Chronic obstructive bronchitis - Treatment

In such a disease as chronic obstructive bronchitis, treatment is meant to be long-term and symptomatic. Due to the fact that chronic obstruction of the lungs is inherent in smokers with many years of experience, as well as people employed in hazardous industries with an increased content of dust in the inhaled air, the main goal of treatment is to stop the negative impact on the lungs.

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Chronic obstructive bronchitis: treatment with modern means

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

However, 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, reduce the frequency and duration of exacerbations, increase performance and tolerance to physical activity.

Treatment of chronic obstructive bronchitis includes:

• non-drug treatment of chronic obstructive bronchitis;
• use of bronchodilators;
• appointment of mucoregulatory therapy;
• correction of respiratory failure;
• anti-infective therapy (during 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 that is not controlled in an outpatient setting, despite the course (persistence of fever, cough, purulent sputum, signs of intoxication, increasing respiratory failure, etc.).
2. Acute respiratory failure.
3. Increased arterial hypoxemia and hypercapnia in patients with chronic respiratory failure.
4. Development of pneumonia against the background of COPD.
5. The appearance or progression of signs of heart failure in patients with chronic pulmonary heart disease.
6. The need to perform relatively complex diagnostic procedures (for example, bronchoscopy).
7. The need for surgical interventions using anesthesia.

The main role in recovery undoubtedly belongs to the patient himself. First of all, it is necessary to give up the harmful habit of smoking cigarettes. The irritating effect that nicotine has on the lung tissue will reduce to zero all attempts to "unblock" the work of the bronchi, improve blood supply in the respiratory organs and their tissues, eliminate coughing fits and bring breathing to a normal state.

Modern medicine offers to combine two treatment options - basic and symptomatic. The basis of basic treatment of chronic obstructive bronchitis is made up of drugs that relieve irritation and congestion in the lungs, facilitate the discharge of sputum, expand the lumen of the bronchi and improve blood circulation in them. These include xanthine drugs, corticosteroids.

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

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

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Chronic obstructive bronchitis - treatment with non-drug methods

The complex of non-drug treatment measures for 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 sanitation of foci of infection, primarily in the oral cavity, and the restoration of nasal breathing, etc. In most cases, clinical manifestations of chronic obstructive bronchitis (cough, sputum and shortness of breath) decrease within a few months after quitting smoking, and the rate of decline in FEV1 and other indicators of external respiration function slows down.

The diet of patients with chronic bronchitis should be balanced and contain sufficient amounts of protein, vitamins and minerals. Of particular importance is the additional intake of antioxidants, such as tocopherol (vitamin E) and ascorbic acid (vitamin C).

The diet of patients with chronic obstructive bronchitis should also include an increased amount of polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic), which are found in seafood and have a unique anti-inflammatory effect due to a decrease in the metabolism of arachidonic acid.

In case of respiratory failure and acid-base imbalance, a hypocaloric diet and restriction of simple carbohydrate intake are advisable, as they increase the formation of carbon dioxide due to their accelerated metabolism and, accordingly, reduce the sensitivity of the respiratory center. 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 using long-term low-flow oxygen therapy in these patients.

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Drug treatment of chronic obstructive bronchitis

Bronchodilators

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

1. beta2-adrenergic receptors by adrenaline and
2. VIP receptors of the NANH (non-adrenergic, non-cholinergic nervous system) by vasoactive intestinal polypeptide (VIP).

On the contrary, narrowing of the bronchial lumen occurs with stimulation:

1. M-cholinergic receptors acetylcholine,
2. receptors for P-substance (NANH systems)
3. alpha adrenergic receptors.

In addition, numerous biologically active substances, including inflammation mediators (histamine, bradykinin, leukotrienes, prostaglandins, platelet activating factor - PAF, serotonin, adenosine, etc.) also have a pronounced effect on the tone of the smooth muscles of the bronchi, contributing mainly to a decrease in the lumen of the bronchi.

Thus, the bronchodilating effect can be achieved in several ways, the most widely used at present being the blockade of M-cholinergic receptors and stimulation of beta2-adrenoreceptors of the bronchi. Accordingly, M-cholinergics and beta2-agonists (sympathomimetics) are used in the treatment of chronic obstructive bronchitis. The third group of bronchodilators used in patients with COPD include methylxanthine derivatives, the mechanism of action of which on the smooth muscles of the bronchi is more complex.

According to modern concepts, the systematic use of bronchodilators is the basis of basic therapy for patients with chronic obstructive bronchitis and COPD. Such treatment of chronic obstructive bronchitis is more effective, the more pronounced the reversible component of bronchial obstruction. However, the use of bronchodilators in patients with COPD, for obvious reasons, has a significantly smaller positive effect than in patients with bronchial asthma, since the most important pathogenetic mechanism of COPD is progressive irreversible obstruction of the airways caused by the formation of emphysema in them. At the same time, it should be taken into account that some modern bronchodilators have a fairly broad spectrum of action. They help reduce bronchial mucosal edema, normalize mucociliary transport, and reduce the production of bronchial secretions and inflammatory mediators.

It should be emphasized that in patients with COPD, the above-described functional tests with bronchodilators are often negative, since the increase in FEV1 after a single use of M-anticholinergics and even beta2-sympathomimetics is less than 15% of the expected value. However, this does not mean that it is necessary to abandon the treatment of chronic obstructive bronchitis with bronchodilators, since the positive effect of their systematic use usually occurs no earlier than 2-3 months after the start of treatment.

Inhalation administration of bronchodilators

It is preferable to use inhalation forms of bronchodilators, since this route of administration of drugs promotes faster penetration of drugs into the mucous membrane of the respiratory tract and long-term maintenance of a sufficiently high local concentration of drugs. The latter effect is ensured, in particular, by repeated entry into the lungs of drugs absorbed through the mucous membrane of the bronchi into the blood and entering the right sections of the heart through the bronchial veins and lymphatic vessels, and from there again into the lungs.

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

Inhalation administration of bronchodilators is provided by using powder inhalers, spacers, nebulizers, etc. When using a metered-dose inhaler, the patient needs certain skills to ensure more complete penetration of the drug into the airways. To do this, after a smooth, calm exhalation, tightly grasp the mouthpiece of the inhaler with your lips and begin to inhale slowly and deeply, press the canister once and continue to inhale deeply. After this, hold your 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.

For elderly patients, who may find it difficult to fully master the skills of using a metered dose inhaler, it is convenient to use so-called spacers, in which the drug in the form of an aerosol is sprayed into a special plastic flask by pressing on the canister immediately before inhalation. In this case, the patient takes a deep breath, holds his breath, exhales into the mouthpiece of the spacer, and then takes another deep breath, without pressing on the canister.

The most effective is the use of compressor and ultrasonic nebulizers (from Latin: nebula - fog), which provide spraying of liquid medicinal substances in the form of finely dispersed aerosols, in which the medicine is contained in the form of particles from 1 to 5 microns in size. This allows to significantly reduce the loss of medicinal aerosol that does not enter the respiratory tract, and also to ensure a significant depth of penetration of the aerosol into the lungs, including the middle and even small bronchi, whereas when using traditional inhalers such penetration is limited to the proximal bronchi and trachea.

The advantages of inhaling medications through nebulizers are:

• the depth of penetration of medicinal fine aerosol into the respiratory tract, including medium and even small bronchi;
• simplicity and convenience of performing inhalations;
• no need to coordinate inhalation with inhalation;
• the possibility of administering high doses of drugs, which allows the use of nebulizers to relieve the most severe clinical symptoms (severe shortness of breath, asthma attacks, etc.);
• the possibility of including nebulizers in the circuit of ventilators and oxygen therapy systems.

In this regard, the introduction of drugs through nebulizers is used primarily in patients with severe obstructive syndrome, progressive respiratory failure, in elderly and senile people, etc. Not only bronchodilators, but also mucolytic agents can be introduced into the respiratory tract through nebulizers.

Anticholinergic drugs (M-anticholinergics)

Currently, M-anticholinergics are considered as first-choice drugs in patients with COPD, since the leading pathogenetic mechanism of the reversible component of bronchial obstruction in this disease is cholinergic bronchial construction. It has been shown that in patients with COPD, anticholinergics are not inferior to beta2-adrenomimetics in terms of bronchodilatory action and are superior to theophylline.

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

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

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Remember:

1. Anticholinergics are the 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-anticholinergics is:
   1. in decreasing the tone of the smooth muscles of the bronchi,
   2. reduction of bronchial mucus secretion and
   3. reducing the process of mast cell degranulation 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 patients with COPD, inhaled forms of anticholinergics are usually used - the so-called quaternary ammonium compounds, which poorly penetrate the mucous membrane of the respiratory tract and practically do not cause systemic side effects. The most common of them are ipratropium bromide (atrovent), oxitropium bromide, ipratropium iodide, tiotropium bromide, which are used mainly in metered-dose aerosols.

The bronchodilator effect begins 5-10 minutes after inhalation, reaching a maximum after approximately 1-2 hours. The duration of action of ipratropium iodide is 5-6 hours, ipratropium bromide (Atrovent) - 6-8 hours, oxitropium bromide 8-10 hours and tiotropium bromide - 10-12 hours.

Side effects

Undesirable side effects of M-cholinoblockers include dry mouth, sore throat, cough. Systemic side effects of M-cholinoblockers, including cardiotoxic effects on the cardiovascular system, are virtually absent.

Ipratropium bromide (Atrovent) is available as a metered-dose aerosol. Prescribed 2 inhalations (40 mcg) 3-4 times a day. Inhalations of Atrovent, even in short courses, significantly improve bronchial patency. Long-term use of Atrovent is especially effective in COPD, which reliably reduces the number of exacerbations of chronic bronchitis, significantly improves oxygen saturation (SaO2) in arterial blood, and normalizes sleep in patients with COPD.

In mild COPD, a course of inhalations of Atrovent or other M-anticholinergics is acceptable, usually during periods of exacerbation of the disease, the duration of the course should not be less than 3 weeks. In moderate and severe COPD, anticholinergics are used continuously. It is important that with long-term therapy with Atrovent, tolerance to the drug and tachyphylaxis do not occur.

Contraindications

M-anticholinergics are contraindicated in glaucoma. Caution should be exercised when prescribing them to patients with prostate adenoma

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Selective beta2-adrenergic agonists

Beta2-adrenergic agonists are rightfully considered the most effective bronchodilators, which are currently widely used to treat chronic obstructive bronchitis. We are talking about selective sympathomimetics, which selectively stimulate the beta2-adrenergic receptors of the bronchi and have almost no effect on beta1-adrenergic receptors and alpha receptors, which are only present in small quantities in the bronchi.

Alpha-adrenoreceptors are found mainly in the smooth muscles of blood vessels, myocardium, central nervous system, spleen, platelets, liver and adipose tissue. In the lungs, a relatively small number of them are localized mainly in the distal parts of the respiratory tract. Stimulation of alpha-adrenoreceptors, 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, an increase in the secretion of mucus in the bronchi and the release of histamine by mast cells.

Beta1-adrenoreceptors are widely represented in the myocardium of the atria and ventricles of the heart, in the cardiac conduction system, in the liver, muscle and adipose tissue, in blood vessels and are 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-adrenoreceptors are found in the smooth muscles of blood vessels, the uterus, adipose tissue, as well as in the trachea and bronchi. It should be emphasized that the density of beta2-adrenoreceptors in the bronchial tree significantly exceeds the density of all distal adrenoreceptors. Stimulation of beta2-adrenoreceptors by catecholamines is accompanied by:

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

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

• universal sympathomimetics that act on both alpha- and beta-adrenergic receptors: adrenaline, ephedrine;
• non-selective sympathomimetics that stimulate both beta1 and beta2-adrenergic receptors: isoprenaline (novodrin, isadrin), orciprenaline (alupept, astmopent), hexaprenaline (ipradol);
• selective sympathomimetics that selectively act on beta2-adrenergic receptors: salbutamol (Ventolin), fenoterol (Berotec), terbutaline (Bricanil) and some prolonged forms.

Currently, universal and non-selective sympathomimetics are practically not used for the treatment of chronic obstructive bronchitis due to the large number of side effects and complications caused by their pronounced alpha and/or beta1 activity.

The selective beta2-adrenomimetics that are widely used today almost never cause serious complications from the cardiovascular system and central nervous system (tremor, headache, tachycardia, rhythm disturbances, arterial hypertension, etc.) that are characteristic of non-selective and especially universal sympathomimetics. 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-adrenergic agonists are divided into short-acting and long-acting drugs.

Short-acting drugs include salbutamol (ventolin, fenoterol (berotek), terbutaline (brikanil), etc. Drugs in this group are administered by inhalation and are considered the drug of choice mainly for relieving attacks of acute bronchial obstruction (for example, in patients with bronchial asthma) and treating chronic obstructive bronchitis. Their action begins 5-10 minutes after inhalation (in some cases earlier), the maximum effect appears after 20-40 minutes, the duration of action is 4-6 hours.

The most common drug in this group is salbutamol (Ventolin), which is considered one of the safest beta-adrenergic agonists. The drugs are most often used by inhalation, for example, using a spinhaler, at a dose of 200 mm no more than 4 times a day. Despite its selectivity, even with inhalation use of salbutamol, some patients (about 30%) experience undesirable systemic reactions in the form of tremor, palpitations, headaches, etc. This is explained by the fact that most of the drug settles in the upper respiratory tract, is swallowed by the patient and is absorbed into the blood in the gastrointestinal tract, causing the described systemic reactions. The latter, in turn, are associated with the presence of minimal reactivity in the drug.

Fenoterol (berotek) has slightly higher activity and a longer half-life compared to salbutamol. However, its selectivity is approximately 10 times less than salbutamol, which explains the worse tolerability of this drug. Fenoterol is prescribed as dosed inhalations of 200-400 mcg (1-2 inhalations) 2-3 times a day.

Side effects are observed with long-term use of beta2-adrenergic agonists. These include tachycardia, extrasystole, increased frequency of angina attacks in patients with coronary heart disease, increased systemic arterial pressure, and others caused by incomplete selectivity of the drugs. Long-term 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 previously administered treatment for chronic obstructive bronchitis. Therefore, in patients with COPD, only sporadic (not regular) use of drugs of this group is recommended, if possible.

Long-acting beta2-adrenergic agonists include formoterol, salmeterol (Sereven), Saltos (sustained-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.

Unlike short-acting beta2-agonists, the effect of the listed prolonged drugs occurs slowly, so they are used mainly for long-term continuous (or course) bronchodilator therapy to prevent the progression of bronchial obstruction and exacerbations of the disease. According to some researchers, prolonged-action beta2-adrenomimetics also have an anti-inflammatory effect, since they reduce vascular permeability, prevent the activation of neutrophils, lymphocytes, macrophages by 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 bronchodilating action (up to 8-10 hours), including when used by inhalation. The drug is prescribed by inhalation at a dose of 12-24 mcg 2 times a day or in tablet form of 20, 40 and 80 mcg.

Volmax (salbutamol SR) is a prolonged-release salbutamol preparation intended for oral administration. The drug is prescribed 1 tablet (8 mg) 3 times a day. The duration of action after a single dose of the drug is 9 hours.

Salmeterol (Serevent) is also a relatively new prolonged beta2-sympathomimetics with a duration of action of 12 hours. In terms of bronchodilating effect, it exceeds the effects of salbutamol and fenoterol. A distinctive feature of the drug is its very high selectivity, which is more than 60 times higher than that of salbutamol, which ensures a minimal risk of developing side systemic effects.

Salmeterol is prescribed in a dose of 50 mcg 2 times a day. In severe cases of broncho-obstructive syndrome, the dose can be increased by 2 times. There is evidence that long-term therapy with salmeterol leads to a significant reduction in the occurrence of COPD exacerbations.

Tactics of using selective beta2-adrenergic agonists in patients with COPD

When considering the issue of the advisability of using selective beta2-adrenomimetics for the treatment of chronic obstructive bronchitis, several important circumstances should be emphasized. Despite the fact that bronchodilators of this group are currently widely prescribed for the treatment of patients with COPD and are regarded as basic therapy drugs for these patients, it should be noted that in real clinical practice their use encounters significant, sometimes insurmountable, difficulties associated primarily with the presence of pronounced side effects in most of them. In addition to cardiovascular disorders (tachycardia, arrhythmia, tendency to increase systemic arterial pressure, tremor, headaches, etc.), these drugs, when used for a long time, can aggravate arterial hypoxemia, since they promote increased perfusion of poorly ventilated parts of the lungs and further disrupt ventilation-perfusion relationships. Long-term use of beta2-adrenergic agonists is also accompanied by hypocapnia, caused by the redistribution of potassium inside and outside the cell, which is accompanied by increasing weakness of the respiratory muscles and deterioration of ventilation.

However, the main disadvantage of long-term use of beta2-adrenergic agonists in patients with broncho-obstructive syndrome is the natural development of tachyphylaxis - a decrease in the strength and duration of the bronchodilator effect, which over time can lead to rebound bronchoconstriction and a significant decrease in the functional parameters characterizing the patency of the airways. In addition, beta2-adrenergic agonists increase the hyperreactivity of the bronchi to histamine and methacholine (acetylcholine), thus causing an aggravation of parasympathetic bronchoconstrictor effects.

Several important practical conclusions follow from what has been said.

1. Considering the high efficiency of beta2-adrenergic agonists in relieving acute episodes of bronchial obstruction, their use in patients with COPD is indicated primarily during exacerbations of the disease.
2. It is advisable to use modern prolonged highly selective sympathomimetics, such as salmeterol (Serevent), although this does not at all exclude the possibility of sporadic (not regular) use of short-acting beta2-adrenergic agonists (such as salbutamol).
3. Long-term regular use of beta2-agonists as monotherapy for patients with COPD, especially the elderly and senile, cannot be recommended as a permanent basic therapy.
4. If patients with COPD still need to reduce the reversible component of bronchial obstruction, and monotherapy with traditional M-anticholinergics is not entirely effective, it is advisable to switch to taking modern combination bronchodilators, including M-cholinergic inhibitors in combination with beta2-adrenomimetics.

Combination bronchodilators

In recent years, combined bronchodilators have found increasing use in clinical practice, including for long-term therapy of patients with COPD. The bronchodilating effect of these drugs is achieved by stimulating beta2-adrenergic receptors of the peripheral bronchi and inhibiting cholinergic receptors of large and medium bronchi.

Berodual is the most common combined aerosol preparation containing the anticholinergic ipratropium bromide (Atrovent) and the beta2-adrenergic agonist fenoterol (Berotec). Each dose of Berodual contains 50 mcg of fenoterol and 20 mcg of atrovent. This combination allows for a bronchodilator effect with a minimal dose of fenoterol. The drug is used both to relieve acute asthma attacks and to treat chronic obstructive bronchitis. The usual dose is 1-2 doses of aerosol 3 times a day. The onset of action of the drug is after 30 seconds, the maximum effect is after 2 hours, the duration of action does not exceed 6 hours.

Combivent is the second combined aerosol preparation containing 20 mcg of the anticholinergic ipratropium bromide (Atrovent) and 100 mcg of salbutamol. Combivent is used 1-2 doses of the preparation 3 times a day.

In recent years, positive experience has been accumulated in the combined use of anticholinergics with prolonged-release beta2-agonists (for example, atrovent with salmeterol).

This combination of bronchodilators of the two described groups is quite common, since the combined drugs have a more powerful and persistent bronchodilatory effect than both components separately.

Combination drugs containing M-cholinergic inhibitors in combination with beta2-adrenomimetics are characterized by a minimal risk of side effects due to a relatively small dose of the sympathomimetic. These advantages of combination drugs allow them to be recommended for long-term basic bronchodilator therapy of patients with COPD when monotherapy with Atrovent is insufficiently effective.

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Methylxanthine derivatives

If taking choliolytics or combined bronchodilators is ineffective, methylxanthine drugs (theophylline, etc.) can be added to the treatment of chronic obstructive bronchitis. These drugs have been successfully used for many decades as effective drugs for the treatment of patients with broncho-obstructive syndrome. Theophylline derivatives have a very broad spectrum of action, going far beyond the bronchodilatory effect alone.

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

In addition, theophylline inhibits mast cell degranulation and the release of inflammatory mediators from them. It also improves renal and cerebral blood flow, increases diuresis, increases the strength and frequency of heart contractions, lowers the pressure in the pulmonary circulation, and 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 relieve acute episodes of bronchial obstruction, for example, in patients with bronchial asthma, as well as for long-term therapy of patients with chronic broncho-obstructive syndrome.

Euphyllin (a compound of theophylline and ethylenediamine) is available in 10 ml ampoules of 2.4% solution. Euphyllin is administered intravenously in 10-20 ml of isotonic sodium chloride solution over 5 minutes. Rapid administration may cause a drop in blood pressure, dizziness, nausea, tinnitus, palpitations, flushing of the face, and a feeling of heat. Euphyllin administered intravenously acts for about 4 hours. With intravenous drip administration, a longer duration of action can be achieved (6-8 hours).

Extended-release theophyllines have been widely used in recent years to treat chronic obstructive bronchitis and bronchial asthma. They have significant advantages over short-acting theophyllines:

• the frequency of drug intake is reduced;
• the accuracy of drug dosing increases;
• a more stable therapeutic effect is ensured;
• prevention of asthma attacks in response to physical exertion;
• The drugs can be successfully used to prevent night and morning attacks of suffocation.

Prolonged theophyllines have a bronchodilator and anti-inflammatory effect. They significantly suppress both the early and late phases of the asthmatic reaction that occur after inhalation of an 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 night symptoms of the disease that persist despite treatment of chronic obstructive bronchitis with anti-inflammatory drugs.

Prolonged theophylline preparations are divided into 2 groups:

1. The first generation drugs act for 12 hours; they are prescribed twice a day. These include: theodur, theotard, theopec, durophyllin, ventax, theogarde, theobid, slobid, euphyllin SR, etc.
2. Second-generation drugs act for about 24 hours; they are prescribed once a day. These include: Theodur-24, Unifil, Dilatran, Euphylong, Filocontin, etc.

Unfortunately, theophyllines act in a very narrow range of therapeutic concentrations of 15 mcg/ml. When the dose is increased, 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);
• CNS dysfunction (hand tremors, 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 treatment of chronic obstructive bronchitis, every 6-12 months and after changing doses and drugs.

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

Sequence and volume of bronchodilator treatment for chronic obstructive bronchitis

• In case of mild and inconstant symptoms of broncho-obstructive syndrome:
  • inhaled M-anticholinergics (atrovent), mainly in the acute phase of the disease;
  • if necessary - inhaled selective beta2-adrenergic agonists (sporadically - during exacerbations).
• For more persistent symptoms (mild to moderate):
  • inhaled M-anticholinergics (atrovent) constantly;
  • if ineffective - combined bronchodilators (berodual, combivent) constantly;
  • if insufficient effectiveness - additionally methylxanthines.
• If treatment is ineffective and bronchial obstruction progresses:
  • consider replacing berodual or combivent with a highly selective prolonged-release beta2-adrenergic agonist (salmeterol) and combining it with an M-anticholinergic;
  • modify drug delivery methods (spensers, nebulizers),
  • continue taking methylxanthines, parenteral theophylline.

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Mucolytic and mucoregulatory agents

Improving bronchial drainage is the most important task in the treatment of chronic obstructive bronchitis. For this purpose, any possible effects on the body should be considered, including non-drug treatments.

1. Drinking plenty of warm fluids helps to reduce the viscosity of sputum and increase the sol layer of bronchial mucus, which facilitates the functioning of the ciliated epithelium.
2. Vibration massage of the chest 2 times a day.
3. Positional bronchial drainage.
4. Expectorants with an emetic-reflex mechanism of action (thermopsis herb, terpin hydrate, ipecac root, etc.) stimulate the bronchial glands and increase the amount of bronchial secretions.
5. Bronchodilators that improve bronchial drainage.
6. Acetylcysteine (fluimucin) viscosity of sputum due to the rupture of disulfide bonds of mucopolysaccharides of sputum. Has antioxidant properties. Increases the synthesis of glutathione, which takes part in detoxification processes.
7. Ambroxol (Lazolvan) stimulates the formation of tracheobronchial secretion of low viscosity due to the depolymerization of acidic mucopolysaccharides of bronchial mucus and the production of neutral mucopolysaccharides by goblet cells. Increases the synthesis and secretion of surfactant and blocks the breakdown of the latter under the influence of unfavorable factors. Enhances the penetration of antibiotics into bronchial secretion and bronchial mucosa, increasing the effectiveness of antibacterial therapy and reducing its duration.
8. Carbocisteine normalizes the quantitative ratio of acidic and neutral sialomucins of bronchial secretions, reducing the viscosity of sputum. Promotes the regeneration of the mucous membrane, reducing the number of goblet cells, especially in the terminal bronchi.
9. Bromhexine is a mucolytic and mucoregulator. Stimulates surfactant production.

Anti-inflammatory treatment of chronic obstructive bronchitis

Since the formation and progression of chronic bronchitis is based on a local inflammatory reaction of the bronchi, the success of treating patients, including patients with COPD, is primarily determined by the ability to inhibit the inflammatory process in the respiratory tract.

Unfortunately, traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are not effective in patients with COPD and cannot stop the progression of clinical manifestations of the disease and the steady decline in FEV1. It is assumed 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 inflammation mediators - prostaglandins and leukotrienes. As is known, all NSAIDs, by inhibiting cyclooxygenase, reduce the synthesis of prostaglandins and thromboxanes. At the same time, due to the activation of the cyclooxygenase pathway of arachidonic acid metabolism, the synthesis of leukotrienes increases, which is probably the most important reason for the ineffectiveness of NSAIDs in COPD.

The mechanism of anti-inflammatory action of glucocorticoids is different, they stimulate the synthesis of protein that inhibits the activity of phospholipase A2. This leads to a limitation of production of the very 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 treatment methods has proven ineffective. However, only 20-30% of COPD patients can improve bronchial patency with these drugs. Even more often, systematic use of glucocorticoids has to be abandoned due to their numerous side effects.

In order to decide on the advisability of long-term continuous use of corticosteroids in patients with COPD, it is suggested to conduct a trial therapy: 20-30 mg/day at a rate of 0.4-0.6 mg/kg (based on prednisolone) for 3 weeks (oral administration of corticosteroids). The criterion for the positive effect of corticosteroids on bronchial patency is an increase in the response to bronchodilators in the bronchodilator test by 10% of the expected values of FEV1 or an increase in FEV1 by at least 200 ml. These indicators may serve as a 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, a new anti-inflammatory drug fenspiride (erespal) has been successfully used to treat chronic obstructive bronchitis and some inflammatory diseases of the upper and lower respiratory tract. It effectively affects 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 the release of thromboxanes, as well as vascular permeability. 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 inflammatory mediators (prostaglandins, leukotrienes, thromboxanes, cytokines, etc.), exerting a pronounced anti-inflammatory effect.

Fenspiride is recommended for use both during exacerbations and for long-term treatment of chronic obstructive bronchitis, being a safe and very well-tolerated drug. During exacerbations of the disease, the drug is prescribed at a dose of 80 mg 2 times a day for 2-3 weeks. In stable COPD (relative remission stage), the drug is prescribed at the same dosage for 3-6 months. There are reports of good tolerability and high efficiency of fenspiride with 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 the respiratory muscles.

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

• decrease in arterial blood PaO2 < 55 mm Hg;
• decrease in SaO2 < 88% at rest or < 85% during a standard 6-minute walk test;
• decrease in PaO2 to 56-60 mm Hg in the presence of additional conditions (edema caused by right ventricular failure, signs of pulmonary heart disease, the presence of P-pulmonale on the ECG or erythrocytosis with a hematocrit above 56%)

In order to train the respiratory muscles in patients with COPD, various individually selected breathing exercises are prescribed.

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

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Antibacterial treatment of chronic obstructive bronchitis

Antibacterial therapy is not indicated during the stable course of COPD. Antibiotics are prescribed only during the period of 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 the amount of sputum and the appearance of purulent elements in it. In other cases, even during the period of exacerbation of the disease and exacerbation of broncho-obstructive syndrome, the benefit of antibiotics in patients with chronic bronchitis has not been proven.

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

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

First-line drugs for exacerbation of chronic bronchitis include aminopenicillins (ampicillin, amoxicillin), which are active against Haemophilus influenzae, pneumococci and Moraxella. It is advisable to combine these antibiotics with ß-lactamase inhibitors (for example, with clavulanic acid or sulbactam), which ensures high activity of these drugs against lactamase-producing strains of Haemophilus influenzae and Moraxella. Recall that aminopenicillins are not effective against intracellular pathogens (chlamydia, mycoplasma and rickettsia).

Cephalosporins of the second and third generations are broad-spectrum antibiotics. They are active against not only gram-positive but also gram-negative bacteria, including strains of Haemophilus influenzae producing ß-lactamases. In most cases, the drug is administered parenterally, although in mild to moderate exacerbations, oral cephalosporins of the second generation (e.g., cefuroxime) can be used.

Macrolides. New macrolides, in particular azithromycin, which can be taken only once a day, are highly effective in treating respiratory infections in patients with chronic bronchitis. A three-day course of azithromycin is prescribed at a dose of 500 mg per day. New macrolides act on pneumococci, Haemophilus influenzae, Moraxella, and intracellular pathogens.

Fluoroquinolones are highly effective against gram-negative and gram-positive microorganisms, especially “respiratory” fluoroquinolones (levofloxacin, cifloxacin, etc.) - drugs with increased activity against pneumococci, chlamydia, and mycoplasma.

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Treatment tactics for chronic obstructive bronchitis

According to the recommendations of the National Federal Program “Chronic Obstructive Pulmonary Diseases”, there are 2 treatment regimens for chronic obstructive bronchitis: treatment of exacerbation (maintenance therapy) and treatment of exacerbation of COPD.

In the remission stage (outside of COPD exacerbation), special attention is paid to bronchodilator therapy, emphasizing the need for an individual choice of bronchodilators. At the same time, in the 1st stage of COPD (mild severity), systematic use of bronchodilators is not provided, and only fast-acting M-anticholinergics or beta2-agonists are recommended as needed. Systematic use of bronchodilators is recommended to begin with the 2nd stage of the disease, with preference given to long-acting drugs. Annual influenza vaccination is recommended at all stages of the disease, the effectiveness of which is quite high (80-90%). The attitude towards expectorants outside of exacerbation is reserved.

There is currently no medication that can affect the main significant feature of COPD: the gradual loss of lung function. Drugs for COPD (in particular, bronchodilators) only alleviate symptoms and/or reduce the incidence of complications. In severe cases, rehabilitation measures and long-term low-intensity oxygen therapy play a special role, while long-term use of systemic glucocorticosteroids should be avoided if possible, replacing them with inhaled glucocorticoids or taking fenspiride.

During exacerbation of COPD, regardless of its cause, the significance of various pathogenetic mechanisms in the formation of the symptom complex of the disease changes, the significance of infectious factors increases, which often determines the need for antibacterial agents, respiratory failure increases, and decompensation of pulmonary heart disease is possible. The main principles of treating exacerbation of COPD are intensification of bronchodilator therapy and prescription of antibacterial agents according to indications. Intensification of bronchodilator therapy is achieved both by increasing doses and by modifying the methods of drug delivery, using spacers, nebulizers, and, in severe obstruction, intravenous administration of drugs. Indications for the prescription of corticosteroids are expanding, their systemic administration (oral or intravenous) in short courses becomes preferable. In severe and moderate exacerbations, it is often necessary to use methods for correcting increased blood viscosity - hemodilution. Treatment of decompensated pulmonary heart disease is carried out.

Chronic obstructive bronchitis - treatment with folk methods

Treatment with some folk remedies helps relieve chronic obstructive bronchitis. Thyme is the most effective herb for fighting bronchopulmonary diseases. It can be consumed as tea, decoction or infusion. You can prepare the medicinal herb at home by growing it in your garden beds or, in order to save time, buy the finished product at the pharmacy. How to brew, infuse or boil thyme is indicated on the pharmacy packaging.

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Thyme tea

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

Pine bud decoction

Excellent for relieving bronchial congestion, reduces the amount of wheezing in the lungs by the fifth day of use. It is not difficult to prepare such a decoction. You do not have to collect pine buds yourself, they are available at any pharmacy.

It is better to give preference to the manufacturer who took care to indicate on the packaging the recipe for preparation, as well as all the positive and negative effects that may occur in people taking a decoction of pine buds. Please note that pine buds should not be taken by people with blood diseases.

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The Magical Licorice Root

Medicinal mixtures can be presented in the form of an elixir or a chest collection. Both are purchased ready-made at the pharmacy. The elixir is taken in drops, 20-40 an hour before meals 3-4 times a day.

The chest collection is prepared as an infusion and taken half a glass 2-3 times a day. The infusion should be taken before meals so that the medicinal effect of the herbs can take effect and have time to "reach" the problematic organs with the blood flow.

Treatment with drugs of both modern and traditional medicine, coupled with persistence and faith in a complete recovery, will help to overcome chronic obstructive bronchitis. In addition, one should not write off a healthy lifestyle, alternating work and rest, as well as taking vitamin complexes and high-calorie foods.