RU2108121C1 - Method to treat bronchial asthma - Google Patents

Abstract

FIELD: medicine, pulmonology, prophylaxis of bronchospasm. SUBSTANCE: method deals with electrostimulation of synocarotid nerves by alternating current of 80-100 Hz through electrodes implanted under these nerves. Electrostimulation is conducted temporarily or just at the moment of paroxysm till its complete elimination or periodically with prophylactic purpose in automatic mode during interparoxysmal period. The switching on of electrostimulation is performed by a radio-frequency method at remote control with the help of transmitting device. During electrostimulation more accurate matching of stimulation current parameters is possible due to application of corresponding control units of transmitting device. In case of automatic stimulation mode stimulator is switched on by programming with the help of a programmed timer of transmitting device. Moreover, the time and duration of switching on should be programmed for a day by taking into account periodicity and duration of dyspnea attacks in one concrete patient. EFFECT: higher efficiency. 1 dwg, 14 tbl

Description

 The invention relates to medicine, namely to methods for treating bronchial asthma.

 A known method of treating bronchial asthma, which consists in the use of hormones of steroidal origin (corticotropin, cortisol, hydrocortisone, prednisolone, etc.) [1]. The mechanism of action of these drugs is based on the restoration of the functional mobility of the devices of the central and autonomic nervous systems, on the local anti-inflammatory effect, as well as on the mobilization of adrenaline and norepinephrine as factors that stop bronchioles spasm. However, the prolonged use of hormones leads to the development of complications in the form of Ishchenko-Cushing's syndrome, an increase in blood sugar, the formation of peptic ulcers, and a decrease in the body's defenses [2].

The closest in essence is a method of treating bronchial asthma, which consists in the use of adrenomimetic substances (adrenaline, isadrin, ephedrine, etc.) [1]. However, this method also has many disadvantages. Due to the fact that these substances act not only on B ₁ , but also on B ₂ adrenoreceptors, with prolonged use, damage to the heart muscle occurs. In severe asthma and the need for frequent use of these drugs, addiction to them occurs, as a result of which the dose increases significantly over time, exacerbating the severity of the disease. The use of medication for bronchial asthma does not effectively prevent attacks of bronchospasm, since in this case the drugs should be taken by patients 2 to 3 hours before the expected onset of the attack, and in patients with bronchial asthma most often attacks occur either late at night or in the early morning. Taking medications with a preventive purpose in the middle of the night is almost unrealistic for patients.

 The aim of the invention is: 1) the prevention of negative side effects when stopping bronchospasm with bronchodilator substances, 2) reducing the time, 3) preventing and stopping attacks of bronchospasm immediately, automatically, without the direct participation of the patient and the doctor.

 The goal is achieved by stimulating the production in the body of its own bronchodilator substances by electrical stimulation of the synocarotid nerves with electric alternating current. Reflexes from carotid glomeruli that are innervated by synocarotid nerves are well studied by physiologists [3]. Their physiological meaning is to maintain the vital functions of the body in extreme conditions. The main effects of electrostimulation of synocarotid nerves: expansion of the bronchi, expansion of the vessels of the brain, reduction of heart rate, stimulation of the adrenal cortex [3, 4].

 In our proposed method, irritating electrodes are implanted under the synocarotid nerves, connected to a receiving device implanted subcutaneously in the upper part of the chest. During an attack of bronchial asthma, the patient includes a transmitting device. In this case, the radio frequency path in the circuit: the receiving device, the electrodes, the synocarotid nerves, turns on the source of alternating electric current, which ultimately leads, due to the implementation of reflexes from the synocarotid glomeruli, to the expansion of the bronchi and the relief of the asthma attack. The transmitting device includes electrical stimulation both in manual mode (when it is switched on directly by the patient), and in automatic mode, which is carried out thanks to the programmable timer available in the transmitting device. On a programmable timer, the clock for turning on the electric stimulator and the duration of the electrical stimulation are pre-set for a day. The program of preventive inclusions of the electric stimulator in automatic mode is selected for each patient specifically, depending on the frequency and time of day of the onset of attacks, as well as their usual duration.

 A comparative analysis of the patent literature of the selected prototype with the proposed method revealed that the common feature among them is the relief of bronchospasm by bronchodilator substances.

The following differences were identified:
- For the relief of bronchospasm, not bronchodilator drugs are used, but bronchodilator substances of the patient's body, the production of which is stimulated by electrostimulation of the synocarotid nerves. This allows you to make the treatment method safer for the patient.

 - In case of irritation of the synocarotid nerves, due to the implementation of the corresponding reflexes, the working conditions of the heart muscle are improved (reduction in the frequency of contractions, increased blood oxygenation).

 When using adrenomimetics, the opposite is true [3, 2].

 - To stop the attack by electrical stimulation, the patient needs less time, since reflexes from the synocarotid zone are realized at lightning speed / 3 /. When using drugs, it takes a certain time for the injection. When inhaled, the effect of the drug is also lightning fast, as patients with asthma, as a rule, have organic damage to the bronchi and lungs in the form of chronic bronchitis or chronic pneumonia, in which the absorption of substances from the mucosa is significantly slowed down.

 - The proposed method allows you to prevent the development of asthma attacks automatically, without the direct and direct participation of the patient or doctor, since the transmitting device, including electrical stimulation by radio frequency, has a programmable timer to activate electrical stimulation at certain hours of the day, when a particular patient is most likely to experience attacks. In the prototype, for the prevention of seizures at certain hours of the day (i.e., for chronotherapy), the patient himself or with the participation of a doctor needs to administer medications to himself, which is almost impossible and not real at night when the seizures develop in the early morning.

 The drawing shows a diagram of the implementation of a method for the treatment of bronchial asthma.

 Designations: 1 - lungs, 2.3 - carotid arteries, 4.5 - carotid glomeruli, 6.7 - synocarotid nerves, 8.9 - electrodes for electrical stimulation, 10 - receiving device, 11 - transmitting device.

 The method is as follows.

 Non-polarizing electrodes (two under each nerve) 8.9 are implanted under the right and left sinocarotid nerves 6.7. The contact pads of the electrodes on the nerve are spaced about 0.2 cm apart. The electrodes are connected to a receiving device 10 implanted in the subcutaneous tissue of the upper chest. During the attack, the patient turns on the transmitting device 11. At the same time, by a radio-frequency method, the receiving device (10) - electrodes (8.9) - sinocarotid nerves (6.7) - turn on the alternating current source of the receiving device (10). The frequency of the current is 80 - 100 Hz, the voltage is 1-3 V, the pulse duration is 0.1 - 0.3 ms. Pulses of a rectangular shape with a duty cycle equal to two. With the passage of electric current through the nerves, their irritation occurs, as a result of which reflexes to the bronchi are realized. There is a relief of bronchospasm. Electrical stimulation is continued until the asthma attack is completely stopped, after which the transmitting device is turned off and the current in the above-mentioned circuit is stopped. In the case of using the method in automatic mode, the clock and duration of the activation of the electric stimulator are programmed on a programmable timer of the transmitting device. Manual activation of electrical stimulation can be carried out against the background of the automatic mode of electrical stimulation.

Example 1. Patient N., 28 years old, suffers from bronchial asthma for 9 years. Diagnosis: bronchial asthma of an infectious-allergic form, moderate. Chronic obstructive bronchitis, without exacerbation. Every year 2 - 3 times in connection with the exacerbation of the disease was treated in hospitals. Over the past 4 years, the disease began to progress steadily, despite the ongoing treatment, including: beclomet 200 mcg x 4 r, aminophylline 0.15 g x 4r, theophedrine 0.5 x 4 r, berotek - up to 3 inhalations during the attack (0 6 mg). The frequency of asthma attacks during periods of short-term remissions of the disease, not exceeding 3 to 4 weeks, was 4 to 5, and during the period of exacerbation reached 9 to 10 per day. During an exacerbation of bronchial asthma, about 1/3 of all asthma attacks were stopped only by intravenous administration of aminophylline (2.4 - 10.0%) or prednisolone (up to 90 mg). At the time of the last admission to the clinic, the patient had an exacerbation of the disease. The results of the examination before surgery: pneumotachometry (in% of the due): VC - 74.2; FEV ₁ - 47.6; MOS ₂₅ - 38.3; MOS ₅₀ - 39.4; MOS ₇₅ - 41.1. Violation of the function of external respiration in obstructive type. A significant reduction in bronchial patency throughout. For therapeutic purposes, the patient was implanted with a stimulator of synocarotid nerves (SKN), electrical stimulation of SKN with current pulses of 80 Hz was started; 0.2 ms; 2B. Duration of sessions - 1 - 2 minutes, with an interval of 3 - 4 hours during the day. Stimulation was carried out daily for a year. A month after the start of electrical stimulation, the patient's condition began to improve: the number of attacks per day did not exceed four. Their duration decreased on average by 2 times. The patient’s need for medications also decreased: beclomet 200 mcg x 2 r; aminophylline - 0.15g x 3 p; theofedrine is canceled, berotek 1 - 2 inhalations (0.2 - 0.4 mg) during the attack. For the relief of seizures, intravenous administration of aminophylline was not required. A stable remission of the disease was achieved. The indicators of pneumotachometry improved: VC - 86.1; FEV ₁ - 53.8; MOS ₂₅ - 46.3; MOS ₅₀ - 43.4; MOS ₇₅ - 45.7. When examining the patient one year after the operation, the condition is satisfactory. The frequency of attacks is no more than 4 per day. Their duration is 1.5 to 2 times less than before surgery. Attacks are easily stopped by one - two inhalations of a berotek. The duration of remissions of the disease during the year increased from 3-4 weeks to 2-2.5 months. In the period of exacerbation of the disease, in contrast to the preoperative period, the frequency of seizures did not exceed 6 - 7 per day; intravenous administration of hormonal drugs was not required for the relief of seizures, as well as hospitalization. Indicators of pneumotachometry through after surgery: VC - 87.7; FEV ₁ - 54.2; MOS ₂₅ - 47.4; MOS ₅₀ - 44.5; MOS ₇₅ - 44.8 - obstructive respiratory dysfunction. A moderate decrease in bronchial patency throughout. A year after the operation, the need for medicines and the patient decreased significantly: beclomete canceled, aminophylline 0.15 x 2p; theofedrine is canceled, berotek - one or two inhalations to stop the attack. Note: VC - vital lung capacity (in% of due), FEV ₁ - volume of forced output in the first second (in% of due); MOS ₂₅ , MOS ₅₀ , MOS ₇₅ - the maximum volumetric speed of the forced output at 25%, 50% and 75% VC, respectively (in% of due).

Example 2. Patient R., 33 years old, suffers from bronchial asthma for 11 years. Diagnosis: atopic asthma, moderate severity. The disease was characterized by severe exacerbations after relatively long remissions (up to 2 months). The severity of the condition during an exacerbation of the disease, as a rule, necessitated the need for inpatient treatment - up to 2 times a year. The frequency of seizures outside remission was 7–9, and during remissions 4–5 per day. Treatment included: aminophylline 0.15 g x 3 r, theophedrine 0.5 x 4 r, beclomete 200 μg x 2 r, berotek - up to 2–3 per attack (up to 0.6 mg), prednisone (5 mg x 3 r). During the last year, the patient developed asthmatic conditions twice in the winter. An allergological study revealed hypersensitivity to most commonly used antibiotics (penicillin, tetracycline, erythromycin, ampiox). Desensitizing therapy did not lead to amelioration of the course of the disease, which caused the patient to resort to surgical treatment. Before the last admission to the clinic, an exacerbation of the disease was diagnosed. The results of the examination before surgery: pneumotachometry (in% of the due): VC - 88.8; FEV ₁ - 43.7; MOS ₂₅ - 41.0; MOS ₅₀ - 38.1; MOS ₇₅ - 35.6 - obstructive breathing dysfunction. A significant reduction in bronchial patency throughout. For therapeutic purposes, an electrostimulator of synocarotid nerves (SKN) was implanted. Stimulation with current pulses of 80 Hz, 0.3 ms, 2B, 2 min, with an interval of 3-4 hours began. One month after the start of electrical stimulation, the patient's condition improved significantly: the frequency of attacks became no more than 2 per day. Attacks were easily stopped by inhalation of berotek (0.2 mg). The need for medicines has decreased: aminophylline 0.15 x 2p, theophedrine 0.5 x 2p, beclomete canceled, prednisone - 5 mg per day. A persistent remission of the disease has been achieved. The indicators of pneumotachometry improved: VC - 92.3; FEV ₁ - 48.5; MOS ₂₅ - 45.3, MOS ₅₀ - 43.2, MOS ₇₅ - 42.4 - a moderate decrease in bronchial patency. The results of the examination of the patient a year after the operation were as follows. The condition is satisfactory. The frequency of attacks per day is no more than three. Attacks are easily stopped by one - two inhalations of a berotek. There were no asthmatic conditions. The need for medications was significantly lower than before surgery: aminophylline 0.15 g, theofedrine canceled, prednisone 5 mg. The duration of remissions increased from 2 to 3.5-4 months. I did not need in-patient treatment during the year. Pneumotachometry indicators improved significantly compared to preoperative ones: VC 93.6; FEV ₁ - 54.1; MOS ₂₅ - 46.6; MOS ₅₀ - 42.2; MOS ₇₅ - 44.8 - a moderate decrease in bronchial patency. The patient returned to work.

Example 3. Patient O., 47 years old, suffers from bronchial asthma for about 21 years. Diagnosis: asthma of mixed genesis, severe course, chronic obstructive bronchitis, without exacerbation. Emphysema. Pneumosclerosis Respiratory failure II degree. Over the past 5 years, a patient with a disability (group I) about a underlying disease. The frequency of asthma attacks during an exacerbation of the disease is 8-10, in remission - up to 6 per day. Before surgery, she received the following treatment: aminophylline 0.3 x 3p, theophedrine 0.5 x 3p; berotek - up to 4 inhalations (up to 0.8 g) per attack, salbutamol up to 4 inhalations per day (40 mg each), ephedrine 0.05 x 2р. About half of suffocation attacks during an exacerbation of bronchial asthma were stopped only by intravenous administration of aminophylline (2.4% - 10.0) or adrenaline (0.1% - 0.5). Each year, the patient had 3-4 asthmatic conditions. Before admission to the clinic, the patient was diagnosed with an exacerbation of the disease. The results of the examination before surgery: pneumotachometry (in% of due); Jelly-63.6; FEV ₁ - 42.3; MOS ₂₅ - 38.6; MOS ₅₀ - 38,4, MOS ₇₅ - 37,2 - mixed breathing dysfunction. A significant reduction in bronchial patency throughout. For therapeutic purposes, a stimulant of synocarotid nerves (SKN) was implanted. Due to the slow healing of postoperative wounds, systematic electrical stimulation of SKN was started only a month after the operation. 2 weeks after the operation, the patient developed a protracted attack of suffocation, which later turned into an asthmatic state. Against the background of an asthmatic condition, electrostimulation of SKN was applied for its treatment - pulses of 90 Hz, 0.1 ms, 2V. The patient's condition before the stimulation is severe, shortness of breath up to 32 per minute. In the lungs in all departments there are many dry rales. Pulse 124 per minute. Blood pressure (BP) 150/100 mm Hg After 10 minutes of stimulation of SKN, the patient's condition improved: respiratory rate - 24 per minute, pulse 92, blood pressure 130/80 mm Hg, wheezing in the lungs became less pronounced. 35 minutes after the start of electrical stimulation of SKN, the asthmatic state was completely stopped. In addition to electrical stimulation, the patient also received 2 inhalations of berotek (0.4 mg) and 600.0 ml of isotonic solution. Previously, before surgery, for the relief of such asthmatic conditions, intravenous administration of aminophylline 2.4% - 20.0, prednisolone - up to 180 mg was mandatory. The asthmatic condition previously lasted at least 3-6 hours against the background of treatment. A month after the operation, systematic therapeutic stimulations of SKN were started. The patient’s condition 2 months after surgery on the background of stimulation of SKN: the frequency of attacks is not more than 3 per day. Attacks are easily stopped by only 1-2 inhalations of berotek or salbutomol. Significantly reduced the need for medication: aminophylline 0.15 x 2p, theophedrine 0.5 x 1p, ephedrine canceled. The indicators of pneumotachometry improved: ZHEL-67.7; FEV ₁ - 58.1; MOS ₂₅ - 44.5; MOS ₅₀ - 42.4; MOS ₇₅ - 45.3 - a moderate decrease in bronchial obstruction, impaired obstructive respiratory function. The patient was examined one year after the operation. During the year, electrical stimulation of SKN was applied according to the above scheme. The condition is satisfactory. The frequency of attacks is no more than 3 per day. Attacks are easily stopped by inhalation of a berotek (0,2 mg). The need for medications decreased significantly compared with preoperative: aminophylline 0.15 x 2p, theofedrine, ephedrine canceled. The duration of remissions increased from 30-40 days (before surgery) to 2.5-3 months. Pneumotachometry indicators: VC 83.1; FEV ₁ - 51.5; MOS ₂₅ - 47.3; MOS ₅₀ - 50.0; MOS ₇₅ - 48,4 - obstructive respiratory function disorder, a moderately pronounced decrease in bronchial patency.

 Before clinical testing, the method was developed on a model of bronchial asthma in guinea pigs in the experiment. Experimental bronchospasm was created by administering, under the conditions of an acute experiment, horse-serum sensitized animals a resolving dose of antigen by a known method [5]. The tone of the bronchi was measured according to the specified method [6]. In most experiments, electrical stimulation of synocarotid nerves stopped bronchospasm.

 The results of clinical trials of the "Method for the treatment of bronchial asthma" (Electrostimulation of synocarotid nerves)

 The method was applied in 32 patients with various forms of bronchial asthma (AD): 1 8-with atopic, 12 - infectious-allergic and 12 - with mixed. There were 5 men and 27 women. The average age of the patients was 42 ± 3 years, and the duration of the disease was on average 10 ± 6 years. Hormone addicts were 20 people. Severe course was in 9 patients, in the rest - moderate.

 To conduct a comparative study with the prototype method (treatment of AD with adrenomimetic substances such as adrenaline, isadrin, ephedrine, etc.), a control group of 30 AD patients was additionally formed (12 with infectious-allergic, 12 with mixed and 6 with atopic forms BA). There were 5 men, 25 women. The average age of the patients was 42 ± 4 years, the duration of the disease on average was 11 ± 4 years. Hormone addicts were 18 people. Severe course was in 15 patients with AD, moderate in others. Drug therapy was carried out for a year. Patients in the control group were prescribed berotek, aminophylline, theofedrine.

 Two stimulation modes were used for treatment: automatic (prophylactic automatic inclusion of the implanted stimulator on the eve of typical asthma attacks for each patient during the day) and manual (when the patient himself turned on the stimulator when an asthma attack occurred. Electrostimulation was carried out by current pulses of 80 - 100 Hz; 1 - 3V ; 0.1 - 0.3 ms, the duration of electrical stimulation often did not exceed 2 minutes, the tables below show the results of comparing the effectiveness of the proposed method and the prototype method.

 Static processing of the material was carried out on a computer "Electronics MK-61" using the student criterion, as well as non-parametric criteria for assessing the reliability of differences in average trends.

 In the table. Figures 1 and 2 show a comparison of the timing of the relief of asthma attacks by electrostimulation of synocarotid nerves (SKN) and inhalation of a berotek adrenomimetic (0.2 mg) in non-hormone-dependent and hormone-dependent asthma patients. It is clearly seen that electrical stimulation stops attacks several times faster.

 The most pronounced bronchodilating effect of electrostimulation of SKN was observed at current parameters of 80-100 Hz; 0.1-0.3 ms; 2B. This can be seen from the table. 4-6.

 In the table. Figure 4 shows the results of stimulation of SKN in the manual mode of switching on the stimulator.

 The greatest severity of the bronchodilating effect of electrical stimulation was observed with a duration of 2 minutes, which can be seen from Table 7.

 Electrical stimulation of SKN after 3 weeks led to a significant decrease in the number of seizures per day in both non-hormone-dependent and hormone-dependent patients with AD. This is clearly seen from the table. 8 and 9. Acceptance of the above adrenomimetic drugs (theofedrine, aminophylline, berotek) did not lead to such an effect in the control group.

 The observed effect of electrical stimulation of SKN in the form of the achieved reduction in the frequency of seizures did not depend on the form of the disease, as can be seen from Table 10. Along with the reduction of seizures, their duration also decreased reliably.

 The bronchodilating effect of the annual course of SKN electrical stimulation was significantly higher than the bronchodilating effect of adrenomimetic drugs in the control group. Reception of hormones by patients did not adversely affect the effectiveness of the method (Tables 11 and 12).

 Electrical stimulation of SKN has led to a significant decrease in the need for AD patients for medications. In patients of the control group, the need for drugs did not change over time. This is clearly seen from table.13. Of particular note is the reduction in hormone requirements after electrical stimulation of SKN.

Treatment of AD patients with electrical stimulation of SKN led to a significant increase in the duration of disease remissions, which was not observed in the control group (Table 14)
After the operation of implantation of a stimulator of SKN, not a single fatal outcome or life-threatening complications were noted. In the control group, these were, as follows from Table 15.

 Thus, the proposed method for the treatment of AD by electrical stimulation of SKN significantly exceeds the prototype method (treatment of AD with adrenomimetic drugs): asthma attacks are several times faster; the bronchodilating effect is not inferior in strength to the effect of adrenomimetics; the frequency and duration of seizures after 3 weeks from the start of electrical stimulation significantly decreases; the effectiveness of the new method does not deteriorate in hormone-dependent patients and does not depend on the form of the disease; the need for basic medications (including hormones) significantly decreases over time; there are no life-threatening complications; the duration of remissions of asthma significantly increases.

Sources of information:
1. Batrak G.E. "Pharmacology", Kiev, 1980, p.188-190.

 2. Putov N.V. "Handbook of pulmonology", L., 1988, S. 34-37.

 2. Anichkov S.V., Belenky M.L. "Pharmacology of carotid glomerulus chemoreceptors. L., 1962, pp. 175-190.

 4. Blinova AM "Blood supply to the brain during reflex influences Message 3. The significance of sinocarotid zones in the regulation of blood supply to the brain during interoreceptor irritation", Bulletin of Experimental Biology and Medicine, 1957, N12, p.3 - 7.

 5. Vershigora A.E. Fundamentals of immunology, Kiev, 1980, p. 206.

 6. Kaminko M.E. Method for recording the tone of bronchial muscles in guinea pigs, g. Pharmacology and Toxicology, 1975, N2, p.229-231.

Claims (1)

 A method of treating bronchial asthma with bronchodilators, characterized in that, in order to prevent side effects from their use, to reduce the time required to stop bronchospasm attacks, and to prevent them, temporary electrostimulation of synocarotid nerves is carried out using electrodes implanted under them, with a current frequency up to 80 - 100 Hz, voltage 1 - 3 V, pulse duration 0.1 - 0.3 ms, and electrical stimulation is carried out both at the time of the attack and for prophylactic purposes, periodically, in automatic mode - interictal period.

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