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

Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease with severity ranging from progressive infantile paralysis and premature death (type I) to limited motor neuron loss and normal life expectancy (type IV). Without disease-modifying therapies, the impact is profound for patients and their families. Improved understanding of the molecular basis of SMA, disease pathogenesis, natural history, and recognition of the impact of standardized care on outcomes has yielded progress toward the development of novel therapeutic strategies and are summarized. Therapeutic strategies in the pipeline are appraised, ranging from SMN1 gene replacement to modulation of SMN2 encoded transcripts, to neuroprotection, to an expanding repertoire of peripheral targets, including muscle. With the advent of preliminary trial data, it can be reasonably anticipated that the SMA treatment landscape will transform significantly. Advancement in presymptomatic diagnosis and screening programs will be critical, with pilot newborn screening studies underway to facilitate preclinical diagnosis. The development of disease-modifying therapies will necessitate monitoring programs to determine the long-term impact, careful evaluation of combined treatments, and further acceleration of improvements in supportive care. In advance of upcoming clinical trial results, we consider the challenges and controversies related to the implementation of novel therapies for all patients and set the scene as the field prepares to enter an era of novel therapies. Ann Neurol 2017;81:355-368.

/pdf/emerging-therapies-and-challenges-in-spinal-muscular-atrophy-4rgcrdhvtv.pdf

Emerging therapies and challenges in Spinal Muscular Atrophy

Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010 the German Society of Pneumology and Mechanical Ventilation (DGP) has leadingly published the guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure". However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the guidelines.For this reason, the updated guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning.In the current guidelines different societies as well as professional and expert associations have been involved when compared to the 2010 guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.The currently updated guidelines are valid for the next three years, following their first online publication on the home page of the Association of the Scientific Medical Societies in German (AWMF) in the beginning of July 2017. A subsequent revision of the guidelines remains the aim for the future.

/pdf/guidelines-for-non-invasive-and-invasive-home-mechanical-4r6dr1z2nh.pdf

[Guidelines for Non-Invasive and Invasive Home Mechanical Ventilation for Treatment of Chronic Respiratory Failure - Update 2017].

228th ENMC International Workshop:: Airway clearance techniques in neuromuscular disorders Naarden, The Netherlands, 3-5 March, 2017.

The aim of this systematic review is to examine the benefit/risk ratio of the use of mechanical insufflation-exsufflation (MI-E) devices for airway clearance in patients with neuromuscular diseases. A search was conducted for relevant studies in MEDLINE, the Cochrane Library, and the Health Technology Assessment Database using the main key words: cough, airway clearance, in-exsufflation. The search limits were studies published in English and French between 1970 and 2014 (literature watch until December 2015). The methodological quality of the studies was assessed using (1) the Cochrane Collaboration's risk of bias tool for randomized controlled trials and (2) the Institute of Health Economics' 20-item checklist for comparative and observational studies. Data were extracted into an evidence table according to (1) study design, (2) population characteristics (including age and type of diseases) and intervention (MI-E associated or not with other interventions), (3) outcome measures, and (4) key findings. Twelve studies met the inclusion criteria (4 randomized controlled trials, 3 comparative studies, and 5 observational studies). The quality of the selected studies was poor. None of the studies reported survival outcome. All studies evaluated change of pulmonary function parameters, such as peak expiratory flow. This review underlines the lack of robust data on mechanical medical devices used for airway clearance. The current scientific evidence does not support the use of MI-E for cough augmentation in patients with neuromuscular diseases, but health-care professionals are faced with the reality of medical practice and the absence of alternatives. Most European and American guidelines recommend the use of MI-E despite low-level evidence. However, even if performing comparative trials in a specific population is difficult, the medical device industry should provide reliable data to assist health-care professionals, providers, and payers in the decision-making process. This is the only way to ensure the best treatment for patients.

http://rc.rcjournal.com/content/respcare/62/2/236.full.pdf

Use of Mechanical Insufflation-Exsufflation Devices for Airway Clearance in Subjects With Neuromuscular Disease

Background: Mechanical insufflation-exsufflation (MI-E), more commonly known as ‘cough assist therapy', is a method which produces inspiratory and expiratory assistance to improve cough performances. However, other alternatives or combinations are possible. Objective: The objective was to compare the effects of mechanical insufflation combined with manually assisted coughing (MAC), insufflation-exsufflation alone and insufflation-exsufflation combined with MAC in neuromuscular patients requiring cough assistance. Methods: Eighteen neuromuscular patients with severe respiratory muscle dysfunction and peak cough flow (PCF) lower than 3 liters/s or maximal expiratory pressure (MEP) lower than +45 cm H2O were studied. Patients were studied under three cough-assisted conditions, which were used in random order: insufflation by intermittent positive-pressure breathing (IPPB) combined with MAC, MI-E and MI-E + MAC. Results: Overall, PCF was higher with IPPB + MAC than with MI-E + MAC or MI-E alone. Among the 12 patients who had higher PCF values with IPPB + MAC than with the two other techniques, 9 exhibited mask pressure swings during MI-E exsufflation, with a transient positive-pressure value due to the expiratory flow produced by the combined patient cough effort and MAC. Each of these 9 patients had higher PCF values (>5 liters/s) than did the other 9 patients when using IPPB + MAC. Conclusion: Our results indicate that adding the MI-E device to MAC is unhelpful in patients whose PCF with an insufflation technique and MAC exceeds 5 liters/s. This is because the expiratory flow produced by the patient's effort and MAC transitorily exceeds the vacuum capacity of the MI-E device, which therefore becomes a transient load against the PCF.

/pdf/comparison-of-three-cough-augmentation-techniques-in-3tfsqixf7r.pdf

Comparison of three cough-augmentation techniques in neuromuscular patients: mechanical insufflation combined with manually assisted cough, insufflation-exsufflation alone and insufflation-exsufflation combined with manually assisted cough.

Peak Cough Flow Fails to Detect Upper Airway Collapse During Negative Pressure Titration for Cough-Assist

BACKGROUND: Breath-stacking, which consists of taking 2 or more consecutive ventilator insufflations without exhaling, is a noninvasive and inexpensive cough-assistance technique for patients with neuromuscular disease. Volumetric cough mode (VCM) is a recently introduced ventilator mode consisting of a programmable intermittent deep breath equal to a set percentage of the baseline tidal volume. Here, our objective was to compare VCM to breath-stacking during volume-control continuous mandatory ventilation in subjects on long-term noninvasive mechanical ventilation at home. METHODS: We included 20 subjects with neuromuscular disease causing severe respiratory muscle dysfunction with a cough peak flow (CPF) RESULTS: CPF increased with both techniques but was higher with VCM than with breath-stacking in 16 subjects. In 17 subjects, CPF was highest with the technique that produced the greatest inspiratory capacity. CONCLUSION: Our results indicate that both breath-stacking and VCM are useful cough-augmentation techniques. Displaying insufflated volumes on the ventilator screen is a simple and accessible method for selecting the most efficient cough-augmentation technique delivered by a home ventilator.

http://rc.rcjournal.com/content/respcare/64/3/255.full.pdf

Aurélien Boré

Papers

Comparison of three cough-augmentation techniques in neuromuscular patients: mechanical insufflation combined with manually assisted cough, insufflation-exsufflation alone and insufflation-exsufflation combined with manually assisted cough.

Peak Cough Flow Fails to Detect Upper Airway Collapse During Negative Pressure Titration for Cough-Assist

Comparison of Two Cough-Augmentation Techniques Delivered by a Home Ventilator in Subjects With Neuromuscular Disease.

Assisted vital capacity to assess recruitment level in neuromuscular diseases.