Pneumology - Original Articles Open access

The decline of respiratory function in amyotrophic lateral sclerosis patients and the role of non-invasive ventilation

Authors

Published
5 November 2026
Issue
Early Access
Section
Pneumology - Original Articles
DOI
10.4081/monaldi.2026.4024

Abstract

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by a poor prognosis, with an average survival of 3 to 5 years from symptom onset. Respiratory failure is the main cause of death, and non-invasive ventilation (NIV) is a cornerstone in the management of ALS patients. This single-center retrospective study was conducted at Siena University Hospital between 2010 and 2024 to analyze respiratory function parameters in ALS patients undergoing NIV, stratified by disease severity and followed over one year, to assess the relationship between lung function decline and the timing of NIV initiation. A total of 49 patients (29 males, 20 females; mean age 67±12 years) were enrolled, and 31 (63%) received NIV. Clinical and functional parameters, including forced vital capacity (FVC), pCO₂, respiratory symptoms at baseline, and longitudinal measurements of sitting FVC (FVCsit%), supine FVC (FVCsup%), and pCO₂, were collected and analyzed over time. Differences in FVC decline were observed according to the timing of NIV initiation. Among non-severe patients, those starting NIV at T0 showed a 22.5% reduction in FVC over a mean follow-up of 12.8±4.8 months. Patients initiating NIV at T2 exhibited a reported FVCsit decline of 26% (p=0.0488) and a survival of 51.3±50 months from NIV initiation, whereas those starting later (T3–T6) showed a greater decline (FVCsit decline 34%, p=0.0002) and shorter survival duration (15.7±28.6 months). These findings describe differences in respiratory function trajectories and observed survival among patients initiating NIV at different follow-up time points. However, the retrospective design, small sample size, baseline differences between groups, and potential confounding and survival-related selection bias limit causal interpretation. Further studies are needed to clarify the relationship between NIV initiation timing and clinical outcomes in ALS.

Keywords

Ethics Approval

Ethical approval for this retrospective study was obtained from the local Ethics Committee of Siena University Hospital (code number 180712 and Markerlung 17431). The study was conducted in accordance with the Declaration of Helsinki.

References

  1. Chio A, Traynor BJ, Lombardo F, et al. Prevalence of SOD1 mutations in the Italian ALS population. Neurology 2008;70:533-7. DOI: https://doi.org/10.1212/01.wnl.0000299187.90432.3f
  2. Chio A, Mora G, Calvo A, et al. Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology 2009;72:725-31. DOI: https://doi.org/10.1212/01.wnl.0000343008.26874.d1
  3. Couratier P, Corcia P, Lautrette G, et al. Epidemiology of amyotrophic lateral sclerosis: a review of literature. Rev Neurol 2016;172:37-45. DOI: https://doi.org/10.1016/j.neurol.2015.11.002
  4. Manjaly ZR, Scott KM, Abhinav K, et al. The sex ratio in amyotrophic lateral sclerosis: a population based study. Amyotroph Lateral Scler 2010;11:439-42. DOI: https://doi.org/10.3109/17482961003610853
  5. Longinetti E, Regodon Wallin A, Samuelsson K, et al. The Swedish motor neuron disease quality registry. Amyotroph Lateral Scler Frontotemporal Degener 2018;19:528-37. DOI: https://doi.org/10.1080/21678421.2018.1497065
  6. Benjaminsen E, Alstadhaug KB, Gulsvik M, et al. Amyotrophic lateral sclerosis in Nordland County, Norway, 2000-2015: prevalence, incidence, and clinical features. Amyotroph Lateral Scler Frontotemporal Degener 2018;19:522-7. DOI: https://doi.org/10.1080/21678421.2018.1513534
  7. Jun KY, Park J, Oh KW, et al. Epidemiology of ALS in Korea using nationwide big data. J Neurol Neurosurg Psychiatry 2019;90:395-403. DOI: https://doi.org/10.1136/jnnp-2018-318974
  8. Turgut N, Birgili O, Varol SaraCoglu G, et al. An epidemiologic investigation of amyotrophic lateral sclerosis in Thrace, Turkey, 2006-2010. Amyotroph Lateral Scler Frontotemporal Degener 2019;20:100-6. DOI: https://doi.org/10.1080/21678421.2018.1525403
  9. Leighton DJ, Newton J, Stephenson LJ, et al. Changing epidemiology of motor neurone disease in Scotland. J Neurol 2019;266:817-25. DOI: https://doi.org/10.1007/s00415-019-09190-7
  10. Zhou S, Zhou Y, Qian S, et al. Amyotrophic lateral sclerosis in Beijing: epidemiologic features and prognosis from 2010 to 2015. Brain Behav 2018;8:e01131. DOI: https://doi.org/10.1002/brb3.1131
  11. Goutman SA, Boss J, Patterson A, et al. High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2019;90:907-12. DOI: https://doi.org/10.1136/jnnp-2018-319785
  12. Ryan M, Zaldivar Vaillant T, McLaughlin RL, et al. Comparison of the clinical and genetic features of amyotrophic lateral sclerosis across Cuban, Uruguayan and Irish clinic-based populations. J Neurol Neurosurg Psychiatry 2019;90:659-65. DOI: https://doi.org/10.1136/jnnp-2018-319838
  13. Palese F, Sartori A, Verriello L, et al. Epidemiology of amyotrophic lateral sclerosis in Friuli-Venezia Giulia, North-Eastern Italy, 2002-2014: a retrospective population-based study. Amyotroph Lateral Scler Frontotemporal Degener 2019;20:90-9. DOI: https://doi.org/10.1080/21678421.2018.1511732
  14. Korner S, Kammeyer J, Zapf A, et al. Influence of environment and lifestyle on incidence and progress of amyotrophic lateral sclerosis in a German ALS population. Aging Dis 2019;10:205-16. DOI: https://doi.org/10.14336/AD.2018.0327
  15. Luna J, Diagana M, Ait Aissa L, et al. Clinical features and prognosis of amyotrophic lateral sclerosis in Africa: the TROPALS study. J Neurol Neurosurg Psychiatry 2019;90:20-9. DOI: https://doi.org/10.1136/jnnp-2018-318469
  16. Shimizu T, Nakayama Y, Matsuda C, et al. Prognostic significance of body weight variation after diagnosis in ALS: a single-centre prospective cohort study. J Neurol 2019;266:1412-20. DOI: https://doi.org/10.1007/s00415-019-09276-2
  17. Seelen M, Toro Campos RA, Veldink JH, et al. Long-term air pollution exposure and amyotrophic lateral sclerosis in Netherlands: a population-based case-control study. Environ Health Perspect 2017;125:097023. DOI: https://doi.org/10.1289/EHP1115
  18. Longinetti E, Fang F. Epidemiology of amyotrophic lateral sclerosis: an update of recent literature. Curr Opin Neurol 2019;32:771-6. DOI: https://doi.org/10.1097/WCO.0000000000000730
  19. De Marchi F, Sarnelli MF, Solara V, et al. Depression and risk of cognitive dysfunctions in amyotrophic lateral sclerosis. Acta Neurol Scand 2019;139:438-45. DOI: https://doi.org/10.1111/ane.13073
  20. Lopiano L, Mauro A, Mutani R. Il Bergamini di neurologia. Milan, Italy: Raffaello Cortina Editore; 2020.
  21. Tiryaki E, Horak HA. ALS and other motor neuron diseases. Contin Lifelong Learn Neurol 2014;20:1185-207. DOI: https://doi.org/10.1212/01.CON.0000455886.14298.a4
  22. Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 2008;40:572-4. DOI: https://doi.org/10.1038/ng.132
  23. Hardiman O, Al-Chalabi A, Chio A, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers 2017;3:17085. DOI: https://doi.org/10.1038/nrdp.2017.71
  24. Miller RG, Mitchell JD, Lyon M, et al. Riluzole for amyotrophic lateral sclerosis. Cochrane Database Syst Rev 2007;24:D001447. DOI: https://doi.org/10.1002/14651858.CD001447.pub2
  25. Traynor BJ, Codd MB, Corr B, et al. Amyotrophic lateral sclerosis mimic syndromes. Arch Neurol 2000;57:109-13. DOI: https://doi.org/10.1001/archneur.57.1.109
  26. National Institute for Health and Care Excellence. Motor neurone disease: assessment and management. NICE guideline NG42; 2016.
  27. Andersen PM, Abrahams S, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. Eur J Neurol 2012;19:360-75. DOI: https://doi.org/10.1111/j.1468-1331.2011.03501.x
  28. Lechtzin N, Scott Y, Busse AM, et al. Early use of non-invasive ventilation prolongs survival in subjects with ALS. Amyotroph Lateral Scler 2007;8:185-8. DOI: https://doi.org/10.1080/17482960701262392
  29. Carratu P, Spicuzza L, Cassano A, et al. Early treatment with noninvasive positive pressure ventilation prolongs survival in ALS patients with nocturnal respiratory insufficiency. Orphanet J Rare Dis 2009;4:10. DOI: https://doi.org/10.1186/1750-1172-4-10
  30. Khamankar N, Coan G, Weaver B, et al. Associative increases in ALS survival duration with non-invasive ventilation initiation and usage protocols. Front Neurol 2018;9:578. DOI: https://doi.org/10.3389/fneur.2018.00578
  31. Vitacca M, Montini A, Lunetta C, et al. Impact of an early respiratory care programme with NIV adaptation in ALS patients. Eur J Neurol 2018;25:556-e33. DOI: https://doi.org/10.1111/ene.13547
  32. Sarasate M, González N, Córdoba-Izquierdo A, et al. Impact of early non-invasive ventilation in ALS: a multicenter randomized controlled trial. J Neuromuscul Dis 2023;10:627-37. DOI: https://doi.org/10.3233/JND-221658
  33. Fiorentino G, Annunziata A, Gaeta AM, et al. Continuous noninvasive ventilation for respiratory failure in ALS: current perspectives. Degener Neurol Neuromuscul Dis 2018;8:55-61. DOI: https://doi.org/10.2147/DNND.S170771
  34. Bourke SC, Tomlinson M, Williams TL, et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006;5:140-7. DOI: https://doi.org/10.1016/S1474-4422(05)70326-4

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