Bronchial asthma: an overview of information

Bronchial asthma is a chronic inflammatory disease of the respiratory tract with the participation of cells (fatty, eosinophils, T-lymphocytes), mediators of allergy and inflammation, accompanied by predisposed persons with hyperreactivity and variable bronchial obstruction, which is manifested by asthma, wheezing, coughing or difficulty breathing, especially night and / or early morning.

Symptoms of bronchial asthma include shortness of breath, a feeling of tightness in the chest and wheezing. The diagnosis is based on anamnesis, physical examination and lung function tests. Treatment of bronchial asthma involves control over trigger factors and drug therapy, usually inhaled beta-agonists and inhaled glucocorticoids. The prognosis is favorable for treatment.

This definition is consistent with the main provisions of the joint report of the National Heart, Lung and Blood Institute (USA) and WHO "Bronchial asthma. The Global Strategy "(1993).

[1], [2], [3], [4], [5]

Epidemiology of bronchial asthma

Since the 1970s, the prevalence of bronchial asthma is continuously increasing, currently it affects about 4-7% of people around the world. Bronchial asthma affects approximately 12% - 17 million people in the US; in the period from 1982 to 1992, the prevalence of bronchial asthma increased from 34.7 to 49.4 per 1000 people. Among people under the age of 18, this indicator is higher (6.1%) than in the 18-64 age group (4.1%), and higher in males before puberty and in women after puberty. Bronchial asthma is also more common among urban residents and among representatives of the Negroid race, as well as some groups of Hispanic origin. The death rate from bronchial asthma has also increased, about 5000 deaths from bronchial asthma are registered annually in the United States. The death rate is 5 times higher among representatives of the Negroid race than among Caucasians. Bronchial asthma is the main cause of hospitalization of children and the most frequent chronic illness leading to missed school in primary school. In 2002, the total cost of treating bronchial asthma was $ 14 billion.

Throughout the world there has been a steady increase in the number of patients with bronchial asthma, which is especially characteristic of economically developed countries.

In the world more than 100 million people suffer from bronchial asthma. The prevalence of bronchial asthma ranges from 3 to 8%. Especially high incidence rates in New Zealand and Australia. In Western Europe, the prevalence of bronchial asthma is 5%.

About 30% of patients with bronchial asthma rarely resort to the use of antiasthmatics, another 30% use them regularly, 20-25% have a severe form of the disease and are forced to resort to several anti-asthmatic drugs, 8-10% suffer from a disabling form of the disease.

[6], [7], [8], [9], [10], [11],

Causes of bronchial asthma

Bronchial asthma is a multifactorial disease, its development depends on the interactions between multiple genetic factors and environmental factors.

Genetic factors responsible for the predisposition to the development of bronchial asthma include the genes of T helper cells type 2 (TN) and their cytokines (IL-4, -5, -9 and -13) and the newly discovered ADAM33 gene that can stimulate smooth musculature of the respiratory tract and proliferation of fibroblasts or regulate the production of cytokines.

The importance of domestic factors (dust mites, cockroaches, domestic animals) and other environmental allergens (pollen) in the development of the disease in older children and adults is proved. Contact with bacterial endotoxin in early childhood can cause the formation of tolerance and protective mechanisms. Air pollution is not directly associated with the development of the disease, although this factor can cause exacerbation of the disease. A diet with a low content of vitamins C and E and fatty omega-3 acids is associated with bronchial asthma, as is obesity. Asthma is also associated with perinatal factors, for example, with young maternal age, poor maternal nutrition, premature birth, low birth weight and artificial feeding. The role of exposure to cigarette smoke in childhood is debatable, in some studies proving a provocative role, in others - a protective effect.

Exposure to nitric oxide and volatile organic compounds is important for the development of a reactive airway dysfunction syndrome (RSDD), a syndrome of persistent reversible airway obstruction in people without an anamnesis of bronchial asthma. Whether the RSDLP is a syndrome or a form of occupational asthma separate from a bronchial asthma is a controversial issue, but both conditions have much similar (eg wheezing, shortness of breath, cough) and respond to glucocorticoids.

[12], [13]

Pathogenesis of bronchial asthma

Genetic factors and environmental factors can interact with each other, determining the balance between T helper type 1 (TH1) and 2 (TH2). According to experts, children are born with a predisposition to proallergic and pro-inflammatory TN immune responses that are characterized by growth and activation of eosinophils and IgE production, but exposure to bacterial and viral infections and endotoxins at an early age shifts the immune system towards TN responses, with suppression of cells TH and tolerance is induced. For developed countries, there are tendencies towards a smaller number of families, fewer children in the family, houses are kept close to ideal cleanliness, children are early started to get vaccinated and treated with antibiotics. All this prevents the exposure of children to environmental factors that suppress immune responses such as TN and form tolerance, which can partly explain the continuous increase in the prevalence of bronchial asthma in developed countries (hygienic hypothesis).

In patients with bronchial asthma these TH cells and other cell types, especially eosinophils and mast cells, but also other subtypes of CD4 + cells and neutrophils form extensive inflammatory infiltrates in the epithelium of the respiratory tract and smooth muscles of the bronchi, leading to desquamation, subepithelial fibrosis and smooth muscle hypertrophy. Hypertrophy of smooth muscles narrows the respiratory tract and increases reactivity to allergens, infections, irritants, parasympathetic excitation (which causes the release of proinflammatory neuropeptides such as substance P, neurokinin A and a peptide associated with the calcitonin gene) and other triggers of bronchoconstriction. An additional contribution to increased airway reactivity is the loss of inhibitors of bronchospasm (secreted by the epithelium relaxing factor, prostaglandin E) and other substances that metabolize endogenous bronchoconstrictors (endopeptidases) due to sloughing of the epithelium and edema of the mucous membrane. The formation of mucus and eosinophilia of peripheral blood are additional classic signs of asthma, which may be secondary manifestations of inflammation of the respiratory tract.

Conventional trigger mechanisms of an attack of bronchial asthma include production factors and environmental allergens; infection (respiratory syncytial virus and parainfluenza virus in young children, ARI and pneumonia in older children and adults); physical stress, especially in cold and dry environments; Inhalation irritants (air pollution) and anxiety, anger and agitation. Aspirin-trigger factor in 30% of patients with older bronchial asthma or with a more severe course of the disease is usually combined with nasal polyposis and congestion in the nasal sinuses. Gastroesophageal reflux disease (GERD) has recently been recognized as a frequent triggering mechanism of bronchial asthma, possibly due to bronchospasm caused by reflux or microaspiration of the acid contents of the stomach. Allergic rhinitis is often combined with bronchial asthma; it is unclear whether these two diseases are different manifestations of the same allergic process, or rhinitis is a separate triggering mechanism of bronchial asthma.

In the presence of triggers, the pathophysiological changes characteristic of bronchial asthma cause reversible obstruction of the airways and uneven pulmonary ventilation. Relative perfusion exceeds the relative ventilation in the obstruction zones, and as a result, the alveolar pressure of O2 decreases and the alveolar voltage of CO2 increases. Most patients can compensate for this condition by hyperventilation, thus supporting Ra-CO2 below normal levels. But with severe exacerbations, diffuse bronchospasm causes severe disruption of gas exchange, the respiratory muscles are not able to create a respiratory effort and provide increased respiratory work. This increases hypoxemia and muscle tension, RaCO2 increases. The result can be respiratory and metabolic acidosis, which, if untreated, can lead to cardiac arrest and respiratory depression.

Depending on the symptoms, bronchial asthma is classified into four categories (in terms of severity): mild intermittent, mild persistent, moderate severity persistent and severe persistent.

Inflammatory process in the bronchi leads to 4 forms of bronchial obstruction:

• acute spasm of smooth muscles of the bronchi;
• subacute swelling of the bronchial mucosa;
• chronic formation of viscous bronchial secretions;
• irreversible sclerotic process in the bronchi.

At the IV National Russian Congress on Respiratory Diseases (Moscow, 1994) the following definition of bronchial asthma was adopted.

Bronchial asthma is an independent disease, which is based on chronic inflammation of the respiratory tract, accompanied by a change in the sensitivity and reactivity of the bronchi and manifested by asthma, asthmatic status or, in the absence of such symptoms, symptoms of respiratory discomfort (paroxysmal cough, distal rales and dyspnea), reversible bronchial obstruction on the background of a hereditary predisposition to allergic diseases outside the pulmonary signs of allergy, eosinophilia of the blood and / or eosin Elijah in the sputum.

Symptoms of bronchial asthma

In the period between exacerbations, patients with mild intermittent or mild persistent bronchial asthma are usually asymptomatic. Patients with more severe course or with exacerbations experience shortness of breath, a feeling of tightness in the chest, audible rales and coughing; cough may be the only symptom in some patients (a cough variant of bronchial asthma). Symptoms can have a circadian rhythm and worsen during sleep, often around 4 am. Many patients with more severe bronchial asthma have nocturnal awakenings (nocturnal asthma).

Symptoms of bronchial asthma include wheezing, a paradoxical pulse (a systolic BP drop> 10 mmHg during inspiration), tachypnea, tachycardia and visible inspiratory effort (using cervical and suprasternal muscles, sitting position vertically, retracted lips, inability speak). The expiratory phase of breathing was prolonged, with an air-to-breath ratio of at least 1: 3. Stridor can be present in both phases or only on exhalation. A patient with severe bronchospasm may not have any audible rales due to a markedly limited flow of air.

A patient with severe exacerbation and threatening respiratory failure usually has some combination of symptoms of altered consciousness, cyanosis, a paradoxical pulse more than 15 mm Hg. , saturation O2 (O2 sat.) less than 90%, PaCO2> 45 mm Hg. Art. (at sea level) and hyperinflation of the lungs. On a roentgenography of a thorax in rare cases pneumothorax or a pneumomediastinum can be found out.

Symptoms of bronchial asthma disappear in the period between acute attacks of bronchial asthma, although mild stridor can be heard during an increased forced expiration, after exercise and at rest in some asymptomatic patients. Increased lungs airiness can change the chest wall in patients with prolonged uncontrolled bronchial asthma, causing the formation of a barrel chest.

All symptoms of bronchial asthma are nonspecific, reversible with timely treatment and usually develop when one or more triggers are applied.

For the correct choice of therapeutic measures for bronchial asthma, the etiological classification of the disease and the severity of bronchial obstruction (the severity of the disease) are of great importance.

The modern etiological classification of bronchial asthma involves the isolation of exogenous, endogenous and mixed forms.

Exogenous (atopic) bronchial asthma is a form of the disease caused by known exogenous (external) etiological fakirs (non-infectious allergens). These factors can be:

• household allergens (home dust - household clicks, ayurgeons of domestic animals, cockroaches, rodents - mice, rats, molds and yeast mushrooms);
• pollen allergens (weeds - timothy, fescue, trees - birch, alder, hazel, etc., weeds - wormwood, swans, ambrosia, etc.);
• medicinal allergens (antibiotics, enzymes, immunoglobulins, serums, vaccines);
• food allergens and food additives;
• professional allergens (dust of wheat flour, flakes of corpuscles and butterfly wings in the silk industry, dust of coffee beans, platinum salts in the metalworking industry, epidermal allergens in animal husbandry).

The main mechanism for the development of this asthma is an immediate-type immune response mediated by specific IgE. This reaction develops due to the interaction of the allergen (antigen) with specific IgE antibodies; fixed mainly on submucous mast cells of the respiratory tract and circulating in the blood basophils. The interaction of antigen with IgE on the surface of these cells leads to their degranulation with the release of biologically active mediators causing bronchospasm, edema of the bronchial mucosa, hypersecretion of mucus and inflammation (histamine, leukotrienes, pro-inflammatory prostaglandins, platelet activating factor, etc.).

Identification of an etiological external factor in patients with exogenous bronchial asthma allows for successful targeted treatment: elimination of allergen or specific desensitization.

Endogenous (non-atopic) bronchial asthma is a form of the disease that is not based on allergic sensitization and is not associated with exposure to a known exogenous allergen. As the etiological factors of bronchial asthma can act:

• metabolic disorders of arachidonic acid ("aspirin" asthma);
• endocrine disorders;
• neuropsychiatric disorders;
• disorders of the receptor balance and electrolyte homeostasis of the respiratory tract;
• exercise stress.

Mixed bronchial asthma is a form of the disease that combines the signs of exogenous (atopic) and endogenous (non-atopic) forms.

Diagnosis of bronchial asthma

The diagnosis of "bronchial asthma" is based on anamnesis and physical examination and is confirmed by lung function tests. It is also important to identify the causes of the disease and exclude diseases that also cause wheezing.

[14], [15], [16], [17], [18],

Lung function tests

Patients suspected of having bronchial asthma should examine lung function to confirm and quantify the severity and reversibility of airway obstruction. The parameters of pulmonary function depend on effort and require careful training of the patient before the test. If possible, the intake of bronchodilators should be suspended before the test: for 6 hours for short-acting beta-agonists such as salbutamol; for 8 hours for ipratropium bromide; for 12-36 h for theophylline; for 24 hours for long-acting beta-agonists, such as salmeterol and formoterol; and for 48 hours for tiotropium.

Spirometry should be performed before and after inhalation of a short-acting bronchodilator. Manifestations of airway obstruction prior to inhalation of the bronchodilator are a reduced volume of forced expiration in the first second (FEV and a decreased ratio of FEV to forced vital capacity of the lungs (FVF / FVC).) The measurement of pulmonary volumes may show an increase in residual volume and / or functional of the residual capacity due to air retention The increase in FEV greater than 12% or more than 0.2 L in response to the bronchodilator confirms reversible obstruction of the airways, although in the absence of this effect, bronchodilators should not be withdrawn.To monitor the course of the disease in patients diagnosed with bronchial asthma, spirometry should be performed at least annually.

Flow-volume loops should also be investigated for the diagnosis or elimination of vocal cord dysfunction, which is a frequent cause of obstruction of the upper respiratory tract, similar to bronchial asthma.

Provocative tests with inhaled methacholine chloride (or with alternative stimuli such as inhaled histamine, adenosine, bradykinin, or physical exertion) for the induction of bronchospasm are prescribed for suspected bronchial asthma with normal spirometry and flow-volume studies, suspicion of a cough variant of bronchial asthma and the absence of contraindications. Contraindications include FEV less than 1L or less than 50%, recent acute myocardial infarction (AMI) or stroke and severe hypertension (systolic BP> 200 mmHg, diastolic BP> 100 mmHg). Decrease in FEV> 20% confirms the diagnosis of bronchial asthma. However, FEV may decrease in response to these drugs and other diseases, such as COPD.

Other tests

In some situations, other tests may be useful.

A study of the diffusivity of carbon monoxide (DLC0) can help distinguish bronchial asthma from COPD. Volumes are normal or elevated in bronchial asthma and are usually reduced in COPD, especially with the development of emphysema.

Chest X-ray can help to exclude the main causes of bronchial asthma or alternative diagnoses such as heart failure or pneumonia. Radiography of the chest in bronchial asthma is usually normal, but can show increased airiness or segmental atelectasis, indicating the bronchial obstruction of mucus. Infiltrates, especially those that arise, then disappear and which are associated with central bronchiectasis, testify to the allergic bronchopulmonary aspergillosis.

Allergic examination is prescribed for all children, whose history presumes allergic triggers (since all children are potentially susceptible to immunotherapy). This study should be considered for adults, whose history indicates a reduction in symptoms when the allergen is stopped, and for those who are considering the option of therapy with anti-1deE antibodies. Skin tests and measurement of allergen-specific IgE by radioallergosorbent testing (PACT) can reveal specific allergic triggers. Elevated blood eosinophil levels (> 400 cells / μL) and nonspecific IgE (> 150 ME) are suspicious, but not diagnostic for allergic asthma, because they can be increased in a variety of conditions.

Sputum analysis for the content of eosinophils is usually not practiced; The detection of a large number of eosinophils is suspicious for bronchial asthma, but the method is neither sensitive nor specific.

Measurement of peak expiratory flow rate (PSV) by inexpensive portable peakflow meters is recommended for home monitoring of disease severity and therapy.

Evaluation of exacerbations

Patients with diagnosed bronchial asthma with exacerbation should perform pulse oximetry and measurement of PSV or FEV. All three indicators determine the severity of the exacerbation and document the response to treatment. PEF values are interpreted in the light of the best individual patient outcomes that can vary widely among patients who equally well control the disease. A decrease of 15-20% from this initial value indicates a significant exacerbation. When the initial values are unknown, the mean values given may in some sense indicate a restriction of the air flow, but not on the degree of deterioration of the patient's condition.

Chest X-ray is not required in most exacerbations, but should be performed in patients with symptoms suspected of pneumonia or pneumothorax.

Indices of arterial blood gases should be obtained in patients with severe respiratory distress syndrome or signs and symptoms of threatening respiratory failure.

[19], [20], [21], [22], [23]

Treatment of bronchial asthma

Treatment of bronchial asthma - both chronic disease and exacerbations - includes control over trigger factors, pharmacotherapy appropriate to the severity of the disease, monitoring the response to treatment and progression of the disease, and educating the patient in order to increase self-control of the disease. The goals of the treatment are to prevent exacerbations and chronic symptoms, including nocturnal awakenings; minimize the need for hospitalizations in the intensive care unit; maintain initial levels of lung function and patient activity and prevent adverse effects of treatment.

Control over trigger factors

Trigger factors can be controlled in some patients using synthetic fiber cushions and impervious mattress covers, frequent washing of bed linen and protective coatings in hot water. Upholstered furniture, soft toys, carpets and pets must be removed (dust mites, animal dander), air dryers must be used in socle and other poorly ventilated, humid rooms (mold). Wet house cleaning reduces the content of dust mite allergens. The fact that it is difficult to control these triggers in an urban environment does not diminish the importance of these measures; elimination of cockroach emissions through house cleaning and extermination of insects is especially important. Vacuum cleaners and filters with high air purification efficiency (HEPA) can reduce symptoms, but their effects on pulmonary function and on the need for drugs are not proven. Sulfite-sensitive patients should avoid consuming red wine. It is also necessary to avoid or if possible control non-allergenic triggers such as cigarette smoke, strong odors, irritating vapors, cold temperatures, high humidity and physical activity. Patients with aspirin-induced bronchial asthma may use paracetamol, choline tri-salicylate, or cyclooxygenase (COX-2) inhibitors instead of non-steroidal anti-inflammatory drugs (NSAIDs). Bronchial asthma is a relative contraindication to the use of nonselective beta-blockers, including drugs for external use, but cardioselective drugs (eg, metoprolol, atenolol) probably do not have any adverse effects.

Of great importance in the treatment of bronchial asthma is the elimination of trigger factors that exacerbate the disease. These include:

• long-term effects of causative factors (allergens or occupational factors) to which the patient's airways are already sensitized;
• exercise stress;
• excessive emotional stress;
• the effect of cold air and weather changes;
• air pollution (tobacco smoke, wood smoke, aerosols, aerosols, etc.);
• respiratory infection;
• some medicinal substances.

[24], [25], [26], [27], [28],

Drug treatment of bronchial asthma

The main classes of drugs commonly used in the treatment of stable bronchial asthma and its exacerbations include bronchodilators beta2-agonists, anticholinergics), glucocorticoids, mast cell stabilizers, leukotriene modifiers and methylxanthines. Preparations of these classes are inhaled or taken perorapno; Inhalation preparations are available in aerosol and powder forms. Using aerosol forms with a spacer or a holding chamber facilitates the flow of drugs into the respiratory tract, and not into the mouth or throat; patients should be trained to wash and dry additional items after each use to prevent bacterial contamination. In addition, the use of aerosol forms requires coordination between inspiration and actuation of the inhaler (drug device) and inhalation; Powder forms reduce the need for coordination, since the drug enters only when the patient inhales. In addition, powder forms reduce the release of fluorocarbon propellants into the environment.

Beta-agonists (beta-adrenergic agents) relax the smooth muscles of the bronchi, suppress the degranulation of mast cells and histamine release, reduce the permeability of capillaries and enhance the purifying capacity of ciliated epithelium, beta-agonists are of short and prolonged action. Beta-agonists of short action (for example, salbutamol) are inhaled 2-8 times as necessary, it is a means of choice for relief of acute bronchospasm and prevention of physical exertion of bronchospasm. Their effect occurs within minutes and lasts up to 6-8 hours, depending on the specific drug. Long-acting drugs that are inhaled before bed or twice a day and whose activity lasts for 12 hours are used for moderate to severe asthma, as well as for mild asthma that causes nocturnal awakenings. Long-acting beta-agonists also act synergistically with inhaled glucocorticoids and allow the use of lower doses of glucocorticoids. Oral beta-agonists have a large number of systemic side effects, and they generally should be avoided. Tachycardia and tremor are the most common acute undesirable effects of inhaled beta-agonists, these effects are dose dependent. Hypokalemia is rare and only mild. The safety of regular long-term use of beta-agonists is controversial; permanent, possibly excessive use is associated with increased lethality, but it is unclear whether this undesirable effect of the drugs or their regular use reflects inadequate control of the disease by other drugs. Acceptance of one or more packages per month assumes inadequate control of the disease and the need to initiate or strengthen another therapy.

Anticholinergic drugs relax the smooth muscles of the bronchi through competitive inhibition of muscarinic (M3) cholinergic receptors. Ipratropium bromide has minimal effect when used in monotherapy with bronchial asthma, but can give an additive effect when combined with short-acting beta-agonists. Adverse effects include dilated pupils, visual impairment, and xerostomia. Tiotropium is an inhaled 24-hour drug that has not been studied well enough for bronchial asthma.

Glucocorticoids inhibit airway inflammation, reverse the inhibition of beta receptor activity, block the synthesis of leukotrienes and inhibit the production of cytokines and the activation of protein adhesins. They block the late response (but not the early response) to inhaled allergens. Glucocorticoids are administered orally, intravenously and by inhalation. With exacerbation of bronchial asthma, early use of systemic glucocorticoids often interrupts exacerbation, reduces the need for hospitalizations, prevents relapses and speeds recovery. Oral and intravenous routes of administration are equally effective. Inhaled glucocorticoids play no role in exacerbation, but are prescribed for prolonged suppression, control and suppression of inflammation and symptoms. They significantly reduce the need for oral glucocorticoids and are considered disease modifying drugs, since they slow or stop the degradation of pulmonary function. Undesirable local effects of inhaled glucocorticoids include dysphonia and oral candidiasis, which can be prevented or minimized when the patient uses the spacer and / or rinses with water after inhalation of the glucocorticoid. All systemic effects are dose-dependent, can occur with oral or inhalation forms and mainly occur with inhalation doses of more than 800 μg / day. Undesirable effects of glucocorticoids are suppression of the pituitary-adrenal axis, osteoporosis, cataracts, skin atrophy, hyperphagia and a slight increase in body weight. It is not known exactly whether inhalation glucocorticoids inhibit growth in children: most children achieve predicted adult growth. Asymptomatic tuberculosis (TB) can be reactivated with systemic use of glucocorticoids.

Mast cell stabilizers inhibit the release of histamine by mast cells, reduce airway hyperreactivity and block early and late reactions to allergens. They are prescribed in the form of prophylactic inhalations to patients with allergic bronchial asthma and bronchial asthma physical effort; but are ineffective after the development of symptoms. Strainers of mast cells are the safest of all anti-asthmatic drugs, but the least effective.

Modifiers of leukotrienes are taken orally and can be used for long-term monitoring and prevention of symptoms in patients with persistent asthma, mild and severe. The main undesirable effect is an increase in the activity of liver enzymes; extremely rare in patients developing clinical syndrome, reminiscent of the syndrome Cherdzhi-Strauss.

Methylxanthines relax the smooth muscles of the bronchi (probably due to non-selective inhibition of phosphodiesterase) and can improve myocardial and diaphragmatic contractility through unknown mechanisms. Methylxanthines probably inhibit the intracellular release of Ca2 +, reduce the permeability of capillaries in the mucosa of the respiratory tract and inhibit the late response to allergens. They reduce infiltration by eosinophils of the bronchial mucosa and T-lymphocytes of the epithelium. Methylxanthines are used for long-term monitoring as a supplement to beta-agonists; Theophylline with sustained release helps in the treatment of nocturnal asthma. Drugs are discontinued because of the large number of unwanted effects and interactions compared to other drugs. Undesirable effects include headache, vomiting, cardiac arrhythmias and convulsions. Methylxanthines have a narrow therapeutic index; a variety of drugs (any drug metabolized using the cytochrome P450 pathway, for example, macrolide antibiotics) and conditions (eg, fever, liver disease, heart failure) alter the metabolism of methylxanthines and their excretion. The levels of theophylline in serum should be periodically monitored and maintained between 5 and 15 μg / ml (28 and 83 μmol / L).

Other drugs are rarely used in certain circumstances. Immunotherapy can be indicated when symptoms are caused by an allergy, as indicated by an anamnesis and confirmed by allergic tests. Immunotherapy is more effective in children than in adults. If the symptoms do not significantly decrease within 24 months, then therapy stops. If symptoms decrease, therapy should last 3 or more years, although the optimal duration is unknown. Sometimes drugs that limit glucocorticoid doses are prescribed to reduce dependence on a large dose of oral glucocorticoids. All of them have significant toxicity. Methotrexate in a low dose (5 to 15 mg per week) can lead to a slight increase in FEV1 and a moderate decrease (3.3 mg / day) of the daily dose of oral glucocorticoid. Gold preparations and cyclosporine are also moderately effective, but toxicity and the need for control limit their use. Omalizumab - antibodies to IgE, created for use in patients with severe allergic bronchial asthma with elevated levels of IgE. The drug reduces the need for oral glucocorticoids and reduces symptoms. The dose is determined by body weight and IgE level according to a special schedule; the drug is administered subcutaneously every 2 weeks. Other drugs for the control of chronic bronchial asthma are inhaled lidocaine, inhaled heparin, colchicine and high doses of intravenous immunoglobulin. The expediency of using these drugs is confirmed by limited data, their effectiveness is not proven; thus, none of them can yet be recommended for clinical use.

[29], [30], [31], [32], [33], [34], [35]

Monitoring of the response to the treatment of bronchial asthma

Peak expiratory flow (PSV), measurement of airflow and airway obstruction help determine the severity of exacerbations of bronchial asthma, documenting the response to treatment and monitoring the trends in the severity of the disease in real-life situations through patient diaries. Home monitoring PSV is especially useful for detecting the progression of the disease and reactions to treatment in patients with moderate and severe persistent bronchial asthma. When bronchial asthma is asymptomatic, one PSV measurement in the morning is sufficient. If the patient's PSV falls below 80% of his personal best score, then control is performed twice a day to assess circadian changes. Circadian changes of more than 20% indicate the instability of the airways and the need to change the therapeutic regimen.

Patient education

The importance of teaching the patient can not be overemphasized. Patients are more successful if they know more about bronchial asthma - what causes an attack, what medications can be used and in what cases, the necessary inhalation technique, how to use a spacer with a DAI and the importance of early use of glucocorticoids in exacerbations. Each patient should have a written plan of action for daily treatment, especially for actions in acute attacks, which are based on the patient's best personal PSV, rather than at medium levels. Such a plan leads to the most qualitative control of bronchial asthma, greatly increasing adherence to therapy. Treatment of exacerbation. The goal of treating asthma exacerbation is to reduce symptoms and restore the patient's best personal PSV. Patients should be trained to independently administer inhalations of salbutamol or a similar beta-agonist of short duration for exacerbation and to measure PSV, if necessary. Patients who feel better after 2-4 breaths from the IDN should use the inhaler 3 times every 20 minutes with separate breaths, and those with PSV levels greater than 80% of the prescribed ones can treat the exacerbation of the home. Patients who do not respond to the drug have severe symptoms or have PSV <80%, should follow the treatment algorithm determined by the doctor, or go to an emergency department for active treatment.

Inhalation bronchodilators beta-agonists and anticholinergics) - the basis for the treatment of bronchial asthma in the emergency department. In adults and older children, salbutamol through DPI with the use of a spacer is as effective as that obtained through a nebulizer. Nebulizer therapy is preferable for younger children due to difficulties in coordinating the DAI and spacer; recent studies indicate that the response to bronchodilator drugs improves when the nabulizer is switched on with the helium-oxygen mixture (heliox), and not only with oxygen. Subcutaneous administration of epinephrine in a 1: 1000 solution or terbutaline is an alternative for children. Terbutaline may be preferable to adrenaline due to a less pronounced cardiovascular effect and a longer duration of action, but it is no longer produced in large quantities and is expensive.  

Subcutaneous administration of beta-agonists is theoretically problematic for adults because of undesirable cardio-stimulating effects. However, clinically evident adverse effects are few, and subcutaneous administration may be useful for patients resistant to maximal inhalation therapy or unable to receive effective nebulization therapy (for example, with severe coughing, weak ventilation, or inability to contact). Nebulizer therapy with ipratropium bromide can be used in conjunction with inhaled salbutamol in patients who do not respond optimally to single salbutamol; some studies confirm the advisability of simultaneous administration of a large dose of beta-agonist and ipratropium bromide as first-line treatment, but there is no evidence of the benefits of continuous beta-agonist inhalation over intermittent. The role of theophylline in treatment is negligible.

Systemic glucocorticoids (prednisolone, methylprednisolone) should be prescribed for all exacerbations except lungs, as they are not required for patients in whom PSV is normalized after 1 or 2 doses of bronchodilator. Intravenous and oral routes of administration are equally effective. Intramuscular methylprednisolone can be administered in the presence of a venous catheter, then the patient can be transferred to oral intake as soon as necessary or at a convenient time. Dose reduction usually begins in 7-10 days and should last 2-3 weeks.

Antibiotics are prescribed only when anamnesis, chest examination or radiography indicates a bacterial infection; most of the infections underlying the exacerbations of bronchial asthma are viral by nature, but in populations of patients, as a result of recent studies, mycoplasmic amyloidias have been detected.

Oxygen therapy is prescribed when patients with exacerbation of asthma have a SaO less than 90% when measured by pulse oximetry or when examining the gas composition of arterial blood; Oxygen therapy is carried out through the nasal cannula or mask with a flow rate or concentration sufficient to correct hypoxemia.

If the cause of exacerbation of bronchial asthma is anxiety, the main thing is to calm the patient and inspire him with confidence. For the use of tranquilizers and morphine, there are relative contraindications, as they are associated with increased mortality and the need for artificial ventilation.

Hospitalization is usually required if the patient's condition does not normalize within 4 hours. The criteria for hospitalization may be different, but the absolute indication is lack of improvement, increasing weakness, recurrence after re-therapy with beta-agonist and a significant decrease in PaO (<50 mmHg. ) or an increase in RACO (> 40 mm Hg), indicating a progression of respiratory failure.

Patients whose condition continues to deteriorate despite intensive therapy are candidates for noninvasive ventilation with positive pressure or, in seriously ill patients and those who do not respond to this method, endotracheal intubation and artificial ventilation. Patients who require intubation respond well to sedation, but muscle relaxants should be avoided because of possible interactions with glucocorticoids that can cause prolonged neuromuscular weakness.

Usually, volumetric cyclical ventilation is used in the assist-control mode, as it provides constant alveolar ventilation with high and variable airway resistance. The device should be tuned to a frequency of 8-14 breaths / min with a high flow rate of inspiration (> 60 l / min - 80 l / min) to prolong exhalation and minimize auto PEEP (positive end-expiratory pressure).

Initial respiratory volumes can be set within 10-12 ml / kg. High peak airway pressures may be generally ignored, since they arise because of high airway resistance and the magnitude of the inspiratory flow and do not reflect the extent of stretching of the lung produced by alveolar pressure. However, if the pressure plateau exceeds 30-35 cm H2O, then the tidal volume should be reduced to 5-7 ml / kg in order to limit the risk of pneumothorax. An exception is the situation where a reduced chest wall response (for example, obesity) or the abdominal cavity (for example, ascites) can make a significant contribution to increased blood pressure. When reduced ventilatory volumes are required, a moderate degree of hypercapnia is allowed, but if the pH of the arterial blood drops below 7.10, a slow infusion of sodium bicarbonate is prescribed to maintain the pH level between 7.20 and 7.25. Once the obstruction of the air flow is reduced and the RASO and pH of the arterial blood are normalized, patients can be quickly removed from ventilation.

It is reported about the effectiveness of other treatments for exacerbations of bronchial asthma, but they are not well understood. Helioks is used to reduce respiratory work and improve ventilation by reducing the turbulent flows characteristic of helium-gas, less dense than O2. Despite the theoretical effects of heliox, studies yield conflicting results on its effectiveness; the lack of a ready-to-use preparation also limits its practical application.

Magnesium sulphate relaxes smooth muscles, but the data on the effectiveness of control of exacerbation of bronchial asthma in the resuscitation departments are contradictory. General anesthesia in patients with asthmatic status causes bronchodilation due to an unclear mechanism, possibly as a result of the direct effect of muscle relaxation in the smooth muscles of the airways or a decrease in the cholinergic tone.

Treatment of chronic bronchial asthma

Adequate use of medicines allows most patients with chronic bronchial asthma to be treated outside emergency and hospital departments. There are many drugs available, their choice and sequence of administration are based on the severity of the disease. "Reducing" therapy - reducing the dose of the drug to the minimum necessary for the control of symptoms - is indicated in bronchial asthma of any severity.

Patients with mild intermittent bronchial asthma do not need drugs on a daily basis. Short-acting beta2-agonists (for example, two inhalations of salbutamol for emergency care) are sufficient to arrest acute symptoms; use them more than twice a week, the use of more than two packs of drugs per year or a weakened reaction to the drug may indicate the need for long-term basic therapy. Regardless of the severity of bronchial asthma, the frequent need for an emergency beta-agonist indicates an unsatisfactory control of bronchial asthma.

Patients with mild persistent asthma (adults and children) should receive anti-inflammatory therapy. Inhaled glucocorticoids in low doses are a method of choice, but some patients can control bronchial asthma with the use of mast cell stabilizers, leukotriene modifiers, or sustained-release theophylline. Short-acting emergency agonists (for example, salbutamol, 2-4 breaths) are used to arrest seizures. Patients who require emergency therapy every day should receive moderate doses of inhaled glucocorticoids or combination therapy.

Patients with moderate persistent bronchial asthma should be treated with inhaled glucocorticoids in a dose that can control bronchial asthma, in combination with long-acting inhaled beta-agonists (formeterol, 2 breaths per day). Long-acting inhaled beta -agonists in the monotherapy regimen are inadequate treatment, but in combination with inhaled glucocorticoids they allow to lower the dose of the latter and are more effective at night symptoms. An alternative to this approach is monotherapy with inhaled glucocorticoids at medium doses or replacing long-acting beta-agonists with leukotriene receptor antagonists or prolonged release theophylline in combination with low or moderate doses of inhaled glucocorticoids. In patients with GERD and moderate bronchial asthma, antireflux treatment can reduce the frequency and dose of drugs needed to control symptoms. In patients with allergic rhinitis and moderate persistent bronchial asthma, nasal glucocorticoids can reduce the incidence of exacerbations of asthma requiring hospitalization.

Patients with severe persistent bronchial asthma are a minority, they require the introduction of several drugs in large doses. The choice includes inhaled glucocorticoids in large doses in combination with long-acting beta-agonists (formoterol) or a combination of an inhaled glucocorticoid, a long-acting beta -agonist and a leukotriene modifier. Short-acting inhaled beta-agonists are prescribed in both cases for emergency relief of symptoms of an attack. Systemic glucocorticoids are assigned to patients who do not adequately respond to these regimens; Dosing in a day helps minimize the undesirable effects associated with daily intake of drugs.

Bronchial asthma of physical effort

To prevent attacks of bronchial asthma, physical effort is usually sufficient inhalation of a short-acting beta agonist or a stabilizer of mast cells before physical exertion. If beta-agonists are ineffective or if the bronchial asthma of physical effort is severe, in most cases the patient has a more severe bronchial asthma than he has, and he needs long-term therapy to control the disease.

[36], [37], [38], [39], [40],

Aspirin bronchial asthma

The main thing for the treatment of aspirin bronchial asthma is to avoid taking NSAIDs. The inhibitors of cyclooxygenase 2 (COX-2), apparently, are not triggers. Modifiers of leukotriene can block the response to NSAIDs. A small group of patients demonstrated successful desensitization in stationary conditions.

[41], [42], [43], [44], [45], [46]

Preparations of the future

A large number of drugs are developed, aimed at specific links of the inflammatory cascade. The possibility of using drugs aimed at IL-4 and IL-13 is being studied.

Bronchial asthma in special groups of people

[47], [48], [49], [50], [51],

Infants, children and adolescents

Bronchial asthma is difficult to diagnose in infants, so cases of hypodiagnosis and inadequate treatment are not uncommon. The empirical use of inhaled bronchodilators and anti-inflammatory drugs can contribute to solving both problems. Drugs can be given through a nebulizer or IDI with a holding chamber with or without a mask to infants and children under 5 years of age who require treatment more than 2 times a week, daily anti-inflammatory therapy with inhaled glucocorticoids (preferably), leukotriene receptor antagonists or cromoglycic acid.

Children over 5 years and teenagers

Children older than 5 years and adolescents with bronchial asthma can be treated the same way as adults, but should strive to maintain physical activity, exercise and exercise. Adequate indicators for lung function tests in adolescents are closer to children's standards. Adolescents and older children should participate in the development of their personal disease control plans and the formulation of therapeutic goals - this significantly improves compliance. The action plan should be known to teachers and school nurses - this guarantees emergency medical care. Cromoglycic acid and nedocromil are often studied in this group of patients, but they are not as effective as inhaled glucocorticoids; long-acting drugs relieve the need to take drugs with them to school.

[52], [53]

Pregnancy and bronchial asthma

About a third of women with bronchial asthma, becoming pregnant, report a decrease in symptoms; a third note the worsening of the course of bronchial asthma (sometimes to a severe degree) and a third do not notice the changes. GERD can be an important component in the development of symptoms of the disease during pregnancy. Control of bronchial asthma during pregnancy should be absolute, as a poorly controlled disease in the mother can lead to increased antenatal mortality, premature delivery and low birth weight. Anti-asthmatic drugs have not shown adverse effects on the embryo, but large, well-controlled studies to prove true safety for the developing fetus have not been carried out.

What is the prognosis of bronchial asthma?

Bronchial asthma is resolved in most children, but approximately 1 in 4 wheeze persists in adulthood, or relapse occurs at an older age. Female sex, smoking, an earlier age of onset, sensitization to house dust mites and airway hyperreactivity are risk factors for persistence and relapse.
 
Approximately 5,000 deaths per year are due to bronchial asthma in the US, most of these cases could be prevented by adequate therapy. Thus, the prognosis is favorable with the availability of necessary drugs and observance of the therapeutic regimen. Death risk factors include the increasing need for oral glucocorticoids before hospitalization, previous hospitalizations for exacerbations, and lower peak flow rates during treatment. Several studies show that the use of inhaled glucocorticoids reduces the incidence of hospitalizations and mortality.

For a long time, the airways in some patients with bronchial asthma undergo permanent structural changes (remodeling), which hinder the return to normal functioning of the lung. Early aggressive use of anti-inflammatory drugs can help prevent this remodeling.