The Relationship Between Arterial Stiffness and Respiratory Failure in Motor Neurone Disease
Condition: Motor Neurone Disease; Hypoxemia and/or Hypercapnia
MeSH terms: Respiratory Insufficiency; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Hypoxia; Hypercapnia
Study type: Observational

Summary: 
      -  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
    

Detailed description: 
      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.
    

Intervention name(s): Non Invasive Ventilation; Without Non Invasive Ventilation
Intervention type(s): Other; Other
Intervention description(s): Assessments for those participants who are being set up onto NIV; Assessments for those participants who are not being set up onto NIV
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with Motor Neurone Disease