Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial.

OBJECTIVE: People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition. DESIGN: An assessor-blind, two-armed, parallel-design randomised controlled clinical trial. SETTING: Secondary care clinics in Iran. PARTICIPANTS: 60 men with breathlessness due to respiratory disease caused by documented mustard gas exposure, mean (SD) age 52.7 (4.36) years, MRC dyspnoea score 3.5 (0.7), St. George's Respiratory Questionnaire (SGRQ) 72.3 (15.2). INTERVENTIONS: Participants were allocated either to a 6-week course of thrice-weekly PR (n=31) or to usual care (n=29), with 6-week data for 28 and 26, respectively. OUTCOME MEASURES: Primary endpoint was change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Secondary endpoints included 6 min walk distance, quadriceps strength and bulk, body composition and health status. For logistical reasons, blood tests that had been originally planned were not performed and 12-month follow-up was available for only a small proportion. RESULTS: At 6 weeks, cycle endurance time increased from 377 (140) s to 787 (343) s with PR vs 495 (171) s to 479 (159) s for usual care, effect size +383 (231) s (p<0.001). PR also improved 6 min walk distance+103.2 m (63.6-142.9) (p<0.001), MRC dyspnoea score -0.36 (-0.65 to -0.07) (p=0.016) and quality of life; SGRQ -8.43 (-13.38 to -3.48) p<0.001, as well as quadriceps strength+9.28 Nm (1.89 to 16.66) p=0.015. CONCLUSION: These data suggest that PR can improve exercise capacity and quality of life in people with breathlessness due to mustard gas lung disease and support the wider provision of this form of care. TRIAL REGISTRATION NUMBER: IRCT2016051127848N1.

Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery.

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212.

Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

COVID-19 managed on respiratory wards and intensive care units: Results from the national COVID-19 outcome report in Wales from March 2020 to December 2021.

BACKGROUND: A COVID-19 hospital guideline was implemented across all 18 acute hospitals in Wales in March 2020, promoting ward management of COVID pneumonitis and data collected across the first 3 Waves of the pandemic (Wave 1 March 1st 2020 to November 1st 2020, Wave 2 November 2st 2020 to February 21st 2021 and Wave 3 June 1st 2021 to December 14th 2021). The aim of this paper is to compare outcomes for patients by admission setting and type of ventilatory support given, with a particular focus on CPAP therapy. METHODS: This is a retrospective observational study of those aged over 18 admitted to hospital with community acquired COVID-19 between March 2020 and December 2021. The outcome of interest was in-hospital mortality. Univariate logistic regression models were used to compare crude outcomes across the waves. Multivariable logistic regression models were used to assess outcomes by different settings and treatments after adjusting for Wave, age, sex, co-morbidity and deprivation. RESULTS: Of the 7,803 records collected, 5,887 (75.4%) met the inclusion criteria. Analysis of those cases identified statistically significant outcome improvements across the waves for all patients combined (Waves 1 to 3: 31.5% to 18.8%, p<0.01), all ward patients (28.9% to 17.7%, p<0.01), and all ICU patients (44.3% to 32.2%, p = 0.03). Sub group analyses identified outcome improvements in ward patients without any oxygen therapy (Waves 1 to 3: 22.2% to 12.7%, p<0.01), with oxygen therapy only (34.0% to 12.9%, p<0.01) and with CPAP only (63.5% to 39.2%, p<0.01). The outcome improvements for ICU patients receiving CPAP only (35.7% to 24.6%, p = 0.31) or invasive ventilation (61.6% to 54.6%, p = 0.43) were not statistically significant though the numbers being admitted to ICU were small. The logistic regression models identified important age and comorbidity effects on outcomes. The multivariable model that took these into account suggested no statistically significantly greater risk of death for those receiving CPAP on the ward compared to those receiving CPAP in ICU (OR 0.89, 95% CI: 0.49 to 1.60). CONCLUSIONS: There were successive reductions in mortality in inpatients over the three Waves reflecting new treatments and better management of complications. Mortality for those requiring CPAP was similar in respiratory wards and ICUs after adjusting for differences in their respective patient populations.

Immediate smoking cessation support during lung cancer screening: long-term outcomes from two randomised controlled trials.

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

Oral nitrate supplementation improves cardiovascular risk markers in COPD: ON-BC, a randomised controlled trial.

BACKGROUND: Short-term studies suggest that dietary nitrate (NO3 -) supplementation may improve the cardiovascular risk profile, lowering blood pressure (BP) and enhancing endothelial function. It is not clear if these beneficial effects are sustained and whether they apply in people with COPD, who have a worse cardiovascular profile than those without COPD. Nitrate-rich beetroot juice (NR-BRJ) is a convenient dietary source of nitrate. METHODS: The ON-BC trial was a randomised, double-blind, placebo-controlled parallel group study in stable COPD patients with home systolic BP (SBP) measurement ≥130 mmHg. Participants were randomly allocated (1:1) using computer-generated, block randomisation to either 70 mL NR-BRJ (400 mg NO3 -) (n=40) or an otherwise identical nitrate-depleted placebo juice (0 mg NO3 -) (n=41), once daily for 12 weeks. The primary end-point was between-group change in home SBP measurement. Secondary outcomes included change in 6-min walk distance (6MWD) and measures of endothelial function (reactive hyperaemia index (RHI) and augmentation index normalised to a heart rate of 75 beats·min-1 (AIx75)) using an EndoPAT device. Plasma nitrate and platelet function were also measured. RESULTS: Compared with placebo, active treatment lowered SBP (Hodges-Lehmann treatment effect -4.5 (95% CI -5.9- -3.0) mmHg), and improved 6MWD (30.0 (95% CI 15.7-44.2) m; p<0.001), RHI (0.34 (95% CI 0.03-0.63); p=0.03) and AIx75 (-7.61% (95% CI -14.3- -0.95%); p=0.026). CONCLUSIONS: In people with COPD, prolonged dietary nitrate supplementation in the form of beetroot juice produces a sustained reduction in BP, associated with an improvement in endothelial function and exercise capacity.

Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis.

BACKGROUND: Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival. METHODS: We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed. RESULTS: 21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75-0.88, p<0.001), gait speed (<0.80 m·s-1) (HR 3.55, 95% CI 1.72-7.36, p<0.001) and gait speed (per 1.0 m·s-1) (HR 7.55, 95% CI 1.11-51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s-1) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72-0.88, p<0.001; OR 3.36, 95% CI 1.42-7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis. CONCLUSION: Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for.

Quitting smoking improves two-year survival after a diagnosis of non-small cell lung cancer.

BACKGROUND: Smoking at diagnosis is associated with worse survival in lung cancer but the effects of quitting smoking on survival remain unclear. METHODS: In a UK multi-centre study (NCT01192256) we followed all 2751 patients with newly diagnosed non-small cell lung cancer (NSCLC) for up to 2 years or until death as part of the observational trial. Patients were offered smoking cessation advice and treatments according to national guidelines and local services. Smoking status was verified by exhaled carbon monoxide levels. Kaplan-Meier survival analysis and Cox Proportional Hazards Modelling examined the effects of quitting smoking on survival at 2 years. FINDINGS: 646 were current smokers at the time of diagnosis. The unadjusted two-year Kaplan-Meier survivor functions for quitters (0.45, 95 %CI 0.37 to 0.53) and continuers (0.32, 0.28 to 0.36) were significantly different (log-rank test p < 0.01). Median survival times were 659 days for quitters and 348 days for continuers. After adjusting for age, sex, stage, performance status, curative intent surgery, radical radiotherapy and comorbidity, the hazard ratio for quitting at diagnosis (0.75, 95 % CI 0.58 to 0.98) indicated a statistically significant reduction in the risk of death across the two-year study period. INTERPRETATION: Quitting smoking is independently and significantly associated with improved survival regardless of stage in NSCLC. We recommend that smoking cessation advice and treatments should be offered to smokers with lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01192256. FUNDING: This work was supported by a 2010 Global Research Award for Nicotine Dependence (GRAND), Pfizer.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

The Economic Potential of Smoking Cessation Interventions at the Point of Diagnosis of Non-Small Cell Lung Cancer.

OBJECTIVES: Stopping smoking has proven benefits in nearly all illnesses but the impact and health economic benefits of stopping smoking after a diagnosis of lung cancer are less well defined. We assessed the cost-effectiveness of smoking cessation (SC) services for patients with newly diagnosed lung cancer against current usual care, where patients are unlikely to receive SC service referral. METHODS: A health economic model was constructed in Excel. The modelled population comprised of patients with a new diagnosis of non-small cell lung cancer (NSCLC). Data from the LungCast data set (Clinical Trials Identifier NCT01192256) were used to estimate model inputs. A structured search of published literature identified inputs not represented in LungCast, including healthcare resource use and costs. Costs were estimated from a 2020/2021 UK National Health Service and Personal Social Services perspective. The model estimated the incremental quality-adjusted life-year (QALY) gained in patients with newly diagnosed NSCLC receiving targeted SC intervention than those receiving no intervention. Extensive one-way sensitivity analyses explored input and data set uncertainty. RESULTS: In the 5-year base case, the model estimated an incremental cost of £14 904 per QALY gained through SC intervention. Sensitivity analysis estimated an outcome range of between £9935 and £32 246 per QALY gained. The model was most sensitive to the estimates of relative quit rates and expected healthcare resource use. CONCLUSION: This exploratory analysis indicates that SC intervention for smokers with patients with newly diagnosed NSCLC should be a cost-effective use of UK National Health Service resources. Additional research with focused costing is needed to confirm this positioning.

Immediate, Remote Smoking Cessation Intervention in Participants Undergoing a Targeted Lung Health Check: Quit Smoking Lung Health Intervention Trial, a Randomized Controlled Trial.

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

Oscillatory positive expiratory pressure therapy in COPD (O-COPD): a randomised controlled trial.

BACKGROUND: Oscillatory positive expiratory pressure (OPEP) devices are intended to facilitate sputum clearance and reduce cough, but there is limited evidence for their effectiveness in COPD, or to guide patient selection. We aimed to assess the impact of OPEP therapy on quality of life and objective measures of cough and sleep disturbance in patients with COPD with regular sputum production. METHODS: We enrolled stable patients with COPD, who reported sputum production every day or most days, into an assessor-blind, parallel-group, randomised controlled trial comparing 3 months of using an Acapella device against usual care (including use of the active cycle of breathing technique). The primary outcome was cough-related quality of life measured using the Leicester Cough Questionnaire (LCQ). Secondary outcomes included fatigue (Functional Assessment of Chronic Illness Therapy, FACIT score) and generic quality of life (EuroQol-5 Dimensions, EQ-5D). In a substudy (n=45), objective monitoring of cough and disturbance/movement during sleep were also available. RESULTS: 122 participants (61/61 OPEP/control) were recruited, 40% female, 17% smokers, FEV1 38 (25-56)% predicted, and age 62±10 years. 103 completed the study (55/48 OPEP/control). Use of OPEP was associated with an improvement in LCQ compared with controls; MD (95% CI) 1.03 (0.71 to 2.10); (p=0.03), FACIT score 4.68 (1.34 to 8.02); (p<0.001) and EQ-5D 4.00 (0.49 to 19.75); (p=0.04). There was also an improvement in cough frequency -60 (-43 to -95) coughs/24 hours (p<0.001), but no statistically significant effect on sleep disturbance was identified. CONCLUSIONS: Regular use of an Acapella device improves symptoms and quality of life in people with COPD who produce sputum daily or most days. TRIAL REGISTRATION NUMBER: ISRCTN44651852.

The effects of sleep disturbance on dyspnoea and impaired lung function following COVID-19 hospitalisation: a prospective multi-centre cohort study

BackgroundSleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. MethodsSleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression. Findings64% (456/714) of participants reported poor sleep quality; 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p<0.001) and sleep efficiency (85.4% vs 88.5%, p<0.001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p<0.001). Overall sleep quality (effect estimate 4.2 (3.0-5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0-4.5)), and sleep regularity (effect estimate 5.9 (3.7-8.1)) were associated with both dyspnoea and impaired lung function (FEV1 and FVC). Depending on the sleep metric, anxiety mediated 13-42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect. InterpretationSleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent. FundingUK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Reporting of data on participant ethnicity and socioeconomic status in high-impact medical journals: a targeted literature review.

OBJECTIVES: To assess the frequency of reporting of ethnicity (or 'race') and socioeconomic status (SES) indicators in high-impact journals. DESIGN: Targeted literature review. DATA SOURCES: The 10 highest ranked general medical journals using Google scholar h5 index. ELIGIBILITY CRITERIA: Inclusion criteria were, human research, reporting participant level data. Exclusion criteria were non-research article, animal/other non-human participant/subject or no participant characteristics reported. DATA EXTRACTION AND SYNTHESIS: Working backwards from 19 April 2021 in each journal, two independent reviewers selected the 10 most recent articles meeting inclusion/exclusion criteria, to create a sample of 100 articles. Data on the frequency of reporting of ethnicity (or 'race') and SES indicators were extracted and presented using descriptive statistics. RESULTS: Of 100 research articles included, 35 reported ethnicity and 13 SES. By contrast, 99 reported age, and 97 reported sex or gender. Among the articles not reporting ethnicity, only 3 (5%) highlighted this as a limitation, and only 6 (7%) where SES data were missing. Median number of articles reporting ethnicity per journal was 2.5/10 (range 0 to 9). Only two journals explicitly requested reporting of ethnicity (or race), and one requested SES. CONCLUSIONS: The majority of research published in high-impact medical journals does not include data on the ethnicity and SES of participants, and this omission is rarely acknowledged as a limitation. This situation persists despite the well-established importance of this issue and International Committee of Medical Journal Editors recommendations to include relevant demographic variables to ensure representative samples. Standardised explicit minimum standards are required.

Mortality Improvements in Adult Patients Hospitalised with Community Acquired COVID-19 in Wales From March 2020 to Decemeber 2021

BackgroundA COVID-19 hospital guideline was implemented across all acute hospitals in Wales in March 2020, and data was collected across the first 3 Waves of the pandemic. We aimed to observe trends in mortality with a focus on ward-based outcomes. MethodsRetrospective case-note review of data for adults admitted to hospital with community acquired COVID-19 between March 2020 and December 2021 Results5887 cases were analysed. Overall mortality from COVID-19 fell from 31.5% in Wave 1 to 22.6% in Wave 2 to 18.8% in Wave 3 (p<0.01). Ward mortality for patients on oxygen fell from 34.6% in Wave 1 to 19.5% in Wave 2 (p<0.01) to 14.3% in Wave 3 (p=0.03). For those managed with CPAP/HFNO on wards, the mortality reduced from 58.9% in Wave 1 to 45.6% in Wave 2 (p=0.05) and further to 42.6% in Wave 3 (p=0.03). The mortality for patients managed with CPAP/HFNO on ICU reduced from 43.8% in Wave 1 to 24.7% in Wave 2 (p=0.12) and further to 20.4% in Wave 3 (p=0.03). Patients receiving CPAP/HFNO on the wards were on average 11 years older and more co-morbid than those on ICU. In Wave 3, 77% of hospital admissions with COVID-19 were unvaccinated with mortality rates of 20.5% compared to 4.8% mortality in those who had received three vaccines (p<0.01). ConclusionsThere were successive reductions in mortality in inpatients over the 3 Waves reflecting new treatments and better management of complications. The impact of vaccines on outcomes of hospitalised patients was notable in Wave 3. Key Messages What is the key question?What are the outcomes from COVID-19 pneumonitis managed on respiratory wards and how have they changed over successive waves of the pandemic? What is the bottom line?Significant improvements in mortality over time were noted in patients requiring oxygen, CPAP or HFNO. Patients managed with these modalities in ICU had lower mortality rates than those on wards, but they were younger and less co-morbid. In wave 3 patients were largely unvaccinated with higher mortality rates than those who were fully vaccinated. Why read on?This is a national study including all acute hospitals in Wales over three waves of the pandemic from March 2020 to December 2021. It is the first paper to demonstrate at a national level the outcomes of ward management of COVID pneumonitis over successive waves.

A comparison of respiratory particle emission rates at rest and while speaking or exercising.

Background: The coronavirus disease-19 (COVID-19) pandemic led to the prohibition of group-based exercise and the cancellation of sporting events. Evaluation of respiratory aerosol emissions is necessary to quantify exercise-related transmission risk and inform mitigation strategies. Methods: Aerosol mass emission rates are calculated from concurrent aerosol and ventilation data, enabling absolute comparison. An aerodynamic particle sizer (0.54-20 µm diameter) samples exhalate from within a cardiopulmonary exercise testing mask, at rest, while speaking and during cycle ergometer-based exercise. Exercise challenge testing is performed to replicate typical gym-based exercise and very vigorous exercise, as determined by a preceding maximally exhaustive exercise test. Results: We present data from 25 healthy participants (13 males, 12 females; 36.4 years). The size of aerosol particles generated at rest and during exercise is similar (unimodal ~0.57-0.71 µm), whereas vocalization also generated aerosol particles of larger size (i.e. was bimodal ~0.69 and ~1.74 µm). The aerosol mass emission rate during speaking (0.092 ng s-1; minute ventilation (VE) 15.1 L min-1) and vigorous exercise (0.207 ng s-1, p = 0.726; VE 62.6 L min-1) is similar, but lower than during very vigorous exercise (0.682 ng s-1, p < 0.001; VE 113.6 L min-1). Conclusions: Vocalisation drives greater aerosol mass emission rates, compared to breathing at rest. Aerosol mass emission rates in exercise rise with intensity. Aerosol mass emission rates during vigorous exercise are no different from speaking at a conversational level. Mitigation strategies for airborne pathogens for non-exercise-based social interactions incorporating vocalisation, may be suitable for the majority of exercise settings. However, the use of facemasks when exercising may be less effective, given the smaller size of particles produced.

An online breathing and wellbeing programme (ENO Breathe) for people with persistent symptoms following COVID-19: a parallel-group, single-blind, randomised controlled trial.

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. FUNDING: Imperial College London.

Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing.

Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12-14 years old) and adults (19-72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002-0.02 ng s-1 from breathing, 0.07-0.2 ng s-1 from speaking (at 70-80 dBA) and 0.1-0.7 ng s-1 from singing (at 70-80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing.