Cost-effectiveness of outpatient versus inpatient non-invasive ventilation setup in obesity hypoventilation syndrome: the OPIP trial.

BACKGROUND: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective. METHODS: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP). RESULTS: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2 and PaCO2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes. DISCUSSION: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference. TRIAL REGISTRATION NUMBERS: NCT02342899 and ISRCTN51420481.

Factors Affecting Domiciliary Non-Invasive Ventilation Compliance.

Few international studies have investigated factors affecting domiciliary non-invasive ventilation (D-NIV) compliance, and data from the UK are limited. We assessed compliance (defined as ≥ 4 h/night for at least 70% of the time) in a retrospective UK population study, at three time points (0-1 month, 3-4 months and 11-12 months), for all patients commenced on D-NIV over a 5-year period. A total of 359 patients were included. Non-compliant vs. compliant patients were significantly younger (median age 64 (IQR 52-72) vs. 67 (58-75) years, p = 0.032) and more likely to have schizophrenia, consistent at both 3-4 months (5% vs. 1%, p = 0.033) and 11-12 months (5% vs. 2%, p = 0.049). Repeated measures ANOVA demonstrated that the minutes [median (IQR)] of D-NIV used significantly increased at the three time points (0-1 month, 3-4 months and 11-12 months) for patients with hypertension [310 (147.5-431) vs. 341 (89-450) vs. 378 (224.5-477.5), p = 0.003]; diabetes [296.5 (132.5-417.5) vs. 342.5 (94.5-438.5) vs. 382 (247.5-476.25), p = 0.002] and heart failure [293 (177-403) vs. 326 (123-398) vs. 365 (212-493), p = 0.04]. In conclusion, younger and comorbid schizophrenic patients have lower D-NIV compliance rates, and our data suggest that persistence with D-NIV over a year may improve overall use.

'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19.

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation.

Autotitrating external positive end-expiratory airway pressure to abolish expiratory flow limitation during tidal breathing in patients with severe COPD: a physiological study.

BACKGROUND: The optimal noninvasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic positive end-expiratory pressure (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD. METHODS: Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdi and EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔP di), transdiaphragmatic pressure-time product (PTPdi) and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP. RESULTS: Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m-2; forced expiratory volume in 1 s 28.4±8.3% predicted), eight had EFLT, and optimal EPAP was 9 (range 4-13) cmH2O. NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdi and at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi (0.80±1.27 cmH2O versus 1.95± 1.70 cmH2O; p<0.05) was reduced compared with baseline. PTPdi (10.3±7.8 cmH2O·s-1 versus 16.8±8.8 cmH2O·s-1; p<0.05) and ΔP di (12.4±7.8 cmH2O versus 18.2±5.1 cmH2O; p<0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline. CONCLUSION: Autotitration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.

Nutritional supplementation during pulmonary rehabilitation in COPD: A systematic review.

Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use. The objective was to report and summarise the current evidence supporting the use of nutritional supplementation to improve outcomes during PR in stable COPD patients. A systematic search was conducted up to 7 August 2019 (registration number CRD42018089142). The preferred reporting items for systematic reviews and meta-analyses guidelines were used. Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online, Allied and Complementary Medicine Database, the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE, Cumulative Index of Nursing and Allied Health Literature and Web of Science. This systematic search generated 580 initial matches, of which 22 studies (917 COPD participants) met the pre-specified criteria and were included. Sixteen of 19 studies that used nutritional supplements in addition to PR did not show additional benefit compared to PR alone when measuring exercise capacity. Nutritional supplements significantly increased body weight in 7 of 11 studies. Body mass index increased significantly in two of six studies. Handgrip strength did not improve, while quadriceps muscle strength significantly improved in 3 of 11 studies. Four of eight studies showed a significant improvement in inspiratory muscle function. Only 2 of 14 studies demonstrated a significant improvement in quality of life with supplementation in addition to PR. There remains insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD due to heterogeneity in supplements, outcome measures and PR programmes. Therefore, controversy remains and further research is needed.

Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO): a pilot randomised controlled trial.

BACKGROUND: Respiratory management of obesity hypoventilation syndrome (OHS) focusses on the control of sleep-disordered breathing rather than the treatment of obesity. Currently, there are no data from randomised trials of weight loss targeted rehabilitation programmes for patients with OHS. INTERVENTION: A 3-month multimodal hybrid inpatient-outpatient motivation, exercise and nutrition rehabilitation programme, in addition to non invasive ventilation (NIV), would result in greater per cent weight loss compared with standard care. METHODS: A single-centre pilot randomised controlled trial allocated patients to either standard care or standard care plus rehabilitation. Primary outcome was per cent weight loss at 12 months with secondary exploratory outcomes of weight loss, exercise capacity and health-related quality of life (HRQOL) at the end of the rehabilitation programme to assess the intervention effect. RESULTS: Thirty-seven patients (11 male, 59.8±12.7 years) with a body mass index of 51.1±7.7 kg/m2 were randomised. At 12 months, there was no between-group difference in per cent weight loss (mean difference -5.9% (95% CI -14.4% to 2.7%; p=0.17)). At 3 months, there was a greater per cent weight loss (mean difference -5% (95% CI -8.3% to -1.4%; p=0.007)), increased exercise capacity (6 min walk test 60 m (95% CI 29.5 to 214.5) vs 20 m (95% CI 11.5 to 81.3); p=0.036) and HRQL (mean difference SF-36 general health score (10 (95% CI 5 to 21.3) vs 0 (95% CI -5 to 10); p=0.02)) in the rehabilitation group. CONCLUSION: In patients with OHS, a 3-month comprehensive rehabilitation programme, in addition to NIV, resulted in improved weight loss, exercise capacity and QOL at the end of the rehabilitation period, but these effects were not demonstrated at 12 months, in part, due to the limited retention of patients at 12 months. TRIAL REGISTRATION NUMBER: Pre-results; NCT01483716.

Parasternal electromyography to determine the relationship between patient-ventilator asynchrony and nocturnal gas exchange during home mechanical ventilation set-up.

INTRODUCTION: Patient-ventilator asynchrony (PVA) can adversely affect the successful initiation of non-invasive home mechanical ventilation (HMV). The aim of this observational study was to quantify the prevalence of PVA during initiation of HMV and to determine the relationship between PVA and nocturnal gas exchange. METHOD: Type and frequency of PVA were measured by surface parasternal intercostal muscle electromyography, thoracoabdominal plethysmography and mask pressure during initiation of HMV. Severe PVA was defined, as previously, as asynchrony affecting ≥10% of breaths. RESULTS: 28 patients (18 male) were enrolled aged 61±15 years and with a body mass index of 35±9 kg/m(2). Underlying diagnoses were neuromuscular disease with or without chest wall disease (n=6), obesity related chronic respiratory failure (n=12) and COPD (n=10). PVA was observed in all patients with 79% of patients demonstrating severe PVA. Triggering asynchrony was most frequent, observed in 24% (IQR: 11-36%) of breaths, with ineffective efforts accounting for 16% (IQR: 4-24%). PVA types were similar between disease groups, with the exception of auto-triggering, which was higher in patients with COPD (12% (IQR: 6-26%)). There was no correlation observed between PVA and time spent with oxygen saturations ≤90%, mean oxygen saturations or transcutaneous carbon dioxide levels during overnight ventilation. CONCLUSIONS: Severe PVA was identified in the majority of patients, irrespective of pathophysiological disease state. This was not associated with ineffective ventilation as evidenced by gas exchange.

Neural respiratory drive predicts clinical deterioration and safe discharge in exacerbations of COPD.

RATIONALE: Hospitalised patients with acute exacerbation of COPD may deteriorate despite treatment, with early readmission being common. OBJECTIVES: To investigate whether neural respiratory drive, measured using second intercostal space parasternal muscle electromyography (EMGpara), would identify worsening dyspnoea and physician-defined inpatient clinical deterioration, and predict early readmission. METHODS: Patients admitted to a single-site university hospital with exacerbation of COPD were enrolled. Spirometry, inspiratory capacity (IC), EMGpara, routine physiological parameters, modified early warning score (MEWS), modified Borg scale for dyspnoea and physician-defined episodes of deterioration were recorded daily until discharge. Readmissions at 14 and 28 days post discharge were recorded. MEASUREMENTS AND MAIN RESULTS: 120 patients were recruited (age 70 ± 9 years, forced expiratory volume in 1 s (FEV1) of 30.5 ± 11.2%). Worsening dyspnoea, defined as at least one-point increase in Borg scale, was associated with increases in EMGpara%max and MEWS, whereas an increase in EMGpara%max alone was associated with physician-defined inpatient clinical deterioration. Admission-to-discharge change (Δ) in the normalised value of EMGpara (ΔEMGpara%max) was inversely correlated with ΔFEV1 (r = -0.38, p < 0.001) and ΔIC (r = -0.44, p < 0.001). ΔEMGpara%max predicted 14-day readmission (OR 1.13, 95% 1.03 to 1.23) in the whole cohort and 28-day readmission in patients under 85 years (OR 1.09, 95% CI 1.01 to 1.18). Age (OR 1.08, 95% CI 1.03 to 1.14) and 12-month admission frequency (OR 1.29, 1.01 to 1.66), also predicted 28-day readmission in the whole cohort. CONCLUSIONS: Measurement of neural respiratory drive by EMGpara represents a novel physiological biomarker that may be helpful in detecting inpatient clinical deterioration and identifying the risk of early readmission among patients with exacerbations of COPD. TRIAL REGISTRATION: NCT01361451.

Cardiovascular disease and risk in COPD: a state of the art review.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) and cardiovascular diseases (CVD) commonly co-exist. Outcomes of people living with both conditions are poor in terms of symptom burden, receiving evidence-based treatment and mortality. Increased understanding of the underlying mechanisms may help to identify treatments to relieve this disease burden. This narrative review covers the overlap of COPD and CVD with a focus on clinical presentation, mechanisms, and interventions. Literature up to December 2023 are cited. AREAS COVERED: 1. What is COPD 2. The co-existence of COPD and cardiovascular disease 3. Mechanisms of cardiovascular disease in COPD. 4. Populations with COPD are at risk of CVD 5. Complexity in the co-diagnosis of COPD in those with cardiovascular disease. 6. Therapy for COPD and implications for cardiovascular events and risk. 7. Cardiovascular risk and exacerbations of COPD. 8. Pro-active identification and management of CV risk in COPD. EXPERT OPINION: The prospective identification of co-morbid COPD in CVD patients and of CVD and CV risk in people with COPD is crucial for optimizing clinical outcomes. This includes the identification of novel treatment targets and the design of clinical trials specifically designed to reduce the cardiovascular burden and mortality associated with COPD. Databases searched: Pubmed, 2006-2023.

Validation of Tracheal Sound-Based Respiratory Effort Monitoring for Obstructive Sleep Apnoea Diagnosis.

Background: Respiratory effort is considered important in the context of the diagnosis of obstructive sleep apnoea (OSA), as well as other sleep disorders. However, current monitoring techniques can be obtrusive and interfere with a patient's natural sleep. This study examines the reliability of an unobtrusive tracheal sound-based approach to monitor respiratory effort in the context of OSA, using manually marked respiratory inductance plethysmography (RIP) signals as a gold standard for validation. Methods: In total, 150 patients were trained on the use of type III cardiorespiratory polygraphy, which they took to use at home, alongside a neck-worn AcuPebble system. The respiratory effort channels obtained from the tracheal sound recordings were compared to the effort measured by the RIP bands during automatic and manual marking experiments. A total of 133 central apnoeas, 218 obstructive apnoeas, 263 obstructive hypopneas, and 270 normal breathing randomly selected segments were shuffled and blindly marked by a Registered Polysomnographic Technologist (RPSGT) in both types of channels. The RIP signals had previously also been independently marked by another expert clinician in the context of diagnosing those patients, and without access to the effort channel of AcuPebble. The classification achieved with the acoustically obtained effort was assessed with statistical metrics and the average amplitude distributions per respiratory event type for each of the different channels were also studied to assess the overlap between event types. Results: The performance of the acoustic effort channel was evaluated for the events where both scorers were in agreement in the marking of the gold standard reference channel, showing an average sensitivity of 90.5%, a specificity of 98.6%, and an accuracy of 96.8% against the reference standard with blind expert marking. In addition, a comparison using the Embla Remlogic 4.0 automatic software of the reference standard for classification, as opposed to the expert marking, showed that the acoustic channels outperformed the RIP channels (acoustic sensitivity: 71.9%; acoustic specificity: 97.2%; RIP sensitivity: 70.1%; RIP specificity: 76.1%). The amplitude trends across different event types also showed that the acoustic channels exhibited a better differentiation between the amplitude distributions of different event types, which can help when doing manual interpretation. Conclusions: The results prove that the acoustically obtained effort channel extracted using AcuPebble is an accurate, reliable, and more patient-friendly alternative to RIP in the context of OSA.

Pilot observational cohort study to determine whether waveform and flow traces from mechanical insufflation-exsufflation (MI-E) can be used to identify laryngeal responses to MI-E and thus optimise treatment algorithms in neuromuscular patients in a tertiary centre: a protocol description.

INTRODUCTION: Patients with neuromuscular disease often have a weak and ineffective cough due to respiratory muscle weakness. One treatment option is mechanical insufflation-exsufflation (MI-E), also known as cough assist, which is known to increase cough strength. However, some patients have a laryngeal response to MI-E, which can make the treatment ineffective. Currently, the only method for assessing this is via nasal endoscopy while using MI-E. Some MI-E devices have onboard secure data (SD) cards, which allow the visualisation of waveforms. We hypothesise that the waveforms can be used to identify laryngeal responses to the MI-E. METHODS AND ANALYSIS: Participants will complete baseline assessments of spirometry, peak cough flow and sniff nasal inspiratory pressure. A nasal endoscope will be used to visualise the larynx during simultaneous MI-E via a mask with a drilled hole. MI-E will be delivered by an experienced physiotherapist. Four cycles of MI-E at a range of prescriptions will be delivered. MI-E waveforms will be downloaded into Care Orchestrator Essence software (Philips, Murraysville). Data will be collected prospectively and reviewed in a descriptive context, providing trends and potential rationales describing the waveforms in comparison to the nasal endoscope videos. ETHICS AND DISSEMINATION: This protocol has been reviewed by the East of England-Cambridge Central Research Ethics Committee, who have granted a favourable ethical opinion. The study opened to recruitment in January 2022 and aims to publish trial results in June 2024. TRIAL REGISTRATION NUMBER: NCT05189600.

Admission prevention in COPD: non-pharmacological management.

Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the commonest causes of hospital admission in Europe, Australasia, and North America. These adverse events have a large effect on the health status of the patients and impose a heavy burden on healthcare systems. While we acknowledge the contribution of pharmacotherapies to exacerbation prevention, our interpretation of the data is that exacerbations continue to be a major burden to individuals and healthcare systems, therefore, there remains great scope for other therapies to influence exacerbation frequency and preservation of quality of life. In this review, the benefits and limitations of pulmonary rehabilitation, non-invasive ventilation, smoking cessation, and long-term oxygen therapy are discussed. In addition, supported discharge, advanced care coordination, and telehealth programs to improve clinical outcome are reviewed as future directions for the management of COPD.

Indications and evidence for domiciliary noninvasive ventilation.

INTRODUCTION: Home noninvasive ventilation (HNIV) has expanded globally, with a greater evidence base for its use. HNIV improves multiple patient related outcomes in patients with chronic hypercapnic respiratory failure. Obesity hypoventilation syndrome (OHS) is rapidly taking over as the primary indication for HNIV and COPD patients who overlap with obstructive sleep apnea hypoventilation syndromes (OSAHS) and are increasingly recognized but add to the complexity of HNIV prescribing. Optimal settings vary for differing diseases, with higher inspiratory pressures often required in those with OHS and COPD, yet which settings translate into greatest patient benefit remains unknown. AREAS COVERED: We cover the evidence base underpinning the common indications for HNIV in COPD, OHS, neuromuscular disease (NMD), and chest wall disease (CWD) and highlight common HNIV modes used. EXPERT OPINION: Active screening for nocturnal hypoventilation in OHS and COPD may be important to guide earlier ventilation. Further research on which HNIV modalities best improve patient related outcomes and the right time for initiation in different patient phenotypes is rapidly needed. Worldwide, clinical research trials should aim to bridge the gap by reporting on patient-related outcomes and cost effectiveness in real-world populations to best understand the true benefit of HNIV amongst heterogenous patient populations.

Current treatment strategies in managing side effects associated with domiciliary positive airway pressure (PAP) therapy for patients with sleep disordered breathing: A systematic review and meta-analysis.

Sleep disordered breathing is commonly treated with positive airway pressure therapy. Positive airway pressure therapy is delivered via a tight-fitting mask with common side effects including: leak, ineffective treatment, residual sleep disordered breathing, eye irritation, nasal congestion, pressure ulcers and poor concordance with therapy. This systematic review and meta-analysis aimed to identify the effectiveness of current treatment strategies for managing side effects associated with positive airway pressure therapy. Five databases were searched and 10,809 articles were screened, with 36 articles included in the review. Studies investigated: dressings, nasal spray/douche, chin straps, heated humidification and interfaces. No intervention either improved or detrimentally affected: positive airway pressure concordance, Epworth Sleepiness Score, residual apnoea hypopnea index or interface leak. The review was limited by study heterogeneity, particularly for outcome measures. Additionally, patient demographics were not reported, making it difficult to apply the findings to a broad clinical population. This review highlights the paucity of evidence supporting treatment strategies to manage side effects of positive airway pressure therapy.

Wearable technology interventions in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is associated with multiple medical and psychological comorbidities. Therefore, future strategies to improve COPD management and outcomes are needed for the betterment of patient care. Wearable technology interventions offer considerable promise in improving outcomes, but prior reviews fall short of assessing their role in the COPD population. In this systematic review and meta-analysis we searched ovid-MEDLINE, ovid-EMBASE, CINAHL, CENTRAL, and IEEE databases from inception to April 2023 to identify studies investigating wearable technology interventions in an adult COPD population with prespecified outcomes of interest including physical activity promotion, increasing exercise capacity, exacerbation detection, and quality-of-life. We identified 7396 studies, of which 37 were included in our review. Meta-analysis showed wearable technology interventions significantly increased: the mean daily step count (mean difference (MD) 850 (494-1205) steps/day) and the six-minute walk distance (MD 5.81 m (1.02-10.61 m). However, the impact was short-lived. Furthermore, wearable technology coupled with another facet (such as health coaching or pulmonary rehabilitation) had a greater impact that wearable technology alone. Wearable technology had little impact on quality-of-life measures and had mixed results for exacerbation avoidance and prediction. It is clear that wearable technology interventions may have the potential to form a core part of future COPD management plans, but further work is required to translate this into meaningful clinical benefit.

Clinicians' Perspectives of Wearable Technology to Detect and Monitor Exacerbations of Chronic Obstructive Pulmonary Disease: Mixed-Method Survey.

Objective: To investigate clinicians' perspectives on the current use of wearable technology for detecting COPD exacerbations, and to identify potential facilitators and barriers to its adoption in clinical settings. Methods: A mixed-method survey was conducted through an online survey platform involving clinicians working with COPD patients. The questionnaires were developed by an expert panel specialising in respiratory medicine at UCL. The questionnaire evaluated clinicians' perspectives on several aspects: the current extent of wearable technology utilisation, the perceived feasibility, and utility of these devices, as well as the potential facilitators and barriers that hinder its wider implementation. Results: Data from 118 clinicians were included in the analysis. Approximately 80% of clinicians did not currently use information from wearable devices in routine clinical care. A majority of clinicians did not have confidence in the effectiveness of wearables and their consequent impact on health outcomes. However, clinicians highlighted the potential value of wearables in helping deliver personalised care and more rapid assistance. Ease of use, technical support and accessibility of data were considered facilitating factors for wearable utilisation. Costs and lack of technical knowledge were the most frequently reported barriers to wearable utilisation. Conclusion: Clinicians' perspectives of the use of wearable technology to detect and monitor COPD exacerbations are variable. While accessibility and technical support facilitate wearable implementation, cost, technical issues, and knowledge act as barriers. Our findings highlight the facilitators and barriers to using wearables in patients with COPD and emphasise the need to assess patients' perspectives on wearable acceptability.

Cross-sectional study evaluating the impact of SARS-CoV-2 variants on Long COVID outcomes in UK hospital survivors.

OBJECTIVES: COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination. DESIGN: Prospective observational cross-sectional study. SETTING: Secondary care tertiary hospital in the UK. PARTICIPANTS: This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021). OUTCOME MEASURES: Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively. RESULTS: 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44). CONCLUSIONS: Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.

Cardiovascular outcomes in patients with COPD-OSA overlap syndrome: A systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory conditions that are independently associated with increased cardiovascular disease (CVD). It is not clear from current evidence whether COPD-OSA overlap syndrome confers an additive risk. This systematic review and meta-analysis investigated whether CVD was more prevalent in patients with overlap syndrome compared to either condition alone. We searched four electronic databases, screened 1826 records against the inclusion criteria. After screening, 18 retrospective, observational studies involving 4613 overlap patients, 16,046 OSA patients and 1679 COPD patients met the inclusion criteria. A random-effects meta-analysis of five studies (I2 = 61%) showed that overlap was associated with a significantly higher risk of hypertension compared to patients with COPD alone (OR = 1.68, 95%CI 1.21-2.35). Overlap was also associated with an increased risk of peripheral vascular disease compared to OSA alone (OR = 3.30 95%CI 2.66-4.10), with a subset of studies also suggesting an increased risk of ischaemic heart disease, heart failure, and cerebrovascular disease. However, it is worth noting that the findings are limited by the considerable heterogeneity of the studies, all of which were observational and retrospective in nature. This review highlights that patients with overlap syndrome have a high prevalence of CVD with some suggestion of an increased risk compared to patients with either condition alone.