Neurobiological and Immunological Mechanisms of Dyspnea in ALS (BIOPNEA)

Neurobiological and Neuro-immunological Mechanisms of Dyspnea in Amyotrophic Lateral Sclerosis

Dyspnea; subjective experience of respiratory discomfort; which produces negative emotional experience, is the most common symptom of patients afflicted with chronic respiratory failure and its treatments are limited. Amyotrophic Lateral Sclerosis (ALS) related - dyspnea, due to diaphragmatic dysfunction, is similar to dyspnea during mechanical inspiratory load (activation of the supplementary motor area, SMA). The perception of pain and dyspnea is processed in similar brain areas (insula, dorsal anterior cingulate cortex, amygdala and medial thalamus) and in ALS; relieving dyspnea by noninvasive ventilation (NIV) is associated with decreased pain thresholds. Otherwise, it is reported systemic elevations of pro-inflammatory cytokines in chronic pain patients, correlating with intensity of pain, and during respiratory load in healthy volunteers.

The objectives are to evaluate the cytokines and endorphins rates variations after initiation of NIV in ALS patients, and to correlate cytokines and endorphins rates with the intensity of the affective component and the intensity of the sensory component of dyspnea.

The investigators will perform a prospective, experimental study, including 30 ALS patients. Dyspnea, ventilatory and cardiac settings, electromyographic recording of the scalene muscle and biological assays (ACTH, endorphin, Neuropeptide P, BDNF, IL1, IL6, IL8, IL10, TNF), will be measured during spontaneous breathing and during NIV at different times after initiation.

The investigators expect a reduction of immunological and neurobiological markers after relieving dyspnea by NIV. This work could lead to the development of new treatments for dyspnea.

Inclusion Criteria:

- Patients with chronic respiratory failure with diaphragmatic dysfunction linked to amyotrophic lateral sclerosis and requiring long-term NIV

Exclusion Criteria:

• Other respiratory disease (COPD, asthma, obstructive sleep apnea)
• Alcohol or psychotropic drug the lasts 24 hours
• Cognitive impairment
• Smoking > 10 PA
• Exacerbation or infection 6 weeks earlier
• Endstage of illness
• Chronic or acute pain (VAS > 3)