Effects of respiratory muscle training on respiratory function in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: MEP p=0.008; MIP p=0.005; SNIP p=0.034; PEF p=0.017; ALSFRS-R p=0.030; FVC p=0.053

• Effect Size: MEP: SMD 0.387; MIP: SMD 0.156; SNIP: SMD 0.216; PEF: SMD 0.205; ALSFRS-R: SMD 0.214; FVC: SMD 0.129 (borderline, non-significant)

• Primary Outcome: Maximal expiratory pressure (MEP) as the outcome with the largest effect size; secondary outcomes include MIP, SNIP, PEF, FVC, and ALSFRS-R

• Nnt Or Sensitivity: NNT cannot be calculated from SMD data without absolute risk thresholds. Effect sizes are small (Cohen's d <0.4 for all outcomes except MEP at 0.387), and GRADE certainty is moderate for MIP only, with low or very low certainty for all other outcomes. Clinical significance of these SMDs in the context of ALS disease progression is uncertain.

• Confidence Interval: MEP: 95% CI 0.192–0.581; MIP: 95% CI 0.089–0.224; SNIP: 95% CI 0.039–0.392; PEF: 95% CI 0.088–0.323; ALSFRS-R: 95% CI 0.039–0.388; FVC: 95% CI −0.003 to 0.262

Clinical Application

RMT is a low-cost, non-pharmacological intervention deliverable in outpatient neurology or respiratory physiotherapy settings. However, standardised protocols, appropriate supervision, and regular monitoring of respiratory function are required. Feasibility is constrained by disease progression, fatigue, and bulbar dysfunction in ALS. In Australia, ALS (motor neurone disease) is managed within multidisciplinary MND clinics aligned with Motor Neurone Disease Australia guidelines and RACGP chronic disease frameworks. Riluzole remains the only TGA-approved disease-modifying pharmacotherapy (PBS-listed). Edaravone has not achieved PBS listing. Respiratory physiotherapy, including RMT, is accessible via Medicare-funded allied health plans (Chronic Disease Management items) and through MND clinic services. The current evidence base does not support RMT as a standard-of-care recommendation but is consistent with individualised, goal-directed physiotherapy as part of multidisciplinary ALS care. Australian clinicians should note that the GRADE certainty ratings (moderate to very low) preclude strong guideline recommendations at this time. Adults with ALS who retain sufficient respiratory muscle function to participate in structured training programmes. Patients with severe respiratory compromise (FVC <50% predicted or requiring non-invasive ventilation) may not be suitable candidates and were likely underrepresented in included trials.

Abstract

BACKGROUND: Respiratory decline is prognostically important in amyotrophic lateral sclerosis (ALS), but the efficacy of respiratory muscle training (RMT) remains uncertain. We synthesized randomized evidence on respiratory and related outcomes. METHODS: We searched databases, specialized registers, and trial registries through June 19, 2025, for randomized RMT trials in ALS. Risk of bias was assessed with the Cochrane tool. Random-effects meta-analyses reported standardized mean differences (SMDs) with 95% confidence intervals (CIs), and certainty was rated with GRADE. RESULTS: Six studies were included; five concurrently randomized trials contributed quantitative data, whereas Pinto 2013 was retained for qualitative context. RMT improved maximal expiratory pressure (MEP; SMD 0.387, 95% CI 0.192-0.581; P = 0.008) and showed small favorable effects on maximal inspiratory pressure (MIP; SMD 0.156, 95% CI 0.089-0.224; P = 0.005), sniff nasal inspiratory pressure (SNIP; SMD 0.216, 95% CI 0.039-0.392; P = 0.034), peak expiratory flow (PEF; SMD 0.205, 95% CI 0.088-0.323; P = 0.017), and ALSFRS-R (SMD 0.214, 95% CI 0.039-0.388; P = 0.030). Forced vital capacity showed a borderline favorable trend (SMD 0.129, 95% CI - 0.003 to 0.262; P = 0.053). Low heterogeneity estimates were imprecise because most endpoints included only three to four small studies. Certainty was moderate for MIP, low for MEP, FVC, and PEF, and very low for SNIP and ALSFRS-R. Exploratory analyses identified no reliable effect modifiers. CONCLUSIONS: RMT was associated with small, directionally consistent improvements mainly in pressure- and flow-based outcomes, whereas effects on FVC and longer-term clinical outcomes remain uncertain. RMT may be considered an individualized adjunct to ALS respiratory care, not a disease-modifying therapy. Larger, longer, standardized trials with patient-important endpoints are needed.

References

1. 1.Lei, Y., Huang, J., Li, M., Zhang, Y., Ye, Z., He, X., Tang, Z., & Wei, J. (2026). Effects of respiratory muscle training on respiratory function in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis. Journal of Neurology. https://doi.org/10.3109/17482968.2012.726227