government, British Lung Foundation, and European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC).

Electronic Prescribing Systems as Tools to Improve Patient Care: A Learning Health Systems Approach to Increase Guideline Concordant Prescribing for Venous Thromboembolism Prevention

Background: Venous thromboembolism (VTE) causes significant mortality and morbidity in hospitalised patients. In England, reporting the percentage of patients with a VTE risk assessment is mandated, but this does not include whether that risk assessment resulted in appropriate prescribing. Full guideline compliance (defined as an assessment and an appropriate action) is rarely reported. Education, audit and feedback enhance guideline compliance but electronic prescribing systems (EPS) can mandate guideline-compliant actions. We hypothesised that EPS-based interventions would increase full VTE guideline compliance more than other interventions. Methods: All admitted patients within University Hospitals Birmingham NHS Foundation Trust were included for analysis between 2011-2020. The proportion of patients who received a fully compliant risk assessment with the recommended action (prophylaxis or not, depending on the risk score) was assessed over time. Interventions included face-to-face feedback based on measured performance (an individual approach) and mandatory risk assessment and prescribing rules into an EPS (a systems approach). Findings: Data from all 235,005 admissions and all 5503 prescribers were included in the analysis. Face-to-face feedback gradually improved full VTE guideline concordance from 70% to 77% (p=<0.001). Changes to the EPS to mandate assessment with prescribing rules increased full VTE compliance to 95% (p=<0.001). Further amendments to the EPS system to reduce erroneous VTE assessments slightly reduced full compliance to 92% (p<0.001), but this was then maintained during two changes to the low molecular weight heparin drug used for VTE prophylaxis. Interpretation: While both feedback and a rules-based EPS intervention improved guideline-compliant VTE management, a systems approach was more effective and benefits were sustained even during changes to formulary drugs. Non-compliance (an assessment without appropriate action or no assessment) was not eradicated despite this mandated system. Further work is needed to understand this and to ensure software changes enhance full guideline compliance. Funding Statement: This work was supported by PIONEER, the Health Data Research Hub in acute care and the HDR-UK Better Care programme. Declaration of Interests: S Gallier, P Nightingale, T Pankhurst, I Woolhouse, MA Berry, M Garrick report no conflicts of interest. S Ball reports funding support from the HDRUK. E Sapey reports funding support from HDRUK, MRC, Wellcome Trust, NIHR, Alpha 1 Foundation, EPSRC and British Lung Foundation. All other authors have nothing to declare. Ethics Approval Statement: This research was conducted under the ethical approvals of PIONEER, a Health data research hub in acute care (East Midlands – Derby Research ethics committee, reference 20/EM/0158).

Living with bronchiectasis during the COVID-19 pandemic

Living with bronchiectasis during the COVID-19 pandemic

Rucaparib in patients with BAP1-deficient or BRCA1-deficient mesothelioma (MiST1): an open-label, single-arm, phase 2a clinical trial

Malignant mesothelioma remains an incurable cancer, with no effective treatments in the setting of relapsed disease. Homologous recombination deficiency predicts sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. In mesothelioma, BRCA1-associated protein 1 carboxy-terminal hydrolase (BAP1), which regulates DNA repair, is frequently mutated. We aimed to test the hypothesis that BAP1-deficient or BRCA1-deficient mesotheliomas would be sensitive to PARP inhibition by rucaparib. We did a single-centre, open-label, single-arm, phase 2a trial in Leicester, UK, with prospective molecular stratification (Mesothelioma-Stratified Therapy 1 [MiST1]). Patients aged 18 years or older who had radiologically progressing, histologically confirmed, malignant mesothelioma after at least one course of systemic treatment; with cytoplasmic-BAP1-deficient or BRCA1-deficient mesothelioma (pleural or peritoneal or other primary localisation), and who met the other inclusion criteria, were deemed eligible. All eligible patients who consented to take part were given rucaparib 600 mg twice a day orally, for six cycles of 28 days, or until disease progression, unacceptable toxicity, withdrawal of consent, or death. Response was measured by CT scan every 6 weeks. The primary outcome was disease control (complete response, partial response, or stable disease) at 12 weeks in all patients who received study drug; secondary outcomes were the safety and toxicity profile, objective response rate (proportion of complete or partial responses), and disease control rate at 24 weeks. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03654833. Between Feb 9 and June 10, 2019, we enrolled 26 molecularly and clinically eligible patients. Ten (38%) of 26 patients were BAP1 negative and BRCA1 negative, 23 patients (89%) were BAP1 negative, and 13 patients (50%) were BRCA1 negative. Disease control rate at 12 weeks was 58% (95% CI 37-77; 15 of 26 patients), and at 24 weeks was 23% (9-44; six of 26 patients). Rucaparib was well tolerated, with 15 (9%) of 166 adverse events being grade 3 or 4, which were seen in nine (35%) of 26 patients, and there were no deaths. The most common grade 1-2 adverse events were nausea (18 [69%] of 26 patients), fatigue (14 patients [54%]), and decreased appetite (ten patients [38%]). The most common grade 3-4 adverse events were upper respiratory tract infection (three patients [12%]) and anaemia (three patients [12%]). All six cycles of rucaparib were received by eight (31%) of 26 patients. One or more dose reductions occurred in nine patients (35%). Rucaparib in patients with BAP1-negative or BRCA1-negative mesothelioma met the prespecified criteria for success, showing promising activity with manageable toxicity. Further investigation of homologous recombination deficiency mutations is planned to refine the identification of predictive biomarkers for PARP inhibition in mesothelioma. University of Leicester (Leicester, UK), Asthma UK and British Lung Foundation Partnership, and the Victor Dahdaleh Foundation (Toronto, ON, Canada).

The Protective Effect of SARS-CoV-2 Antibodies in Scottish Healthcare Workers

Background: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. The extent of that increased risk compared to the general population and the groups most at risk have not been extensively studied. It is also not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection.Methods: A prospective observational study of health and social care workers in NHS Tayside (Scotland, UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general Tayside population, were studied for comparison. New infections post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection.Results: A total of 2063 health and social care workers were recruited for this study. 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85-6.16, pConclusion: In this study, HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all of the infected individuals developed an antibody response and this was 85% effective in protecting against re-infection with SARS-CoV-2.Funding Statement: NHS Tayside COVID-19 Research Fund, JDC is supported by the British Lung Foundation Chair of Respiratory Research.Declaration of Interests: JDC reports grants and personal fees from GlaxoSmithKline, Boehringer-Ingelheim, Astrazeneca, Pfizer, Bayer Healthcare, Grifols, Napp, Insmed and Zambon outside the submitted work; All other authors report no conflicts of interest.Ethics Approval Statement: West of Scotland Research Ethics committee, approval number 20/WS/0078.

Dance for people with chronic breathlessness: a transdisciplinary approach to intervention development

ObjectivesA transdisciplinary research approach was used to develop a holistic understanding of the physical and psychosocial benefits of dance as an intervention for people living with chronic breathlessness.MethodsThe dance programme...

Perceptions of Anonymised Data Use and Awareness of the NHS Data Opt-Out Amongst Patients, Carers and Healthcare Staff

Introduction: Public awareness and support for secondary health data use may vary by health care experience and participant demographics. Those in England can “opt out” of data secondary use. We explored the awareness, support for and concerns about anonymised healthcare data secondary use and the NHS data opt-out system amongst patients, carers, healthcare staff and the public within the West Midlands. Methods: A patient and public engagement program was completed between February 2019 and July 2020 through PIONEER, conducted at University Hospitals Birmingham NHS Foundation Trust and public venues. This program included patient and public workshops, questionnaires regarding anonymised health data use and feedback discussion groups. Results: Central themes of the benefits and concerns for health data use were agreed by patient and public participants. Key public and patient priorities were projects leading to patient benefit, oversight by the NHS as a trusted organisation, increasing awareness of the NHS data opt-out, and ongoing transparency and public/patient involvement. Questionnaires (308 respondents) showed 31.8% were aware of the NHS data opt-out. 93.8% were happy for their data to be used for NHS research, 84.8% for academic research and 68.4% by health companies. However, opinion varied across groups (age, gender or public, patient, NHS staff and volunteers).Four action points were agreed in workshops based on these results: namely, education regarding the NHS opt-out, increased public awareness of data use, public involvement in data requests with NHS oversight, and transparency including reporting data use and subsequent patient benefit. Conclusion: Use of anonymised healthcare data for secondary purposes is acceptable to most patients, carers and healthcare workers. However, awareness is limited, including of the NHS data opt-out system. Initiatives to improve awareness and publicise potential benefits are needed amongst patients, healthcare staff and the public. Funding Statement: This work was supported by PIONEER, the Health Data Research UK (HDR-UK) Health Data Research Hub in acute care. HDR-UK is an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. Declaration of Interests: CA, BC, KD, GP, EM, MO’H, CM, AI, CC, ML, SM, SG, SP, JA, RD, AR, HF have no conflicts of interest. GG reports funding from HDR-UK. AKD reports funding from HDRUK, The Wellcome Trust and Fight for Sight. ES reports funding from the Wellcome Trust, MRC, HDR-UK, Alpha 1 Foundation (A1F), British Lung Foundation and NIHR. Ethics Approval Statement: PIONEER is an ethically-approved research database and analytical environment (East Midlands – Derby Research Ethics 20/EM/0158). This PPIE work was conducted following ethical approval from the University of Birmingham Ethical Committee (reference ERN_20-0118).

Neutrophil Extracellular Traps are Increased in Severe Bronchiectasis and Reduced by Long-Term Azithromycin Treatment

Background: Bronchiectasis is predominantly a neutrophilic inflammatory disease. There are no established therapies that directly target neutrophilic inflammation because of a lack of understanding of the underlying mechanisms leading to severe disease. Neutrophil extracellular trap (NET) formation is a mode of host defence that has been implicated in multiple inflammatory diseases. Methods: We conducted a series of UK and international studies to investigate the role of NETs in disease severity and treatment response in bronchiectasis. Nano LC/MS-MS was used to identify proteomic markers associated with disease severity, defined using the bronchiectasis severity index (BSI) (n=40). These were validated in two cohorts (n=175 and n=275) using a validated immunoassay to measure NETs. 20 patients with acute exacerbations of bronchiectasis were treated with intravenous antibiotics for 14 days and proteomics used to identify proteins associated with treatment response. Two studies of long-term macrolide treatment, one in bronchiectasis and a post-hoc analysis of the AMAZES trial in asthma, investigated the effect of macrolide treatment on NETs. Findings: 96 proteins were differentially expressed in sputum between severe and mild bronchiectasis. The most abundant and most discriminating were proteins known to be NET proteins. This was validated in two observational cohorts where sputum NETs were associated with BSI, quality of life, lung function, future risk of hospital admissions and mortality. Antibiotic treatment in 20 patients was associated with 23 significantly down-regulated and 16 up-regulated proteins, with the “neutrophil degranulation” pathway being most strongly implicated in response. Patients with Pseudomonas aeruginosa infection had a blunted proteomic and clinical response to treatment. Treatment with low dose azithromycin was associated with a significant reduction in NETs in sputum over 12 months in both bronchiectasis and asthma. Interpretation: NETs are identified as a key marker of disease severity and treatment response in bronchiectasis. Funding: Supported by the Scottish Government Chief Scientist Office (Senior Clinical Fellowship to JDC) and British Lung Foundation through the BLF Chair of Respiratory Research. Supported by the European Bronchiectasis Network (EMBARC), a European Respiratory Society Clinical Research Collaboration. Declaration of Interests: None to declare Ethics Approval Statement: The studies were approved by local research ethics committees and patients provided informed consent.

Respiratory patient experience of measures to reduce risk of COVID-19: findings from a descriptive cross-sectional UK wide survey

ObjectivesTo assess the experience of people with long-term respiratory conditions regarding the impact of measures to reduce risk of COVID-19.DesignAnalysis of data (n=9515) from the Asthma UK and British Lung...