asthma due to diffuse neuroendocrine system pathology
of Hospital Therapy, The I.P. Pavlov Medical University, St.Petersburg,
aspirin-sensitive asthma; melatonin; platelets; nitric
May 17, 2002
Accepted: May 22, 2002
clinical data on aspirin-sensitive asthma (ASA) indicate that
ASA patients have certain disturbances in the nervous, endocrine,
immune and other body systems. It has been found that such
patients have a lower melatonin (MT) production in daytime,
a pathology of the platelet membrane-receptor complex, and
a pathological response to exogenic MT and acetylsalicylic
acid. A hypothesis has been suggested in which ASA is considered
as apudopathy caused by dysfunction of MT-producing cells.
The decreased MT production and the disturbed cell sensitivity
to MT lead to pathological changes in individual organs and
functional systems. As a result, there is an enhanced lipid
peroxidation, an excessive production of reactive oxygen radicals,
and a reduced inhibitory action of MT on the 5-lipoxygenase
and NO-synthase activities. The lower MT content also results
in an intense aggregation of platelets, activating these cells
and increasing the production of leukotrienes and nitric oxide.
These changes disturb the pulmonary microcirculation, causing
the bronchial obturation syndrome even in patient who do not
take aspirin or other nonsteroidal anti-inflammatory drugs.
The lower basic production of MT is also responsible for a
lower content of its metabolite endogenic acetylsalicylic
acid, thereby increasing the sensitivity of melatonin-producing
cells, in particular of platelets, to this acid. So, even
minimal aspirin doses inhibit the activity of COX-1, which
shunts the already abnormal metabolism of arachidonic acid.
This, in turn, leads to a greater production of leukotrienes
and, hence, to a severe course of the disease.
This hypothesis has become the basis for a new pathogenetic
approach to the treatment of ASA patients by correcting the
melatonin content with peptide bioregulators the epiphysis
extracts Epithalamin and Epiphamin.
ASA aspirin-sensitive asthma
NSAIDS nonsteroidal antiinflammatory drugs
ATA aspirin-tolerant asthma
APUD diffuse neuroendocrine system
NO nitric oxide
COX-1 cyclooxygenase 1
asthma (ASA) occurs in 20% of patients with bronchial asthma
and is tending to increase its rate [1, 2]. Its characteristic
symptom is intolerance to aspirin and other nonsteroidal antiinflammatory
drugs (NSAIDS), which is manifested as acute asthma attack,
often with recurrent polypose rhinosinusopathy, the latter known
as the "asthmatic triad".
Recently, the European Coordination Committee has been set up
to coordinate the research on aspirin-sensitive asthma, with
special emphasis on its pathogenesis and effective therapy .
Since the attempts to prove an allergic nature of this type
of asthma have failed [4,5,6], a hypothesis has been put forth
that ASA is due to an enhanced production of leukotrienes, which
cause a persistent and intense contraction of the bronchial
smooth muscles, to edema, eosinophils infiltration of the bronchial
tree, and mucous hypersecretion [7,8]. The high production of
leukotrienes is attributed by some researchers to LTC4 synthase
hyperexpression  and by others to the inhibition of endogenic
PGE2 synthesis, which controls the leukotriene synthesis in
the absence of NSAIDS . However, this hypothesis explains
only the mechanism of aspirin-induced bronchoconstriction but
fails to account for the disease gravity, its rapid progress,
and the addiction to glucocorticoid hormones of even those patients
who do not take aspirin or other NSAIDS.
Our clinical and laboratory studies of 133 ASA patients and
143 aspirin-tolerant (ATA) patients indicate that the former
exhibit nervous, endocrine, immune and other functional disturbances
prior to the asthmatic syndrome [11,12]. The ASA patients show
early indications of psychological disorders, manifesting themselves
as alarm-depressive or asthenoneurotic syndromes. The disease
origin in 18,3% of the patients was found to be associated with
a psychological stress, which provoked an acute recurrent asthmatic
syndrome in 78,6% of ASA patients. ... ...