Treatment of bronchial asthma in children

Treatment of bronchial asthma consists of:

• Conducting elimination measures aimed at reducing or eliminating the impact of causative allergens.
• Pharmacotherapy.
• Allergen-specific immunotherapy.
• Education of patients and their families.

Indications for hospitalization for bronchial asthma

• Severe exacerbation:
  • difficulty breathing at rest, forced position, refusal to eat in infants, agitation, drowsiness or confusion, bradycardia or dyspnea (respiratory rate more than 30 per minute);
  • loud wheezing or no wheezing;
  • heart rate (HR) over 120 beats per minute (in infants over 160 beats per minute);
  • PSV less than 60% of predicted or best individual value, even after initial treatment;
  • child exhaustion.
• Absence of a rapid and sustained for at least 3 hours obvious response to a bronchodilator.
• No improvement after initiation of glucocorticosteroid treatment for 2-6 hours.
• Further deterioration of the condition.
• History of life-threatening exacerbations of bronchial asthma or hospitalization in the intensive care unit, intubation due to exacerbation of bronchial asthma.
• Social disadvantage.

Pharmacotherapy for bronchial asthma

There are two large groups of drugs used to treat asthma in children:

• means of basic (supportive, anti-inflammatory) treatment;
• symptomatic.

Basic treatment drugs for bronchial asthma include:

• Drugs with anti-inflammatory and/or prophylactic effect (glucocorticosteroids, antileukotriene drugs, cromones, anti-IgE-peptides);
• long-acting bronchodilators (long-acting beta2-adrenergic agonists, slow-release theophylline preparations).

The highest clinical and pathogenetic efficiency is currently demonstrated with the use of ICS. All drugs of basic anti-inflammatory treatment are taken daily and for a long time. This principle of using anti-inflammatory drugs (basic) allows achieving control over the disease and maintaining it at the proper level. It should be noted that in the territory of the Russian Federation for the basic treatment of asthma in children using combination drugs containing ICS (salmeterol + fluticasone (seretide) and budesonide + formoterol (symbicort)) with a 12-hour break. only a stable dosing regimen is registered. Other schemes are not allowed in children.

Medicines that relieve the symptoms of bronchial asthma:

• inhaled short-acting beta2-adrenergic agonists (the most effective bronchodilators);
• anticholinergic drugs;
• immediate-release theophylline preparations;
• Oral short-acting beta2-adrenergic agonists.

These drugs are also called "first aid" drugs; they are used to eliminate broncho-obstruction and the accompanying acute symptoms (wheezing, chest tightness, cough). This regimen of drug use (i.e. only when there is a need to eliminate the symptoms of asthma that have appeared) is called "on-demand regimen".

Medicines for the treatment of bronchial asthma are administered in various ways: orally, parenterally and by inhalation. The latter is preferable. When choosing an inhalation device, the efficiency of drug delivery, cost/efficiency, ease of use and the patient's age are taken into account. Three types of inhalation devices are used in children: nebulizers, metered-dose aerosol inhalers and powder inhalers.

Delivery systems for bronchial asthma (age priorities)

Means	Recommended age group	Comments
Metered dose inhaler (MDI)	>5 years	It is difficult to coordinate the moment of inhalation and pressing the valve of the canister, especially for children. About 80% of the dose settles in the oropharynx, it is necessary to rinse the mouth after each inhalation
BAI. breath-activated	>5 years	The use of this delivery device is indicated for patients who are unable to coordinate the moment of inhalation and pressing the valve of conventional MDIs. It cannot be used with any of the existing spacers, except for the "optimizer" for this type of inhaler
Powder inhaler	>5 years	With proper technique, inhalation can be more effective than MDI. Rinse mouth after each use to reduce systemic absorption.
Spacer	>4 years <4 years when used Face mask	The use of a spacer reduces the deposition of the drug in the oropharynx, allows the use of MDI with greater efficiency, in the presence of a mask (included with a spacer) it can be used in children under 4 years of age
Nebulizer	<2 years Patients of any age who cannot use a spacer or spacer/facemask	Optimal delivery system for use in specialist and intensive care units, as well as in emergency care, as it requires the least effort from the patient and physician

Anti-inflammatory (basic) drugs for the treatment of bronchial asthma

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Inhaled glucocorticoids and combination products containing them

Currently, inhaled glucocorticosteroids are the most effective drugs for controlling bronchial asthma, so they are recommended for the treatment of persistent bronchial asthma of any severity. In school-age children, maintenance therapy with ICS allows controlling the symptoms of bronchial asthma, reduces the frequency of exacerbations and the number of hospitalizations, improves the quality of life, improves the function of external respiration, reduces bronchial hyperreactivity and reduces bronchoconstriction during physical exertion. The use of ICS in preschool children suffering from bronchial asthma leads to a clinically significant improvement in the condition. including a score for daytime and nighttime cough, wheezing and shortness of breath, physical activity, the use of emergency drugs and the use of health care resources. In children, beclomethasone, fluticasone, budesonide are used. The use of these drugs in low doses is safe: when prescribing higher doses, it is necessary to remember the possibility of side effects. There are low, medium and high doses of drugs used for basic treatment.

Calculated equipotent daily doses of inhaled glucocorticoids

Preparation

Low daily doses, mcg

Average daily doses, mcg

High daily doses, mcg

Doses for children under 12 years of age

Beclomethasone dipropionate 1 '	100-200	>200-400	>400
Budesonide'	100-200	>200-400	>400
Fluticasone	100-200	>200-500	>500

Doses for children over 12 years of age

Beclomethasone dipropionate	200 500	>500-1000	>1000-2000
Budesonide	200-400	>400-800	>800-1600
Fluticasone	100-250	>250-500	>500-1000

ICS are included in combination drugs for the treatment of asthma [salmeterol + fluticasone (seretide) and formoterol + budesonide (symbicort)]. A large number of clinical studies have shown that the combination of long-acting beta2-adrenergic agonists and low-dose ICS is more effective than increasing the dose of the latter. Combined treatment with salmeterol and fluticasone (in one inhaler) promotes better control of bronchial asthma than a long-acting beta2-adrenergic agonist and ICS in separate inhalers. With long-term therapy with salmeterol and fluticasone, almost every second patient can achieve complete control of bronchial asthma (according to a study that included patients aged 12 years and older). Significant improvement in treatment efficacy indicators is noted: PSV, FEV1, frequency of exacerbations, quality of life. In the event that the use of low doses of ICS in children does not allow achieving control over bronchial asthma, it is recommended to switch to the use of a combination drug, which may be a good alternative to increasing the dose of ICS. This was shown in a new prospective multicenter double-blind randomized study in parallel groups lasting 12 weeks, which compared the effectiveness of a combination of salmeterol and fluticasone at a dose of 50/100 mcg 2 times a day and a 2-fold higher dose of fluticasone propionate (200 mcg 2 times a day in 303 children aged 4-11 years with persistent symptoms of bronchial asthma, despite previous treatment with low doses of ICS). It turned out that regular use of a combination of fluticasone / salmeterol (seretide) prevents symptoms and ensures control over asthma as effectively as a twice higher dose of ICS. Seretide treatment is associated with a more pronounced improvement in lung function and a reduction in the need for asthma symptom relief medications with good tolerability: in the Seretide group, the increase in morning PEF was 46% higher, and the number of children with a complete absence of the need for "rescue therapy" was 53% higher than in the Fluticasone Propionate group. The use of a combination of formoterol/budesonide in a single inhaler provides better control of asthma symptoms compared to budesonide alone in patients who previously did not have symptom control with ICS.

Effect of ICS on growth

Uncontrolled or severe asthma slows childhood growth and reduces final adult height. No long-term controlled studies have shown any statistically or clinically significant effect on growth with ICS treatment at a dose of 100-200 mcg/day. Slowing of linear growth is possible with long-term administration of any ICS at a high dose. However, children with asthma receiving ICS achieve normal growth, although sometimes later than other children.

Effect on bone tissue

No studies have shown a statistically significant increase in the risk of bone fractures in children receiving ICS.

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Effect on the hypothalamic-pituitary-adrenal system

Treatment with ICS at a dose of <200 mcg/day (in terms of budesonide) is not associated with any significant suppression of the hypothalamic-pituitary-adrenal system. Clinically significant changes are also usually not characteristic of higher doses.

Oral candidiasis

Clinically evident thrush is rare and is probably related to concomitant antibiotic treatment, high doses of ICS, and high frequency of inhalations. Use of spacers and mouth rinses reduces the incidence of candidiasis.

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Other side effects

With regular basic anti-inflammatory treatment, no increase in the risk of cataracts and tuberculosis was observed.

Leukotriene receptor antagonists

Antileukotrienes provide partial protection against exercise-induced bronchospasm for several hours after administration. Addition of antileukotrienes to treatment when low-dose ICS are ineffective provides moderate clinical improvement, including a statistically significant reduction in the frequency of exacerbations. Clinical efficacy of treatment with antileukotrienes has been demonstrated in children over 5 years of age with all degrees of asthma severity, but these drugs are usually inferior to low-dose ICS. Antileukotrienes (zafirlukast, montelukast) can be used to enhance treatment in children with moderate asthma when the disease is not adequately controlled with low-dose ICS. When leukotriene receptor antagonists are used as monotherapy in patients with severe and moderate asthma, moderate improvements in lung function (in children aged 6 years and older) and asthma control (in children aged 2 years and older) are observed. Zafirlukast has moderate efficacy in relation to respiratory function in children aged 12 years and older with moderate and severe asthma.

Cromones

Cromones have a weak anti-inflammatory effect and are inferior in effectiveness even to low doses of ICS. Cromoglycic acid is less effective than ICS in relation to clinical symptoms, respiratory function, exercise-induced asthma, and airway hyperreactivity. Long-term treatment with cromoglycic acid in bronchial asthma in children does not differ significantly in effectiveness from placebo. Nedocromil prescribed before physical activity reduces the severity and duration of bronchoconstriction caused by it. Nedocromil, like cromoglycic acid, is less effective than ICS. Cromones are contraindicated in exacerbations of bronchial asthma, when intensive therapy with fast-acting bronchodilators is necessary. The role of cromones in the basic treatment of bronchial asthma in children is limited, especially in preschool age, due to the lack of evidence of their effectiveness. A meta-analysis conducted in 2000 did not allow a clear conclusion to be made about the effectiveness of cromoglycic acid as a means of basic treatment of bronchial asthma in children. Drugs of this group are not used for initial therapy of moderate and severe asthma. The use of cromones as a basic treatment is possible in patients with complete control of bronchial asthma symptoms. Cromones should not be combined with long-acting beta2-adrenergic agonists, since the use of these drugs without ICS increases the risk of death from asthma.

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Anti-IgE drugs

Anti-IgE antibodies are a fundamentally new class of drugs currently used to improve control of severe persistent atopic bronchial asthma. Omalizumab, the most studied, first and only drug in this group recommended for use, is approved for the treatment of uncontrolled bronchial asthma in adults and children over 12 years of age in various countries around the world. The high cost of treatment with omalizumab, as well as the need for monthly visits to the doctor for injection of the drug, are justified in patients requiring repeated hospitalizations, emergency medical care, using high doses of inhaled and / or systemic glucocorticoids.

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Long-acting methylxanthines

Theophylline is significantly more effective than placebo in controlling asthma symptoms and improving lung function, even at doses below the usually recommended therapeutic range. However, the use of theophyllines for the treatment of asthma in children is problematic due to the possibility of severe acute (cardiac arrhythmia, death) and delayed (behavioral disturbances, learning problems, etc.) side effects. Therefore, the use of theophyllines is possible only under strict pharmacodynamic control. (Most clinical guidelines for the treatment of asthma in various US states do not allow theophyllines for use in children at all.)

Long-acting beta ₂ -adrenergic agonists

Classification of beta ₂ -adrenergic agonists:

• short-acting, fast-acting (salbutamol);
• long-acting:
• fast-acting (formoterol);
• with a slower onset of action (salmeterol).

Salbutamol is the "gold standard" for relieving asthma symptoms on an "as needed" basis.

Long-acting inhaled beta2-adrenergic agonists

The drugs of this group are effective in maintaining control of bronchial asthma. They are used on a regular basis only in combination with ICS and are prescribed when standard initial doses of the ICS used do not allow achieving control of the disease. The effect of these drugs lasts for 12 hours. Formoterol in the form of inhalations exerts its therapeutic effect (relaxation of the smooth muscles of the bronchi) after 3 minutes, the maximum effect occurs 30-60 minutes after inhalation. Salmeterol begins to act relatively slowly, a significant effect is noted 10-20 minutes after inhalation of a single dose of 50 mcg, and an effect comparable to that of salbutamol occurs after 30 minutes. Due to the slow onset of action, salmeterol should not be prescribed to relieve acute symptoms of bronchial asthma. Since the effect of formoterol develops faster than salmeterol, this allows formoterol to be used not only for prevention, but also for relief of symptoms. However, according to the recommendations of GIN A (2006), long-acting beta2-adrenergic agonists are used only in patients already receiving regular maintenance treatment with ICS.

Children tolerate treatment with long-acting inhaled beta2-adrenergic agonists well, even with prolonged use, and their side effects are comparable to those of short-acting beta2-adrenergic agonists (in the case of their use on demand). Drugs of this group are prescribed only in combination with basic ICS treatment, since monotherapy with long-acting beta2-adrenergic agonists without ICS increases the likelihood of death in patients! Due to conflicting data on the effect on exacerbations of bronchial asthma, these drugs are not the drugs of choice for patients who require two or more maintenance treatments.

Long-acting oral beta2-adrenergic agonists

Drugs in this group include long-acting formulations of salbutamol. These drugs can help control nighttime asthma symptoms. They can be used in addition to ICS if the latter in standard doses do not provide sufficient control of nighttime symptoms. Possible side effects include cardiovascular stimulation, anxiety, and tremor. These drugs are rarely used in pediatric clinical practice.

Anticholinergic drugs

Inhaled anticholinergic drugs are not recommended for long-term use (basic treatment) in children with bronchial asthma.

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Systemic glucocorticoids

Although systemic GCS are effective against bronchial asthma, it is necessary to take into account adverse effects during long-term treatment, such as suppression of the hypothalamic-pituitary-adrenal system, weight gain, steroid diabetes, cataracts, arterial hypertension, growth retardation, immunosuppression, osteoporosis, mental disorders. Given the risk of side effects with long-term use, oral glucocorticoids are used in children with asthma only in the case of severe exacerbations, both against the background of a viral infection and in its absence.

Allergen-specific immunotherapy

Allergen-specific immunotherapy reduces the severity of symptoms and the need for medications, reduces allergen-specific and non-specific bronchial hyperreactivity. Conducted by an allergist.

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Emergency treatment (first aid drugs)

Inhaled beta2-adrenergic agonists of rapid action (short-acting) are the most effective of the existing bronchodilators, they are the drugs of choice for the treatment of acute bronchospasm. This group of drugs includes salbutamol, fenoterol and terbutaline.

Anticholinergics have a limited role in the treatment of asthma in children. A meta-analysis of studies of ipratropium bromide in combination with beta2-adrenergic agonists in acute asthma found that the use of an anticholinergic drug was associated with statistically significant, albeit modest, improvements in lung function and a reduction in the risk of hospitalization.

Emergency medications for asthma

Preparation	Dose	Side effects	Comments
Beta2-agonists
Salbutamol (MDI)	1 dose - 100 mcg; 1-2 inhalations up to 4 times a day	Tachycardia, tremor, headache, irritability	Recommended only in "on-demand mode"
Salbutamol (nebulizer)	2.5 mg/2.5 ml
Fenoterol (DAI)	1 dose - 100 mcg; 1-2 inhalations up to 4 times a day
Fenoterol (solution for nebulizer treatment)	1 mg/ml
Anticholinergic drugs
Ipratropium bromide (MAI) from 4 years	1 dose - 20 mcg; 2-3 inhalations up to 4 times a day	Minor dryness and unpleasant taste in the mouth	Mainly used in children under 2 years of age
Ipratropium bromide (solution for nebulizer treatment) from birth	250 mcg/ml
Combination drugs
Fenoterol + ipratropium bromide (MDI)	2 inhalations up to 4 times a day	Tachycardia, skeletal muscle tremor, headache, irritability, slight dryness and unpleasant taste in the mouth	Side effects are characteristic and are listed for each of the drugs included in the combination.
Fenoterol + ipratropium bromide (solution for nebulizer treatment)	1-2 ml
Short-acting theophylline
Aminophylline (euphyllin) in any dosage form	150 mg; >3 years at 12-24 mg/kg per day	Nausea, vomiting, headache, tachycardia, cardiac arrhythmia	Currently, the use of aminophylline to relieve asthma symptoms in children is not justified.

Assessment of the level of control of bronchial asthma

Evaluation of each patient's condition includes determining the extent of current treatment, the degree of compliance with the doctor's recommendations, and the level of asthma control.

Asthma control is a complex concept that includes, according to GINA recommendations, a combination of the following indicators:

• minimal or no (less than 2 episodes per week) daytime asthma symptoms;
• no restrictions in daily activities and physical exercise;
• absence of night symptoms and awakenings due to bronchial asthma;
• minimal or no need (less than 2 episodes per week) for short-acting bronchodilators;
• normal or nearly normal lung function tests;
• absence of exacerbations of bronchial asthma.

According to GINA (2006), three levels are distinguished: controlled, partially controlled and uncontrolled bronchial asthma.

Currently, several tools for integrated assessment have been developed. One of them is the Childhood Asthma Control Test, a validated questionnaire that allows the doctor and patient (parent) to quickly assess the severity of bronchial asthma manifestations and the need to increase the volume of treatment.

The available literature data on the treatment of bronchial asthma in children aged 5 years and younger do not allow detailed recommendations to be made. ICS are the drugs with the best confirmed effects in this age group; low doses of ICS are recommended at the second stage as means of initial maintenance treatment.

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Treatment of bronchial asthma aimed at maintaining control

The choice of drug therapy depends on the current level of asthma control and current therapy. Thus, if the treatment does not provide control over bronchial asthma, it is necessary to increase the volume of therapy (move to a higher level) until control is achieved. If it is maintained for 3 months or more, it is possible to reduce the volume of maintenance therapy in order to achieve the minimum volume and the lowest doses of drugs sufficient to maintain control. If partial control over bronchial asthma is achieved, it is necessary to consider the possibility of increasing the volume of treatment taking into account more effective approaches to therapy (i.e. the possibility of increasing doses or adding other drugs), their safety, cost and patient satisfaction with the achieved level of control.

Steps of treatment aimed at achieving control of bronchial asthma (based on the GINA guidelines, 2006)

Most medications used in asthma have a fairly favourable benefit/risk ratio compared with medications used to treat other chronic diseases. Each step includes treatment options that may serve as alternatives when choosing maintenance treatment for asthma, although they are not equally effective. The extent of treatment increases from step 2 to step 5; however, at step 5, the choice of treatment also depends on the availability and safety of medications. Most patients with symptomatic persistent asthma who have not previously received maintenance treatment should begin treatment at step 2. If the clinical manifestations of asthma at initial evaluation are severe and indicate lack of control, treatment should be started at step 3.

Correspondence of treatment steps to clinical characteristics of bronchial asthma

Treatment steps	Clinical characteristics of patients
Step 1	Short-term (up to several hours) symptoms of bronchial asthma during the day (cough, wheezing, shortness of breath, occurring <2 times a week) or its rarer nighttime symptoms. During the interictal period, there are no manifestations of asthma or night awakenings; lung function is within normal limits. PSV <80% of predicted values
Step 2	Symptoms of bronchial asthma more than once a week, but less than once every 8 days. Exacerbations can disrupt patients' activity and nighttime sleep. Night symptoms more than 2 times a month. Functional indicators of external respiration are within the age norm. During the inter-attack period, there are no symptoms of bronchial asthma or night awakenings, and tolerance to physical activity is not reduced. PSV >80% of expected values
Step 3	Symptoms of bronchial asthma are noted daily. Exacerbations disrupt the child's physical activity and nighttime sleep. Night symptoms more than once a week. In the interictal period, episodic symptoms are observed, and changes in the function of external respiration persist. Exercise tolerance may be reduced. PSV 60-80% of the required values
Step 4	Frequent (several times a week or daily, several times a day) occurrence of bronchial asthma symptoms, frequent nighttime attacks of suffocation. Frequent exacerbations of the disease (once every 1-2 months). Limitation of physical activity and severe impairment of external respiratory function. During the period of remission, clinical and functional manifestations of bronchial obstruction persist. PSV <60% of predicted values
Step 5	Daily daytime and nighttime symptoms, several times a day. Severe limitation of physical activity. Severe impairment of lung function. Frequent exacerbations (once a month or more often). During the period of remission, pronounced clinical and functional manifestations of bronchial obstruction persist. PSV <60% of predicted values

At each stage of treatment, patients should use drugs to quickly relieve asthma symptoms (quick-acting bronchodilators).

However, their regular use is one of the signs of uncontrolled bronchial asthma, indicating the need to increase the volume of maintenance treatment. That is why reducing or eliminating the need for emergency therapy drugs is an important goal and criterion for the effectiveness of treatment.

Step 1 - use of as-needed relievers is only for patients who have not received maintenance treatment. In case of more frequent symptoms or episodic worsening of the condition, patients are indicated for regular maintenance therapy (see Step 2 or above) in addition to as-needed relievers.

Steps 2–5 include a combination of an as-needed reliever with regular maintenance therapy. Low-dose ICS is recommended as initial maintenance therapy for asthma in patients of any age at Step 2. Alternative agents include inhaled anticholinergics, short-acting oral beta2-agonists, or short-acting theophylline. However, these agents have a slower onset of action and a higher incidence of side effects.

Step 3 involves a combination of a low-dose ICS with a long-acting inhaled beta2-agonist as a fixed-dose combination. Because of the additive effect of the combination therapy, patients usually require low doses of ICS; an increase in the ICS dose is only necessary in patients whose asthma has not been controlled after 3–4 months of treatment. The long-acting beta2-agonist formoterol, which has a rapid onset of action when used alone or in a fixed-dose combination with budesonide, has been shown to be at least as effective as short-acting beta2-agonists in relieving acute asthma. However, monotherapy with formoterol is not recommended for symptom relief, and this drug is always used in combination with an ICS. In all children, especially those aged 5 years and younger, combination therapy has been studied to a lesser extent than in adults. However, a recent study showed that adding a long-acting beta2-agonist is more effective than increasing the ICS dose. A second treatment option is to increase the ICS dose to medium doses. For patients of any age receiving medium or high doses of ICS via a metered-dose inhaler, a spacer is recommended to improve delivery of the drug to the airways, reduce the risk of oropharyngeal side effects, and reduce systemic absorption of the drug. Another alternative treatment option at step 3 is a combination of a low-dose ICS with an antileukotriene drug, which can be replaced by a low dose of sustained-release theophylline. These treatment options have not been studied in children aged 5 years and younger.

The choice of drugs at Step 4 depends on the previous prescriptions at Steps 2 and 3. However, the order of addition of additional drugs should be based on evidence of their comparative effectiveness obtained in clinical trials. Whenever possible, patients whose asthma is not controlled at Step 3 should be referred to a specialist to exclude alternative diagnoses and/or difficult-to-treat asthma. The preferred treatment approach at Step 4 is a combination of medium- to high-dose glucocorticoids with a long-acting inhaled beta2-agonist. Long-term use of high-dose ICS is associated with an increased risk of side effects.

Step 5 treatment is necessary for patients who have not responded to high-dose ICS in combination with long-acting beta2-agonists and other maintenance therapy. The addition of an oral glucocorticoid to other maintenance therapy may increase the response, but is associated with severe adverse events. The patient should be advised of the risk of adverse events, and all other asthma treatment alternatives should be considered.

If control over bronchial asthma is achieved with the basic treatment of a combination of ICS and a long-acting beta2-adrenergic agonist and is maintained for at least 3 months, a gradual reduction in its volume is possible. It should begin with a reduction in the ICS dose by no more than 50% over 3 months while continuing treatment with a long-acting beta2-adrenergic agonist. If complete control is maintained while using low doses of ICS and long-acting beta2-agonists twice daily, the latter should be discontinued and the use of ICS should be continued. Achieving control with cromones does not require a reduction in their dose.

Another scheme for reducing the volume of basic treatment in patients receiving long-acting beta2-agonists and ICS involves discontinuing the former at the first stage while continuing monotherapy with glucocorticoid at the dose that was in the fixed combination. Subsequently, the amount of ICS is gradually reduced by no more than 50% over 3 months, provided that complete control over bronchial asthma is maintained.

Monotherapy with long-acting beta2-agonists without ICS is unacceptable, as it may increase the risk of death in patients with bronchial asthma. Maintenance treatment is discontinued if complete control of bronchial asthma is maintained with the use of the minimum dose of anti-inflammatory drug and there is no recurrence of symptoms for 1 year.

When reducing the volume of anti-inflammatory treatment, it is necessary to take into account the spectrum of patients' sensitivity to allergens. For example, before the flowering season, patients with bronchial asthma and pollen sensitization should not categorically reduce the doses of basic agents used; on the contrary, the volume of treatment for this period should be increased.

Escalation of treatment in response to loss of asthma control

The volume of treatment in case of loss of asthma control (increase in the frequency and severity of asthma symptoms, need for inhalation of beta2-adrenergic agonists for 1-2 days, decrease in peak flowmetry values or worsening of exercise tolerance) should be increased. The volume of asthma treatment is adjusted for 1 year in accordance with the spectrum of sensitization by causative allergens. To relieve acute bronchial obstruction in patients with bronchial asthma, a combination of bronchodilators (beta2-adrenergic agonists, anticholinergics, methylxanthines) and glucocorticoids is used. Preference is given to inhalation forms of delivery, which allow achieving a rapid effect with minimal overall impact on the child's body.

Current recommendations for reducing the doses of various drugs of the basic treatment may have a fairly high level of evidence (mainly B), but they are based on data from studies that assessed only clinical parameters (symptoms, FEV1), without determining the effect of reduced treatment volume on inflammatory activity and structural changes in asthma. Thus, recommendations for reducing the volume of therapy require further studies aimed at assessing the processes underlying the disease, and not just clinical manifestations.

The need for long-term maintenance combination therapy for bronchial asthma has been confirmed in a study evaluating the efficacy of various pharmacological regimens. A randomized, double-blind study was conducted during the first year, followed by an open trial for the next 2 years, as close as possible to routine clinical practice. Patients receiving salmeterol + fluticasone (seretide, 50/250 mcg 2 times a day) had a 3-fold lower need to increase the volume of treatment than patients using fluticasone propionate (250 mcg 2 times a day) and salmeterol (50 mcg 2 times a day) regimens. The use of combination therapy in comparison led to a significant decrease in the frequency of asthma exacerbations, improved bronchial patency, and decreased bronchial hyperreactivity compared to patients who received each of the drugs separately. After 3 years, complete asthma control was achieved in 71% of patients treated with seretide and in 46% of those receiving fluticasone propionate. Good tolerability of the studied drugs was established in all observations. This study, using adult patients as an example, shows for the first time that achievement of bronchial asthma control in most patients with long-term treatment with seretide is possible.

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Management of patients aimed at achieving control of bronchial asthma

The goal of asthma treatment is to achieve and maintain control of the clinical manifestations of the disease. With medication therapy developed by the physician in collaboration with the patient and family members, this goal can be achieved in most patients. Depending on the current level of control, each patient is prescribed treatment corresponding to one of five "steps of therapy"; during this process, it is constantly assessed and adjusted based on changes in the level of asthma control.

The entire treatment cycle includes:

• assessment of the level of control of bronchial asthma;
• treatment aimed at achieving it;
• treatment to maintain control.

Patient education

Education is a necessary and important part of a comprehensive treatment program for children with asthma, which involves establishing a partnership between the patient, his/her family and the healthcare professional. Good mutual understanding is very important as a basis for further compliance.

Objectives of educational programs:

• informing about the need for elimination measures;
• training in the technique of using medicinal products;
• information on the basics of pharmacotherapy;
• training in monitoring disease symptoms, peak flowmetry (for children over 5 years old), and keeping a self-monitoring diary;
• drawing up an individual action plan in case of exacerbation.

Prognosis for bronchial asthma

In children with recurrent wheezing episodes associated with acute viral infection, no atopic features, and no family history of atopic diseases, symptoms usually resolve by preschool age and asthma does not develop later, although minimal changes in lung function and bronchial hyperreactivity may persist. If wheezing occurs at an early age (before 2 years) in the absence of other symptoms of familial atopy, the likelihood that it will persist into later life is low. In young children with frequent wheezing episodes, a family history of asthma, and manifestations of atopy, the risk of developing asthma at age 6 years is significantly increased. Male gender is a risk factor for the development of asthma in the prepubertal period, but there is a high probability that asthma will disappear by adulthood. Female gender is a risk factor for persistent bronchial asthma in adulthood.