Bronchial asthma

Description:

Bronchial asthma is a chronic retsidviruyushchy inflammatory disease of a respiratory organs which pathogenetic essence is the hyperreactivity of bronchial tubes connected with immunopathological mechanisms, and the main clinical symptom of a disease is the suffocation attack owing to inflammatory hypostasis of a mucous membrane of bronchial tubes, a bronchospasm and hypersecretion of slime.
For a better understanding about complexity of a definition of a problem we give one more definition of a disease (from materials of the International consensus on problems of diagnosis and treatment of bronchial asthma): "Bronchial asthma represents sosby a chronic inflammatory respiratory disease in which development a set of elements, including smooth muscle cells and eosinophils take part.  With hypersensitivity the similar inflammation causes the symptoms which are usually connected with existence of widespread obstruction of respiratory tracts of various degree of manifestation in people, reversible also increase in sensitivity of respiratory tracts to various incentives is spontaneous or under the influence of the carried-out treatment, and".
Hyperreactivity, both specific, and nonspecific, is the main universal pathogenetic symptom of bronchial asthma, and is the cornerstone of instability of respiratory tracts. Singular cellular elements of an inflammation at bronchial asthma are eosinophils, glaky muscle cells, T-limfatsity and macrophages.

Reasons of Bronchial asthma:

In an etiology of bronchial asthma the following factors matter:
1. Heredity. Genetic aspects in a question of the reasons of development of bronchial asthma are of great importance. In the conducted researches it was reported about  concordance cases that is when both from unioval twins had bronchial asthma. In clinical practice family cases of incidence when at the ill asthma of mother children also get sick with this illness often meet. As a result of the kliniko-genealogical analysis it is revealed that at 1/3 patients the disease has hereditary character. With emphasis on the hereditary nature of a disease point to atopic bronzialny asthma. In this case, in the presence of asthma at one of parents, the probability of asthma at the child makes 20 — 30% and if both parents are sick, this probability reaches 75%. The research within which watched formation of an atopy at newborns in families of farmers was conducted and at monozygotic twins showed that, despite genetic predisposition, development of a disease can be prevented excepting provocative allergens and by correction of an immune response during pregnancy. By the Norwegian scientists it is established that the place and time of the birth do not influence formation of allergic reactions and bronchial asthma.

2. Professional factors. Influence of biological and mineral dust, including derevesny, flour, cotton, etc., harmful gases and evaporations on developing of respiratory diseases was investigated at 9144 people in 26 centers in the research ECRHS. Women generally contacted to biological dust, and men by 3 — 4 times more often than women — to mineral dust, harmful gases and evaporations. At the same time it is revealed that  chronic cough with expectoration arose at the persons contacting to harmful factors in this population more often cases for the first time of the arisen bronchial asthma are registered. At the same time it is revealed that even at reduction of contact with a harmful professional factor, eventually nonspecific hyperreactivity of bronchial tubes at persons with professional asthma does not disappear. Weight of professional asthma generally is defined by duration of a disease and expressiveness of symptoms, does not depend on age, sex, a harmful professional factor, an atopy, smoking.

3. Ecological factors. the 9-year epidemiological research ECRHS-II which included 6588 healthy faces which were affected by a number of adverse factors during the specified period (exhaust gases, smoke, the increased humidity, harmful evaporations, etc.), showed that 3% observed at the end of a research had complaints corresponding to defeat of respiratory system. After the statistical analysis of demographic, epidemiological and clinical data the conclusion was drawn that from 3 to 6% of new cases are provoked by influence of pollyutant.

4. Food. The researches in many countries devoted to influence of character of food on the course of a disease showed that the persons using products of plant origin, juice vitamin-rich, cellulose, antioxidants, have an insignificant tendency to more favorable course of bronchial asthma. Respectively the use of the animal products rich with fats, proteins and the refined digestible carbohydrates, is connected with a severe disease and frequent aggravations.

5.  Alcohol. According to a research of the Danish scientists, members of the European respiratory society (ERS), moderate alcohol intake reduces risk to ache with asthma. According to a research the weekly use of 10-60 ml of alcohol levels chances "to get" asthma, inhaling pollen of flowering plants, proteic matters of cats and dogs, house dust and even kitchen cockroaches. Ten "cubes" of alcohol are the standard foreign "drink" corresponding to a bottle of light beer or an incomplete glass of wine. At the same time absolutely teetotal people, and also the persons abusing alcohol have the increased chances of development of asthma.

6. Detergents. the 10-year research ECRHS in 10 European Union countries showed that various detergents including cleaning aerosols contain the substances provoking asthma at adults; using these means connect about 18% of new cases.

7. Microorganisms. Long time existed idea of existence of asthma of the infectious and allergic nature (Ado and Bulatov's classification), according to this theory viruses, fungi, bacteria participate in a pathogeny of bronchial asthma.

8. Acute and chronic stress.

Pathogeny:

Pathogenetic mechanisms of bronchial asthma are up to the end not studied. If the patient has a genetic predisposition, then after an organism sensitization allergen as a result of imperfection of control of T lymphocytes of synthesis of reagins concentration of immunoglobulins of a class E increases. At the same time there is a fixing of antibodies on receptors of membranes of mast cells. After contact with "trigger" proskhodit release of a histamine, the slowly reacting anaphylaxis substance (SRAS), a chemotactic factor of eosinophils, etc. The cascade of consecutive immunological reactions (1 type - anaphylactic, atopic, reaginic, immediate hypersensitivity - GNT) in of course mitoga leads to development of a bronchospasm and consequently - to clinical signs of suffocation.  Thus, the immunopathological "option of an inflammation" works, that is at bronchial asthma allergic reaction and an inflammation in bronchial tubes are continuous interconnected. In a pathogeny of bronchial asthma an important role is played also by other types of immunopathological reactions: type 3 - immunocomplex (a so-called phenomenon of Artyus) at which the main factor causing a bronchospasm are lizosomalny enzymes; type 4 - cellular (hypersensitivity of the slowed-down type - GZT). On the one hand, the difficult immunopathological pathogeny of a disease in many respects defines variability (and unpredictability, up to long-term spontaneous remissions) character of a course of bronchial asthma at the specific patient (as a result of change of the main type of immunopathological reaction), with another, - explains inefficiency of the majority of anti-inflammatory means (the glucocorticoids influencing all types of immunopathological reactions have the most effective antiinflammatory effect).

At certain stages of a course of bronchial asthma, along with immunopathological mechanisms, secondary disturbances among which the important place is taken by neuroreflex reactions can gain a certain value.

Symptoms of Bronchial asthma:

For a clinical picture of a bronchial astmykharakterna such symptoms as disturbance of breath in the form of an asthma and cough. These symptoms arise after contact with allergen that is of great importance in diagnosis. Also seasonal variability of symptoms and presence of relatives with bronchial asthma or other atopic diseases is noted. At a combination to rhinitis symptoms of asthma can or appear only in a certain season, or be present constantly with seasonal deteriorations. Seasonal increase in level in air of certain aeroallergens (for example Alternaria pollen, birches, herbs and ambrosias) causes development of aggravations in some patients.
The specified symptoms can also develop at contact with nonspecific substances (smoke, gases, pungent smells) or after an exercise stress 9 so-called asthma of physical tension), can become aggravated at night and decrease in response to basic therapy.

The most typical symptom of bronchial asthma is the suffocation attack. At this time the patient sits in forced situation, having bent forward, holding hands a table, with the raised upper shoulder girdle, the thorax gets a cylindrical form. The patient takes a short breath and without pause the long painful exhalation accompanied with remote rattles. Breath happens to participation of auxiliary muscles of a thorax, a shoulder girdle, prelum abdominale. Intercostal spaces are expanded, involved and located horizontally. Perkutorno is defined a bandbox pulmonary sound, shift of the lower bounds of lungs down, the excursion of pulmonary fields is hardly defined.
Often, especially at long attacks, there is a pain in the lower part of a thorax connected with hard work of a diaphragm. The aura of an attack which is shown sneezing, cough, rhinitis, urticaria can precede an attack of suffocation, the attack can be followed by cough with a small amount of a vitreous phlegm, also the phlegm can separate at the end of an attack. At auscultation the weakened breath, dry scattered rattles is defined. At once after tussive pushes increase in number of the whistling rattles, both in an inspiratory phase, and on an exhalation, especially in zadnenizhny departments is heard that is connected with secretion of a phlegm in a gleam of bronchial tubes and its passage. In process of a phlegm otkhozhdeniye the number of rattles decreases and breath from weakened becomes rigid.
Rattles can be absent at patients with heavy aggravations owing to heavy restriction of an air flow and ventilation. In the period of an aggravation also cyanosis, drowsiness, difficulties at a conversation are noted, tachycardia. The blown-up thorax is a consequence of the increased pulmonary volumes — it is necessary to provide "raspravleniye" of respiratory tracts and disclosure of small bronchial tubes. The combination of a hyperventilation and bronchial obstruction considerably increases work of respiratory muscles.
Between attacks at patients it can not be observed any symptoms of a disease. During the mezhpristupny period at patients the whistling rattles at auscultation confirming existence of residual bronchial obstruction most often come to light. Sometimes (and sometimes along with the expressed obstruction of bronchial tubes) the whistling rattles can be absent or be found only during the forced exhalation.

Also cases of bronchial asthma which clinical picture is characterized only by cough are described. Such option of asthma call tussive. It is more often widespread among children, the most expressed symptoms usually are noted at night at frequent day lack of symptoms. In diagnosis the research of variability of indicators of function of breath or bronchial hyperreactivity, and also a phlegm eosinophilia is of importance. The tussive option of asthma should be distinguished with eosinophilic bronchitis at which cough and an eosinophilia of a phlegm are noted, however indicators of function of breath and bronchial reactivity remain normal.

Bronchial asthma of physical tension. At some patients the only trigger of an attack is physical activity. The attack usually develops in 5 — 10 min. after the termination of loading and is rare — during loading. Patients sometimes note long cough which independently passes within 30 — 45 min. Attacks are more often provoked by run, inhalation of dry cold air matters at the same time. The diagnosis of bronchial asthma is spoken well by the termination of an attack after inhalation β2-агонистов or prevention of symptoms thanks to inhalation β2-агонистами to loading. The main diagnostic method — the test with 8-minute run.

Treatment of Bronchial asthma:

Treatment of bronchial asthma has to be complex and long. As therapy the drugs of basic therapy influencing the disease mechanism by means of which patients control asthma, and also symptomatic drugs which are influencing only smooth muscles of a bronchial tree and removing a suffocation attack are used.

Carry bronkhodilyatator to drugs of symptomatic therapy:
      1. β2-адреномиметики
      2. xanthines
Carry to drugs of basic therapy:
      1. the corticosteroids applied it is inhalation
      2. kromona
      3. antagonists of leukotriene receptors
      4. monoclones.

Basic therapy needs to be accepted since without it the need for inhalation of bronchodilators (symptomatic means) grows. In this case and in case of insufficiency of a dose of basic drugs growth of need for bronchodilators is a sign of an uncontrollable course of a disease.

Kromona.
Carry such drugs to kromona as кромогликат sodium (Intal) and nedokromit sodium (Tayled). These means are shown as basic therapy of bronchial asthma with an intermittent and easy current. Kromona IGKS are less strong by the efficiency. As there are indications for purpose of IGKS already at easy degree of bronchial asthma, kromona are gradually forced out more convenient in use inhalation glucocorticosteroids. Also transition to kromona from IGKS on condition of complete control over symptoms the minimum doses of IGKS is not justified.

Inhalation glucocorticosteroids.
At asthma inhalation glucocorticosteroids to which the majority collateral действиев system steroids is not peculiar are applied. At inefficiency of inhalation corticosteroids add glucocorticosteroids for system use.

IGKS — the main group of drugs for treatment of bronchial asthma. Classification of inhalation glucocorticosteroids depending on chemical structure is given below:
      Not halogenated:
            - циклесонид (Alvesko)
            - будесонид (Pulmikort, Benakort)
      Chlorinated:
            - beclomethasone Dipropionas (Becotidum, Beklodzhet, Klenil, Beklazon Eko, Beklazon Eko Easy Breath)
            - mometazona furoate (Асмонекс)
      Fluorinated:
            - флунизолид (Ingakort)
            - Triamcinolonum acetonide
            - азмокорт
            - flutikazona propionate (Fliksotid)

Inhalation glucocorticosteroids render antiinflammatory effect that is connected with suppression of activity of cells of an inflammation, reduction of products of cytokines, intervention in metabolism of arachidonic acid and synthesis of prostaglandins and leukotrienes, decrease in permeability of vessels of a microcirculator bed, prevention of direct migration and activation of cells of an inflammation, increase in sensitivity of b-receptors of smooth muscles. Under the influence of inhalation glucocorticosteroids there is an increase in synthesis of antiinflammatory protein lipokortina-1, by inhibition interleykina-5 increase apoptosis of eosinophils that leads to decrease in their kolichesktv, stabilization of cellular membranes. Unlike system glucocorticosteroids, tropna IGKS to fatty tissue, have a short elimination half-life, are quickly inactivated, possess local (topical) action thanks to what have the minimum system manifestations. The most important property — lipophilicity thanks to which IGKS collect in respiratory tracts is slowed down their release from fabrics and their affinity to a glucocorticoid receptor increases. Pulmonary bioavailability of IGKS depends on percent of hit of drug in lungs (that is defined by type of the used inhaler and correctness of the technology of inhalation), existence or lack of the carrier (the best indicators have the inhalers which are not containing freon) and on absorption of drug in respiratory tracts.

The concept of step approach was until recently glavenstvuyushchiy concept of purpose of IGKS that means that at more severe forms of a disease higher doses of IGKS are appointed.

In the provided table of a predstvalena equivalent doses of IGKS, mkg.

International name          Low doses Average doses High doses
Beclomethasone Dipropionas              200 — 500 500 — 1000    1000
Budesonid                                    200 — 400 400 — 800 800
Flunizolid                        500 — 1000        1000 — 2000 2000
Flutikazona                        propionate 100 — 250 250 — 500 500
Triamsinolona                    acetonide 400 — 1000 1000 — 2000 2000

For today inhalation glucocorticoids are drug of the first choice and basis in treatment of bronchial asthma despite degree of its expressiveness. According to the concept of step approach: "The severity of a current OH is higher, the high doses of inhalation steroids should be applied". In a number of researches it is shown that at the patients who began treatment of IGKS not later than 2 years from the beginning of a disease essential advantages in improvement of control over asthma symptoms, in comparison with begun such therapy after 5 years and more are noted.
Except "pure" glucocorticoids inhalers may contain combinations of drugs.

Simbikort Turbukhaler.
There are fixed combinations of IGKS and prolonged β2-адреномиметиков, the combining means of basic therapy and symptomatic means. According to the global strategy of GINA, the fixed combinations are the most effective remedies of basic therapy of bronchial asthma as allow to remove an attack and at the same time are remedy. Two such fixed combinations enjoy the greatest popularity:
      - салметерол + флутиказон (Tevakomb or Seretid of 25/50, 25/125 and 25/250 mkg / dose, Seretid Multidisk of 50/100, 50/250 and 50/500 mkg / dose)
      - формотерол + будесонид (Simbikort Turbukhaler of 4,5/80 and 4,5/160 mkg / dose).

Seretid Multidisk.
Seretid is a part of drug салметерол in a dose of 25 mkg / a dose in the dosed aerosol inhaler and the 50th MSC/dose in the device "Multidisk". The maximum and admissible daily dose of a salmeterol — 100 mkg, that is the maximum frequency rate of use of Seretid makes 2 breaths 2 times for the dosed inhaler and 1 breath 2 times for Multidisk adaptation. The inhaler Simbikort is shown if it is necessary to increase a therapeutic dose. It contains формотерол which maximum and admissible daily dose makes 24 mkg, does possible to be inhalated by Simbikort to 8 times a day. In the research SMART the risk connected using a salmeterol in comparison with placebo is revealed. Besides, indisputable advantage of a formoterol is also that he begins to act right after inhalation, but not in 2 hours as салметерол.

Concept of a flexible drug dosing.
Lack of the concept of step approach is that it accurately does not mean achievement of the goal (decrease in frequency of attacks, night symptoms, decrease in frequency of aggravations, simplification of physical activity), and just dictates a certain dose of basic therapy at this or that degree of manifestation of a symptom complex. Researches in Europe and America showed that the level of control over asthma symptoms even in the countries with the developed health system is low. The concept of flexible dosing was checked in researches with drug симбикорт (будесонид 80 or 160 mkg + формотерол 4,5 mkg). It is safe to be inhalated simbikorty to 8 times a day therefore if there is a need to increase IGKS dose, it is possible just to increase number of inhalations of drug. Inhalation of a simbikort provides immediate broncholitic effect and increase in a dose of IGKS. The patient after training can regulate the dose of IGKS, applying симбикорт is more often, is more rare — from 1 to 8 times a day. Thus the concept of flexible dosing is that the patient begins treatment with average doses of a simbikort and then, proceeding from own health, raises or reduces a dose by means of the same inhaler.

Authors of the concept of flexible dosing put forward the following theses:
  - Flexible dosing is more convenient for the patient.
  - It is possible to reduce the general dose of IGKS as after improvement of a condition of the patient quickly reduces number of inhalations, so, it is possible to reduce risk of NLR when using IGKS.
  - The total cost of treatment falls.
  - The quantity of aggravations as temporary increase in a dose of a simbikort allows to prevent their development decreases.

The conducted randomized clinical trials devoted to flexible dosing of a simbikort demonstrate that use of flexible dosing allows to reach quicker control over asthma symptoms in comparison with the fixed doses of drugs, it is essential to reduce the frequency of exacerbations of asthma, to reduce material inputs by treatment. In a number of researches compared симбикорт in the mode of flexible dosing and серетид, the best results belong to a simbikort. Also theoretically for flexible dosing also other drugs can be used, but now there are no these independent multicenter randomized researches, about efficiency of their use.

Glucocorticosteroids for system use.
Glucocorticosteroids to system use or system glucocorticosteroids (SGKS) can be applied by intravenously small doses at exacerbations of asthma, orally short courses or is long. Intravenous administration of high doses of SGKS (pulse therapy) is much less often used.
SGKS can be applied is long at inefficiency of inhalation glucocorticosteroids. At the same time bronchial asthma is characterized as steroidozavisimy and the severe disease is appropriated.
At use of system glucocorticoids there are by-effects: disturbance of a mineralization of bones, increase in arterial pressure, a diabetes mellitus, suppression of functional activity гипоталамо - pituitary and adrenal system, a cataract, glaucoma, obesity, thinning of skin with formation of striya and the increased capillary permeability, muscular weakness. Therefore along with purpose of system glucocorticosteroids begin therapy according to the prevention of osteoporosis. For oral administration Prednisonum, Prednisolonum, Methylprednisolonum (Methypredum), a hydrocortisone are used. These drugs have smaller, than other GKS, mineralokortikoidny activity, unsharply expressed action on cross-striped muscles and rather short elimination half-life. Long administration of drug Triamcinolonum (Polcortolonum) is fraught with side effects, such as development of muscular dystrophy, weight loss, weaknesses, gastrointestinal tract diseases. Dexamethasone is not applied is long orally at bronchial asthma because of the expressed suppression of function of bark of adrenal glands, ability to detain liquid and low affinity to pulmonary receptors of GKS.

Establishment of the reasons which resulted in need of this type of treatment is important. Here list of the most important of them:
    1. Iatrogenic
            - not purpose of IGKS
            - underestimation of severity at the previous stages
            - attempt of control of an inflammation in the period of an aggravation low doses of GKS that leads to purpose of system GKS to long term
            - use of non-selective and slaboselektivny β-blockers ((((((((((propranolol, атенолол)
            - the wrong selection of system of delivery for IGKS
            - the incorrect diagnosis of bronchial asthma where respiratory symptoms are a consequence of other pathology (system vasculites, a system scleroderma, a dermatomyositis, a bronchopulmonary aspergillosis, a gastroesophageal reflux disease, hysteria etc.)
      2. Low комплайнс.
      3. The continuing exposure of allergens.
In 5% of total quantity of cases of purpose of glucocorticosteroids the steroidorezistentnost, that is resistance of steroid receptors to steroid drugs takes place.
In this regard allocate two types of patients:
      1. Carry patients of whom true steroid resistance is characteristic to the 2nd type of patients. Patients of this group have  no side effects at long reception of high doses of system glucocorticoids.
      2. Carry patients with the acquired resistance who have side effects from reception of system steroids to the 1st group of patients. For overcoming such resistance appoint the raised doses of glucocorticosteroids, and appoint drugs which have addiktivny effect.

At SGKS dose decline the doctor has to estimate correctly a clinical picture of a disease, assume the possible reasons of a steroidozavisimost and to appoint the maximum doses of highly effective IGKS. Control of functions of breath, a daily pikfloumetriya and the accounting of reception β2-агонистов on requirement is obligatory. It is necessary to reduce SGKS gradually against the background of reception of the maximum doses of IGKS, for example reducing a dose not earlier than each 3 — 4 weeks, in order to avoid development of complications. Reasonablly at each reduction of a dose to carry out blood test in which pay attention to increase of SOE and an eosinophilia that  can demonstrate manifestation of a general disease, including a vasculitis, to investigate the basal level of cortisol as after the termination of long therapy by overwhelming doses of SGKS development of adrenal insufficiency is possible. To reduce doses of IGKS it is allowed only after full cancellation of SGKS.

Anti-leukotriene drugs.
Now the following antagonists of leukotrienes are known:
      - зафирлукаст (Akolat)
      - montelukast (Singulyar)
      - пранлукаст
The mechanism of effect of drugs of this group consists in bystry elimination of a basal tone of respiratory tracts which is created by leukotrienes owing to chronic activation of 5-lipoksigenazny fermental system. Thanks to it this group of drugs was widely used at aspirinovy bronchial asthma in which pathogeny the strengthened activation of 5-lipoksigenazny system and hypersensitivity of receptors to leukotrienes takes place. Antagonists of leukotrienes are especially effective at this form of asthma which therapy quite often causes difficulties.
Зафирлукаст promotes reliable improvement in comparison with placebo of indicators of OFV1, PSV and to elimination of symptoms at addition to IGKS.
Use of montelukast in combination with IGKS and prolonged β2-агонистами, especially in the presence of allergic rhinitis, allows to improve quicker control over a disease, to lower IGKS dose.
The research which is recently conducted in Great Britain showed that antagonists of receptors to leukotrienes are also effective, as well as the inhalers containing glyukortikosteroida. Anti-leukotriene drugs, such as Montelukast (Singulyar) and Zafirlukast (Akolat), underwent a randomized controlled research in group of 650 patients with bronchial asthma within 24 months. Results of a research are published in New England Journal of Medicine. Authors of a research believe that use of anti-leukotriene drugs is possible at the 4th of 5 patients with bronchial asthma, in particular at those patients who do not want to apply GKS-inhalers because of their side effects or because of a steroidofobiya.

Monoclones.
Rather recently new drug — Omalizumab (Novartis is made under a trade name Ksolar) representing a concentrate of antibodies to IgE was developed. This drug  connects free immunoglobulin E in blood, causing thereby restriction of degranulation and to an exit of biologically active agents which start early allergic reactions.
Ksolar can be applied at persons 12 years with average and heavy forms of persistent bronchial asthma, with allergic asthma which triggers are year-round allergens, confirmed with skin tests or a research of specific IgE are more senior.
Drug is investigated in Study 1 and Study 2 with total quantity of patients 1071 aged from 12 up to 76 years receiving beclomethasone Dipropionas, divided into 2 groups (receiving subcutaneously ксолар or placebo). Ksolar's addition to the available therapy of IGKS allow to lower considerably IGKS dose, having kept at the same time control over asthma symptoms. According to Study 3 where as IGKS a flutikazona propionate was chosen, it was allowed to add dlitelnodeystvuyushchy bronchodilators and in which heavier patients took part to therapy, differences between ksolary and placebo was not revealed.

β2-адреномиметики long action.
To β2-адреномиметикам long action carry now:
    -  формотерол (Oksis, Foradil)
    -  салметерол (Серевент)
    -  индакатерол
Foradil — формотерол firms Novartis.
According to the research SMART small, but statistically significant increase in the fatal cases in group of a salmeterol connected with respiratory complications is defined (24 in comparison with 11 in group of placebo; relative risk [RR]=2,16; 95% the confidence interval [CI] made 1,06 — 4,41), the cases of death caused by asthma (13 in comparison with 3 in group of placebo; RR=4,37; 95% of CI were made by 1,25 — 15,34), and also the combined cases of death connected with asthma (37 in comparison with 22 in group of placebo; RR=1,71; 95% of CI were made by 1,01 — 2,89). At the same time a number of researches in which participated формотерол showed safety of a formoterol in a daily dose to 24 mkg as concerning respiratory, and cardiovascular complications. In the research FACET where Oksis was used, it became clear that addition of a formoterol reduces the frequency of easy and heavy attacks of bronchial asthma as to low to doses of a budesonid (by 26% for heavy attacks and for 40% for easy attacks), and to high (high doses of a budesonid without formoterol reduced the frequency of heavy attacks by 49% and lungs for 39%, with formoteroly — respectively for 63 and 62%).

β2-адреномиметики short action.
The range β2-адреномиметиков short action is presented by the following drugs:
    - Fenoterolum (беротек)
    - salbutamol (Ventolinum)
    - тербуталин (brikanit)
Are the most effective of the existing bronchial spasmolytics and therefore they possess the first place among drugs of stopping of acute symptoms of asthma at any age. The inhalation way of introduction as it provides more bystry effect at lower dose and smaller side effects is preferable. Inhalation β2-агониста provides the expressed protection against a bronchospasm against the background of an exercise stress and other provocative factors, during 0,5-2 h.

Xanthines.
Carry the Euphyllinum used for the emergency stopping of an attack and the theophylline with long action accepted orally to group of xanthines. These drugs were used to β2-адреномиметиков and in some situations are used now. Efficiency of theophylline as the monotherapy and therapy appointed in addition to IGKS or even SGKS at children is shown 5 years are aged more senior. It is more effective than placebo, eliminates day and night symptoms and improves function of lungs, and the maintenance therapy provides them a protective effect at loading. Addition of theophylline at children with heavy asthma, allows to improve control and to lower GKS dose. Preference is given to drugs of the slowed-down release with the studied absorption and full bioavailability regardless of meal (Teopek, Teotard). Now therapy by derivatives of xanthines has auxiliary value as a method of stopping of attacks at small efficiency, or absence of other groups of drugs.

Drugs of other groups.
Expectorant drugs improve department of a phlegm. They, especially at their use via the nebulizer, reduce viscosity of a phlegm, promote a loosening of mucous traffic jams and delay of their education. For strengthening of effect at a viscous phlegm reception of liquid of 3 — 4 l of liquid a day is recommended. Has effect after reception of expectorant drugs via the nebulizer carrying out a postural drainage, percussion and vibration massage of a thorax. As the main otkharkivayushch of drugs use iodine drugs, гвайфенезин, N-Acetylcysteinum, Ambroxol.
At asthma complication bacterial infections showed use of antibacterial agents, most often it is sinusitis, bronchitis and pneumonia. At children up to 5 years asthma is complicated by a viral infection more often, in these cases antibiotics are not appointed. Aged from 5 up to 30 years there can be mycoplasmal pneumonia, at the same time appoint tetracycline or erythromycin. The most widespread causative agent of pneumonia at persons is more senior than 30 years — Streptococcus pneumoniae against which penicillin and cephalosporins are effective. At suspicion of pneumonia carry surely out microscopy of the smear of a phlegm painted across Gram and its crops.

Allergenspetsifichesky immunotherapy (ASIT).
One of traditional ways of treatment of bronchial asthma influencing its immunological nature. ASIT possesses such therapeutic action which extends to all stages of allergic process and is absent at the known pharmacological drugs. Action of ASIT covers actually immunological phase and leads to switching of an immune response from Th2-type on Th1-type, brakes both early, and late phases of the IgE-mediated allergic reaction, oppresses a cellular picture of an allergic inflammation and nonspecific fabric hyperreactivity. It is carried out to patients from 5 to 50 years at exogenous bronchial asthma. Through certain periods enter subcutaneously allergen, gradually increasing a dose. Duration of carrying out a course — not less than 3 months. The allergenspetsifichesky immunotherapy  with allergens of domestic mites whereas ASIT with allergens of house dust is ineffective is most effective. Simultaneous use no more than 3 types of the allergens entered with an interval not less than 30 minutes is allowed.
Except allergens for treatment of bronchial asthma administrations of hystoglobulin are also used. Within the last decade nasal and sublingual ways of administration of allergens are entered into practice. So far in Russia several types of oral allergens for carrying out ASIT (pollen of trees, mushrooms, mites) are registered.

Use of nebulizers.
At bronchial asthma an important point in implementation of successful therapy is delivery of medicine to the inflammation center in bronchial tubes to achieve this result it is necessary to receive an aerosol of the set dispersion. The special devices called by nebulizers are for this purpose used. The nebulizer redstavlyat itself the inhaler making an aerosol with particles of given size. The general principle of operation of the device consists in creation of a finely divided aerosol of the substance entered into it which at the expense of small particle sizes will get deeply into small bronchial tubes which preferential and suffer from obstruction.
2 types of nebulizers — ultrasonic and compressor are most widespread in Russia. Each of them has both the advantages, and shortcomings.
Ultrasonic, more compact and quiet, are suitable for carrying with themselves, but with their help it is impossible to enter Solutio oleosa and suspensions. Compressor at the expense of the air pump are rather big, they demand a stationary power supply from the alternating current main, due to operation of the same compressor quite noisy, but they have important advantage, with their help it is possible to enter suspensions and Solutio oleosa, and they are about 40 — 50% cheaper than similar ultrasonic models.

Elimination of risk factors.
Elimination of risk factors allows to improve the course of a disease considerably. At patients with allergic asthma first of all allergen elimination matters. There are data that in urban areas at children with atopic bronchial asthma individual complex actions for removal of allergens in houses led to decrease in morbidity bronchial asthma.
Domestic ticks live and breed in various parts of the house therefore their full destruction is impossible. In one of researches it is shown that use of covers for mattresses allowed to reduce a little bronchial hyperreactivity at children. Use of covers, removal of dust and destruction of the centers of dwelling of mites showed reduction of frequency of symptoms in populations of children in orphanages.

Domestic animals. In the presence of a hyperreactivity to hair of animals it is necessary to remove animals from the house, however completely it is impossible to avoid contact with allergens of animals. Allergens get into many places, including into schools, transport and buildings in which never supported animals.

Smoking. Passive smoking increases the frequency and weight of symptoms at children therefore it is necessary to exclude completely smoking in rooms where there are children. In addition to increase in expressiveness of symptoms of asthma and deterioration in function of lungs in the remote period, active smoking is followed by decrease in efficiency of IGKS therefore all smoking patients should advise insistently to leave off smoking.

Flu and other infections. It is necessary to carry out whenever possible annual vaccination against flu. The inactivated influenza vaccines seldom are complicated by side effects and are usually safe at persons with asthma 3 years, even are more senior at asthma which is difficult giving in to treatment. Patients should secure themselves and against other infections (rhinitises, sinusitis), especially in cold season.

Medicines. Use  of aspirin and NPVP is contraindicated to patients with aspirinovy asthma. Reception of β-blockers, especially non-selective is also undesirable.

There is also special gymnastics for patients with bronchial asthma. This method is called Buteyko's method.
Supporters of this method are considered that one of the reasons leading to development and aggravation of symptoms of bronchial asthma is decrease in alveolar ventilation of carbon dioxide. The main objective at treatment of bronchial asthma by means of respiratory gymnastics of Buteyko is gradual increase in percentage of carbon dioxide in air of lungs that allows to reduce hypersecretion for very short term and swelled a mucous membrane of bronchial tubes, to lower the raised tone of unstriated muscles of a wall of bronchial tubes and by that to eliminate clinical displays of a disease. The method includes use of the breathing exercises directed to reduction of an alveolar hyperventilation and/or the dosed exercise stress. During breathing exercises offer the patient by means of various respiratory the technician gradually to reduce breath depth to norm.
Speleoterapiya (Greek speleon — a cave) — a treatment method long stay in conditions of a peculiar microclimate of natural karst caves, grottoes, salt mines, artificially passable excavations of metal, salt and potash mines.
Halotherapy (Greek hals — salt) a treatment method stay in artificially created microclimate of salt caves where the major operating factor is the high-disperse dry salt aerosol (галоаэрозоль). Treatment in salt caves  is widely applied as in the resort, and city medical centers. Aerosols of salts slow down reproduction of microflora of respiratory tracts, preventing development of inflammatory process. Adaptation of an organism to a specific microclimate of a speleochamber is followed by activation of sympaticoadrenal system, strengthening of production of hormones endocrine organs. The quantity of the englobing macrophages and T lymphocytes increases, the content of A, G and E immunoglobulins decreases, lizotsimny activity of blood serum increases. At patients with bronchial asthma the halotherapy promotes lengthening of the period of remission and transition of the patient to lower severity that involves also a possibility of transition to smaller doses and more sparing means of basic medicamentous therapy.

Prevention:

Bronchial  asthma is the disease relating to those which  can be prevented by the timely and correctly planned prevention measures. It should be noted that prevention of asthma is often much more effective than its treatment. For this reason prevention of asthma needs to pay the most close attention.

Proceeding from pathogenetic aspects of development of asthma, methods of prevention of asthma are defined: prevention of development of an allergy and prevention of persistent infections of respiratory tracts. Prevention of asthma is carried out in several steps. In this regard we distinguish primary, secondary and tertiary prevention of bronchial asthma.
Primary prevention of asthma.
Provides measures for the prevention of asthma at healthy people. The main direction of primary prevention of asthma consists in the prevention of development of an allergy and chronic diseases of respiratory tracts (for example, chronic bronchitis). Measures of primary prevention of asthma differ at children and adults a little.

Primary prevention of asthma at children. The most frequent form of asthma at children is atopic asthma which is directly connected with other forms of an allergy. At the same time in development of an allergy in children the main role is played by improper feeding in the first years of life and unfavorable conditions of life. Preventive measures of asthma (and allergies) at children include:
• Breastfeeding of newborns and children of the first year of life. The breastfeeding role as measures of prevention of asthma and others a type of allergic diseases is proved by numerous clinical trials. Breast milk favorably influences development of immune system of an organism and promotes formation of normal intestinal microflora.
• Timely introduction of auxiliary food also is a measure of prevention of asthma and allergy. Modern recommendations about feeding of children of the first year of life provide introduction of auxiliary food not earlier than on the 6th month of the first year of life. At the same time is strictly forbidden to give to children such high-allergenic products as bee honey, chocolate, eggs, nuts, a citrus and so forth.
• An exception of unfavorable conditions in the child's environment. It is shown that the children contacting to tobacco smoke or the irritating chemicals have an allergy much more often and more often get sick with bronchial asthma.
• It is necessary to carry out prevention and early treatment of chronic diseases of respiratory bodies at children -  bronchitis, sinusitis, tonsillitis, adenoides.
Primary prevention of asthma at adults. At adults the most common cause of bronchial asthma as it was already mentioned above, chronic respiratory diseases (such as chronic bronchitis) and long contact with the irritating substances are (tobacco smoke, chemicals on site of work). So methods of prevention of bronchial asthma at adults come down to elimination of the irritating factors and treatment of chronic diseases of respiratory bodies.
Secondary prevention of bronchial asthma.
Secondary prevention of asthma includes measures for prevention of a disease at sensibilized persons or patients at a stage have preasthmas, but not having asthma yet. The category of patients for performing secondary prevention of asthma is selected by the following criteria:
• Persons whose relatives already have bronchial asthma;
• Existence of various allergic diseases (food allergy, atopic dermatitis, allergic rhinitis, eczema and so forth);
• The sensitization proved by means of immunological methods of a research.
For secondary prevention of bronchial asthma at this group of persons preventive treatment is carried out by antiallergic drugs. Also methods on desensitization can be used.
Tertiary prevention of asthma.
Patsiyetam, having bronchial asthma, tertiary prevention is shown. Tertiary prevention of asthma is applied to reduction of weight of a current and the prevention of exacerbations of a disease. The main method of prevention of asthma at this stage consists in an exception of contact of the patient with the allergen causing asthma attack (the eliminative mode).
For high-quality carrying out the eliminative mode it is necessary to know what allergen (or group of allergens) is caused by asthma attacks in the patient. The most widespread allergens are house dust, cockroaches, micromites, wool of domestic animals, mold fungi, some types of food, pollen of plants.
For prevention of contact of an organism of the patient with these allergens it is necessary to follow certain sanitary and hygienic rules:
• Indoors, in which the patient lives it is necessary to carry out regular wet cleaning (1-2 times a week), the patient for the period of cleaning has to leave the room;
• All carpets and upholstered furniture, and also other objects in which dust can collect have to be removed from the room in which lives sick asthma. Also from the room of the patient it is necessary to carry away houseplants;
• Bed clothes of the patient need to be washed every week in hot water (60 ̊С) with laundry soap;
• Use of special covers which do not allow to get dust, for pillows and mattresses;
• Exception of contact with domestic animals;
• It is reasonable to carry out measures for fight against cockroaches and other insects;
• It is necessary to exclude all products causing an allergy from a diet of the patient.
Correctly planned and executed measures for prevention of bronchial asthma are an effective remedy of prevention and treatment of this disease. Modern medical practice show that the correct carrying out measures of prevention of asthma often is enough for treatment of a disease or for considerable reduction of need of the patient for antiasthmatic drugs.