The Relationship Between Arterial Stiffness and Respiratory Failure in Motor Neurone Disease
The Relationship Between Arterial Stiffness and Respiratory Failure in Motor Neurone Disease
-  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)