Severe Persistent Asthma Clinical Trial
Official title:
Treatment of Bronchial Severe Asthma With Bronchial Thermoplasty. Assessment of Efficacy and Safety of Treatment, Study of Effects on Neuronal and Chemosensitive Component of the Bronchial Mucosa Pre and Post Treatment
In severe bronchial asthma the mechanism of inflammation and bronchospasm is complex and
still not clarified. The smooth muscle cells play an important role from the mechanical
point of view, as a culmination of neurogenic stimuli and inflammatory cytokines that
determine as final effect the bronchospasm and over time a hypertrophy of the muscular coat.
There are some other hypothesis that the smooth muscle cells may play a role as central
regulator of chemical mediators that cause bronchospasm and inflammation, although there are
currently no firm conclusions 2 According to other studies3,the nerve receptors TRANSIENT
RECEPTOR POTENTIAL VANILLOID TYPE 1 have a great importance in the complex mechanism of
airway inflammation too. (There are at least 4)
These receptors would intervene according to the following mechanism:
1. Irritants on the bronchial mucosa stimulate the TRANSIENT RECEPTOR POTENTIAL VANILLOID
TYPE 1 present on afferent endings of sensory fibers, unmyelinated C (chemiosensitive
neurons)
2. On the same afferent axon acting factors with the activation effect (lowering the
activation threshold, increase the expression, promote the translocation of TRPV1
receptor on the membrane). Among these factors the neurotrophins of which the most
important NERVE GROWTH FACTOR (NGF)
3. The activation of TRPV1 (through release of Ca2 + +) determines two efferent responses:
1. CENTRALLY-MEDIATED
2. LOCAL AXON Reflex
Investigators hypothesized that BT may have a strong influence on the destruction of nerve
receptors TRPV1 and unmyelinated nerve fibers located in the mucosa going to stop
reflections both central and local authorities responsible for the activation of
bronchospasm. In support of this hypothesis, there are some anatomical studies4, which show
that these receptors are more numerous at the level of main bronchi which are the main
target of BT. Please note in this context that it is already known that in thermoablations
commonly used in cardiology it is used a radio frequency with development of heat controlled
to 65 °, as in the BT, able to interrupt the circuit nervous responsible for the activation
of the circuit causing the abnormal 'arrhythmia.
The mechanism of action the bronchial thermoplasty exerts the positive action demonstrated by the studies through is not yet well understood yet. The only action on the denaturation and destruction of the smooth muscle layer of the bronchi at intermediate and high caliber perhaps not fully explain its action, taking into account that most of the smooth muscle loading of the small airways is minimally altered by the procedure. From the premises outlined in the section on the mechanism of inflammation we hypothesized that BT may have a strong influence on the destruction of nerve receptors TRPV1 and unmyelinated nerve fibers located in the mucosa going to stop reflections both central and local authorities responsible for the activation of bronchospasm. In support of this hypothesis, there are some anatomical studies4, which show that these receptors are more numerous at the level of main bronchi which are the main target of BT. Please note in this context that it is already known that in thermoablations commonly used in cardiology it is used a radio frequency with development of heat controlled to 65 °, as in the BT, able to interrupt the circuit nervous responsible for the activation of the circuit causing the abnormal 'arrhythmia. ;
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
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