Respiratory Complications in ALS

Respiratory Complications Associated With ALS and Their Treatments

Respiratory failure is the leading cause of death in motor neuron disease (MND) patients. Symptoms of respiratory dysfunction in MND patients include sleep disturbance, excessive daytime somnolence, morning headaches and cognitive changes. Almost all MND patients will develop respiratory problems during the course of their disease. In a small percentage of MND patients, respiratory failure may present as the primary symptom at onset, whereas more commonly it develops later in the disease.

Study Overview

• Status: Completed
• Conditions: Pneumonia; Motor Neuron Disease
• Intervention / Treatment: Other: Questionaires

Detailed Description

Respiratory failure is the leading cause of death in motor neuron disease (MND) patients. Symptoms of respiratory dysfunction in MND patients include sleep disturbance, excessive daytime somnolence, morning headaches and cognitive changes. Almost all MND patients will develop respiratory problems during the course of their disease. In a small percentage of MND patients, respiratory failure may present as the primary symptom at onset, whereas more commonly it develops later in the disease. (1) Forced vital capacity (FVC), taken either supine or erect, is the most commonly used measurement tool of respiratory function. Such measures are well recognized predictors of survival (2), with supine FVC a more accurate marker of diaphragmatic weakness (1). However, FVC may not be sensitive for the detection of early respiratory failure and can be technically difficult to perform in patients with severe bulbar weakness (3). Other respiratory measures include maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), sniff nasal inspiratory pressure (SNIP) and, less commonly, formal assessment of arterial blood gases (ABG). Interpretation of the trends of these measures over time, combined with the clinical picture, determines appropriate respiratory management. Significantly, the advent of non-invasive ventilation (NIV) has provided clear benefit in terms of improving symptoms, QOL and prolonging survival by up to 7 months in MND patients, making NIV a central armamentarium of respiratory management in these patients (4) Bilevel ventilation devices (Bi-PAP) are most commonly used as initial therapy. There are no established evidence-based guidelines regarding optimal timing for initiation of NIV.Some studies suggest that an early introduction of NIV may increase survival (5), reduce respiratory-related energy expenditure (6) and improve adherence to therapy and QOL (7).Once initiated, poor optimisation of NIV represents an independent risk factor for mortality (8) However, there are no randomized control trial data available that have compared the specific parameters of bilevel modes of ventilation across various patient cohorts. Different strategies have been used to optimize patient comfort, including adjusting the type of mask and fittings, providing humidified air and testing different Bi-PAP pressure settings. Despite these measures, up to 30% of MND patients cannot tolerate therapy due to secondary effects of anxiety, emotional lability from pseudobulbar palsy, excessive salivation, claustrophobia and nasal bridge soreness (8) Importantly, the key factors that affect overall compliance with this treatment are the presence of bulbar dysfunction with bulbar onset patients six times less likely to tolerate NIV than those with limb onset disease (9) Future efforts must be focused on determining more accurate testing for early respiratory failure, optimal time to initiate NIV and the comfortable adaptation of NIV devices for patients with bulbar weakness

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• United Kingdom
  • Liverpool, United Kingdom
    • LiverpoolUHNHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patient population with ALS

Description

Inclusion Criteria:

Patients with ALS

Exclusion Criteria:

None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival after initiation of assisted ventilation	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at one month and six months or longer		1 month and 6 months
Quality of life assessed using validated health status questionnaires	Any validated functional rating scale, such as the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) or the ALSFRS-Revised (if available)	1 year
Time of initiation of diagnosis of MND and initiation of NIV		1 year

Collaborators and Investigators

• Sponsor: Liverpool University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): September 22, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: REC:20/L0/0275

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will make the research available to any MND researchers/patients

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No