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.

Neural respiratory drive predicts long-term outcome following admission for exacerbation of COPD: a post hoc analysis.

Neural respiratory drive (NRD), as reflected by change in parasternal muscle electromyogram (EMGpara), predicts clinical deterioration and safe discharge in patients admitted to hospital with an acute exacerbation of COPD (AECOPD). The clinical utility of NRD to predict the long-term outcome of patients following hospital admission with an AECOPD is unknown. We undertook a post hoc analysis of a previously published prospective observational cohort study measuring NRD in 120 patients with AECOPD. Sixty-nine (57.5%) patients died during follow-up (median 3.6 years). Respiratory failure was the most common cause of death (n=29; 42%). In multivariate analysis, factors independently associated with an increased mortality included NRD (HR 2.14, 95% CI 1.29 to 3.54, p=0.003), age (HR 2.03, 95% CI 1.23 to 3.34, p=0.006), PaCO2 at admission (HR 1.83, 95% CI 1.06 to 3.06, p=0.022) and long-term oxygen use (HR 2.98, 95% CI 1.47 to 6.03, p=0.002). NRD at hospital discharge could be measured in order to assess efficacy of interventions targeted to optimise COPD and reduce mortality following an AECOPD. Original clinicaltrial.gov number: NCT01361451.

Non-invasive ventilation for obese patients with chronic respiratory failure: Are two pressures always better than one?

Obesity-related respiratory failure is increasingly common but remains under-diagnosed and under-treated. There are several clinical phenotypes reported, including severe obstructive sleep apnoea (OSA), isolated nocturnal hypoventilation with or without severe OSA and OSA complicating chronic obstructive pulmonary disease (COPD). The presence of hypercapnic respiratory failure is associated with poor clinical outcomes in each of these groups. While weight loss is a core aim of management, this is often unachievable, and treatment of sleep-disordered breathing with positive airway pressure (PAP) therapy is the mainstay of clinical practice. Although there are few long-term clinical efficacy trials, the lack of equipoise would prevent the utilization of an untreated control group. The current data support the use of PAP therapy to improve respiratory failure and is associated with improvements in health-related quality of life, reduced healthcare utilization and reduced mortality. Both continuous PAP (CPAP) and non-invasive ventilation (NIV) appear safe and effective in patients with obesity-related respiratory failure and OSA, with or without COPD, and the current evidence would not support a single therapy choice in all patients. There are no studies of CPAP in patients with isolated nocturnal hypoventilation, and NIV would be the current recommendation in this patient group. Whichever starting therapy is used, titration should be performed to correct sleep-disordered breathing and reverse chronic respiratory failure, with consideration of step-down of the treatment based on a clinical re-evaluation. In contrast, failure to reach physiological and clinical treatment targets should lead to the consideration of treatment escalation.

Home mechanical ventilation for chronic obstructive pulmonary disease: What next after the HOT-HMV trial?

The benefits of acute non-invasive ventilation to treat acidotic exacerbations of chronic obstructive pulmonary disease (COPD) are well-established. Until recently, the evidence for home mechanical ventilation (HMV) to treat patients with stable COPD had been lacking. This has subsequently been addressed by the application of higher levels of pressure support combined with targeted management of chronic respiratory failure, which demonstrated a reduction in all-cause mortality. Similarly, the previous trial of home oxygen therapy (HOT) and HMV delivered following an acute exacerbation failed to demonstrate an improvement in outcome. With the focus on patients with persistent hypercapnic respiratory failure in the recovery phase following a life-threatening exacerbation combined with targeted reduction in carbon dioxide, HOT and HMV (HOT-HMV) was shown to be clinically effective in reducing the time to readmission or death and cost effective in both the United Kingdom and United States healthcare systems. Future work will need to focus on promoting adherence to home ventilation and novel auto-titrating ventilator modes to facilitate and optimize the set-up of overnight ventilatory support in different target population such as COPD patients with obstructive sleep apnoea and COPD patients with episodic nocturnal hypoventilation.

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.

Uptake of telehealth implementation for COPD patients in a high-poverty, inner-city environment: A survey.

This study aimed to investigate computer and internet access and education attained in patients with chronic obstructive pulmonary disease (COPD) as potential barriers to implementation of telemedicine. We prospectively assessed 98 patients admitted with an acute exacerbation of COPD (mean age: 70.5 ± 9.3 years; force expired volume in the first second: 0.75 ± 0.39 L; 59% male) recording educational level attained and home computer and internet access. Hospital readmission surveillance occurred up to 2.7 (2.6-2.8) years following the index hospital admission. Only 16% of patients had a computer and only 14% had internet access; this group were younger and more educated than those without a computer. There was no difference in hospital readmissions over 2 years between those with and without access to a computer or internet. Only 12% of the whole cohort were educated to a school leaving age of 16 years and this group were more likely to be still working. School leaving age was directly associated with fewer hospital readmissions ( r = 0.251, p = 0.031). In conclusion, these data highlight the current challenges to the widespread implementation of telehealth in COPD patients as there is limited availability of computer and internet access with such patients demonstrating a lower level of education achievement.

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.

The Effect of Pressure Changes During Mechanical Insufflation-Exsufflation on Respiratory and Airway Physiology.

BACKGROUND: Respiratory muscle weakness can impair cough function, leading to lower respiratory tract infections. These infections are an important contributor to morbidity and mortality in patients with neuromuscular disease. Mechanical insufflation-exsufflation (MIE) is used to augment cough function in these patients. Although MIE is widely used, there are few data to advise on the optimal technique. Since the introduction of MIE, the recommended pressures to be delivered have increased. There are concerns regarding the use of higher pressures and their potential to cause lung derecruitment and upper airway closure. RESEARCH QUESTION: What is the impact of high-pressure MIE (HP-MIE) on lung recruitment, respiratory drive, upper airway flow, and patient comfort, compared with low-pressure MIE (LP-MIE), in patients with respiratory muscle weakness? STUDY DESIGN AND METHODS: Clinically stable patients using domiciliary MIE with respiratory muscle weakness secondary to Duchenne muscle dystrophy, spinal cord injury, or long-term tracheostomy ventilation received LP-MIE (30/-30 cm H2O) and HP-MIE (60/-60 cm H2O) in a random sequence. Lung recruitment, neural respiratory drive, and cough peak expiratory flow were measured throughout, and patients reported comfort and breathlessness following each intervention. RESULTS: A total of 29 patients (10 with Duchenne muscle dystrophy, eight with spinal cord injury, and 11 with long-term tracheostomy ventilation) were included in this study. HP-MIE augmented cough peak expiratory flow compared with LP-MIE (mean cough peak expiratory flow HP-MIE 228 ± 81 L/min vs LP-MIE 179 ± 67 L/min; P = .0001) without any significant change in lung recruitment, neural respiratory drive, or patient-reported breathlessness. However, in patients with more pronounced respiratory muscle weakness, HP-MIE resulted in an increased rate of upper airway closure and patient discomfort that may have an impact on clinical efficacy. INTERPRETATION: HP-MIE did not lead to lung derecruitment or breathlessness compared with LP-MIE. However, it was poorly tolerated in individuals with advanced respiratory muscle weakness. HP-MIE generates more upper airway closure than LP-MIE, which may be missed if cough peak expiratory flow is used as the sole titration target. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02753959; URL: www. CLINICALTRIALS: gov.

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.

Quality of life in patients with chronic respiratory failure on home mechanical ventilation.

Home mechanical ventilation (HMV) is a treatment for chronic respiratory failure that has shown clinical and cost effectiveness in patients with underlying COPD, obesity-related respiratory failure and neuromuscular disease (NMD). By treating chronic respiratory failure with adequate adherence to HMV, improvement in patient-reported outcomes including health-related quality of life (HRQoL) have been evaluated using general and disease-specific quantitative, semi-qualitative and qualitative methods. However, the treatment response in terms of trajectory of change in HRQoL is not uniform across the restrictive and obstructive disease groups. In this review, the effect of HMV on HRQoL across the domains of symptom perception, physical wellbeing, mental wellbeing, anxiety, depression, self-efficacy and sleep quality in stable and post-acute COPD, rapidly progressive NMD (such as amyotrophic lateral sclerosis), inherited NMD (including Duchenne muscular dystrophy) and obesity-related respiratory failure will be discussed.

Cardioprotective medication in Duchenne muscular dystrophy: a single-centre cohort study.

Background: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder characterised by progressive muscle wasting impacting mobility, ventilation and cardiac function. Associated neuromuscular cardiomyopathy remains a major cause of morbidity and mortality. We investigated the effects of cardioprotective medications [angiotensin-converting enzyme inhibitors (ACE-I), beta-blockers] on clinical outcomes in DMD patients. Methods: This was a retrospective cohort study (reference: 2021/12469) of DMD patients at a tertiary centre between 1993-2021 screening the electronic records for demographics, comorbidities, medication, disease specific features, echocardiography, hospitalisations, and ventilator use. Results: A total of 68 patients were identified aged 27.4 (6.6) years, of which 52 were still alive. There was a difference in body mass index (BMI) between survivors and deceased patients [23.8 (5.9) vs. 19.9 (3.8) kg/m2, P=0.03]. Home mechanical ventilation (HMV) was required in 90% of patients, 85% had DMD associated cardiomyopathy. About 2/3 of all hospitalisations during the observation period were secondary to cardiopulmonary causes. The left ventricular ejection fraction (LVEF) at initial presentation was 44.8% (10.6%) and declined by 3.3% [95% confidence interval (CI): 0.4% to -7.0%] over the follow up period (P=0.002). A total of 61 patients were established on ACE-I for 75.9% (35.1%), and 62 were on beta-blockers for 73.6% (33.5%) of the follow up period. There was a significant LVEF decline in those taking ACE-I for limited periods compared to those permanently on ACE-I (P=0.002); a similar effect was recorded with beta-blockers (P=0.02). Conclusions: Long-term use of ACE-I and beta-blockers is associated with a reduced decline in LVEF in patients with DMD and may be protective of adverse cardiovascular ill health.

Nocturnal Hypoxemia Associates With Symptom Progression and Mortality in Patients With Progressive Fibrotic Interstitial Lung Disease.

BACKGROUND: OSA and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (F-ILD), but their relationship with disease outcomes remains unclear. RESEARCH QUESTION: What is the relationship between NH and OSA and clinical outcomes in patients with F-ILD? STUDY DESIGN AND METHODS: This was a prospective observational cohort study of patients with F-ILD and without daytime hypoxemia. Patients underwent home sleep study at baseline and were followed up for at least 1 year or until death. NH was defined as ≥ 10% of sleep with oxygen saturation of < 90%. OSA was defined as an apnea-hypopnea index of ≥ 15 events/h. RESULTS: Among 102 participants (male, 74.5%; age, 73.0 ± 8.7 years; FVC, 2.74 ± 0.78 L; 91.1% idiopathic pulmonary fibrosis), 20 patients (19.6%) demonstrated prolonged NH and 32 patients (31.4%) showed OSA. No significant differences were found between those with and without NH or OSA at baseline. Despite this, NH was associated with a more rapid decline in both quality of life as measured by the King's Brief Interstitial Lung Disease questionnaire (change, -11.3 ± 5.3 points in the NH group vs -6.7 ± 6.5 in those without NH; P = .005) and higher all-cause mortality at 1 year (hazard ratio, 8.21; 95% CI, 2.40-28.1; P < .001). No statistically significant difference was seen between the groups in annualized change in measures of pulmonary function testing. INTERPRETATION: Prolonged NH, but not OSA, is associated with worsening disease-related quality of life and increased mortality in patients with F-ILD.

The impact of the COVID-19 pandemic on home mechanical ventilation services: A national survey.

The COVID-19 pandemic has caused major disruption to healthcare services globally. We present the findings of a national survey of home mechanical ventilation (HMV) services in England and Wales. 30 HMV services (60%) responded. There was a significant reduction in outpatient services with 93% of services not offering routine face-to-face appointments, although most centres were able to offer emergency appointments for ventilation review and set-up. HMV inpatient capacity was reassigned, and HMV service staff re-deployed in the majority of centres (97%). The initial wave of the COVID-19 pandemic left a service backlog of a median of 87 outpatient appointments [range 0-1500] and a median of 4 patients (range 0-100) awaiting NIV set-up.

Home parasternal electromyography tracks patient-reported and physiological measures of recovery from severe COPD exacerbation.

Physiological phenotyping using daily home-based assessments reveals early improvement in load-capacity-drive imbalance following #AECOPD and feasibility of home parasternal electromyography measurement, which tracks symptoms, health status and spirometry https://bit.ly/3o6I0Ty.