Objectives The treatment of tobacco dependence in patients admitted to hospital is a priority for the National Health Service in England. We aimed to conduct an economic analysis of a pilot ‘opt-out’ tobacco dependence treatment intervention adapted from the Ottawa Model of Smoking Cessation.Design Observational cost analysis of an inpatient tobacco dependence treatment intervention, and matched cohort study comparing readmission costs between patients who received the intervention and benchmarked equivalents who did not.Setting 11 acute inpatient wards in a major teaching hospital in London, England.Participants 673 patients who smoked, admitted between 1 July 2020 and 30 June 2021.Interventions The intervention consisted of the systematic identification of smoking status, automatic referral to tobacco dependence advisors, provision of pharmacotherapy and behavioural support throughout the hospital stay and telephone support for 6 months after discharge.Primary and secondary outcome measures The primary outcomes were cost-per-patient, cost-per-quit and incremental cost effectiveness ratio among patients who received the intervention. The secondary outcomes were patient-level readmission costs and bed-days from 6 months after discharge, compared between the intervention group and a group of matched benchmark patients who smoked but did not receive the intervention.Results The total cost of the intervention was £178 105. On the basis of 104 patients who reported not smoking at 6 months, the cost-per-quit was £1712.55, equating to an estimated age-adjusted incremental cost per life year gained of £3325. Among 611 patients who were successfully matched to a benchmark cohort, readmissions for patients in the intervention group cost £492 k less than their benchmark equivalents over 21 months from 1 January 2021 to 30 September 2022 (£266 k vs £758 k), incurred 414 fewer bed days (303 vs 717) and readmitted at a lower rate (5% vs 11%). There were reduced readmission rates and costs among all patients who received the intervention compared with their benchmarked equivalents, regardless of smoking status at 6 months, except among those who opted out.Conclusions A pilot ‘opt-out’ tobacco dependence treatment intervention implemented in an acute hospital setting in London demonstrated value for money through reduced readmission rates and costs among all patients who received it.

BACKGROUND & AIM:Globally, more than 100 000 people die annually from opioid overdose. Although strongly implicated in heroin overdose deaths, acute opioid-induced respiratory depression is poorly understood, and few laboratory studies have been completed in human subjects. It is an area of undone science. Using a human laboratory overdose model, our research question was: what is the strength of the association between increasing dose of diamorphine and degree of respiratory depression in people prescribed injectable diamorphine for heroin use disorder? DESIGN:Single-blind, Phase IV, non-randomised, dose-escalation clinical trial. SETTING:King's Clinical Research Facility, London, UK. PARTICIPANTS:Four participants prescribed injectable diamorphine as treatment for heroin use disorder [all male, median (range) age 63 (59-72)]. INTERVENTIONS:The following dosing schedule was implemented (as a % of participant's usual prescribed diamorphine dose): visit 1-100%; visit 2-110%; visit 3-120%; visit 4-100%. Usual dose: 97.5 mg (30 mg-200 mg). MEASUREMENTS:Physiological measures included: pulse oximetry (SpO2%), end-tidal CO2 (ETCO2%), transcutaneous CO2, respiratory rate and parasternal electromyography to measure neural respiratory drive index (NRDI). Recordings were made continuously from 3 mins pre-dose to 60 mins post-dose. FINDINGS:Respiratory measures from baseline to post-dose across all dose sessions had ranges of: 89.7%-99.5% SpO2%; 4.8%-7.7% ETCO2%; 5.2-13.4 breaths/minute respiratory rate; 51.2 min-1-165.9 min-1 NRDI across all participants. All diamorphine doses caused some reduction in respiratory function. There was no clear difference between diamorphine dose and the degree of respiratory depression, based on descriptive analyses. CONCLUSIONS:A dose-escalation clinical trial of people prescribed injectable diamorphine for heroin addiction found that the degree of respiratory depression caused by diamorphine does not appear to be dose dependent; however, the changes seen at diamorphine doses to which participants were accustomed suggest that participants had only partial tolerance to the respiratory depressant effect of diamorphine.

Background The National Health Service in England aims to implement tobacco dependency treatment services in all hospitals by 2024. We aimed to assess the uptake of a new service, adapted from the Ottawa Model of Smoking Cessation, and its impact on 6-month quit rates and readmission or death at 1-year follow-up. Methods We conducted a pragmatic service evaluation of a tobacco dependency service implemented among 2067 patients who smoked who were admitted to 2 acute hospitals in London, England, over a 12-month period from July 2020. The intervention consisted of the systematic identification of smoking status, automatic referral to tobacco dependence specialists, provision of pharmacotherapy and behavioural support throughout the hospital stay, and telephone support for 6 months after discharge. The outcomes were (i) patient acceptance of the intervention during admission, (ii) quit success at 6 months after discharge, (iii) death, or (iv) readmission up to 1 year following discharge. Multivariable logistic regression was used to estimate the impact of a range of clinical and demographic variables on these outcomes. Results The majority (79.4%) of patients accepted support at the first assessment. Six months after discharge, 35.1% of successfully contacted patients reported having quit smoking. After adjustment, odds of accepting support were 51–61% higher among patients of all non-White ethnicity groups, relative to White patients, but patients of Mixed, Asian, or Other ethnicities had decreased odds of quit success (adjusted odds ratio (AOR) = 0.32, 95%CI = 0.15–0.66). Decreased odds of accepting support were associated with a diagnosis of cardiovascular disease or diabetes; however, diabetes was associated with increased odds of quit success (AOR = 1.88, 95%CI = 1.17–3.04). Intention to make a quit attempt was associated with a threefold increase in odds of quit success, and 60% lower odds of death, compared to patients who did not intend to quit. A mental health diagnosis was associated with an 84% increase in the odds of dying within 12 months. Conclusions The overall quit rates were similar to results from Ottawa models implemented elsewhere, although outcomes varied by site. Outcomes also varied according to patient demographics and diagnoses, suggesting personalised and culturally tailored interventions may be needed to optimise quit success.

Background Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. Methods This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. Results 88 participants (48% female, mean± sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS −1.10±1.44 versus BLVR −0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS −36.1% (95% CI −54.6– −10%) versus BLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm. Conclusion Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Background Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. Methods This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. Results 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS −1.10±1.44 versus BLVR −0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS −36.1% (95% CI −54.6– −10%) versus BLVR −30.1% (95% CI −53.7– −9%); p=0.81). There was one death in each treatment arm. Conclusion Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments. In this first randomised study to compare lung volume reduction surgery and endobronchial valve placement in people who are suitable for both treatments, surgery did not produce substantially superior outcomes at 1 year post-procedure http://bit.ly/3D0DjoN

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

Introduction Although lung volume reduction surgery and bronchoscopic lung volume reduction with endobronchial valves have both been shown to improve lung function, exercise capacity and quality of life in appropriately selected patients with emphysema, there are no direct comparison data between the two procedures to inform clinical decision-making. Methods and analysis We describe the protocol of the CELEB study, a randomised controlled trial which will compare outcomes at 1 year between the two procedures, using a composite disease severity measure, the iBODE score, which includes body mass index, airflow obstruction, dyspnoeaand exercise capacity (incremental shuttle walk test). Ethics and dissemination Ethical approval to conduct the study has been obtained from the Fulham Research Ethics Committee, London (16/LO/0286). The outcome of this trial will provide information to guide treatment choices in this population and will be presented at national and international meetings and published in peer-reviewed journals. We will also disseminate the main results to all participants in a letter. Trial registration number ISRCTN19684749 ; Pre-results.

Respiratory muscles are skeletal muscles whose function is to pump air in and out of the lungs. The chest wall muscles, diaphragm, and other muscles, including abdominal muscles, neck muscles, and upper limb muscles, may be broadly divided into inspiratory or expiratory muscles, according to whether their actions increase or decrease the capacity of the thoracic cage. The recruitment of individual muscles also depends on whether ventilatory requirements are high or low. Respiratory muscles share the common structural, physiological, and biochemical features of skeletal muscles, but are adapted to meet their unique task of being able to be active throughout life. These features determine their ability to generate contractile force, which is translated into inspiratory or expiratory pressure, and their resistance to fatigue. An imbalance between the load on the respiratory muscles and their capacity, resulting in breathlessness and ultimately respiratory failure, is a consequence of obstructive and restrictive respiratory disorders, and neuromuscular disease.

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMG para and sMMG para , and sEMG lic and sMMG lic , respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMG para , sMMG para , sEMG lic , sMMG lic , mouth pressure (P mo ), and volume (V i ) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMG para%max , fSEsMMG para%max , fSEsEMG lic%max , and fSEsMMG lic%max ). fSEsMMG para%max , fSEsEMG para%max , and fSEsEMG lic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. P mo -derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, V i -derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of P mo and V i to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice.

Background: Opioid-related deaths are increasing globally and are usually caused by respiratory failure. Aims & Objectives: To investigate risk factors for respiratory depression (RD) in Opioid Use Disorder (OUD) through study of the relationship between RD and drug use characteristics. Methods: Four groups were compared (Table 1): OUD with comorbid COPD (OUD-COPD, n=13); OUD without COPD (OUD, n=7); opioid-naïve COPD patients (COPD, n=13); and healthy controls (HC, n=7). SpO2%, end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and neural respiratory drive index (NRDI) derived from 2nd intercostal space parasternal muscle electromyography were recorded continuously during resting tidal breathing. RD was defined as any of: ETCO2 per breath >6.6kPa, TcCO2 >6kPa, apnoea or SpO2%<90% for >10s. Results: RD indices were observed in all OUD-COPD and OUD participants, but in only 2/7 HC and 2/13 COPD patients. Results of bivariate correlation analysis are shown in Table 2. Conclusions: Our data suggest that RD is common in OUD and is influenced by opioid agonist treatment dose and drug use duration. Capnography and NRDI are potentially useful to the study of overdose risk.

BACKGROUND:Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. METHODS:There were four groups of participants: 1) OUD plus COPD ('OUD-COPD', n = 13); 2) OUD without COPD ('OUD', n = 7); 3) opioid-naïve COPD patients ('COPD'n = 13); 4) healthy controls ('HC'n = 7). Physiological indices, including pulse oximetry (SpO2%), end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and second intercostal space parasternal muscle electromyography (EMGpara), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO2%< 90% for > 10 s, ETCO2 per breath > 6.6 kPa, TcCO2 overall mean > 6 kPa, respiratory pauses > 10 s RESULTS: At least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher's exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). CONCLUSIONS:Undetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-naïve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.

This study aims to investigate noninvasive indices of neuromechanical coupling (NMC) and mechanical efficiency (MEff) of parasternal intercostal muscles. Gold standard assessment of diaphragm NMC requires using invasive techniques, limiting the utility of this procedure. Noninvasive NMC indices of parasternal intercostal muscles can be calculated using surface mechanomyography (sMMGpara) and electromyography (sEMGpara). However, the use of sMMGpara as an inspiratory muscle mechanical output measure, and the relationships between sMMGpara, sEMGpara, and simultaneous invasive and noninvasive pressure measurements have not previously been evaluated. sEMGpara, sMMGpara, and both invasive and noninvasive measurements of pressures were recorded in twelve healthy subjects during an inspiratory loading protocol. The ratios of sMMGpara to sEMGpara, which provided muscle-specific noninvasive NMC indices of parasternal intercostal muscles, showed nonsignificant changes with increasing load, since the relationships between sMMGpara and sEMGpara were linear (R2 = 0.85 (0.75–0.9)). The ratios of mouth pressure (Pmo) to sEMGpara and sMMGpara were also proposed as noninvasive indices of parasternal intercostal muscle NMC and MEff, respectively. These indices, similar to the analogous indices calculated using invasive transdiaphragmatic and esophageal pressures, showed nonsignificant changes during threshold loading, since the relationships between Pmo and both sEMGpara (R2 = 0.84 (0.77–0.93)) and sMMGpara (R2 = 0.89 (0.85–0.91)) were linear. The proposed noninvasive NMC and MEff indices of parasternal intercostal muscles may be of potential clinical value, particularly for the regular assessment of patients with disordered respiratory mechanics using noninvasive wearable and wireless devices.

Introduction Physical activity (PA) and sleep quality are commonly impaired in COPD, are associated with increased exacerbation frequency, healthcare utilisation and death, and deteriorate during acute exacerbations (AECOPD). Their post-discharge trajectories following hospitalisation with AECOPD and associations with patient-reported and physiological outcomes have not been reported. This study aimed to evaluate (1) daily changes in PA and sleep, (2) influences of individual characteristics on PA and sleep and (3) relationships between PA and sleep and patient-reported and physiological outcomes following severe AECOPD. Methods Prospective, single-centre observational study (NCT03443505,NCT01361451). Hospitalised AECOPD patients underwent wrist-worn actigraphy monitoring for 28 days post-discharge and were evaluated 1- and 4-weeks post-discharge. Results Data from 1601 days and 1415 nights from 67 patients were analysed. Mean±SD/median(IQR) age 69±9, 57% female, BMI 22.4(18.9–28.4)kg/m2, FEV1 27%predicted, 24% readmitted within 28 days. Using repeated measures ANOVA, PA increased in the 4 weeks post-discharge (F=8.47,p<0.001) and was lower in those with FEV1 <30%predicted (figure 1a), and total sleep time fell (F=2.70,p=0.049). A circadian rhythm of PA was plotted using 2,898,935 30-second epochs (figure 1b). Linear mixed-model regression demonstrated associations between PA and age (β=-2.37,p=0.01) and lean mass (β=2.45,p=0.002). PA was lower in males (β=-49.84,p=0.001), on weekends (β=-5.49, p=0.01) and in those who died within 1-year (β=-41.24,p=0.04), and was associated with total sleep time (TST) (β=0.01,p=0.003), EXACT score (β=-0.97,p=0.002), COPD assessment test (β=-1.63,p=0.02), FEV1 (β=46.38,p<0.001), inspiratory capacity (β=44.17,p<0.001), PImax (β=2.14,p<0.001) and neural respiratory drive, measured using parasternal EMG (β=-2.12,p=0.01). Patients readmitted within 28-days exhibited poorer sleep quality than non-readmitted patients (TST: β=-110,p=0.004, latency: β=34,p=0.03). Conclusions This study provides a novel insight into the improvement in daytime activity occurring in the 28 days following hospital discharge after severe COPD exacerbation. Physical activity related inversely to age, symptom burden, health status and neural respiratory drive, and positively to lean mass, respiratory muscle strength, expiratory airflow and inspiratory capacity. Total sleep time fell following hospital discharge, and sleep quality was lower in readmitted patients. Future research is needed to evaluate the impact of targeted interventions that enhance physical activity and sleep quality on hospital readmission in this high-risk population.

Background: A fall of 20 % in forced expiratory volume in the first second (FEV1) with a cumulative dose of histamine <= 7.8 mu mol is considered to indicate bronchial hyperactivity, but no method exists for patients who cannot perform spirometry properly. Here we hypothesized that increases in respiratory central output measured by chest wall electromyography of the diaphragm (EMGdi-c) expressed as a function of tidal volume (EMGdi-c/ VT) would have discriminative power to detect a 'positive' challenge test. Methods: In a physiological study EMGdi was recorded from esophageal electrode (EMGdi-e) in 16 asthma patients and 16 healthy subjects during a histamine challenge test. In a second study, EMGdi from chest wall surface electrodes (EMGdi-c) was measured during a histamine challenge in 44 asthma patients and 51 healthy subjects. VT was recorded from a digital flowmeter during both studies. Results: With histamine challenge test the change in EMGdi-e/VT in patients with asthma was significantly higher than that in healthy subjects (104.2 % +/- 48.6 % vs 0.03 % +/- 17.1 %, p < 0.001). Similarly there was a significant difference in the change of EMGdi-c/VT between patients with asthma and healthy subjects (90.5 % +/- 75.5 % vs 2.4 % +/- 21.7 %, p < 0.001). At the optimal cut-off point (29 % increase in EMGdi-c/VT), the area under the ROC curve (AUC) for detection of a positive test was 0.91 (p < 0.001) with sensitivity 86 % and specificity 92 %. Conclusions: We conclude that EMGdi-c/VT may be used as an alternative for the assessment of bronchial hypersensitivity and airway reversibility to differentiate patients with asthma from healthy subjects.

Introduction In the UK, opioid-related deaths are at record numbers after continually increasing year-on-year (ONS, 2019). This increase is believed to be driven by an ageing cohort of people with Opioid Use Disorder (OUD) and a high prevalence of comorbidities including chronic obstructive pulmonary disease (COPD). Our previous findings suggest that the degree of acute opioid-induced respiratory depression is greatest in OUD patients with chronically-suppressed neural respiratory drive (NRD) as a consequence of drug misuse (Jolley et al.,2015). We investigated the severity of respiratory depression in OUD and tested whether OUD exhibit more severe respiratory depression than matched controls. Methods A convenience sample of opioid addicts receiving treatment at a community Drug & Alcohol Treatment Centre were recruited: OUD with normal lung function (OUD) and OUD with comorbid COPD (OUD-LD). OUD groups were matched with healthy controls (HC) and COPD patients with no history of drug/alcohol addiction (LD-Controls) from our laboratory database. SpO2%, end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and NRD index (NRDI), quantified using second intercostal space parasternal muscle electromyography (EMGpara), were measured continuously over 40mins at rest. Significant respiratory depression was defined as: SpO2%<90% for >10s, ETCO2 per breath >6.5kPa, TcCO2 overall mean >6.5kPa, respiratory pauses (absence of inspiratory airflow) >10s. Results Seven OUD patients (5M/2F, age: 48(46–52), FEV1%pred(%): 96.1(90.5–96.5), FEV%FVC(%): 74.7(71.9–76.8)), 13 OUD-LD (11M/2F, age: 49(42–55), FEV1%pred(%): 77.1(66.8–90.1), FEV%FVC(%): 60.2(48.7–64.3)), 7 HC (6M/1F, age: 50(45–57), FEV1%pred(%): 100(97.5–110.3), FEV%FVC(%): 75(69.7–78.5)) and 13 LD-Controls (10M/3F, age: 66(62–72), FEV1%pred(%): 60(52.8–74.5), FEV%FVC(%): 52(45–57)) were studied. At least one of the respiratory depression indicators was detected in all 20 participants with OUD (Table1). Overall, there was a greater frequency of significant respiratory depression in both OUD groups compared to controls, most commonly ETCO2>6.5kPa (p=0.021;Table1). NRDI was significantly higher in LD-Controls than OUD-LD (217(43.7–504.5) min-1 and 148.5 (35–172.6) min-1, respectively (p<0.01)), but there was no significant difference between OUD and HC (87.6(51.7–115.3) min-1 and 76.9(52.8–164.2) min-1, respectively (p=0.7)). Conclusions Respiratory depression is frequently present in OUD patients with comorbid COPD and significantly more severe than in opioid-naïve controls. Further studies are required to determine the association between respiratory depression and overdose risk. Please refer to page A193 for declarations of interest related to this abstract.

Background: Parasternal electromyography (EMGpara) is a non-aerosol generating method of quantifying neural respiratory drive (NRD), and tracks clinical trajectory in acute and stable chronic respiratory disease (D'Cruz et al. 2021). Aim: To test the hypothesis that NRD is raised in survivors of severe COVID-19 pneumonitis. Methods: 2nd intercostal space EMGpara was recorded at rest in consecutive patients attending King's College Hospital post-COVID clinic at 6-8 weeks post hospital discharge. Root mean square (RMS) EMGpara per breath, RMS EMGpara normalised to volitional maximum (EMGpara%max), neural respiratory drive index (NRDI=EMGpara%max x respiratory rate) and respective standardised residuals (z-scores) (Macbean et al. 2016) were calculated, z-scores>1.64 defining values above normal range. Associations and differences between variables and groups were explored using Spearman correlation and Mann-Whitney U tests. Results: 26 patients were studied, mean±SD age 57±16 years, 64% male. EMGpara%max and NRDI were raised (Table 1). EMGpara%max was associated with inpatient chest x-ray RALE score (rs=0.50 p=0.01), not mMRC dyspnoea (rs=0.35 p=0.08), with no significant differences between those who received invasive mechanical ventilation and those who did not (Table 1). Conclusions: Increased NRD suggests impaired respiratory mechanics in COVID-19 survivors. Detailed mechanistic studies, including evaluation of respiratory muscle function, are warranted.