الفهرس 
BRONCHIAL ASTHMAOnly 14 pages are availabe for public view
 |  | from | 190 |  |  |
| | | from | 190 | | |
Abstract
Asthma is a chronic disorder characterized by airway inflammation, reversible airway obstruction and AHR; in which eosinophils, MCs, neutrophils, cytokines and mediators play important roles in its pathogenesis. These different inflammatory cells are involved in asthma, although the precise role of each cell type is not yet certain. Many different mediators (such as histamine, PG, LTs and kinins) have been implicated in asthma.
Researchers suggest that some genetic variants may only cause asthma when they are combined with specific environmental exposures, and otherwise may not be risk factors for asthma.
The aim of this work was to present a new vision of asthma as it is a neurogenic disease (Neuroasthma) and to study scientific background of effective use of anticonvulsants for pharmacotherapy of bronchial asthma.
Many different neuromediators have been implicated in asthma pathogenesis:
. Neurotrophins (NTs) are a family of proteins that induce the survival, development and function of neurons. NTs, such as NGF, BDNF, NT-3 and NT-4, exert their function by binding two different receptor subtypes. The low-affinity pan-neurotrophin receptor p75NTR and the tropomyosin receptor kinases (Trks) TrkA, TrkB and TrkC. NTs promote airway inflammation by interaction with different immune cell subtypes and contribute to an altered neuronal control of the airways.
. Several peptides have been demonstrated in mammalian lung. Some of them are present in the innervation of the mucosa, submucosa, smooth muscle and blood vessels and are called neuropeptides. Release of neuropeptides, including tachykinins and CGRP, from sensory nerves via an axon or local reflex causes ASM contraction and modulates immune cell functions, which then leads to neurogenic inflammation.
. Opioid alkaloids and peptides, such as morphine and the endogenous opioid peptides, modulate the function of lymphocytes and other cells involved in host defense and immunity. Apart from the presence of the classical opioids and their receptors in the lung and their functional role, a new group of peptides such as nociceptin and endomorphins has been characterized in the airways.
. GABA is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABAA/GABAC) channels and metabotropic (GABAB) receptors. GABAA channels and GABAB receptors have been functionally identified on peripheral nerves in the lung. Many studies have revealed complex GABA signaling systems in the AECs, ASM and inflammatory cells.
Bronchial asthma is mainly paroxysmal inflammatory disease and neurogenic inflammation may play important role in asthma mechanisms. Airways inflammation during asthma also is more neurogenic than immune process. The role of allergies is very important during asthma, but allergies may be only an initial trigger factor for neurogenic development of asthma as a chronic disease.
So, bronchial asthma may be a neurogenic paroxysmal inflammatory disease (Neuroasthma) with the complex pathogenic mechanism, including two levels of components: 1) multiple trigger components and 2) central neurogenic generator component.
Until today, management of bronchial asthma was held in two main directions:
1) Modification of factors inducing allergic reaction and interference on the certain stages of allergic reaction.
2) Interference with peripheral bronchial receptors. Both these directions do finally affect the trigger factors.
Considering the bronchial asthma as a neurogenic paroxysmal and inflammatory disease having certain similar pathogenic mechanisms with epilepsy, migraine, trigeminal neuralgia and breath-holding spells, a 3rd direction in the management of bronchial asthma is suggested: application of anticonvulsive agents for the control of activity of generator neurogenic mechanisms of bronchial asthma.
This kind of medication has been successfully applied in many trials: in more than 70% of patients with asthma some AEDs induced complete and stable remission. This new approach leads to the prevention of asthmatic attacks and opens up new perspectives for the management of this disease.