Chronic obstructive bronchitis: treatment

With such a disease as chronic obstructive bronchitis treatment is meant long-term and symptomatic. Because the chronic obstruction of the lungs is inherent in smokers with many years of experience, as well as people engaged in harmful industries with an increased content of dust in the inspired air, the main goal of treatment is to stop the negative impact on the lungs.

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

Chronic obstructive bronchitis: treatment with modern means

Treatment of chronic obstructive bronchitis in most cases is an extremely difficult task. First of all, this is explained by the main regularity of the development of the disease - the steady progression of bronchial obstruction and respiratory failure due to the inflammatory process and hyperreactivity of the bronchi and the development of persistent irreversible violations of bronchial patency caused by the formation of obstructive pulmonary emphysema. In addition, the low effectiveness of treatment of chronic obstructive bronchitis is due to their late referral to the doctor, when there are already signs of respiratory failure and irreversible changes in the lungs.

Nevertheless, modern adequate complex treatment of chronic obstructive bronchitis in many cases allows to reduce the rate of progression of the disease leading to an increase in bronchial obstruction and respiratory failure to reduce the frequency and duration of exacerbations, increase work capacity and tolerance to physical activity.

Treatment of chronic obstructive bronchitis includes:

• non-pharmacological treatment of chronic obstructive bronchitis;
• use of bronchodilators;
• the appointment of mukoregulatory therapy;
• correction of respiratory failure;
• anti-infective therapy (with exacerbations of the disease);
• anti-inflammatory therapy.

Most patients with COPD should be treated on an outpatient basis, according to an individual program developed by the attending physician.

Indications for hospitalization are:

1. Exacerbation of COPD, not controlled in outpatient settings, despite the course (persistence of fever, cough, separation of purulent sputum, signs of intoxication, increasing respiratory insufficiency, etc.).
2. Acute respiratory failure.
3. Increased arterial hypoxemia and hypercapnia in patients with chronic respiratory failure.
4. The development of pneumonia in COPD.
5. The appearance or progression of signs of heart failure in patients with chronic pulmonary heart disease.
6. The need for relatively complex diagnostic manipulations (for example, bronchoscopy).
7. The need for surgical interventions with the use of anesthesia.

The main role in recovery belongs undoubtedly to the patient himself. First and foremost, it is necessary to abandon the pernicious habit of cigarettes. The irritating effect that nicotine exerts on the lung tissue will nullify all attempts to "unblock" the work of the bronchi, improve blood circulation in the respiratory organs and their tissues, remove the coughing spells and bring the breath into a normal state.

Modern medicine suggests combining two treatment options - basic and symptomatic. The basis of the basic treatment of chronic obstructive bronchitis are such drugs that relieve irritation and stagnation in the lungs, facilitate the passage of sputum, expand the lumen of the bronchi and improve blood circulation in them. This includes xanthine series preparations, corticosteroids.

At the stage of symptomatic treatment, mucolytics are used, as the main means for fighting cough and antibiotics, in order to exclude the attachment of secondary infection and the development of complications.

Periodic physiotherapy and therapeutic exercises for the chest area are shown, which greatly facilitates the outflow of viscous sputum and ventilation of the lungs.

[5], [6], [7],

Chronic obstructive bronchitis - treatment with non-pharmacological methods

The complex of non-medicinal treatment measures in patients with COPD includes unconditional cessation of smoking and, if possible, elimination of other external causes of the disease (including exposure to household and industrial pollutants, repeated respiratory viral infections, etc.). Of great importance are the sanation of foci of infection, primarily in the oral cavity, and the restoration of nasal breathing, etc. In most cases, a few months after stopping smoking, the clinical manifestations of chronic obstructive bronchitis (cough, sputum and dyspnea) decrease and the rates of FEV1 and other respiratory function indicators slow.

The diet of patients with chronic bronchitis should be balanced and contain a sufficient amount of protein, vitamins and minerals. Particular importance is attached to the additional intake of antioxidants, for example tocopherol (vitamin E) and ascorbic acid (vitamin C).

Nutrition in patients with chronic obstructive bronchitis should also include an increased amount of polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic) contained in marine products and possessing a peculiar anti-inflammatory effect due to a decrease in the metabolism of arachidonic acid.

With respiratory insufficiency and violations of the acid-base state, a hypocaloric diet and a restriction of the intake of simple carbohydrates, increasing due to their accelerated metabolism, the formation of carbon dioxide, and correspondingly, reducing the sensitivity of the respiratory center, are advisable. According to some data, the use of a hypocaloric diet in severe COPD patients with signs of respiratory failure and chronic hypercapnia is comparable in effectiveness to the results of long-term low-flow oxygen therapy in these patients.

[8], [9]

Medication for chronic obstructive bronchitis

Bronchodilators

The tone of the smooth musculature of the bronchi is regulated by several neurohumoral mechanisms. In particular, the dilatation of the bronchi develops with stimulation:

1. beta2-adrenoceptors with epinephrine and
2. VIP receptors of the NASH (non-adrenergic, noncholinergic nervous system) vasoactive intestinal polypeptide (VIP).

Conversely, the narrowing of the lumen of the bronchi arises with stimulation:

1. M-cholinergic receptors with acetylcholine,
2. receptors to P-substance (NANH-system)
3. alpha-adrenergic receptors.

In addition, numerous biologically active substances, including inflammatory mediators (histamine, bradykinin, leukotrienes, prostaglandins, platelet activating factor - FAT, serotonin, adenosine, etc.) also exert a pronounced effect on the tone of the smooth muscles of the bronchi, reducing the clearance of the bronchi.

Thus, the bronchodilation effect can be achieved in several ways, at which the blockade of M-cholinergic receptors and stimulation of beta2-adrenergic receptors of the bronchi are currently most widely used. In accordance with this, M-holinolytics and beta2-agonists (sympathomimetics) are used in the treatment of chronic obstructive bronchitis. The third group of bronchodilator drugs that are used in patients with COPD include methylxanthine derivatives, the mechanism of their action on the smooth muscles of the bronchi is more complicated

According to modern ideas, the systematic use of bronchodilators is the basis of basic therapy in patients with chronic obstructive bronchitis and COPD. Such treatment of chronic obstructive bronchitis is the more effective the more. The reversible component of bronchial obstruction is expressed. True, the use of bronchodilators in COPD patients for obvious reasons has a significantly lower positive effect than in patients with bronchial asthma, since the most important pathogenetic mechanism of COPD is the progressive irreversible airway obstruction caused by the formation of emphysema in them. At the same time, it should be borne in mind that some of the modern bronchodilator preparations have a fairly wide range of action. They contribute to reducing the edema of the bronchial mucosa, the normalization of mucociliary transport, reducing the production of bronchial secretions and inflammatory mediators.

It should be emphasized that often in patients with COPD described above functional tests with bronchodilators are negative, since the increase in FEV1 after single application of M-holinolitikov and even beta2-sympathomimetics is less than 15% of the proper value. However, this does not mean that it is necessary to refuse from the treatment of chronic obstructive bronchitis with bronchodilators, since the positive effect of their systematic use usually comes not earlier than 2-3 months after the start of treatment.

Inhalation of bronchodilators

It is preferable to use inhalation forms of bronchodilators, since such a way of administration of drugs promotes faster penetration of drugs into the mucosa of the respiratory tract and long-term preservation of a sufficiently high local concentration of drugs. The latter effect is provided, in particular, by repeated entry into the lungs of medicinal substances absorbed through the mucous membrane of the bronchi into the blood and entering the bronchial veins and lymphatic vessels in the right heart, and thence again into the lungs

An important advantage of the inhalation route of bronchodilator administration is the selective effect on the bronchi and a significant limitation of the risk of developing side effects of the system.

Inhalation administration of bronchodilators is provided by the use of powder inhalers, spacers, nebulizers, etc. When using a metered inhaler, the patient needs certain skills in order to ensure a more complete ingestion of the drug into the airways. To do this, after a smooth calm exhalation, the mouthpiece of the inhaler is tightly wrapped around the lips and starts to inhale slowly and deeply, press the balloon once and continue to take a deep breath. After that they hold their breath for 10 seconds. If two doses (inhalations) of the inhaler are prescribed, you should wait at least 30-60 seconds, then repeat the procedure.

In patients of senile age, who find it difficult to master fully the habits of using a metered inhaler, it is convenient to use so-called spacers in which the aerosol drug is sprayed in a special plastic flask just before the inhalation by pressing the can. In this case, the patient takes a deep breath, holds his breath, exhales into the mouthpiece of the spacer, then again takes a deep breath, no longer pressing the can.

The most effective is the use of compressor and ultrasonic nebulizers (from lat .: nebula - fog), in which liquid medication is dispensed in the form of fine aerosols, in which the drug is contained in the form of particles with a size of 1 to 5 microns. This makes it possible to significantly reduce the loss of medicinal aerosol that does not enter the respiratory tract, and also provide a significant penetration depth of the aerosol into the lungs, including medium and even small bronchi, whereas with conventional inhalers such penetration is limited to proximal bronchi and trachea.

The advantages of inhalation of drugs through nebulizers are:

• the penetration depth of the medicinal fine aerosol into the respiratory tract, including medium and even small bronchi;
• simplicity and convenience of inhalation;
• lack of coordination of inspiration with inhalation;
• the possibility of introducing high doses of medicines, which makes it possible to use nebulizers for relief of the most severe clinical symptoms (pronounced dyspnea, attack of suffocation, etc.);
• the possibility of incorporating nebulizers into the ventilator circuit and oxygen therapy systems.

In this regard, the introduction of drugs through nebulizers is used primarily in patients with severe obstructive syndrome, progressive respiratory insufficiency, in elderly and senile patients and so-called. Through nebulizers, it is possible to inject into the respiratory tract not only bronchodilators, but also mucolytic agents.

Anticholinergic drugs (M-cholinolytics)

Currently, M-holinolitiki are regarded as the first choice drugs in COPD patients, since the leading pathogenetic mechanism of the reversible component of bronchial obstruction in this disease is cholinergic bronchoconstriction. It is shown that in patients with COPD holinolitiki on the strength of bronchodilator action are not inferior to beta2-adrenomimetics and exceed theophylline.

The effect of these bronchodilators is associated with competitive inhibition of acetylcholine on the receptors of postsynaptic membranes of the smooth muscles of the bronchi, mucous glands and mast cells. As is known, excessive stimulation of cholinergic receptors not only leads to an increase in the tone of smooth muscles and an increase in the secretion of bronchial mucus, but also to the degranulation of mast cells, leading to the release of a large number of inflammatory mediators, which ultimately enhances the inflammatory process and the hyperreactivity of the bronchi. Thus, cholinolytics inhibit the reflex response of smooth muscles and mucous glands, caused by activation of the vagus nerve. Therefore, their effect manifests itself both with the use of the drug before the onset of the action of the irritating factors and with the already developed process.

It should also be remembered that the positive effect of cholinolytics is primarily manifested at the level of the trachea and large bronchi, since it is here that there is a maximum density of cholinergic receptors.

[10], [11], [12]

Remember:

1. Cholinolytics serve as first choice drugs in the treatment of chronic obstructive bronchitis, since parasympathetic tone in this disease is the only reversible component of bronchial obstruction.
2. The positive effect of M-cholinolytics is:
   1. in reducing the tone of the smooth muscles of the bronchi,
   2. decrease the secretion of bronchial mucus and
   3. reducing the degranulation of mast cells and limiting the release of inflammatory mediators.
3. The positive effect of anticholinergics is primarily manifested at the level of the trachea and large bronchi

In COPD patients, inhalation forms of anticholinergics are usually used - so-called quaternary ammonium compounds, which penetrate poorly through the mucous membrane of the respiratory tract and practically do not cause systemic side effects. The most common of these are ipratropium bromide (atrovent), oxytropium bromide, ipratropium iodide, tiotropium bromide, which is used primarily in metered aerosols.

The bronchodilating effect begins 5-10 minutes after inhalation, reaching a maximum in about 1-2 hours. The duration of action of ipratropium iodide is 5-6 hours, ipratropium bromide (atrovent) 6-8 hours, oxytropium bromide 8-10 h and tiotropium bromide - 10-12 hours.

Side effects

Among the undesirable side effects of M-holinoblokatorov include dry mouth, sore throat, cough. Systemic side effects of blockade of M-cholinergic receptors, including cardiotoxic effects on the cardiovascular system, are practically absent.

Ipratropium bromide (atrovent) is available in the form of a dosed aerosol. Assign 2 inhalations (40 mcg) 3-4 times a day. Inhalation of atrovent even by short courses significantly improves bronchial patency. Especially effective in COPD is the long-term use of atrovent, which reliably reduces the number of exacerbations of chronic bronchitis, significantly improves oxygen saturation (SaO2) in arterial blood, normalizes sleep in COPD patients.

In COPD of mild severity, the course of administration of inhalations of Atrovent or other M-cholinolithicone is acceptable, usually during periods of exacerbation of the disease, the duration of the course should not be less than 3 weeks. With COPD of moderate to severe severity, anticholinergics are used continuously. It is important that with prolonged therapy, the patient does not experience tolerance to taking the drug and tachyphylaxis.

Contraindications

M-holinoblokatory are contraindicated in glaucoma. Care should be taken when they are prescribed for patients with prostate adenoma

[13], [14], [15],

Selective beta2-adrenomimetics

Beta-2 adrenomimetics are rightly considered to be the most effective bronchodilators, which are now widely used for the treatment of chronic obstructive bronchitis. We are talking about selective sympathomimetics, which selectively exert a stimulating effect on beta2-adrenoreceptors of the bronchi and almost do not affect beta 1-adrenergic receptors and alpha receptors, only a small number present in the bronchi.

Alpha-adrenergic receptors are mainly determined in the smooth muscles of blood vessels, in the myocardium, CNS, spleen, platelets, liver and adipose tissue. In the lungs, a comparatively small number of them is located mainly in the distal parts of the respiratory tract. Stimulation of alpha-adrenergic receptors, in addition to pronounced reactions from the cardiovascular system, central nervous system and platelets, leads to an increase in the tone of the smooth muscles of the bronchi, increased secretion of mucus in the bronchi and the release of histamine mast cells.

Beta-1 adrenergic receptors are widely represented in the myocardium of the atria and ventricles of the heart, in the conduction system of the heart, in the liver, in muscle and adipose tissue, in the blood vessels and almost absent in the bronchi. Stimulation of these receptors leads to a pronounced reaction from the cardiovascular system in the form of positive inotropic, chronotropic and dromotropic effects in the absence of any local response from the respiratory tract.

Finally, beta2-adrenergic receptors are found in the smooth muscles of vessels, uterus, adipose tissue, as well as in the trachea and bronchi. It should be emphasized that the density of beta2-adrenergic receptors in the bronchial tree significantly exceeds the density of all distal adrenoreceptors. Stimulation of beta2-adrenergic receptors with catecholamines is accompanied by:

• relaxation of the smooth muscles of the bronchi;
• a decrease in histamine release by mast cells;
• activation of mucociliary transport;
• stimulation of epithelial cell production of bronchial relaxation factors.

Depending on the ability to stimulate alpha, beta1 or beta2-adrenergic receptors, all sympathomimetics are divided into:

• universal sympathomimetics, affecting both alpha- and beta-adrenoreceptors: epinephrine, ephedrine;
• nonselective sympathomimetics, stimulating both beta1 and beta2-adrenergic receptors: isoprenaline (Novorin, isadrin), orciprenaline (alupeptin, astomopent) hexaprenaline (ipradol);
• selective sympathomimetics, selectively acting on beta2-adrenoreceptors: salbutamol (ventolin), fenoterol (berotek), terbutaline (bricanil), and some prolonged forms.

At present, for the treatment of chronic obstructive bronchitis, universal and nonselective sympathomimetics are practically not used because of the large number of side effects and complications due to their pronounced alpha and / or beta1 activity

Widely used, currently, selective beta2-adrenomimetics almost do not cause serious complications from the side of the cardiovascular system and the CNS (tremor, headache, tachycardia, rhythm disturbances, arterial hypertension, etc.) peculiar to the nonselective and all the more universal sympathomimetres. Nevertheless it should be borne in mind that the selectivity of various beta2-adrenomimetics is relative and does not completely exclude beta1-activity.

All selective beta2-adrenomimetics are divided into short and long-acting drugs.

Short-acting medicines include salbutamol (ventolin, fenoterol (berotek), terbutaline (bricanil), etc. Drugs of this group are administered by inhalation and are considered a means of choice mainly for relief of attacks of acute bronchial obstruction (for example, in patients with bronchial asthma) and treatment chronic obstructive bronchitis.Their action begins 5-10 minutes after inhalation (in some cases before), the maximum effect is manifested in 20-40 minutes, the duration of the action is 4-6 hours.

The most common drug of this group is salbutamol (ventolin), which is considered one of the safest beta-adrenomimetics. Drugs are more often used by inhalation, for example, using a spinner, in a dose of 200 mm no more than 4 times a day. Despite its selectivity, even with the inhalation application of salbutamol, some patients (about 30%) experience unwanted systemic reactions in the form of tremors, palpitations, headaches, and the like. This is because most of the drug is deposited in the upper respiratory tract, swallowed by the patient and absorbed into the blood in the gastrointestinal tract, causing the described systemic reactions. The latter, in turn, are related to the presence of minimal reactivity in the preparation.

Fenoterol (berotek) has a somewhat greater activity compared with salbutamol and a longer half-life. However, its selectivity is about 10 times lower than salbutamol, which explains the poor tolerability of this drug. Fenoterol is administered in the form of metered-dose inhalations of 200-400 μg (1-2 breaths) 2-3 times a day.

Side effects are observed with prolonged use of beta2-adrenomimetics. These include tachycardia, extrasystole, increased episodes of angina in patients with IHD, elevation of systemic arterial pressure, and others caused by incomplete selectivity of drugs. Prolonged use of these drugs leads to a decrease in the sensitivity of beta2-adrenergic receptors and the development of their functional blockade, which can lead to an exacerbation of the disease and a sharp decrease in the effectiveness of previous treatment of chronic obstructive bronchitis. Therefore, COPD patients are recommended, if possible, only sporadic (non-regular) use of drugs of this group.

Long-acting beta2-adrenomimetics include formoterol, salmeterol (sulfur), saltos (delayed-release salbutamol), and others. The prolonged effect of these drugs (up to 12 hours after inhalation or oral administration) is due to their accumulation in the lungs.

In contrast to the short-acting beta2-agonists, the effect is slow in the listed long-acting drugs, therefore they are used mainly for long-term permanent (or course) bronchodilator therapy to prevent the progression of bronchial obstruction and exacerbations of the disease. In the opinion of some researchers, beta2-adrenomimetics of prolonged action also have an anti-inflammatory effect action, as they reduce vascular permeability, prevent the activation of neutrophils, lymphocytes, macrophage inhibiting the release of histamine, leukotrienes and prostaglandins from mast cells and eosinophils. A combination of long-acting beta2-adrenomimetics with inhaled glucocorticoids or other anti-inflammatory drugs is recommended.

Formoterol has a significant duration of bronchodilator action (up to 8-10 hours), including with inhalation. The drug is administered by inhalation in a dose of 12-24 μg 2 times a day or in tableted form at 20, 40 and 80 μg.

Volmax (salbutamol SR) is a prolonged preparation of salbutamol intended for reception per os. The drug is prescribed 1 tablet (8 mg) 3 times a day. The duration of action after a single dose of 9 hours.

Salmeterol (sulfur) also refers to relatively new prolonged beta2-sympathomimetics with a duration of 12 hours. The strength of bronchodilating effect exceeds the effects of salbutamol and fenoterol. The distinctive features of the drug is a very high selectivity, which is more than 60 times higher than that of salbutamol, which provides a minimal risk of developing side effects of systemic effects.

Salmeterol is prescribed in a dose of 50 mcg 2 times a day. In severe bronchial obstructive syndrome, the dose can be increased 2-fold. There is evidence that prolonged therapy with salmeterol leads to a significant decrease in the occurrence of exacerbations of COPD.

Tactics of the use of selective beta2-adrenomimetics in patients with COPD

Considering the expediency of the use of selective beta2-adrenomimetics for the treatment of chronic obstructive bronchitis, several important circumstances should be emphasized. Despite the fact that the bronchodilators of this group are now widely prescribed in the treatment of COPD patients and are regarded as preparations of basic therapy, patients should be noted that in real clinical practice their use encounters significant, sometimes insurmountable, difficulties, primarily related to presence at the majority of them the expressed by-effects. In addition to cardiovascular disorders (tachycardia, arrhythmias, tendency to elevation of systemic arterial pressure, tremor, headaches, etc.), these drugs with prolonged use can aggravate arterial hypoxemia, because they promote perfusion of poorly ventilated lungs and further violate ventilation-perfusion relations. Prolonged use of beta2-adrenomimetics is also accompanied by hypocapnia caused by redistribution of potassium inside and outside the cell, which is accompanied by an increase in the weakness of the respiratory muscles and deterioration in ventilation.

However, the main disadvantage of prolonged use of beta2-addressymmetrics in patients with bronchial obstructive syndrome is the regular formation of tachyphylaxis - a decrease in the strength and duration of the bronchodilator effect, which over time can lead to ricochet bronchoconstriction and a significant decrease in the functional parameters characterizing the patency of the airways. In addition, beta2-adrenomimetics increase the hyperactivity of the bronchial tubes to histamine and methacholine (acetylcholine), thus causing an exacerbation of parasympathetic bronchoconstrictor influences.

From what has been said, several important conclusions in practical terms follow.

1. Given the high efficiency of beta2-adrenomimetics in the management of acute episodes of bronchial obstruction, their use in patients with COPD is shown primarily at the time of exacerbations of the disease.
2. It is advisable to use modern, prolonged highly selective sympathomimetics, for example, salmeterol (sulfur), although this does not exclude the possibility of sporadic (non-regular) administration of short-acting beta2-adrenomimetics (such as salbutamol).
3. Prolonged regular use of beta2-agonists as monotherapy in patients with COPD, especially elderly and senile, can not be recommended as a permanent basic therapy.
4. If COPD patients still need to reduce the reversible component of bronchial obstruction and monotherapy with traditional M-cholinolytics is not fully effective, it is advisable to switch to the use of modern combined bronchodilators, including M-cholinergic inhibitors in combination with beta2-adrenomimetics.

Combined bronchodilators

In recent years, combined bronchodilators have been increasingly used in clinical practice, including long-term therapy for COPD patients. The bronchodilator effect of these drugs is provided by stimulation of beta2-adrenergic receptors of peripheral bronchi and inhibition of cholinergic receptors of large and medium bronchi.

Berodual is the most common combined aerosol preparation containing anticholinergic ipratropium bromide (atrovent) and beta2-adrenostimulator fenoterol (berotek). Each dose of berodual contains 50 μg of fenoterol and 20 μg of atrovent. This combination allows you to get a bronchodilator effect with a minimal dose of fenoterol. The drug is used both for relief of acute attacks of suffocation, and for the treatment of chronic obstructive bronchitis. The usual dose is 1-2 doses of aerosol 3 times a day. The beginning of the drug - after 30 seconds, the maximum effect - after 2 hours, the duration of the action does not exceed 6 hours.

Combinent is the second combined aerosol preparation containing 20 μg. Cholinolytics of ipratropium bromide (atrovent) and 100 μg of salbutamol. Combine used for 1-2 doses of the drug 3 times a day.

In recent years, the positive experience of combined use of anticholinergics with beta2-agonists of prolonged action (for example, atrovent with salmeterol) began to accumulate.

This combination of bronchodilators of the two described groups is very common, as combined drugs have a more powerful and persistent bronchodilator effect than both components alone.

Combined drugs containing M-cholinergic inhibitors in combination with beta2-adrenomimetics are characterized by a minimal risk of side effects due to a relatively low dose of sympathomimetic. These advantages of combined drugs allow us to recommend them for long-term basic bronchodilator therapy of COPD patients with insufficient effectiveness of monotherapy with atrovent.

[16], [17], [18], [19]

Derivatives of methylxanthines

If the reception of holiolytic or combined bronchodilators is not effective, the drugs of the methylxanthine series (theophylline, etc.) can be added to the treatment of chronic obstructive bronchitis. These drugs have been used successfully for many decades as effective medicines for the treatment of patients with bronchial obstructive syndrome. Theophylline derivatives have a very wide spectrum of action, which goes far beyond the bronchodilator effect alone.

Theophylline inhibits phosphodiesterase, resulting in the accumulation of cAMP in smooth muscle cells of the bronchi. This facilitates the transport of calcium ions from myofibrils to the sarcoplasmic reticulum, which is accompanied by relaxation of smooth muscles. Theophylline also blocks the purine receptors of the bronchi, eliminating the bronchoconstrictive effect of adenosine.

In addition, theophylline inhibits the degranulation of mast cells and the isolation of inflammatory mediators from them. It also improves renal and cerebral blood flow, increases diuresis, increases the strength and frequency of heart contractions, lowers pressure in a small circle of circulation, improves the function of the respiratory muscles and diaphragm.

Short-acting drugs from the theophylline group have a pronounced bronchodilator effect, they are used to arrest acute episodes of bronchial obstruction, for example, in patients with bronchial asthma, as well as for prolonged therapy of patients with chronic bronchial obstructive syndrome.

Euphyllin (compound theophyllip and ethylenediamine) is released in ampoules of 10 ml of a 2.4% solution. Euphyllin is administered intravenously in 10-20 ml of isotonic sodium chloride solution for 5 minutes. With rapid administration, it is possible to drop blood pressure, dizziness, nausea, tinnitus, palpitations, redness of the face and a feeling of heat. Introduced intravenously, euphyllin acts for about 4 hours. With intravenous drip, a longer duration of action (6-8 hours) can be achieved.

The theophyllines of prolonged action in recent years are widely used for the treatment of chronic obstructive bronchitis and bronchial asthma. They have significant advantages over short-range theophyllines:

• decreases the frequency of medication;
• the accuracy of dosing of drugs increases;
• provides a more stable therapeutic effect;
• prevention of asthma attacks in response to physical stress;
• drugs can be successfully used to prevent night and morning attacks of suffocation.

Prolonged theophyllines have a bronchodilator and anti-inflammatory effect. They largely suppress both the early and late phases of the asthmatic reaction that occur after the inhalation of the allergen, and also have an anti-inflammatory effect. Long-term treatment of chronic obstructive bronchitis with prolonged theophyllines effectively controls the symptoms of bronchial obstruction and improves lung function. Since the drug is released gradually, it has a longer duration of action, which is important for the treatment of nocturnal symptoms of the disease, which persist despite treatment of chronic obstructive bronchitis with anti-inflammatory drugs.

Prolonged theophylline preparations are divided into 2 groups:

1. Preparations of the 1st generation are active for 12 hours; they are prescribed 2 times a day. These include: theodore, theotard, theopek, durofillin, ventax, theogard, teobid, slobid, euphyllin SR, and others.
2. Preparations of the second generation last about 24 hours; they are prescribed once a day. These include: theodur-24, uniphil, dilatran, euphylong, phylocontin, and others.

Unfortunately, theophyllines act in a very narrow range of therapeutic concentrations of 15 μg / ml. With increasing doses, a large number of side effects occur, especially in elderly patients:

• gastrointestinal disorders (nausea, vomiting, anorexia, diarrhea, etc.);
• cardiovascular disorders (tachycardia, rhythm disturbances, up to ventricular fibrillation);
• disorders of the central nervous system (tremor of hands, insomnia, agitation, convulsions, etc.);
• metabolic disorders (hyperglycemia, hypokalemia, metabolic acidosis, etc.).

Therefore, when using methylxanthines (short and prolonged action), it is recommended to determine the level of theophylline in the blood at the beginning of the treatment of chronic obstructive bronchitis, every 6-12 months and after changing doses and preparations.

The most rational sequence of bronchodilators in COPD patients is as follows:

Sequence and volume of bronchodilator treatment of chronic obstructive bronchitis

• With slightly expressed and inconsistent symptoms of bronchial obstruction syndrome:
  • inhalation M-holinolitiki (atrovent), mainly in the phase of exacerbation of the disease;
  • if necessary, inhaled selective beta2-adrenomimetics (sporadically - during exacerbations).
• With more consistent symptoms (mild and moderate severity):
  • inhalation M-holinolitiki (atrovent) constantly;
  • with insufficient effectiveness - combined bronchodilators (fermented, combinent) constantly;
  • with insufficient effectiveness - addition of methylxanthine.
• At low efficiency of treatment and progression of bronchial obstruction:
  • to consider the replacement of berodual or a combination with the use of a highly selective beta2-adrenomimetic of prolonged action (salmeterol) and combination with M-cholinolytics;
  • Modify the methods of drug delivery (spencers, nebulayers),
  • continue taking methylxanthines, theophylline parenterally.

[20], [21], [22], [23], [24],

Mucolytic and mucoregulatory agents

Improvement of bronchial drainage is the most important task of treating chronic obstructive bronchitis. To this end, any possible effects on the body, including non-drug treatments, should be considered.

1. A plentiful warm drink helps to reduce the viscosity of sputum and increase the sol-layer of bronchial mucus, which facilitates the functioning of the ciliated epithelium.
2. Vibratory massage of the chest 2 times a day.
3. Positional drainage of bronchi.
4. Expectorants with an emetic-reflex mechanism of action (grass of thermopsis, terpinhydrate, Ipecacuanas root, etc.) stimulate the bronchial glands and increase the amount of bronchial secretion.
5. Bronchodilators, improving the drainage of bronchi.
6. Acetylcysteine (flumucin), viscosity of sputum due to rupture of disulfide bonds of mucopolysaccharides of sputum. It has antioxidant properties. Increases the synthesis of glutathione, which takes part in detoxification processes.
7. Ambroxol (lazolvan) stimulates the formation of a tracheobronchial secretion of reduced viscosity due to the depolymerization of acid mucopolysaccharides of bronchial mucus and the production of neutral mucopolysaccharides by goblet cells. It increases the synthesis and secretion of the surfactant and blocks the disintegration of the latter under the influence of unfavorable factors. Strengthens the penetration of antibiotics into the bronchial secretion and bronchial mucosa, increasing the effectiveness of antibiotic therapy and shortening its duration.
8. Carbocysteine normalizes the quantitative ratio of acidic and neutral sialomucines to bronchial secretions, reducing the viscosity of sputum. Promotes regeneration of the mucous membrane, reducing the number of goblet cells, especially in terminal bronchi.
9. Bromhexine is a mucolytic and a mucoregulant. Stimulates the production of surfactant.

Anti-inflammatory treatment of chronic obstructive bronchitis

Since the formation and progression of chronic bronchitis is based on the local inflammatory response of the bronchi, the success of the treatment of patients, including patients with COPD, is primarily determined by the possibility of inhibition of the inflammatory process in the airways.

Unfortunately, traditional non-steroidal anti-inflammatory drugs (NSAIDs) are not effective in COPD patients and can not stop the progression of clinical manifestations of the disease and a steady decline in FEV1. It is suggested that this is due to the very limited, one-sided effect of NSAIDs on the metabolism of arachidonic acid, which is the source of the most important inflammatory mediators - prostaglandins and leukotrienes. As is known, all NSAIDs, by inhibiting cyclooxygenase, reduce the synthesis of prostaglandins and thromboxanes. At the same time, activation of the cyclooxygenase pathway of arachidonic acid metabolism increases the synthesis of leukotrienes, which is probably the most important cause of ineffectiveness of NSAIDs in COPD.

Another mechanism is the anti-inflammatory effect of glucocorticoids, which stimulate the synthesis of protein that inhibits the activity of phospholipase A2. This leads to a limitation of the production of the source of prostaglandins and leukotrienes, arachidonic acid, which explains the high anti-inflammatory activity of glucocorticoids in various inflammatory processes in the body, including COPD.

Currently, glucocorticoids are recommended for the treatment of chronic obstructive bronchitis, in which the use of other methods of treatment has proved ineffective. Nevertheless, only 20-30% of patients with COPD manage to improve bronchial patency with these drugs. More often we have to abandon the systematic use of glucocorticoids due to their numerous side effects.

To solve the question of the advisability of prolonged continuous use of corticosteroids in patients with COPD, it is suggested to perform a trial therapy: 20-30 mg / day. At the rate of 0.4-0.6 mg / kg (according to prednisolone) for 3 weeks (taking oral corticosteroids). The criterion for the positive effect of corticosteroids on bronchial patency is the increase in response to bronchodilators in the bronchodilator test by 10% of the proper values of OBB1 or an increase in FEV1 of at least 200 ml. These indicators can be the basis for long-term use of these drugs. At the same time, it should be emphasized that at present there is no generally accepted point of view on the tactics of using systemic and inhaled corticosteroids in COPD.

In recent years, for the treatment of chronic obstructive bronchitis and certain inflammatory diseases of the upper and lower respiratory tract, a new anti-inflammatory drug fenspiride (erespal) has been successfully used, effectively acting on the mucous membrane of the respiratory tract. The drug has the ability to suppress the release of histamine from mast cells, reduce leukocyte infiltration, reduce exudation and release of thromboxanes, as well as permeability of blood vessels. Like glucocorticoids, fepspiride inhibits the activity of phospholipase A2 by blocking the transport of calcium ions necessary for the activation of this enzyme.

Thus, fepspiride reduces the production of many mediators of inflammation (prostaglandins, leukotrienes, thromboxanes, cytokines, etc.), having a pronounced anti-inflammatory effect.

Fenspiride is recommended to be used both for exacerbation and for long-term treatment of chronic obstructive bronchitis, being a safe and very well tolerated drug. When the disease worsens, the drug is prescribed in a dose of 80 mg twice a day for 2-3 weeks. With a stable course of COPD (the stage of relative remission), the drug is prescribed in the same dosage for 3-6 months. There are reports of good tolerability and high efficacy of fenspiride for continuous treatment for at least 1 year.

[25], [26], [27], [28], [29], [30]

Correction of respiratory failure

Correction of respiratory failure is achieved through the use of oxygen therapy and training of respiratory muscles.

Indications for long-term (up to 15-18 hours per day) low-flux (2-5 liters per minute) of oxygen therapy both in hospital and at home are:

• decrease in PaO2 arterial blood <55 mm Hg. P.
• reduction of SaO2 <88% at rest or <85% with a standard sample with 6-minute walking;
• a decrease in PaO2 to 56-60 mm Hg. Art. In the presence of additional conditions (edema due to right ventricular failure, signs of the pulmonary heart, the presence of P-pulmonale on the ECG or erythrocytosis with a hematocrit above 56%)

For the purpose of training respiratory muscles in COPD patients, various schemes of individually selected respiratory gymnastics are prescribed.

Intubation and ventilation is indicated in patients with severe progressive respiratory failure, increasing arterial hypoxemia, respiratory acidosis, or signs of hypoxic brain damage.

[31], [32]

Antibacterial treatment of chronic obstructive bronchitis

In the period of stable course of COPD antibiotic therapy is not indicated. Antibiotics are prescribed only during the exacerbation of chronic bronchitis in the presence of clinical and laboratory signs of purulent endobronchitis, accompanied by an increase in body temperature, leukocytosis, symptoms of intoxication, an increase in sputum and the appearance of purulent elements in it. In other cases, even the period of exacerbation of the disease and exacerbation of bronchial obstructive syndrome, the use of antibiotics in patients with chronic bronchitis has not been proven.

It has already been mentioned above that the most common exacerbations of chronic bronchitis are caused by Streptococcus pneumonia, Haemophilus influenzae, Moraxella catanalis, or the association of Pseudomonas aeruginosa with morocell (in smokers). In elderly, weakened patients with a severe course of COPD, staphylococci, Pseudomonas aeruginosa and Klebsiella may predominate in bronchial contents. On the contrary, in patients of a younger age, intracellular (atypical) pathogens: chlamydia, legionella, or mycoplasma often become the causative agent of the inflammatory process in the bronchi.

Treatment of chronic obstructive bronchitis usually begins with the empirical administration of antibiotics, taking into account the spectrum of the most frequent pathogens of exacerbations of bronchitis. Selection of an antibiotic based on the sensitivity of flora in vitro is carried out only if the empirical antibiotic therapy is ineffective.

For first-line drugs with exacerbation of chronic bronchitis include aminopenicillins (ampicillin, amoxicillin), active against hemophilic rods, pneumococci and mora seksely. It is advisable to combine these antibiotics with inhibitors of ß-lactamases, (for example, with clavulonic acid or sulbactam), which provides a high activity of these drugs to lactamase-producing strains of hemophilic rod and moraxella. Recall that aminopenicillins are not effective against intracellular pathogens (chlamydia, mycoplasmas and rickettsia).

Cephalosporins of II-III generation belong to broad-spectrum antibiotics. They are active against not only gram-positive, but also gram-negative bacteria, including haemophilic rod strains producing ß-lactamase. In most cases, the drug is administered parenterally, although with mild to moderate severity of exacerbation, oral cephalosporins of the second generation (for example, cefuroxime) may be used.

Macrolides. High efficacy for respiratory infections in patients with chronic bronchitis have new macrolides, in particular azithromycin, which can be taken only once a day. Assign a three-day course of azithromycin at a dose of 500 mg per day. New macrolides act on pneumococci, haemophilus rod, moraxella, and intracellular pathogens.

Fluoroquinolones are highly effective against gram-negative and gram-positive microorganisms, especially "respiratory" fluoroquinolones (levofloxacin, cykloxacin, etc.) - drugs with increased activity against pneumococci, chlamydia, mycoplasmas.

[33], [34], [35], [36], [37], [38], [39], [40]

Tactics of treatment of chronic obstructive bronchitis

According to the recommendations of the National Federal Program Chronic Obstructive Lung Disease, two treatment regimens for chronic obstructive bronchitis are distinguished: treatment of exacerbation (maintenance therapy) and treatment of exacerbation of COPD.

In the stage of remission (without exacerbation of COPD), bronchodilator therapy is of particular importance, emphasizing the need for an individual choice of bronchodilators. In this case, in the first stage of COPD (mild severity), the systematic use of bronchodilators is not foreseen, and only high-speed M-cholinolytics or beta2-agonists are recommended as needed. Systematic use of bronchodilators is recommended starting with the second stage of the disease, with preference given to long-acting drugs. Annual anti-influenza vaccination is recommended at all stages of the disease, the effectiveness of which is high enough (80-90%). Attitude to expectorants outside the exacerbation - restrained.

Currently, there is no medication that can affect but the main significant feature of COPD: the gradual loss of pulmonary functions. Medications in COPD (in particular, bronchodilators) only alleviate the symptoms and / or reduce the incidence of complications. In severe cases, a special role is played by rehabilitation measures and prolonged low-intensity oxygen therapy, whereas long-term use of systemic glucocorticosteroids should be avoided whenever possible, by replacing them with inhaled glucocorticoids or by taking fenspiride

With exacerbation of COPD, regardless of its cause, the significance of various pathogenetic mechanisms in the formation of the symptom-complex of the disease increases, the significance of infectious factors increases, which often determines the need for antibacterial agents, increases respiratory insufficiency, and the possible decompensation of the pulmonary heart. The main principles of treatment for exacerbation of COPD are the intensification of bronchodilating therapy and the appointment of antibacterial drugs according to indications. Intensification of bronchodilating therapy is achieved both by increasing doses, and by modifying the delivery methods of drugs, using spacers, nebulizers, and with severe obstruction - intravenous administration of drugs. Expanded indications for the appointment of corticosteroids, it becomes preferable to their systemic appointment (oral or intravenous) in short courses. In severe and moderate exacerbations, it is often necessary to use methods for correcting high blood viscosity - hemodilution. Treatment of decompressed pulmonary heart is performed.

Chronic obstructive bronchitis - treatment with alternative methods

It helps to remove chronic obstructive bronchitis treatment with some alternative means. Thyme, the most effective herb for fighting bronchopulmonary diseases. It can be used in the form of tea, decoction or infusion. To prepare medicinal herbs can be at home, growing it on the beds of your garden or, in order to save time, buy a finished product in the pharmacy. How to brew, insist or boil the thyme - indicated on the chemist's packaging.

[41], [42], [43]

Tea from thyme

If there is no such instruction, then you can use the simplest recipe - to make tea from thyme. To do this, take 1 tablespoon chopped herb thyme, put in a porcelain teapot and pour boiling water. Drink 100 ml of this tea 3 times a day, after a meal.

Decoction of pine buds

Perfectly removes stagnation in the bronchi, reduces the number of wheezing in the lungs by the fifth day of use. Prepare such a decoction is not difficult. Pine kidneys do not need to be collected by themselves, they are available in any pharmacy.

It is better to give preference to the manufacturer who took care to indicate on the packaging the preparation recipe, as well as all the positive and negative actions that can occur in people taking decoction of pine buds. Pay attention that pine buds should not be taken to people with blood diseases.

[44], [45], [46], [47], [48], [49]

Magical root of licorice

Medicinal potions can be presented in the form of an elixir or breast-feeding. Both are purchased in ready-made form in the pharmacy. Elixir is taken by drops, 20-40 per hour before meals 3-4 times a day.

Breast collection is prepared in the form of infusion and is taken half a glass 2-3 times a day. Take infusion should be before eating, so that the medicinal action of the herbs could enter into force and have time to "get" to the problem organs with the blood flow.

It will help to defeat chronic obstructive bronchitis treatment with drugs and modern and alternative medicine in the compartment with perseverance and belief in complete recovery. In addition, you should not write off a healthy lifestyle, alternation of work and rest, as well as the intake of vitamin complexes and high-calorie food.