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.

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.

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.

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.

Long-term adherence to home mechanical ventilation: a 10-year retrospective, single-centre cohort study.

BACKGROUND: Sleep-disordered breathing (SBD) can be associated with hypercapnic respiratory failure (HRF). Home Mechanical Ventilation (HMV) is the preferred long-term treatment for patients with chronic HRF. We reviewed the database of a large tertiary referral centre for HMV to study the long-term adherence to HMV in chronic hypercapnic patients. METHODS: Data on adherence and characteristics of patients who received HMV for the treatment of SDB were collected over a decade using electronic patient records. The primary outcome parameter in this study was annual non-adherence rate (patients with HMV usage of <4 hours/night in the service divided by the number of all new patients of the same year), secondary outcomes were patients' characteristics and reasons for low adherence. HMV adherence clinics were established to improve uptake. RESULTS: Two thousand and two hundred twenty-eight patients with HRF were under active follow-up on HMV at the end of the recording period. In contrast, a total of 1,900 patients had their HMV contracts terminated over the course of a decade (due to non-adherence, transfer to other services or death). Out of those, 222 patients {62 [52-72] years, body-mass index, BMI 40 [35-43] kg/m2, 58.1% male, Epworth Sleepiness Scale, ESS 9 [4-15] points, 4% oxygen desaturation index, 4%ODI 32 [20-71] × hour-1, TcCO2 6.6 [6.0-7.2] kPa} met the non-adherence criteria (nocturnal usage 0-4 hours). The annual non-adherence rate was 25.5% of all new setups in 2010, and declined to 3.4% in 2019 (relative reduction of 86%, P<0.001). Patients with Obstructive Sleep Apnoea/Obesity Hypoventilation Syndrome (58.2%), Neuromuscular Diseases (NMD) (26.8%) and COPD (13.6%) accounted for most cases of this non-adherent cohort. The vast majority of the patients (96.1%) were established on full-face masks. In 23.4% of patients, substantial weight loss (>10%) was the most common reason for low adherence; general displeasure (21.3%), uncontrolled symptoms (12.8%), claustrophobia (6.7%), mood (4.8%) and mask intolerance (4.3%) caused problems as well. CONCLUSIONS: Non-adherence to HMV in patients with chronic HRF can affect significant proportions of patients. However, the non-adherent rate substantially decreases when individual treatment solutions are offered in multi-disciplinary clinics.

Home mechanical ventilation: back to basics.

Over recent decades, the use of home mechanical ventilation (HMV) has steadily increased worldwide, with varying prevalence in different countries. The key indication for HMV is chronic respiratory failure with alveolar hypoventilation (e.g., neuromuscular and chest wall disease, obstructive airway diseases, and obesity-related respiratory failure). Most modern home ventilators are pressure-targeted and have sophisticated modes, alarms, and graphics, thereby facilitating optimization of the ventilator settings. However, different ventilators have different algorithms for tidal volume estimation and leak compensation, and there are also several different circuit configurations. Hence, a basic understanding of the fundamentals of HMV is of paramount importance to healthcare workers taking care of patients with HMV. When choosing a home ventilator, they should take into account many factors, including the current condition and prognosis of the primary disease, the patient's daily performance status, time (hr/day) needed for ventilator support, family support, and financial costs. In this review, to help readers understand the basic concepts of HMV use, we describe the indications for HMV and the factors that influence successful delivery, including interface, circuits, ventilator accessories, and the ventilator itself.

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.

Time-to-death in chronic respiratory failure on home mechanical ventilation: A cohort study.

BACKGROUND AND OBJECTIVE: Home mechanical ventilation (HMV) is used in heterogeneous conditions underlying chronic hypercapnic respiratory failure, but there are sparse data on long-term clinical outcomes. The aim was to systematically analyse the time and the circumstances of death on HMV. METHODS: All-cause mortality data of HMV patients were prospectively collected between 2008 and 2018 in a large tertiary centre. Data were categorised into diagnostic groups including neuromuscular disease (NMD), chest wall disease (CWD), chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), overlap syndrome of COPD and OSA (overlap) and other group. The primary outcome was time-to-death from initiation of HMV. RESULTS: 1210 deaths were recorded over a 10-year period. Median time-to-death was 19.5 [6-55] months and differed between groups (Kruskal Wallis p < 0.001). CWD (98.5 [23.5-120] months) and slowly progressive NMD (64.5 [28-120] months) had the longest time-to-death on HMV, while OHS (33 [13-75] months) and overlap syndrome (30.5 [14.5-68.5] months) had a longer median time-to-death than COPD (19.5 [7-42.5] months) and motor neurone disease (7 [3-14] months). Daily adherence to HMV of greater than 4 h/night was associated with better outcomes (10 [3-24] vs. 30 [10-76] months; p < 0.001). 43% with confirmed location of death died outside the hospital. CONCLUSIONS: The time-to-death on home mechanical ventilation varies widely across disease groups with chronic respiratory failure and seems to be associated with daily usage time. TRIAL REGISTRATION: researchregistry.com UIN: researchregistry4122.

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.

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.

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.