The complexity of multidisciplinary respiratory care in amyotrophic lateral sclerosis.

Motor neurone disease/amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with no known cure, where death is usually secondary to progressive respiratory failure. Assisting people with ALS through their disease journey is complex and supported by clinics that provide comprehensive multidisciplinary care (MDC). This review aims to apply both a respiratory and a complexity lens to the key roles and areas of practice within the MDC model in ALS. Models of noninvasive ventilation care, and considerations in the provision of palliative therapy, respiratory support, and speech and language therapy are discussed. The impact on people living with ALS of both inequitable funding models and the complexity of clinical care decisions are illustrated using case vignettes. Considerations of the impact of emerging antisense and gene modifying therapies on MDC challenges are also highlighted. The review seeks to illustrate how MDC members contribute to collective decision-making in ALS, how the sum of the parts is greater than any individual care component or health professional, and that the MDC per se adds value to the person living with ALS. Through this approach we hope to support clinicians to navigate the space between what are minimum, guideline-driven, standards of care and what excellent, person-centred ALS care that fully embraces complexity could be. Educational aims: To highlight the complexities surrounding respiratory care in ALS.To alert clinicians to the risk that complexity of ALS care may modify the effectiveness of any specific, evidence-based therapy for ALS.To describe the importance of person-centred care and shared decision-making in optimising care in ALS.

Prevalence of central sleep apnea in people with tetraplegic spinal cord injury: a retrospective analysis of research and clinical data.

STUDY OBJECTIVES: Over 80% of people with tetraplegia have sleep-disordered breathing (SDB), but whether this is predominantly obstructive or central is unclear. This study aimed to estimate the prevalence of central sleep apnea (CSA) in tetraplegia and the contributions of central, obstructive, and hypopnea respiratory events to SDB summary indices in tetraplegia. METHODS: Research and clinical data from 606 individuals with tetraplegia and full overnight polysomnography were collated. The proportions of different respiratory event types were calculated; overall and for mild, moderate, and severe disease. The prevalence of Predominant CSA (Central Apnea Index [CAI] ≥ 5 and more central than obstructive apneas) and Any CSA (CAI ≥ 5) was estimated. Prevalence of sleep-related hypoventilation (SRH) was estimated in a clinical sub-cohort. RESULTS: Respiratory events were primarily hypopneas (71%), followed by obstructive (23%), central (4%), and mixed apneas (2%). As severity increased, the relative contribution of hypopneas and central apneas decreased, while that of obstructive apneas increased. The prevalence of Predominant CSA and Any CSA were 4.3% (26/606) and 8.4% (51/606) respectively. Being male, on opiates and having a high tetraplegic spinal cord injury were associated with CSA. SRH was identified in 26% (26/113) of the clinical sub-cohort. CONCLUSIONS: This is the largest study to characterize SDB in tetraplegia. It provides strong evidence that obstructive sleep apnea is the predominant SDB type; 9-18 times more prevalent than CSA. The prevalence of CSA was estimated to be 4%-8%, significantly lower than previously reported.

The role of lung volume recruitment therapy in neuromuscular disease: a narrative review.

Respiratory muscle weakness results in substantial discomfort, disability, and ultimately death in many neuromuscular diseases. Respiratory system impairment manifests as shallow breathing, poor cough and associated difficulty clearing mucus, respiratory tract infections, hypoventilation, sleep-disordered breathing, and chronic ventilatory failure. Ventilatory support (i.e., non-invasive ventilation) is an established and key treatment for the latter. As survival outcomes improve for people living with many neuromuscular diseases, there is a shift towards more proactive and preventative chronic disease multidisciplinary care models that aim to manage symptoms, improve morbidity, and reduce mortality. Clinical care guidelines typically recommend therapies to improve cough effectiveness and mobilise mucus, with the aim of averting acute respiratory compromise or respiratory tract infections. Moreover, preventing recurrent infective episodes may prevent secondary parenchymal pathology and further lung function decline. Regular use of techniques that augment lung volume has similarly been recommended (volume recruitment). It has been speculated that enhancing lung inflation in people with respiratory muscle weakness when well may improve respiratory system "flexibility", mitigate restrictive chest wall disease, and slow lung volume decline. Unfortunately, clinical care guidelines are based largely on clinical rationale and consensus opinion rather than level A evidence. This narrative review outlines the physiological changes that occur in people with neuromuscular disease and how these changes impact on breathing, cough, and respiratory tract infections. The biological rationale for lung volume recruitment is provided, and the clinical trials that examine the immediate, short-term, and longer-term outcomes of lung volume recruitment in paediatric and adult neuromuscular diseases are presented and the results synthesised.

A Randomized Controlled Clinical Trial of Lung Volume Recruitment in Adults with Neuromuscular Disease.

Rationale: Clinical care guidelines advise that lung volume recruitment (LVR) be performed routinely by people with neuromuscular disease (NMD) to maintain lung and chest wall flexibility and slow lung function decline. However, the evidence base is limited, and no randomized controlled trials of regular LVR in adults have been published. Objectives: To evaluate the effect of regular LVR on respiratory function and quality of life in adults with NMD. Methods: A randomized controlled trial with assessor blinding was conducted between September 2015 and May 2019. People (>14 years old) with NMD and vital capacity <80% predicted were eligible, stratified by disease subgroup (amyotrophic lateral sclerosis/motor neuron disease or other NMDs), and randomized to 3 months of twice-daily LVR or breathing exercises. The primary outcome was change in maximum insufflation capacity (MIC) from baseline to 3 months, analyzed using a linear mixed model approach. Results: Seventy-six participants (47% woman; median age, 57 [31-68] years; mean baseline vital capacity, 40 ± 18% predicted) were randomized (LVR, n = 37). Seventy-three participants completed the study. There was a statistically significant difference in MIC between groups (linear model interaction effect P = 0.002, observed mean difference, 0.19 [0.00-0.39] L). MIC increased by 0.13 (0.01-0.25) L in the LVR group, predominantly within the first month. No interaction or treatment effects were observed in secondary outcomes of lung volumes, respiratory system compliance, and quality of life. No adverse events were reported. Conclusions: Regular LVR increased MIC in a sample of LVR-naive participants with NMD. We found no direct evidence that regular LVR modifies respiratory mechanics or slows the rate of lung volume decline. The implications of increasing MIC are unclear, and the change in MIC may represent practice. Prospective long-term clinical cohorts with comprehensive follow-up, objective LVR use, and clinically meaningful outcome data are needed. Clinical trial registered with anzctr.org.au (ACTRN12615000565549).

Respiratory muscle training in neuromuscular disease: a systematic review and meta-analysis.

BACKGROUND: Neuromuscular disease causes a progressive decline in ventilatory function which respiratory muscle training may address. Previous systematic reviews have focussed on single diseases, whereas this study systematically reviewed the collective evidence for respiratory muscle training in children and adults with any neuromuscular disease. METHODS: Seven databases were searched for randomised controlled trials. Three reviewers independently reviewed eligibility, extracted characteristics, results, determined risk of bias and combined results using narrative synthesis and meta-analysis. RESULTS: 37 studies (40 publications from 1986-2021, n=951 participants) were included. Respiratory muscle training improved forced vital capacity (standardised mean difference (SMD) 0.40 (95% confidence interval 0.12-0.69)), maximal inspiratory (SMD 0.53 (0.21-0.85)) and maximal expiratory pressure (SMD 0.70 (0.35-1.04)) compared to control (usual care, sham or alternative treatment). No impact on cough, dyspnoea, voice, physical capacity or quality of life was detected. There was high degree of variability between studies. DISCUSSION: Study heterogeneity (children and adults, different diseases, interventions, dosage and comparators) suggests that the results should be interpreted with caution. Including all neuromuscular diseases increased the evidence pool and tested the intervention overall. CONCLUSIONS: Respiratory muscle training improves lung volumes and respiratory muscle strength in neuromuscular disease, but confidence is tempered by limitations in the underlying research.

Routine lung volume recruitment in boys with Duchenne muscular dystrophy: a randomised clinical trial.

BACKGROUND: Impaired cough results in airway secretion retention, atelectasis and pneumonia in individuals with Duchenne muscular dystrophy (DMD). Lung volume recruitment (LVR) stacks breaths to inflate the lungs to greater volumes than spontaneous effort. LVR is recommended in DMD clinical care guidelines but is not well studied. We aimed to determine whether twice-daily LVR, compared with standard of care alone, attenuates the decline in FVC at 2 years in boys with DMD. METHODS: In this multicentre, assessor-blinded, randomised controlled trial, boys with DMD, aged 6-16 years with FVC >30% predicted, were randomised to receive conventional treatment or conventional treatment plus manual LVR twice daily for 2 years. The primary outcome was FVC % predicted at 2 years, adjusted for baseline FVC % predicted, age and ambulatory status. Secondary outcomes included change in chest wall distensibility (maximal insufflation capacity minus FVC) and peak cough flow. RESULTS: Sixty-six boys (36 in LVR group, 30 in control) were evaluated (median age (IQR): 11.5 years (9.5-13.5), median baseline FVC (IQR): 85% predicted (73-96)). Adjusted mean difference in FVC between groups at 2 years was 1.9% predicted (95% CI -6.9% to 10.7%; p=0.68) in the direction of treatment benefit. We found no differences in secondary outcomes. CONCLUSION: There was no difference in decline in FVC % predicted with use of twice-daily LVR for boys with DMD and relatively normal lung function. The burden associated with routine LVR may outweigh the benefit. Benefits of LVR to maintain lung health in boys with worse baseline lung function still need to be clarified. TRIAL REGISTRATION NUMBER: NCT01999075.

Rapidly and slowly progressive neuromuscular disease: differences in pulmonary function, respiratory tract infections and response to lung volume recruitment therapy (LVR).

INTRODUCTION: Reduced lung volumes are a hallmark of respiratory muscle weakness in neuromuscular disease (NMD). Low respiratory system compliance (Crs) may contribute to restriction and be amenable to lung volume recruitment (LVR) therapy. This study evaluated respiratory function and the immediate impact of LVR in rapidly progressive compared to slowly progressive NMD. METHODS: We compared vital capacity (VC), static lung volumes, maximal inspiratory and expiratory pressures (MIP, MEP), Crs and peak cough flow (PCF) in 80 adult participants with motor neuron disease ('MND'=27) and more slowly progressive NMDs ('other NMD'=53), pre and post a single session of LVR. Relationships between respiratory markers and a history of respiratory tract infections (RTI) were examined. RESULTS: Participants with other NMD had lower lung volumes and Crs but similar reduction in respiratory muscle strength compared with participants with MND (VC=1.30±0.77 vs 2.12±0.75 L, p<0.001; Crs=0.0331±0.0245 vs 0.0473±0.0241 L/cmH2O, p=0.024; MIP=39.8±21.3 vs 37.8±19.5 cmH2O). More participants with other NMD reported an RTI in the previous year (53% vs 22%, p=0.01). The likelihood of having a prior RTI was associated with baseline VC (%predicted) (OR=1.03 (95% CI 1.00 to 1.06), p=0.029). Published thresholds (VC<1.1 L or PCF<270 L/min) were, however, not associated with prior RTI.A single session of LVR improved Crs (mean (95% CI) increase = 0.0038 (0.0001 to 0.0075) L/cmH2O, p=0.047) but not VC. CONCLUSION: These findings corroborate the hypothesis that ventilatory restriction in NMD is related to weakness initially with respiratory system stiffness potentiating lung volume loss in slowly progressive disease. A single session of LVR can improve Crs. A randomised controlled trial of regular LVR is needed to assess longer-term effects.

Objective measurement of lung volume recruitment therapy: laboratory and clinical validation.

Lung volume recruitment manoeuvres are often prescribed to maintain respiratory health in neuromuscular disease. Unfortunately, no current system accurately records delivered dose. This study determined the performance characteristics of a novel, objective, manual lung volume recruitment bag counter ('the counter') with bench and healthy volunteer testing, as well as in individuals with neuromuscular disease. We undertook (1) bench test determination of activation threshold, (2) bench and healthy volunteer fidelity testing during simulated patient interface leak and different pressure compressions and (3) comparisons with self-report in individuals with neuromuscular disease. The data are reported as summary statistics, compression counts, percentage of recorded versus delivered compressions and concordance (Cohen's kappa (K) and absolute agreement). RESULTS: Minimum counter activation pressure under conditions of zero leak was 1.9±0.4 cm H2O. No difference was observed between the number of repetitions delivered and recorded during high airway pressure condition. Interface leak approximating 25% resulted in underestimation of repetition counts, and once the leak was at 50% or beyond, the counter recorded no activity. Faster sampling frequency collected data with more fidelity. Counter data agreed with diary self-report during community trials (16 participants, 960 participant days, 77% agreement, Cohen's Κ=0.66 and p<0.001). Disagreement typically favoured more diary reported (18%) than counter (5%) sessions. CONCLUSIONS: The performance characteristics of a new lung volume recruitment counter have been established in both laboratory and community settings. Objective usage and dosage data should accelerate new knowledge development and better translation of lung volume recruitment therapy into policy and practice.

Pneumothorax in neuromuscular disease associated with lung volume recruitment and mechanical insufflation-exsufflation.

A 25-year-old male with Duchenne muscular dystrophy and a 73-year-old male with motor neurone disease both presented with chest pain and increasing dyspnoea following routine mechanical insufflation-exsufflation or lung volume recruitment, on a background of long-term non-invasive ventilation. In each case, chest radiograph revealed a pneumothorax. In both cases the pneumothorax fully resolved following insertion of an intercostal catheter. There was no immediate recurrence and the patients were discharged home and ceased ongoing prophylactic respiratory therapy, although one person had recurrent pneumothoraces subsequently. This rare but serious complication highlights the need for careful risk/benefit analysis by clinicians prescribing these therapies.

Randomised controlled trial of polysomnographic titration of noninvasive ventilation.

Noninvasive ventilation (NIV) settings determined during wakefulness may produce patient-ventilator asynchrony (PVA) during sleep, causing sleep disruption and limiting tolerance. This study investigated whether NIV titrated with polysomnography (PSG) is associated with less PVA and sleep disruption than therapy titrated during daytime alone.Treatment-naive individuals referred for NIV were randomised to control (daytime titration followed by sham polysomnographic titration) or PSG (daytime titration followed by polysomnographic titration) groups. Primary outcomes were PVA and arousal indices on PSG at 10 weeks. Secondary outcomes included adherence, gas exchange, symptoms and health-related quality of life (HRQoL).In total, 60 participants were randomised. Most (88.3%) had a neuromuscular disorder and respiratory muscle weakness but minor derangements in daytime arterial blood gases. PVA events were less frequent in those undergoing polysomnographic titration (median (interquartile range (IQR)): PSG 25.7 (12-68) events·h-1 versus control 41.0 (28-182) events·h-1; p=0.046), but arousals were not significantly different (median (IQR): PSG 11.4 (9-19) arousals·h-1 versus control 14.6 (11-19) arousals·h-1; p=0.258). Overall adherence was not different except in those with poor early adherence (<4 h·day-1) who increased their use after polysomnographic titration (mean difference: PSG 95 (95% CI 29-161) min·day-1 versus control -23 (95% CI -86-39) min·day-1; p=0.01). Arterial carbon dioxide tension, somnolence and sleep quality improved in both groups. There were no differences in nocturnal gas exchange or overall measures of HRQoL.NIV titrated with PSG is associated with less PVA but not less sleep disruption when compared with therapy titrated during daytime alone.

Respiratory adjuncts to NIV in neuromuscular disease.

Muscle weakness is an intrinsic feature of neuromuscular diseases (NMD). When the respiratory muscles are involved, the ability to take a deep breath is compromised, leading to reduced lung volumes and a restrictive ventilatory impairment. Inspiratory, expiratory and bulbar muscle weakness can also impair cough, which may impede secretion clearance. Non-invasive ventilation (NIV) is an established and indispensable therapy to manage hypoventilation and respiratory failure. The role of other therapies that support respiratory health is less clearly defined, and the evidence of efficacy is also harder to summarize as the underlying data are of a lesser quality. This narrative review appraises the evidence for respiratory therapies in adults with NMD and respiratory system involvement. Techniques that assist lung inflation and augment cough, such as lung volume recruitment (LVR) and mechanical insufflation-exsufflation (MI-E), are a particular focus of this review. The evidence suggests that LVR, MI-E and various combinations thereof have clinical utility generally, but important methodological limitations limit the strength of clinical recommendations and hamper the integration of evidence into practice. Future trials should prospectively assess the long-term impact of LVR and cough augmentation on clinical outcomes and burden of care in addition to lung mechanics, as well as determine clear predictors of benefit from these techniques.

Airway clearance techniques in neuromuscular disorders: A state of the art review.

This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied.

A randomised controlled trial of CPAP versus non-invasive ventilation for initial treatment of obesity hypoventilation syndrome.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is the most common indication for home ventilation, although the optimal therapy remains unclear, particularly for severe disease. We compared Bi-level and continuous positive airways pressure (Bi-level positive airway pressure (PAP); CPAP) for treatment of severe OHS. METHODS: We conducted a multicentre, parallel, double-blind trial for initial treatment of OHS, with participants randomised to nocturnal Bi-level PAP or CPAP for 3 months. The primary outcome was frequency of treatment failure (hospital admission, persistent ventilatory failure or non-adherence); secondary outcomes included health-related quality of life (HRQoL) and sleepiness. RESULTS: Sixty participants were randomised; 57 completed follow-up and were included in analysis (mean age 53 years, body mass index 55 kg/m2, PaCO2 60 mm Hg). There was no difference in treatment failure between groups (Bi-level PAP, 14.8% vs CPAP, 13.3%, p=0.87). Treatment adherence and wake PaCO2 were similar after 3 months (5.3 hours/night Bi-level PAP, 5.0 hours/night CPAP, p=0.62; PaCO2 44.2 and 45.9 mm Hg, respectively, p=0.60). Between-group differences in improvement in sleepiness (Epworth Sleepiness Scale 0.3 (95% CI -2.8, 3.4), p=0.86) and HRQoL (Short Form (SF)36-SF6d 0.025 (95% CI -0.039, 0.088), p=0.45) were not significant. Baseline severity of ventilatory failure (PaCO2) was the only significant predictor of persistent ventilatory failure at 3 months (OR 2.3, p=0.03). CONCLUSIONS: In newly diagnosed severe OHS, Bi-level PAP and CPAP resulted in similar improvements in ventilatory failure, HRQoL and adherence. Baseline PaCO2 predicted persistent ventilatory failure on treatment. Long-term studies are required to determine whether these treatments have different cost-effectiveness or impact on mortality. TRIAL REGISTRATION NUMBER: ACTRN12611000874910, results.

Cough Augmentation in Subjects With Duchenne Muscular Dystrophy: Comparison of Air Stacking via a Resuscitator Bag Versus Mechanical Ventilation.

BACKGROUND: Air stacking improves cough effectiveness in people with Duchenne muscular dystrophy (DMD) and respiratory muscle weakness. However, it is not known whether air stacking is more effective via a resuscitator bag or a home ventilator. METHODS: This prospective randomized study investigated the effect of air stacking via a volume-cycled home ventilator versus via a resuscitator bag in participants with DMD. Maximum insufflation capacity and peak expiratory flow during spontaneous (cough peak flow) and air stacking-assisted cough maneuvers (air stacking-assisted cough peak flow) were measured. RESULTS: Fifty-two adult DMD subjects receiving noninvasive ventilation were included in the study: 27 participants performed air stacking via their home ventilator (home-ventilator group; age = 25.3 ± 5.1 y; forced vital capacity (FVC) = 809 ± 555 mL), and 25 participants used a resuscitator bag (resuscitator-bag group; age = 24.7 ± 5.7 y, FVC = 807 ± 495 mL). Following a single training session, air stacking could be performed successfully by 89% (home ventilator) and 88% (resuscitator bag) of participants. There were comparable maximum insufflation capacities (1,481 mL for the home-ventilator group vs 1,344 mL for the resuscitator-bag group, P = .33) and mean air stacking-assisted cough peak flow values (199 L/min for the home-ventilator group vs 186 L/min for the resuscitator-bag group, P = .33) between techniques. Air stacking-assisted cough peak flow increased significantly compared with baseline in both groups (mean increase: +51% [home ventilator] vs +49% [resuscitator bag], P < .001), with individual air stacking-assisted cough peak flow improvements ranging from -20 to 245%. CONCLUSIONS: Cough augmentation is an important component of the respiratory management of people with a neuromuscular disorder. No difference in cough effectiveness as measured by air stacking-assisted cough peak flow was found in air stacking via a ventilator compared with via a resuscitator bag. Both methods achieved mean air stacking-assisted cough peak flow values of >160 L/min. Provision of an inexpensive resuscitator bag can effectively improve cough capacity, and it is simple to use, which may improve access to respiratory care in people with DMD.

Improved survival with an ambulatory model of non-invasive ventilation implementation in motor neuron disease.

Non-invasive ventilation (NIV) increases survival and quality of life in motor neuron disease (MND). NIV implementation historically occurred during a multi-day inpatient admission at this institution; however, increased demand led to prolonged waiting times. The aim of this study was to evaluate the introduction of an ambulatory model of NIV implementation. A prospective cohort study was performed. Inclusion criteria were referral for NIV implementation six months pre- or post-commencement of the Day Admission model. This model involved a 4-h stay to commence ventilation with follow-up in-laboratory polysomnography titration and outpatient attendance. Outcome measures included waiting time, hospital length of stay, adverse events and polysomnography data. Results indicated that after changing to the Day Admission model the median waiting time fell from 30 to 13.5 days (p < 0.04) and adverse events declined (4/17 pre- (three deaths, one acute admission) vs. 0/12 post-). Survival was also prolonged (median (IQR) 278 (51-512) days pre- vs 580 (306-1355) days post-introduction of the Day Admission model; hazard ratio 0.41, p = 0.04). Daytime PaCO2 was no different. In conclusion, reduced waiting time to commence ventilation and improved survival were observed following introduction of an ambulatory model of NIV implementation in people with MND, with no change in the effectiveness of ventilation.