Aspirin-sensitive asthma due to diffuse neuroendocrine system pathology.
Available 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.
Evsyukova
Helen V
HV
Department of Hospital Therapy, The I.P. Pavlov Medical University, Raevsky st. 7, appt. 7, 194064 St. Petersburg, Russia. ond@aport.ru
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000473:pathology*; D006801:Humans; D009490:Neurosecretory Systems / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin