Aspirin-induced asthma

Term Aspirin-induced asthma AIA is used for notation of a clinical situation when one of Bronchoconstriction factors are non-steroidal anti-inflammatory drugs (NSAID) including Acidum acetylsalicylicum - aspirin. In most cases AIA it is combined with atonic or with an infectious-dependent bronchial asthma, however it can be observed and as the isolated form of disease - "pure" AIA. Among observed by us sick of a bronchial asthma at use of special tests for intolerance NSAID the given form of disease in the isolated kind or in a combination has been taped almost at third of patients.

As have shown researches, therapeutic and toxic action of aspirin are bound to the same biochemical process which invariably arises at contact NSAID to a membrane of cells. Thus aspirin interferes with a metabolism of one and; the main components of a cellular membrane - arachidonic acid. In norm there are two pathes of a metabolism of arachidonic acid. Enzyme cyclooxygenase transforms an Arachidonate into Prostaglandinums, thromboxanes and a prostacyclin, the part from which possesses Bronchoconstriction properties, for example, Prostaglandinum F2a thromboxane A2. Other products of a cyclooxygenase path of scission of arachidonic acid, on the contrary, render antiinflammatory and bronchodilators action: Prostaglandinum E2, a prostacyclin. The second path of disintegration of arachidonic acid with the assistance of lipoxygenase enzyme leads to formation of eicosanoids exclusive proinflammatory and Bronchoconstriction properties. Them name leukotrienes. It is revealed, that Acidum acetylsalicylicum inactivates cyclooxygenase, quenching, thus, formation of prostacyclins G2 and H2, precursors of other metabolites of arachidonic acid. Blockage of a prostaglandin metabolism promotes production of eicosanoids of leukotrienes, and also 15 hydroxy tetraen acid, possessing ability to involve in itself eosinocytes, is a biochemical basis aspirin a bronchospasm as aspirin quenches development of Prostaglandinums with broncho dilating properties.

Great value of leukotrienes in pathogenesis AIA proves to be true good efficacyy of blockers of a lipoxygenase, and also leukotrienes receptors at the given category of patients. Besides, as have shown observations, intensity of an aspirin bronchospasm positively correlates with activity NSAID, and anaesthetising and the resolvents which are not possessing property to quench a cycleoxygenase (CO), for example, paracetamol, sodium Salicylas, aminosalicylate, a benzydamine, a dextropropoxyphene, etc. are well tolerated by patients AIA.

Proceeding from the leukotrienes theory, it is possible to explain presence of the refractory season arising after an aspirin bronchospasm and proceeding 24-72 hours. During a refractoriness there is resynthesis CO to the subsequent restoration of a prostaglandin metabolism.

This theory, however, does not answer the important question - why ­ universal property of aspirin to quench CO only at patients AIA clinically shows in the form of a bronchospasm and other symptoms anaphylactoid. This problem tried to solve Ameisen with co-authors. The biochemical marker yes in thrombocytes has been found. The deficiency of Prostaglandinum H2 arising after an inactivation by aspirin CO has appeared it. On reduction of production of Prostaglandinum H2 a thrombocyte, and only it, reacts intensifying of functional activity with the subsequent hyperproduction of leukotrienes. Addition of synthetic Prostaglandinum H2 completely prevented an aspirin bronchospasm. On the contrary, blockage of receptors of prostaglandin H2 provoked reaction of thrombocytes without participation of aspirin at patients AIA. Healthy humans, and also asthmas sick of not aspirin form did not possess similar reaction of thrombocytes on NSAID. Thus it was possible to explain development in patients AIA of attacks of a dyspnea without reception NSAID. The product of cells of the central excitatory system can serve in this situation as a bronchospasm mediator - a melatonin which on the structure and ability to oppress CO is similar on NSAID.

For statement of diagnosis AIA anamnesis data about reaction of the patient to reception of anaesthetising or febrifugal preparations have great value. The part of patients can have accurate indicatings on development of an attack of a dyspnea after application NSAID. It is necessary to specify, however, that a certain part of patients AIA do not accept NSAID, nevertheless attacks of a dyspnea at them are provoked by the use in nutrition connatural a sal and a Pilate, and also the products preserved by means of Acidum acetylsalicylicum (including house preparation). The appreciable part of patients is not informed that various NSAID are a part of such often used combined preparations as Citramonum (Acidum acetylsalicylicum and Phenacetinum), askofen (Acidum acetylsalicylicum and Phenacetinum), Pentalginum (Amidopyrinum and analginum), Sedalgin (Acidum acetylsalicylicum and Phenacetinum), etc.

It is extremely important to ask to the patient with a bronchial asthma a question on efficacyy of application of tablets of Theophedrinum for cupping of an attack of a dyspnea. Patients with AIA usually specify or in Theophedrinum inefficiency, or note its two-phasic action: in the beginning comes broken or weakening of an attack of a dyspnea (action of ephedrine entering into its structure), and then in 40-60 minutes the bronchospasm accrues again because of presence at Amidopyrinum and Phenacetinum Theophedrinum.

For acknowledgement of diagnosis AIA provocative tests in vivo or tests in vitro now can be used. At performance of the provocative test in vivo use or aspirin reception (or others NSAID) inside, or inhalate solution aspirin - a lysine with the subsequent monitoring of indicators of bronchial passableness. It is necessary to specify, however, in necessity of exact observance of technology of carrying out of assays in vivо. In connection with possibility of development of a serious attack of a dyspnea (especially at carrying out of the inhalation test) the given research to be spent only the doctor-allergist Can is necessary special equipment and presence of the personnel, ready to assist at bronchospasm development.

Having surveyed 100 sick bronchial asthma by means of provocation by aspirin prescribed inside we have found, that approximately aspirin caused in third of examinees of different degree a bronchospasm which sometimes is not fixed clinically, in third of cases - a bronchodilatation, at other patients reaction of a bronchial arbour was absent. Attempt of treatment sick of a bronchial asthma with action of aspirin by appointment NSAID in half of cases has ended with transformation bronchodilatation the answer in Bronchoconstriction in a week of reception of a medicine. In our opinion, the persons reacting to assay with reception of aspirin by a bronchodilatation can be carried in risk bunch on development of developed clinical picture AIA.

Recently for diagnostics AIA tests in vitro are used also, in particular, research of production of leukotrienes at an incubation of blood cells with indometacin, and also the chemiluminescent test developed in our laboratory - Application within three years of the chemiluminescent test has shown its high sensitivity and specificity, possibility of fast reception of the answer.

Pathological influence NSAID on a respiratory organs at patients AIA shows on all extent of pneumatic pathes. Debuts AIA, as a rule, with long, as though an unmotivated rhinitis which gradually passes in a polypous rhinosinusitis at 20-25 % of patients. It is necessary to notice, that sometimes the polygroove amazes also others mucous, for example, a stomach, an intestine, in single instances and genitourinary pathes. The first attacks of a dyspnea quite often arise after reception NSAID in connection with concomitant disease. Cases when medicine reception came to an end tragically are described. The serious aspirin dyspnea at a number of patients is accompanied urticata by enanthesises, gastrointestinal implications (abdominal pains, vomiting, a liquid chair), the rhinoconjunctivitis. Intravenous injections of the preparations containing NSAID - Baralginum are especially dangerous, etc. As well as other forms of a bronchial asthma, AIA can begin in the childhood, proving as an asthma of physical effort, being clinically characterised by symptoms chronic eosinophilic (on sputum structure) a bronchitis with exacerbations after virus catarrhs of a respiratory organs. There are data that at intolerance NSAID the phagocytosis is broken, other parts of immunodefence suffer also. It shows persistent flow of inflammatory diseases, especially respiratory tracts.

To 10 % of patients AIA react on exoallergens, i.e. suffer simultaneously atopic form of disease. The clinical picture in these cases differs from purely exogenous form - seasonal prevalence of exacerbations is not expressed, there is no accurate effect of elimination of allergens, the specific desensitisation is carried out hardly and, as a rule, is ineffective.

Most effective method of treatment AIA is the desensitisation aspirin at which successful realisation there comes clinical stabilisation of flow of the disease, confirmed with negative takes of aspirin tests. The desensitisation is a mean of formation of tolerance to NSAID at patients AIA by means of microprovocations by Acidum acetylsalicylicum or other preparations. Also as well as provocative tests with aspirin, the desensitisation can be spent only in a specialised medical institution. Cуществуют various procedures of a desensitisation aspirin. For example, with 2-3 hour interval to the patient prescribe consistently 3, 30, 60, 100, 150, 325 and 650 mg of aspirin. At faster mean to the patient give aspirin every 30 minute desensitisation the patient who without damage to health is capable to accept 650 mg of aspirin is considered. Similar procedures quite often come to an end with a serious exacerbation of a bronchial asthma, therefore it is more preferable to begin a desensitisation with the minimum doses, enlarging them in a day. We recommend to use for selection of an initial dose of aspirin the provocative test with a preparation. That quantity of Acidum acetylsalicylicum which caused nonperishable depression of bronchial passableness, and is prescribed as an initial dose for a desensitisation. If next day there was no falling of indicators of function of an external respiration then aspirin dose doubles, at depression of indicators - the dose applied the day before repeats. A desensitisation spend the patient after cupping of exacerbation AIA at absence at them staxises, a peptic ulcer of a stomach or a duodenum, pregnancy. As basic therapy AIA use inhalations fed, Tilade, glucocorticoids (Becotidum, Aldecin, Inhacort, etc.) . Advantage of the dosed glucocorticoid preparation for inhalation application the Aldecin is presence of a demountable nasal attachment that is especially important taking into account polypous rhinosinusopathy often met at patients AIA.

For reduction of sensitivity of the patient to NSAID and in cases of bad shipping of a desensitisation the hemosorption is prescribed, in a week after which carrying out it is possible to continue the begun pathogenetic therapy. Sometimes, at rather low sensitivity of the patient to aspirin (a dose provoking depression of indicators of bronchial passableness not less than on 15 %, - 100 mg of a preparation and more), hemosorption realisation completely desensitisates patient AIA to NSAID. At high sensitivity (aspirin dose - less than 10 mg) prior to the beginning of a desensitisation are recommended to carry out 1 - 2 procedures of hemosorptions with a week interval but only then to start a desensitisation. In the presence of a stomach or duodenum peptic ulcer it is possible to try to desensitisate patient AIA by means of inhalations or injections aspirin - a lysine. The initial dose gets out during the spent assay (inhalationly or intramusculary). To completely desensitisated patient AIA reception of maintenance doses of aspirin further is prescribed. As last dose it is recommended to use 1 tablet of a preparation (0,25 or 0,5), depending on weight of the patient, in day within a month, further - in two days within a year, under the control of conditions mucous a stomach (for a year of observation to spend a gastroscopy not less than two times). The preparation is prescribed after meal with the reference to wash down with its alkaline mineral water.

When AIA it is combined with exo allergy, carrying out of the specific desensitisation, which efficacyy is recommended against reception of doses of aspirin bolstering a refractoriness at tolerance to NSAID sharply increases.