Introduction There remains a paucity of data comparing ambulatory initiation of home non-invasive ventilation (NIV) with a model requiring inpatient admission.1 In our institution, a Quality Improvement (QI) project was performed where an ambulatory model for NIV initiation was developed and evaluated. Methods Ambulatory pathways were formulated for NIV initiation in the outpatient setting, alongside outreach and initiation of NIV for inpatients referred within regional hospitals. The primary outcome measure was 'compliance with NIV' defined as NIV use ≥4 hours/night for ≥75% of nights.2 Results Between 6.1.20 and 1.7.20, 76 referrals for home NIV were assessed within the ambulatory model. Of these, NIV was not indicated in 3 cases and contraindicated in 1 case, while 2 trialled NIV and declined it, leaving 70 patients who commenced home NIV (n=36 following COVID-19 ward 'closure'). Neuromuscular disease was the principal diagnosis in 41% (29/70) with MND comprising 20/29 neuromuscular cases; see table 1. Ventilator interaction data was available for 68 patients where mean NIV use was 5.21 (SD 3.98) hours/night. Of those established by ambulatory pathway, 62% (42/68) were deemed 'compliant' with NIV in comparison to previous data reporting compliance in 62% (56/90) of subjects established through inpatient admission2. It was calculated that delivery of the ambulatory pathway resulted in a cost saving of £197,967 for this period, achieved principally by admission avoidance based on previous length of stay data and Level 2 bed costings. Conclusions An ambulatory model for initiation of home NIV appears to be as effective in achieving compliance as inpatient admission, while carrying health economic benefits. Ambulatory treatment pathways enabled us to deliver service continuity during the COVID-19 pandemic. References Mandal S, Arbane G, Murphy P. et al. Medium-term cost-effectiveness of an automated non-invasive ventilation outpatient set-up versus a standard fixed level non-invasive ventilation inpatient set-up in obese patients with chronic respiratory failure: a protocol description. BMJ Open. 2015; 5; e007082. Ward K, Chakrabarti B, Ashcroft H. et al. Compliance with non-invasive ventilation (NIV) at 90 days may be associated with use of NIV in the first 2 weeks: investigation of telemonitoring data. AJRCCM. 2018; 197; A1463.

Introduction Cardiopulmonary exercise test (CPET) is widely used in preoperative assessment and cardiopulmonary rehabilitation. The effect of peripheral arterial disease (PAD) on oxygen delivery (VO 2 ) measured by CPET is not known. The aim of this study was to investigate the effect of PAD on VO 2 measurements during CPET. Methods and analysis We designed a prospective cohort study, which will recruit 30 patients with PAD, who will undergo CPET before and after treatment of iliofemoral occlusive arterial disease. The main outcome measure is the difference in VO 2 at the lactate threshold (LT) between the 2 CPETs. The secondary outcome measure is the relationship between change in VO 2 at the LT and peak exercise pretreatment and post-treatment and haemodynamic measures of PAD improvement (ankle–brachial index differential). For VO 2 changes, only simple paired bivariate comparisons, not multivariate analyses, are planned, due to the small sample size. The correlation between ABI and VO 2 rise will be tested by linear regression. Ethics and dissemination The study was approved by the North West-Lancaster Research and Ethics committee (reference 15/NW/0801). Results will be disseminated through scientific journal and scientific conference presentation. Completion of recruitment is expected by the end of 2016, and submission for publication by March 2017. Trial registration number NCT02657278.

An increased incidence of pulmonary barotrauma in patients receiving CPAP for #COVID19 pneumonia was observed during the second peak of infections at this centre in the UK https://bit.ly/3qeSTp9.

Background: CPAP enables the delivery of a greater FiO2 in hypoxic patients and has been suggested as a therapeutic option in patients with COVID-19 pneumonia. Its efficacy is as of yet unknown, and questions remain over when to use, and in which patient group. Aims: To describe outcomes in NFE patients with COVID-19 pneumonia treated with CPAP at Aintree University Hospital, Liverpool, UK. To compare these outcomes to a retrospective matched control group who did not receive CPAP therapy. Methods: NFE patients who received CPAP between March-May 2020 were identified. Each patient had radiologically confirmed COVID-19 pneumonia, with acute oxygen desaturation while receiving high flow oxygen. 21 consecutive controls were retrospectively matched by disease severity, age, sex, ethnicity and clinical frailty score (CFS). Results: There was no statistical difference between survival to discharge in the CPAP group compared to the control group (p=0.469). Key results are shown in Table 1 below: Conclusions: Our data suggests a limited role for CPAP in comorbid patients with late-stage COVID-19 pneumonia. However, we note that further investigation is required.

Purpose: This project will investigate the potential of gold nanostar (NS)-labeled mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA) using optoacoustic imaging (OAI). OAI, specifically multi-spectral optoacoustic tomography (MSOT) has excellent resolution at increasing depths and capabilities in functional imaging. A novel gold nanoparticle - the nanostar has been developed to enhance the signal response in OAI as well as to permit tracking of MSCs. Different nanostar surface coatings have been investigated for their uptake and effects on MSC characteristics: methoxy (NS-OMe) and carboxyl (NS-COOH). SPIONs (superparamagnetic iron oxide nanoparticles) were used to functionalize the NS (NS-SPIONs) and permit dual OAI and magnetic resonance imaging (MRI). Available carboxyl groups also allow for the conjugation of an antibody to NS, which will permit the tracking of MSC-derived extracellular vesicles (EVs). The aims of this project include optimization of MSC labeling and investigation of MSC phenotype post-labeling. Methods: Methods to assess uptake of NS included transmission electron microscopy (TEM), Image Stream X analysis (ISX) and MSOT. To assess MSC characteristics following NS labeling, viability, tri-lineage differentiation and surface marker expression were also assessed. In vivo imaging of NS in the knee joint was performed using MSOT. Results: NS-OMe have shown efficient cellular internalization and no discernable effects on MSC characteristics. The efficiency of cellular uptake of NS-COOH was shown to be sub-optimal. ISX has the capacity to both image and quantify NS conjugated to an antibody inside cells and confirmed these initial findings demonstrating that only 20% of MSCs contained NS-COOH conjugated to an antibody. MSC uptake of NS-SPIONs has also been investigated using MSOT and efficient uptake has been demonstrated. NS-SPIONs will be further studied to determine the optimal concentration for MSOT imaging. Finally, preliminary work has explored the capacity of MSOT to detect an intra-articular injection of NS. An enhanced signal in the knee joint (b) in comparison to baseline (no injection) (a) due to the presence of NS can be seen as indicated by the white arrows in the image below. Conclusions: Different nanostar surface coatings demonstrate variability in MSC uptake and internalization. NS-OMe demonstrated the most efficient uptake by cells while NS-COOH was least efficient. NS-SPIONs have also demonstrated uptake and internalization by MSCs but further work is required to elucidate the optimal concentration for labeling. This work will coincide with in vivo imaging of nanoparticles in the knee joint to determine the limit of detection of the MSOT and the minimum concentration of nanoparticles in cells required for detection with MSOT.

Background Patients sustaining a Spinal Cord Injury (SCI) may require long-term mechanical ventilation via a tracheostomy. Little UK data exists regarding outcomes of such patients following hospital discharge. We aimed to define the characteristics and chart the outcomes of adult SCI patients discharged with tracheostomy ventilation from a tertiary spinal injuries unit. Methodology The records of patients discharged with long-term tracheostomy ventilation from the Northwest Regional Spinal Injuries Centre were retrospectively analyzed with comorbidity defined using ICD-10 coding. Results The records of 47 patients (Age 51 years (Range 66 years), LOS 366 days (Range 1738 days), 72% male) with SCI discharged with long-term tracheostomy ventilation between1982 and 2019 were available for analysis. 83% (39/47) were classified as sustaining a Traumatic SCI with the level of injury on discharge being C0–1 in 15%, C2–4 in 62% and C5–6 in 15%. 68% (32/47) and 17% (8/47) were classified as ASIA-A and ASIA-B respectively on discharge. 68% (32/47) were exclusively on a normal diet/fluids whilst 23% (11/47) were exclusively fed by a gastrostomy tube. 53% (25/47) were discharged on 24 hour ventilation whilst 47% (22/47) were discharged on a minimum of nocturnal ventilation but less than 24 hour ventilation. 72% (34/47) were discharged to their own place of residence whilst 28% (13/47) were discharged to Institutional Care. 9% (4/47) of subjects had died 12 months post hospital discharge increasing to 17% (8/47) who had died at 3 years post hospital discharge and 21% (10/47) who had died by 5 years post discharge. A coded diagnosis of underlying Pulmonary Disease was associated with death at 12 months (p=0.04) but did not appear to be a significant adverse prognostic factor by 3 or 5 years post discharge. Advanced age was associated with death at 5 years (64 (11) years v 41 (20) years). The level of injury, ASIA classification, length of stay and degree of ventilator dependence did not appear to be linked to survival. Conclusion Patients diagnosed as SCI with long-term tracheostomy ventilation have favourable outcomes following hospital discharge. A coded diagnosis of pulmonary disease predicts early mortality in this group.

Introduction: Intermittent overnight oximetry is used to monitor the effectiveness of home NIV. Aim: The aim of this study was to determine if patients change their ventilator use on the night they have oximetry. Objectives: To compare NIV use when having oximetry to 7 days later. Methods: The Lumis ventilator comes with remote access for 3 months. Consecutive patients issued with a Lumis ventilator were identified who had oximetry within the first 3 months of issue. NIV Use on the night of oximetry was compared with 7 days later using paired t-tests. Results: 168 patients were issued a Lumis of which 25 (15%) had oximetry within 3 months. 16/25 (64%) received NIV for single aetiology respiratory failure (OHS 9, copd 3, skeletal 3, neuromuscular 2) and 9 (36%) for overlap (ohs/copd 6, ohs/skeletal 1, OHS/central apnoea/drugs 2).20 received bi-level ST mode, 8 dynamic modes e.g. IVAPS. 7 had oxygen. Oximetry results –median (range) were ODI 7.8 (0.3-51), Median SpO2 94 (84-99), time <90 40mins (0-399). Using a combined measure of optimal oximetry (ODI<5, Median SpO2>92%, Time <90% <30mins). 5/25 were optimal, 6 failed on one criteria, 9 on 2 and 5 on 3. The mean use of NIV on oximetry was 380 (SD 206) vs 319 mins (232) 7 days later. As a group there was no stat difference between the two nights (mean 60 mins more on oximetry , 95%CI 43 less to 165 more, p=0.24). However in some cases large differences in use were seen in either direction- range 377 less to 647 more. This is clinically important when assessing adequacy of NIV. Conclusion: Oximetry is best interpreted with NIV compliance data as there can be large and and unpredictable differences in use between nights when oximetry is and is not used.

Background OSA is an increasingly recognised disease and successfully treated with CPAP. There are ever increasing demands on sleep services in the UK, in terms of provision, compliance and safety. One possible solution is the use of remote monitoring soon after CPAP set-up to determine usage patterns, residual apnoea-hypopnoea index (AHI) and mask problems. We have analysed our remote monitoring database to assess new patients with OSA set-up on CPAP. Method Retrospective data was collected from patients with OSA commenced on CPAP from start of June 2017 for thirty days. All patients referred to the Aintree University Hospital Sleep service had a cardio-respiratory sleep study and subsequently, if appropriate, referral for CPAP. All patients with OSA were commenced on a Resmed Airsense S10 device with humidification, using a predictive algorithm, and had an assessment for an appropriate interface. All data was collected with patient consent using Resmed Airview. Results Data was available in 71 patients (male 70%) for at least two weeks within this time period. Mean CPAP usage was 5 hours 4 mins with 84.5% using full face masks. Mean Residual AHI was low at 8.5 with small numbers of residual central events recorded (Table 1). See Table for more details Conclusion Remote monitoring provides a large amount of useful data which can potentially help improve CPAP provision in the UK. There is large proportion of patient with nocturnal hypoventilation, and despite effective treatment with CPAP, a group with a residual increase in AHI. Non-compliance and mask leak are identified issues and twenty patients used CPAP for less than an hour a night, with seven of those not at all. Remote monitoring allows early detection of non-compliance and an opportunity for earlier intervention to improve management in this patient group

INTRODUCTION:β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD.METHODS:People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker.RESULTS:48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD.CONCLUSIONS:In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry.TRIAL REGISTRATION NUMBER:NCT02106286.

Introduction The occurrence of Spinal Cord Injury (SCI) is often complicated by the need for assisted ventilation. This study charts the weaning outcomes of mechanically ventilated SCI subjects admitted over a 10 year period to a regional Spinal Injuries unit. Methodology Acute SCI subjects with Tetraplegia admitted from April 2007–2017 to the Northwest Regional Spinal Injuries Centre (NWRSIC) were identified. Only those presenting with all 3 criteria: a) admission injury level C1-C6 b) admission ASIA score A-C and c) need for mechanical ventilation on arrival to the NWRSIC were included in the final analysis. Results The cohort consisted of 84 subjects (mean age 57 (SD 18) years; 76% male; 81 surviving to discharge). On admission, the level of injury was C1–3 in 28% (C1–3 ASIA A 20%; C1–3 ASIA B 2%; C1–3 ASIA C 6%) and C4–6 in 72% (C4–6 ASIA A 38%; C4–6 ASIA B 17%; C4–6 ASIA C 17%). On admission, 86% (72/84) were tracheostomy ventilated 24 hours/day, 12% (10/84) tracheostomy ventilated at night only and 2% (2/84) using NIV. By discharge, 13% (11/81) were tracheostomy ventilated 24 hours/day (including 2 Phrenic nerve paced), 13% (11/81) tracheostomy ventilated at night only, 7% (6/81) prescribed nocturnal NIV with 65% (53/81) breathing independently. Thus, when taking the entire cohort, 63% (53/81) achieved complete Ventilatory liberation, 12% (10/81) weaned to nocturnal tracheostomy ventilation only and 6% (5/81) were weaned to NIV whilst no further weaning was possible in 16% (13/81). The ability to breathe independently by discharge was found to correlate with level of injury on admission (CC 0.39; p<0.001), level of injury on discharge (CC 0.47; p<0.001) and non-significant trend with improvement in neurological function during admission (CC 0.21; p=0.06) but not age or gender. Conclusion Our data demonstrates that in a cohort of consecutive SCI patients requiring mechanical ventilation on admission to a regional Spinal injuries unit, weaning from mechanical ventilation was possible in 84% of subjects with 63% being liberated completely from Ventilatory support by discharge. The use of NIV in the SCI cohort appears to be an emergent strategy during the weaning process.

BACKGROUNDImpaired sleep quality is common and associated with an increased risk of cardiovascular disease (CVD), thought to be mediated through adverse effects on established vascular risk factors, particularly hypertension. We determined if a web-delivered sleep intervention (sleep-hygiene education, stimulus control, and cognitive behavioral therapy) reduces blood pressure compared to vascular risk factor education (standard care) alone.METHODSPhase II randomized, blinded, controlled trial of 134 participants without CVD with mild sleep impairment and blood pressure 130-160/< 110 mm Hg. The primary outcome was the difference in the mean change in 24-hour ambulatory systolic blood pressure (SBP) over 8 weeks between intervention and control groups. Secondary outcomes included measures of sleep quality and psychosocial health, namely Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI).RESULTSParticipants in the sleep intervention group showed significantly greater improvements in sleep quality, including ISI [difference in mean improvement 2.8; 95% confidence interval (CI), 1.3-4.4], PSQI (1.1; 95% CI, 0.1-2.2), sleep condition indicator (0.8; 95% CI, 0.2-1.4), and psychosocial health, including BDI (2.0; 95% CI, 0.3-3.7) and BAI (1.4; 95% CI, 0.02-2.8). The mean improvement in 24-hour ambulatory SBP did not differ between the sleep intervention (0.9 mm Hg) and control (0.8 mm Hg) arms, (difference in mean improvement 0.1; 95% CI, -3.4 to 3.2).CONCLUSIONA simple, low-cost, web-delivered sleep intervention is feasible and significantly improves sleep quality and measures of psychosocial health in individuals with mild sleep impairment but does not result in short-term improvements in blood pressure.

Introduction: Pulse Transit Time (PTT) represents a non-invasive marker of sleep fragmentation in OSAS. Little is known regarding PTT in sleepy subjects exhibiting nocturnal Inspiratory Flow Limitation (IFL) in the absence of apneas or desaturation.Materials and methods: The IFL cohort was gender and age matched to subjects with OSAS and a cohort where Sleep Disordered Breathing (SBD)/IFL was absent ("Non Flow Limited" or NFL cohort); PTT Arousal index (PIT Ar) defined by number of PIT arousals per hour.Results: 20 subjects meeting criteria for the IFL cohort were aged and gender matched with OSAS and "NFL" subjects. Females comprised 65% of the IFL cohort; the mean BMI of the IFL cohort was significantly higher than the NFL cohort (34.25 v 28.90; p = 0.016) but not when compared to the OSAS cohort (34.25 v 3631; p = 0.30). The PTT Ar in the IFL cohort (33.67 h) was significantly higher than the NFL cohort (23.89 h) but significantly lower than the OSAS cohort (55.21 h; F = 8.76; p < 0.001). PIT Ar was found to positively correlate with AHI (CC = 0.46; p < 0.001), ODI (CC = 0.47; p < 0.001) and RDI (CC = 0.49; p < 0.001). Within the IFL cohort, PTT Ar positively correlated with age (CC = 0.501; p = 0.024) but not gender and BMI.Conclusion: The PIT Arousal Index increased proportionately with severity of SDB with significantly higher markers of arousal in sleepy subjects exhibiting nocturnal IFL when compared to controls. Subjects exhibiting IFL were predominantly female with an elevated BMI. IFL may thus represent a significant pathogenic entity in the development of daytime sleepiness. (C) 2016 Elsevier Ltd. All rights reserved.

Introduction Hospital readmission following treatment for a life-threatening exacerbation of COPD with acute NIV is frequent and associated with an adverse impact in terms of lung function and health related quality of life. They have been identified as a priority area in the NHS with financial penalties for any patient readmitted within 28 days following discharge. Method A multicentre open labelled randomised controlled trial recruited patients with persistent hypercapnia (PaCO2 > 7 kPa) 2–4 weeks following resolution of acute acidosis. Patients were randomised to either home oxygen therapy (HOT) or HOT and home mechanical ventilation (HOT-HMV). HMV was titrated overnight to control nocturnal hypercapnia. Follow up was for 12 months. The primary outcome, 12-month admission free survival, has been reported previously demonstrating a significant treatment effect (ERS 2016). Secondary outcome analysis included 28-day all-cause hospital readmission and 12 month exacerbation rate. Results 116 patients were randomised (HOT = 59, HOT-HMV = 57), age 67 ± 10 years, FEV1 0.6 ± 0.2 L, PaCO2 7.9 ± 0.9 kPa. 28-day readmission was 22 (37%) in the HOT and 7 (12%) in the HOT-HMV arm (unadjusted HR 0.27, 0.12 to 0.63, p = 0.003; adjusted HR 0.26, 0.11 to 0.61, p = 0.002) (Figure 1). 12 month exacerbation rate was reduced from median 5 (1 to 9) per year in the HOT arm to 4 (2to 6) in the HOT-HMV arm (unadjusted HR 0.64 (0.44 to 0.94); p = 0.022; adjusted HR 0.66, 0.46 to 0.95, p = 0.026). Conclusion The addition of HMV to HOT in patients with persistent hypercapnia following an acute life-threatening exacerbation of COPD reduces both 28-day readmission and 12 month exacerbation frequency. These data strongly support a change in clinical practice in the management of patients with severe COPD and persistent hypercapnia. Abstract S115 Figure 1 Time to hospital re-admission by treatment arm

Background: Little guidance exists on patient selection for home non-invasive ventilation (NIV) after acute NIV. The role of home NIV in pure COPD is inconclusive (Struik et al. Thorax 2014). Aims: Evaluation of the effect of a referral proforma (RPF) on patient characteristics and outcomes. Methods: The RPF was developed based on current evidence. Data collection pre- and post-RPF included diagnosis, length of stay and survival (Oct 912–Feb 915). Results: Pre-RPF, 55 referrals were received (3.7/month); 8 transfers were not given NIV. Post-RPF, 62 referrals were received (4.8/month), of whom only 25 (40.3%) were referred by RPF. All post-RPF transfers were given NIV; 2 declined. Gender and age varied little (Table One). No significant difference in length of stay, 6- and 12-month survival was seen (pre-RPF v. post-RPF; and pre-RPF v. post-RPF by RPF only). Fewer COPD patients were referred post-RPF (33.9% v. 47.3%, p=0.14). Those referred by RPF were significantly less likely to have COPD than pre-RPF (20.0% v. 47.3%, p=0.02), with increased OHS (obesity hypoventilation; 35.1% v. 21.8%, p=0.04). Referrals without RPF showed similar COPD rates to pre-RPF (47.3% v. 43.2%, p=0.71). Conclusion: While home NIV in COPD is debated, an RPF may improve practice while highlighting the challenges of changing existing behaviours (Stoller, Respiratory Care 2010).

Background: Wireless monitoring and titration of NIV (non-invasive ventilation) has been reported in one European centre (Pinto et al. J Neurol Neurosurg Psychiatry 2010); this is now available in a standard UK device. Aim: Pilot evaluation of the effectiveness of therapy, data transfer and remote modification. Methods: Eligible patients included those new to or already using NIV, excluding patients with likely ventilator dependency; 3 patients were issued Lumis 150 VPAP ST-A devices for trial (Resmed, UK). Results: Ventilator interaction data has been visible since initiation. Patient A: Leak was seen to exceed recommendations for this device and circuit (24LPM), with a median of 59.2LPM. Mask and setting change has been undertaken and monitored remotely, avoiding inpatient titration or 110km travel; median leak is now 5.2LPM. Patient B: Satisfactory compliance (all days >4hours), tidal volume (median 944ml) and minute ventilation (median 13.5LPM) seen; no modifications made. Patient C: Symptomatic sleep disordered breathing and poor compliance with CPAP led to trial of NIV. Remote data shows that NIV was used 19 times in 28 days (average 2.1h/night). Tidal volumes are satisfactory (median 697ml) but continued low compliance has guided input. Conclusion: Remote NIV titration and monitoring is available and effective, allowing targeted input and potential streamlining of initiation and follow-up.