Provision, cough efficacy and treatment satisfaction of mechanical insufflation-exsufflation in a large multicenter cohort of patients with amyotrophic lateral sclerosis.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Amyotrophic Lateral Sclerosis*/complications ; Amyotrophic Lateral Sclerosis*/therapy ; Amyotrophic Lateral Sclerosis*/physiopathology ; Cough*/therapy ; Cough*/etiology ; Insufflation*/methods ; Patient Satisfaction*; Humans ; Male ; Female ; Middle Aged ; Aged ; Treatment Outcome ; Longitudinal Studies ; Germany ; Adult

Competing Interests: Declarations. Competing interests: AM has received presentation and consulting fees from Merz Pharma GmbH & Co., KGaA, ITF Pharma GmbH, Zambon GmbH and Roche Pharma AG. JCK has received personal fees from AbbVie, Biogen, Ipsen, Roche and Zambon. TM has received consulting fees from Cytokinetics, GSK and Desitin Arzneimittel GmbH, and has served on scientific advisory boards for Cytokinetics, GSK and TEVA. TM and CM are founders of the internet platform Ambulanzpartner and hold shares in Ambulanzpartner Soziotechnologie APST GmbH. SP has participated on advisory boards of Biogen and has received consulting fees from Biogen. AKR received speaker fees from Amylyx Pharmaceuticals and served on advisory boards for Biogen and Argenx outside of the submitted work. All other authors declare that they have no conflicts of interest.
In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited systematic research on MI-E provision, symptom alleviation, or patient satisfaction. The research platform Ambulanzpartner coordinated this longitudinal observational study conducted in 12 German ALS centers from July 2018 to September 2023. Patients were enrolled based on ALS-related cough deficiency requiring MI-E therapy. The study recorded provision, reasons for withholding MI-E, clinical parameters, therapy frequency, subjective cough deficiency, and symptomatic relief. Satisfaction with MI-E therapy was determined by the likelihood of recommendation. Out of 694 ALS patients indicated for MI-E, 527 (75.9%) received the therapy. The primary reason for non-provision was that the patient had died before provision (n = 66 of 167; 39.5%). These patients were significantly more affected as represented by higher progression rates and lower cough peak flows (CPF) at the time of MI-E indication (p < 0.05). Most patients who received MI-E used it daily (n = 290 of 370; 78.4%). Self-assessed cough deficiency correlated with clinical measurements, especially for patients with higher deficits. At follow-up visits, patients reported reduced cough deficiency (p < 0.001). Frequent MI-E use was linked to greater symptom relief and higher likelihood of recommending the therapy. This study highlights the symptomatic and palliative potential of MI-E therapy for ALS patients.
(© 2025. The Author(s).)

De Carvalho, M., Swash, M. & Pinto, S. Diaphragmatic neurophysiology and respiratory markers in ALS. Front. Neurol. 10, 143 (2019). (PMID: 10.3389/fneur.2019.00143)
Kiernan, M. C. et al. Amyotrophic lateral sclerosis. Lancet 377, 942–955 (2011). (PMID: 10.1016/S0140-6736(10)61156-7)
Niedermeyer, S., Murn, M. & Choi, P. J. Respiratory failure in amyotrophic lateral sclerosis. Chest 155, 401–408 (2019). (PMID: 10.1016/j.chest.2018.06.035)
Tabor-Gray, L. C., Gallestagui, A., Vasilopoulos, T. & Plowman, E. K. Characteristics of impaired voluntary cough function in individuals with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Front. Degener. 20, 37–42 (2019). (PMID: 10.1080/21678421.2018.1510011)
Tabor-Gray, L., Vasilopoulos, T. & Plowman, E. K. Differences in voluntary and reflexive cough strength in individuals with amyotrophic lateral sclerosis and healthy adults. Muscle Nerve 62, 597–600 (2020). (PMID: 10.1002/mus.27040)
Sales De Campos, P., Olsen, W. L., Wymer, J. P. & Smith, B. K. Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review. Chron. Respir. Dis. 20, 147997312311759 (2023). (PMID: 10.1177/14799731231175915)
McGeachan, A. J. et al. A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Front. Degener. 18, 1–9 (2017). (PMID: 10.1080/21678421.2016.1221433)
Bach, J. R. Noninvasive respiratory management of patients with neuromuscular disease. Ann. Rehabil. Med. 41, 519 (2017). (PMID: 10.5535/arm.2017.41.4.519)
Sancho, J., Servera, E., Bañuls, P. & Marín, J. Effectiveness of assisted and unassisted cough capacity in amyotrophic lateral sclerosis patients. Amyotroph. Lateral Scler. Front. Degener. 18, 498–504 (2017). (PMID: 10.1080/21678421.2017.1335324)
Morrow, B. et al. Cough augmentation techniques for people with chronic neuromuscular disorders. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD013170 (2018). (PMID: 10.1002/14651858.CD013170)
Toussaint, M. et al. 228th ENMC International Workshop: Airway clearance techniques in neuromuscular disorders Naarden, The Netherlands, 3–5 March, 2017. Neuromuscul. Disord. 28, 289–298 (2018). (PMID: 10.1016/j.nmd.2017.10.008)
Georges, M. et al. Proposals from a French expert panel for respiratory care in ALS patients. Respir. Med. Res. 81, 100901 (2022).
Chatwin, M. et al. Airway clearance techniques in neuromuscular disorders: A state of the art review. Respir. Med. 136, 98–110 (2018). (PMID: 10.1016/j.rmed.2018.01.012)
Homnick, D. N. Mechanical insufflation-exsufflation for airway mucus clearance. Respir. Care 52, 1296–1305 (2007).
Ferreira de Camillis, M. L. et al. Effects of mechanical insufflation-exsufflation on airway mucus clearance among mechanically ventilated ICU subjects. Respir. Care 63, 1471–1477 (2018). (PMID: 10.4187/respcare.06253)
Suárez, A. A. et al. Peak flow and peak cough flow in the evaluation of expiratory muscle weakness and bulbar impairment in patients with neuromuscular disease. Am. J. Phys. Med. Rehabil. 81, 506–511 (2002). (PMID: 10.1097/00002060-200207000-00007)
Auger, C., Hernando, V. & Galmiche, H. Use of mechanical insufflation-exsufflation devices for airway clearance in subjects with neuromuscular disease. Respir. Care 62, 236–245 (2017). (PMID: 10.4187/respcare.04877)
Morrow, B., Zampoli, M., Van Aswegen, H. & Argent, A. Mechanical insufflation-exsufflation for people with neuromuscular disorders. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD010044.pub2 (2013). (PMID: 10.1002/14651858.CD010044.pub2)
Tzeng, A. C. & Bach, J. R. Prevention of pulmonary morbidity for patients with neuromuscular disease. Chest 118, 1390–1396 (2000). (PMID: 10.1378/chest.118.5.1390)
Khamankar, N., Coan, G., Weaver, B. & Mitchell, C. S. Associative increases in amyotrophic lateral sclerosis survival duration with non-invasive ventilation initiation and usage protocols. Front. Neurol. 9, 578 (2018). (PMID: 10.3389/fneur.2018.00578)
Petri, S. et al. Guideline “motor neuron diseases” of the German Society of Neurology (Deutsche Gesellschaft für Neurologie). Neurol. Res. Pract. 5, 25 (2023). (PMID: 10.1186/s42466-023-00251-x)
Miller, R. G. et al. Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 73, 1218–1226 (2009). (PMID: 10.1212/WNL.0b013e3181bc0141)
Windisch, W. S2k-Leitlinie Nichtinvasive und invasive Beatmung als Therapie der chronischen respiratorischen Insuffizienz—Revision 2017 (Georg Thieme Verlag, 2018).
Andersen, T. et al. Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis. Thorax 72, 221–229 (2017). (PMID: 10.1136/thoraxjnl-2015-207555)
Andersen, T. M. et al. Laryngeal responses to mechanically assisted cough in progressing amyotrophic lateral sclerosis. Respir. Care 63, 538–549 (2018). (PMID: 10.4187/respcare.05924)
Mitropoulou, G., Heinzer, R., Janssens, J.-P., Von Garnier, C. & Prella, M. Home use of mechanical insufflation/exsufflation in adult patients in Western Switzerland. Respiration 102, 341–350 (2023). (PMID: 10.1159/000529166)
Sancho, J., Servera, E., Díaz, J. & Marín, J. Predictors of ineffective cough during a chest infection in patients with stable amyotrophic lateral sclerosis. Am. J. Respir. Crit. Care Med. 175, 1266–1271 (2007). (PMID: 10.1164/rccm.200612-1841OC)
Arcuri, J. F., Abarshi, E., Preston, N. J., Brine, J. & Pires Di Lorenzo, V. A. Benefits of interventions for respiratory secretion management in adult palliative care patients—a systematic review. BMC Palliat. Care 15, 74 (2016). (PMID: 10.1186/s12904-016-0147-y)
Von Elm, E. et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. J. Clin. Epidemiol. 61, 344–349 (2008). (PMID: 10.1016/j.jclinepi.2007.11.008)
Brooks, B. R., Miller, R. G., Swash, M. & Munsat, T. L. El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1, 293–299 (2000). (PMID: 10.1080/146608200300079536)
Maier, A. et al. Use and subjective experience of the impact of motor-assisted movement exercisers in people with amyotrophic lateral sclerosis: A multicenter observational study. Sci. Rep. 12, 9657 (2022). (PMID: 10.1038/s41598-022-13761-6)
Fürstenau, D., Klein, S., Vogel, A. & Auschra, C. Multi-sided platform and data-driven care research: A longitudinal case study on business model innovation for improving care in complex neurological diseases. Electron. Mark. 31, 811–828 (2021). (PMID: 10.1007/s12525-021-00461-8)
Meyer, T. et al. Remote digital assessment of amyotrophic lateral sclerosis functional rating scale—a multicenter observational study. Amyotroph. Lateral Scler. Front. Degener. 24, 175–184 (2023). (PMID: 10.1080/21678421.2022.2104649)
Sancho, J. et al. Waveforms analysis in patients with amyotrophic lateral sclerosis for enhanced efficacy of mechanically assisted coughing. Respir. Care 67, 1226–1235 (2022). (PMID: 10.4187/respcare.09978)
Chatwin, M. & Wakeman, R. H. Mechanical insufflation-exsufflation: Considerations for improving clinical practice. J. Clin. Med. 12, 2626 (2023). (PMID: 10.3390/jcm12072626)
Maier, A. et al. Online assessment of ALS functional rating scale compares well to in-clinic evaluation: A prospective trial. Amyotroph. Lateral Scler. 13, 210–216 (2012). (PMID: 10.3109/17482968.2011.633268)
Kimura, F. et al. Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology 66, 265–267 (2006). (PMID: 10.1212/01.wnl.0000194316.91908.8a)
Calvo, A. et al. Prognostic role of slow vital capacity in amyotrophic lateral sclerosis. J. Neurol. 267, 1615–1621 (2020). (PMID: 10.1007/s00415-020-09751-1)
Polkey, M. I. et al. Respiratory muscle strength as a predictive biomarker for survival in amyotrophic lateral sclerosis. Am. J. Respir. Crit. Care Med. 195, 86–95 (2017). (PMID: 10.1164/rccm.201604-0848OC)
Plowman, E. K. et al. Voluntary cough airflow differentiates safe versus unsafe swallowing in amyotrophic lateral sclerosis. Dysphagia 31, 383–390 (2016). (PMID: 10.1007/s00455-015-9687-1)
Alarcan, H. et al. Evaluation of arterial blood gas parameters as prognostic markers in amyotrophic lateral sclerosis. Eur. J. Neurol. 30, 1611–1618 (2023). (PMID: 10.1111/ene.15779)
Krol, M. W., de Boer, D., Delnoij, D. M. & Rademakers, J. J. The Net Promoter Score—an asset to patient experience surveys?. Health Expect. 18, 3099–3109 (2015). (PMID: 10.1111/hex.12297)
Meyer, T. et al. Treatment expectations and perception of therapy in adult patients with spinal muscular atrophy receiving nusinersen. Eur. J. Neurol. 28, 2582–2595 (2021). (PMID: 10.1111/ene.14902)
Meyer, R. et al. Patient-reported outcome of physical therapy in amyotrophic lateral sclerosis: Observational online study. JMIR Rehabil. Assist. Technol. 5, e10099 (2018). (PMID: 10.2196/10099)
Reichheld, F. F. & Markey, R. The Ultimate Question 2.0: How Net Promoter Companies Thrive in a Customer-Driven World (Harvard Business Review Pr, 2011).
Spittel, S. et al. Non-invasive and tracheostomy invasive ventilation in amyotrophic lateral sclerosis: Utilization and survival rates in a cohort study over 12 years in Germany. Eur. J. Neurol. 28, 1160–1171 (2021). (PMID: 10.1111/ene.14647)
Logroscino, G. et al. Incidence of amyotrophic lateral sclerosis in Europe. J. Neurol. Neurosurg. Psychiatry 81, 385–390 (2010). (PMID: 10.1136/jnnp.2009.183525)
Manjaly, Z. R. et al. The sex ratio in amyotrophic lateral sclerosis: A population based study. Amyotroph. Lateral Scler. 11, 439–442 (2010). (PMID: 10.3109/17482961003610853)
McCombe, P. A. & Henderson, R. D. Effects of gender in amyotrophic lateral sclerosis. Gend. Med. 7, 557–570 (2010). (PMID: 10.1016/j.genm.2010.11.010)
Dardiotis, E. et al. Body mass index and survival from amyotrophic lateral sclerosis: A meta-analysis. Neurol. Clin. Pract. 8, 437–444 (2018). (PMID: 10.1212/CPJ.0000000000000521)
Chatwin, M. & Simonds, A. K. Long-term mechanical insufflation-exsufflation cough assistance in neuromuscular disease: Patterns of use and lessons for application. Respir. Care 65, 135–143 (2020). (PMID: 10.4187/respcare.06882)
Mahede, T. et al. Use of mechanical airway clearance devices in the home by people with neuromuscular disorders: Effects on health service use and lifestyle benefits. Orphanet J. Rare Dis. 10, 54 (2015). (PMID: 10.1186/s13023-015-0267-0)
Veldhoen, E. S. et al. Evidence for beneficial effect of daily use of mechanical insufflation-exsufflation in patients with neuromuscular diseases. Respir. Care 68, 531–546 (2023). (PMID: 10.4187/respcare.09664)
Fontana, G. A. & Widdicombe, J. What is cough and what should be measured?. Pulm. Pharmacol. Ther. 20, 307–312 (2007). (PMID: 10.1016/j.pupt.2006.11.009)
Van Den Bergh, O., Van Diest, I., Dupont, L. & Davenport, P. W. On the psychology of cough. Lung 190, 55–61 (2012). (PMID: 10.1007/s00408-011-9347-7)
Gebrehiwet, P. et al. Time from amyotrophic lateral sclerosis symptom onset to key disease milestones: Analysis of data from a multinational cross-sectional survey. Amyotroph. Lateral Scler. Front. Degener. 25, 345–357 (2024). (PMID: 10.1080/21678421.2023.2297795)
Umayahara, Y. et al. Cough sound-based estimation of vital capacity via cough peak flow using artificial neural network analysis. Sci. Rep. 13, 8461 (2023). (PMID: 10.1038/s41598-023-35544-3)

Date Created: 20250302 Date Completed: 20250302 Latest Revision: 20250511

20250511

PMC11873142

10.1038/s41598-025-91692-8

40025240