Description

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by upper and lower motor neuron degeneration, leading to muscle weakness, functional decline, and ultimately respiratory failure. Respiratory muscle weakness causes restrictive ventilatory impairment and a progressive decrease in forced vital capacity (FVC), which is strongly associated with survival. Because no curative therapy exists, respiratory rehabilitation aimed at maintaining pulmonary function and chest wall compliance plays an important role in extending quality of life and survival.

Lung volume recruitment therapy (LVRT) is a respiratory rehabilitation method that uses assisted lung inflation to expand the lungs and maintain compliance. It is commonly performed with a manual resuscitation bag (bag-valve-mask, BVM) by stacking multiple breaths to reach maximum insufflation capacity (MIC). However, this conventional method requires voluntary glottic closure to maintain air stacking. In people with ALS who have bulbar symptoms or tracheostomy, this ability is often lost, making conventional LVRT difficult or impossible.

To overcome this limitation, a device-based approach known as lung insufflation capacity (LIC) training was developed. The LIC Trainer is a licensed medical device in Japan that allows air stacking through a one-way valve mechanism, enabling passive insufflation without voluntary glottic control. The device incorporates a safety valve that automatically opens at pressures above 60 cmH₂O to prevent barotrauma and a manual relief valve allowing patient-controlled exhalation. Although the LIC Trainer has been used clinically in Japan since 2016, evidence regarding its long-term effects in ALS remains limited.

This prospective single-center interventional study aims to evaluate the effects of LIC training on respiratory function and survival in adults with ALS at the National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. Participants are diagnosed with ALS according to the El Escorial or Awaji criteria, are 20 years of age or older, and are not using noninvasive ventilation (NIV) and do not have a tracheostomy at the start of LIC training. Key exclusion criteria include other chronic pulmonary diseases, severe cardiac dysfunction, and conditions that preclude study assessments.

After providing written informed consent, participants receive education on LIC training from a physical therapist and are provided with an LIC Trainer and bag-valve-mask for home use. They are instructed to perform a set of insufflation cycles, typically around 10 per session, twice daily. Training logs are maintained by participants and reviewed at each visit to monitor adherence and safety. Outpatient follow-up visits occur every 3 months for up to 36 months.

At each visit, respiratory function (percent predicted FVC, LIC, MIC, cough peak flow \[CPF\], and assisted CPF) and functional status (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised \[ALSFRS-R\]) are assessed. Clinical events such as respiratory infections, hospitalizations, tracheostomy, and death are also recorded. The primary outcome is overall survival, defined as the time from initiation of LIC training to tracheostomy or death. Secondary outcomes include longitudinal changes in respiratory function and ALSFRS-R scores, as well as the frequency of respiratory infections.

Data from this intervention group will be compared with a matched historical control cohort derived from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. Propensity score matching will be used to balance baseline characteristics such as age, sex, site of onset, percent predicted FVC, body mass index (BMI), ALSFRS-R, and use of riluzole and edaravone. Survival will be analyzed using Kaplan-Meier estimates and Cox proportional hazards models, and repeated measures of respiratory and functional outcomes will be analyzed using linear mixed-effects models. This study is expected to clarify whether early and sustained LIC training can help maintain lung and chest wall compliance, slow the decline in respiratory function, and potentially extend survival in ALS.