• Patients with Motor Neurone Disease (MND) admitted to Lane Fox Unit /Royal Brompton Hospital and/or reviewed in Lane Fox Unit /Royal Brompton Hospital clinics and/or outreach review will be approached for participation in the study

• Physiological assessment and measurement of arterial stiffness will be performed in all patients at baseline and after the use of non invasive ventilation for 6 weeks.

• MND patients not requiring mechanical ventilation will serve as controls since non invasive ventilation cannot be withheld from MND patients in type II respiratory failure.

• Data will be analysed to look for differences between groups, relationships in baseline or change from baseline in respiratory physiological measures, inflammatory indices, breathlessness, and arterial stiffness.

  • Age, Height, Weight
  • History and Physical Examination
  • Evaluation of dysponea: mMRC, Borg Scale (Seated-Supine)
  • Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R)
  • Sleep Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ-5)
  • 24 hour blood pressure monitor
  • Carotid-femoral pulse wave velocity
  • Respiratory Muscle Strength - Maximal Inspiratory Pressure, Maximal Expiratory Pressure, and Sniff Nasal Inspiratory Pressure
  • Spirometry - FEV1 and FVC
  • Arterial Blood Gas
  • CRP and fibrinogen (clinically)
  • Breathe CO exhale

The stiffness of the arterial wall is highly relevant to cardiovascular disease. Large elastic arteries and smaller muscular conduit arteries become stiffer with ageing, a process that is accelerated in the presence of cardiovascular disease. Arterial stiffness increases also with various disease states, including hypertension, diabetes mellitus, obesity, smoking, hypercholesterolemia, and kidney disease. Numerous techniques have been developed to measure arterial stiffness, either in single vessels or in entire muscular arterial trees. These techniques have increasingly been shown to improve stratification of cardiovascular risk and risk reduction beyond that provided by conventional risk factors. Furthermore, large artery stiffness, measured via carotid-femoral pulse wave velocity, independently predicts the risk of cardiovascular events in both clinical and community-based cohorts.

Abnormalities in arterial stiffness have been noted in disorders characterized by hypoxia with or without hypercapnia. These abnormalities could be driven by the risk factors for those conditions (e.g. cigarette smoke, obesity). In COPD, all studies are consistent showing a significant increase in arterial stiffness compared with ex-smokers without airway obstruction and nonsmoker healthy control subjects. The severity of airway obstruction is consistently related to arterial stiffness in COPD. Furthermore, airflow limitation arising from cigarette smoking, but not airflow limitation in non-smokers, was associated with arterial stiffness in a general population independently of established risk factors. The presence of OSA was associated with higher arterial stiffness indices independent of major confounders. In this context, OSA is associated with increased arterial stiffness independent of blood pressure.

Non invasive ventilation has been shown to reduce arterial stiffness in obstructive sleep apnea. In particular, there are studies that have examined the impact of continuous positive airway pressure (CPAP) on arterial stiffness (measured with pulse wave velocity) in OSA patients. Other studies have examined changes in arterial stiffness (measured with other than pulse wave velocity method) after treatment of OSA with CPAP. Furthermore, to the best of our knowledge no investigation exists on the impact of non invasive bilevel positive airway pressure ventilation on arterial stiffness in neuromuscular disease.

The Lane Fox Unit, the UK's largest weaning, rehabilitation and home ventilation unit, is treating neuromuscular patients. In neuromuscular disease, especially in MND, confounding factors as obesity, cigarette smoke, hypertension, and diabetes mellitus can be excluded. This gives the opportunity to determine whether hypoxemia and/or hypercapnia alone cause arterial stiffness. Furthermore, in this pilot study it will be investigated whether non invasive ventilation has any effect on arterial stiffness in MND patients.

Inclusion Criteria:

• MND diagnosis
• The ability to perform the respiratory function testing satisfactorily
• Stable clinical and functional state for at least four weeks before testing
• BMI 20-30 kg•m-2

Exclusion Criteria:

• Pregnancy
• Aged <18, >80
• Significant physical or psychiatric comorbidity that would prevent compliance with trial protocol
• Unstable clinical state
• Use of mechanical ventilation
• Cardiovascular disorders (history, physical examination)
• Known lung disease, such as asthma or COPD or any other cause of hypoxemia and/or hypercapnia but MND (history, physical examination, CXR review [High Resolution Computed Tomography if CXR is not compatible with neuromuscular disease alone])
• Airway obstruction (FEV1/FVC<0.75)
• Diabetes mellitus
• Obesity (BMI>30 kg•m-2)
• Smoking history (>10 pack∙years or active smoker)

Patients with Motor Neurone Disease

No individual participant data will be available