The method of treatment of acute bronchopneumonia complicated by atelectasis

 

(57) Abstract:

The invention relates to medicine, namely to pulmonology, and may find application in the treatment of acute pneumonia in children in the presence of atelectasis as a complication of pneumonia. The method is to use selective rehabilitation bronchoscopy and the introduction of pulmonary surfactant in the form of the drug, "surfactant-BL", which is injected once or 2-3 times at intervals of 2-3 days in the amount of 100-300 mg. The method provides a high frequency full (or partial) resolution of atelectasis and reduced treatment time of patients. It significantly reduces the number of necessary rehabilitation fibrobronchoscopy and the likelihood of transfer of the disease into a chronic state. 1 C.p. f-crystals, 1 table.

The invention relates to medicine, more specifically to the lung, and may find application in the treatment of various forms of lung disease.

The present invention relates to the treatment mainly children aged 1 month to 14 years with acute bronchopneumonia (ABPN), complicated by atelectasis (atelectasis) (AT), which occur in different periods of the development of pneumonia and is characterized by resistance to tradicionalmente, the sub-segments) of the lung, which is on the chest x-ray looks like a darkening in the form of a triangle usually with clear boundaries.

At an acute bronchopneumonia complicated by the formation of persistent atelectasis (atelectasis), see acute infiltrative lesion of the lung parenchyma bacterial or bacterial-viral etiology, accompanied by symptoms of General intoxication (poor appetite, fever or low grade fever, tachycardia, weakness, disturbances of function of external respiration (inspiratory, expiratory or mixed dyspnea, cough), modified physical data (local shortening of percussion sound over an area AT, dry and mixed moist rales) and there are clear signs of sub-segmental, segmental or lobar AT on the radiograph (Rg-MMA) chest. These are characterized by AT resistance (the existence of more than 5 to 7 days) and the lack of resolution (smoothing) using traditional methods of treatment (TSL). When AT TSL, which developed as a complication ABPN antibacterial and (or) of antiviral therapy, immunokorrigiruyuschuyu, mucolytic therapy and physical therapy (ERT) methods of influence. To after the, ukraicskimi drugs and angioprotectors (trental, aminophylline), phonophoresis of aminophylline and laser therapy. Along with this applies inhalation therapy spasmo and mukolitikami (lazolvan, atrovent and berodual). In addition, in the treatment apply massage and physical therapy (physical therapy) [1, 2].

In the absence of a rapid (5 - 7 days) the effect of this therapy is used invasive method of treatment AT. It consists in the use of rehabilitation broncho - and fibrobronchoscopy (FBS) with lavirovaniem (lavage) zone AT isotonic sodium chloride solution of 0.9% with the addition of mucolytics are presented [1, 2].

Diseases of the respiratory organs are on the first place among the General morbidity of children (79000 per 100,000 children under the age of 14 annually). This applies to all respiratory diseases, and not only ABPN (3]. However, you can provide more accurate data on the incidence of ABPN children for 1998 S.-Petersburg. It is 2866 patients receiving inpatient treatment, and 8960 children treated at home. Extrapolation of these values to the population of Russia in relation to ABPN in children treated in the hospital, gives the value of 85980 patients annually.

The frequency of occurrence of AT as complications ABPN children astradur ABPN, complicated AT.

This suggests that any new method that is more effective in comparison with TSL pulmonary disease, deserves the attention of specialists.

It is important to note that the traditional methods of treatment lasting AT are characterized by the following major drawbacks:

1. Complete resolution of atelectasis occurs in 57%- 60% of cases and requires to achieve this result, multiple (5 or 6) rehabilitation broncho - or FBS. This procedure is extremely traumatic, and in children up to 10 years requires General anesthesia. The procedure often leads to short-term (within 1-2 days) the deterioration of the General condition of patients.

2. The long existence AT often (10%-12% of cases) leads to vibrazioni area (segment) of the lung, persistence in this area bacterial (purulent) infection, development of deforming bronchitis with lots of pneumosclerosis or the formation of bronchiectasis. In the latter case there is a necessity of surgical treatment of such patients.

The most common causes of development ABPN are bacterial or bacterial-viral infection, immune-genetically determined structural features and liminate bronchial secretions), unstable premorbid condition, moved ABPN at an early age (in the first year of life).

In the last 4 - 5 years along with the traditional methods of treatment AT trying to use selective introduction of preparations of pulmonary surfactant (ARTICLE). In General, these works relate to treatment AT multiple injuries that occur on the background of long-term anaesthesia in the process of conducting large abdominal operations or operations on the heart. However, these individual works relate to treatment AT that occur directly in the treatment process (operation), not acute inflammatory process, what are ABPN. These "fresh" AT sometimes also not amenable to treatment by traditional methods.

With regard to the treatment of persistent (more than 5 - 7 days) atelectasis occurring as a complication ABPN, then such work, wherever used drugs pulmonary surfactant, we found.

The most widely pulmonary surfactant preparations used in the treatment of respiratory distress syndrome of newborns (RDTS) [5].

Known synthetic (Exosurf, Glaxo-Wellcome, USA - UK; ALEC, Britanica, UK), semisynthetic (Surfactant-TA, Tokyo Tanabe, Tokyo, Japan; Survanta, Ross/Abbott Lab, Chicago, USA) and natural uis, USA; CLSE, Rochester, NY, USA; Surfactant - HL [6] and Surfactant-BL [7] .

Drugs Surfactant-HL and Surfactant-BL developed at the Central research radiology Institute of the RF Ministry of health (cnrri MOH), S.-Petersburg. Surfactant-HL permitted for medical use by a decision of the Pharmacological Committee (FC) RF Ministry of health (Protocol No. 3 from 15.04.99). Surfactant-BL approved for clinical trials in RDS infants (Protocol FC MH RF N 14 26.09.96) and RDS adults (Protocol FC MH RF N 5 from 28.08.98). State Pharmacopoeia Committee in 1998 approved VFS on Surfactant-BL (N 42-3120-98). Clinical trials of Surfactant-BL successfully pass in 12 health facilities of Moscow, S.-Petersburg, Chelyabinsk and Yekaterinburg and currently more than 60 infants received treatment with this drug, and more than 40 adults and younger and older age. By the end of 1999, these tests must be completed and the reports of the clinics will be presented in the Pharmacological Committee of the health Ministry to permit the medical use of Surfactant-BL. Currently in cnerry MOH created the basis for the production of drugs pulmonary surfactants with a capacity of 30 thousand bottles a year, and it will allow Nasrollah

4 Some of the main characteristics of these products are given in table. 1 [6, 7, 8].

There is a method of treating acute AT the patient 48 years old [9]. The authors describe the treatment of the patient, who is on artificial lung ventilation (ALV) in the intensive care unit after a serious road injuries. On day 9 of a patient's resuscitation he was found AT the left lung, not amenable to smoothing the traditional methods of treatment. Against IVL (each light) patient bolus injected drug surfactant Exosurf in the amount of 50 mg/kg within a few hours after the injection of the surfactant on the back of continued mechanical ventilation were unfolding AT the left lung and normalization of blood gas composition.

There is a method of treatment AT the patient 35 years, which in connection with the persistence of Staphylococcus aureus occurred a spontaneous abortion on term of 7-8 weeks [10]. The patient developed sepsis, respiratory distress syndrome of adults (rdsw), later began pneumonia caused by Pseudomonas aeruginosa, and there was incomplete AT the left lung. Against IVL (each light) with FBS was introduced on 1 g of natural lung surfactant Alveofact. The patient otmechalos atelectasia lung.

However, the above-mentioned methods of treatment AT, which developed as a complication ABPN, characterized by

1. long-term treatment of patients,

2. the need to use multiple (4-6) traumatic broncho - or fibrobronchoscopy (children up to 10 years under General anesthesia),

3. lack of efficiency of treatment (full resolution is observed only AT 58 - 60% of cases),

4. a large number of cases (AT) transition in the chronic form, complicated by bronchiectasis and require further surgical treatment.

As already mentioned, we found no papers relating to the application of lung surfactant for the treatment of AT, which developed as a complication ABPN in children.

The only message on the treatment of bilateral pneumonia in a child 1 year 4 months who followed the so-called migratory atelectasis on the background of severe bilateral pneumonia made by us in [11], which we take as a prototype.

The girl is in critical condition with a diagnosis of generalized viral-bacterial infection, bilateral krupnouzlovaya pneumonia, migratory lobar atelectasis, DN III severity. The girl in the conditions of mechanical ventilation in 2 in the form of a spray through a nebulizer. Moreover, before the introduction of the ARTICLE the child was on a ventilator for 10 days without positive dynamics in relation to the severity of the condition and trends ABPN. Migrating AT is characterized by the fact that there are short-term (2-3 days), and then occurs in a different place. This behavior AT primarily associated not with the pathological process in the parenchyma of the lung area, in which there is inflammation (pneumonia), and with a pathological condition of the bronchial tree. Such migrating AT mostly found in children with bronchopulmonary dysplasia. After the second session inhalation of the drug during the day has been a significant improvement of the General condition of the child, normalized parameters, blood gases, the girl was exuberan, mechanical ventilation discontinued and migrating AT she disappeared.

Prototype method, and its counterparts, has the same disadvantages. In addition, this case treatment for AT bronchogenic origin, and not as complications ABPN. However, the successful result obtained for the child, allowed us to use the introduction pulmonary surfactant in the treatment AT that arose as a complication ABPN that, again, is not described to present the decidability (elimination) AT complicating ABPN and reduced treatment time.

This result is achieved by the fact that pulmonary surfactant is administered once or 2 to 3 times with an interval of 2 to 3 days in the number of 100 - 300 mg on the introduction using selective fibrobronchoscopy, and upon detection of the expressed inflammation of the wall of the bronchus surfactant is injected through 2-3 days with repeated bronchoscopy.

It is advisable to use natural pulmonary surfactant containing phospholipids 89 - 93.8% of neutral lipids from 4.2 to 9% and surfaceassociated proteins 2%.

Doing professionally treatment ABPN complicated resistant AT and in the last year and with the use of pulmonary surfactant preparations, we got several children positive results in full, within 3-5 days, unfolding AT after two or three times after the injection.

This fact has motivated us to conduct special monitoring for diseases with different modes of ART-therapy in children with different periods (up to 10 days) from the date of discovery AT. We have introduced drugs surfactant selectively, bolus in lobar, segmental or sub-segmental bronchi, applying preliminary lavirovaniem zone AT isotonic Rast the cases positive results of this treatment regimen, we attempted to distribute it for treatment AT from limitation periods up to 45 days.

Getting good results of treatment of 6 children with ABPN with AT, in three of which the duration of occurrence of segmental AT was 30 - 45 days, we believe the proposed scheme ART therapy optimal.

For treatment we used Surfactant-BL obtained from the lung of cattle, or Surfactant-HL of amniocytes fluid of pregnant women. These ARTICLES contain 89% - 93.8% of phospholipids, 4,2% -9% neutral lipids and 2.0% surfaceassociated proteins, which we have introduced in the number of 100 - 300 mg 1 - 3 times in 2 to 3 days.

Introduction surfactant selectively in the area AT where there are structural and functional damage to alveolitis, as we have shown in the experiment leads to the restoration of alveolitis second type of cells synthesizing surfactant [12] . The massive introduction of the emulsion ART, which in the alveolar space is in the form of vesicular structures with a very large surface, leads to sorption of toxic components on this surface and their removal at the expense of mucocilliary clearance from sputum.

Re-introduction of surfactant, if not AT raspravljati is the incurred in connection with the destruction of its bacterial flora and cells of inflammation (polymorphonuclear white cells and their degrading enzymes).

The use of a preparation containing, as said above, and 2.0% surfaceassociated proteins, is in our opinion a very important component of the proposed method. Such proteins are absent in synthetic drugs surfactant (Exosurf) is contained in an amount of 0.1% in semi-synthetic drugs (Survanta) and 1.0% - 1.5% natural (Alveofact, Infasurf and CLSE) (see tab. 1).

1. These proteins are very important for the manifestation of the ability of phospholipid surfactant to reduce surface tension at the phase boundary (the surface of the alveoli - air), while synthetic drugs, such as Exosurf, do not contain these proteins. The reduction of surface tension on the surface of lung alveoli, carried out by phospholipids in cooperation with surfaceassociated proteins, facilitates the process of disclosure of the alveoli during inspiration, thus reducing the required effort of the muscles of the chest [13].

2. These proteins bind the resistance of the native surfactant to inactivation, hemitriccus activity of surfactant in relation to the alveolar ohms in relation to the course of inflammation, the ability to stimulate complementability and antibody-dependent capture of pathogenic bacteria and viruses alveolar macrophages, and so on [14, 15, 16].

3. They also inhibit in vitro the ability of polymorphonuclear leukocytes and alveolar macrophages to excretion (release) cytokines - molecular components of proinflammatory cascade. The last damage alveolo-capillary membrane is the basic structural and functional element of pulmonary gas exchange [17].

The introduction of surfactant in the second FBS (at first it was not introduced due to inflammatory swelling of the wall of the bronchus) allows after a slight readjustment of the feeding bronchus to enter into the zone AT a powerful drug, which in this case is a natural surfactant.

The amount of added surfactant (100-300 mg) daily for 1-3 days is small, and, despite the high cost of drugs pulmonary surfactant, may be available to treat a wide range of patients. This is very important considering the high cost of drugs surfactant [18, 19].

The proposed treatment regimen ABPN with AT can significantly improve the full eliminatio AT, to achieve a substantial increase in partial represento cases, in which the AT passes in the chronic form, and requires further surgical intervention.

The method consists in the following.

A sick child to the clinic ABPN complicated AT, at first FBS with advanced lavirovaniem zone AT injected bolus selectively in the amount of 2.5-5.0 ml of physiological solution of sodium chloride 100 - 300 mg of Surfactant. In the case of incomplete elimination AT FBC with the introduction of the ARTICLE are repeated one or two times in the same dose. The drug is usually limited to 1 to 3 doses.

The essence of the method is illustrated by the following examples.

Example 1.

Boy Alex, 5,5 years, N East. disease 1442, was treated in XI Department (Department of infectious pulmonology) children's hospital (children's hospital) N 19. K. A. St Petersburg (S.-Petersburg) with 04.02.99 on 19.02.99 diagnosed with acute segmental pneumonia (S6-S10 segments of the lung), respiratory failure (NAM) -I severity. Complication: AT S8-S10 (the numbering of the segments of the lung) in the lower lobe of the left lung. Reactive pleuritis. When the complaint of coughing, Muco-purulent sputum, weakness. A state of moderate severity, moderate intoxication syndrome, DN-1. When obschenie wheezing. On the chest x-ray: infiltration focal-drain nature S6-S10, partial AT S8-S10. Laboratory: relative neutrophilia with left shift, ESR - 20 mm/hour. Ill for 20 days prior to admission. Onset of the disease: influenza, Rg-MMA (16 day of illness) revealed infiltrative changes, the term AT the time of receipt at children's hospital No. 19 - 20 days.

Treatment: one course of antibiotics, aminophylline 6 mg/kg per day, physiotherapy (OFWs), physiotherapy (physical therapy). On the first day of hospitalization conducted rehabilitation FBS with the introduction of 150 mg of Surfactant-HL volume of 5.0 ml of physiological solution (FR). The Rg-MMA 3 days after the introduction of the ARTICLE full resolution AT (on the 23rd day of its formation) and clinical and radiological resolution of pneumonia. Child received 150 mg of ARTICLE one, the time resolution AT 3 days after the introduction of the ARTICLE and even after 3 days the child was discharged home.

Example 2.

Girl Irina S. 4 years and 10 months, N East. disease 13730, was treated in the eleventh unit of children's hospital No. 19 with 25.11.98 on 17.12.98 with a diagnosis of acute focal-drain driver (S4-S10) bronchopneumonia, DN-II, reactive pleuritis, complication - AT S4-S5 of the right lung. Complaints unproductive cough, weakness. When entering the state average taglogo, breathing hard, weakened over S4-S5 right, no rales. The Rg-Miu: infiltrate S4-S10, AT S4-S5. Laboratory - moderate leukocytosis. Ill 11 days prior to admission, low-grade fever for 5 days, cough. Radiographically on day 5 of illness revealed infiltrative changes AT identified on the 8th day of the disease.

Treatment: two courses of antibiotics, aminophylline 5 mg/kg / day), exercise therapy, massage. Conducted two FBS (when the first FBS ARTICLE was not introduced because of a pronounced inflammatory activity of the wall of the inlet bronchus). After the first FBS radiographically AT unchanged. Three days after the first FBS during the second FBS entered bolus selectively in the area AT 100 mg Surfactant-HL volume of 5.0 ml FR. Subjectively, the next day after the introduction of the ARTICLE marked detoxification effect: decreased NAM and the severity of the condition, to reduce fatigue, appetite, the child has become more lively and cheerful. The Rg-MMA 4 days after the introduction of CT - full resolution and AT clinical and radiological resolution of pneumonia.

Results: the patient received 100 mg ARTICLE and 4 days after its introduction AT disappeared, the child was discharged home after 2 days.

Example 3.

Girl Daria P. 3.5 years, N East.annaa (S6 - S10) bronchopneumonia, DN-1. Complication - AT S7 of the right lung, reactive pleuritis. When receiving a satisfactory condition, without visible intoxication syndrome. Mosaic percussion over the lower lobes on the right, breathing hard, dry and small moist rales. The Rg-Miu: focal infiltration, AT S7. Laboratory and without signs of clinical activity. Girl ill 25 days before admission to the clinic. The disease began with an acute respiratory viral infection (ARVI), on the 4th day of the disease appeared persistent cough, on the 19th day of illness on Rg-Miu chest revealed AT.

Treatment: two courses of antibiotics, aminophylline 7 mg/kg / day), exercise therapy, massage. Conducted two FBS (when the first FBS - 27 day of illness, the ARTICLE was not introduced because of a pronounced inflammatory activity of the wall of the inlet bronchus). 3 days after the first FBS radiographically AT unchanged. During the second FBS entered bolus selectively in the area AT 100 mg Surfactant-HL volume of 5.0 ml FR. When Rg-control after 3 days full resolution and AT clinical and radiological resolution of pneumonia.

Results: the patient received 100 mg ARTICLE, 3 days after its introduction AT disappeared and the child was discharged home.

Example N 4.

Anna W. 12 years, East. B. N 12777, nahoopii, DN-II. Complication - AT S4-S5 of the left lung. When entering a state of moderate severity, with pronounced symptoms of intoxication, easing breathing over reed segments, crieteria wheezing. Radiographically - sided pneumonic infiltration with AT the left S4-S5. Laboratory - moderate leukocytosis.

The girl is sick during the week before admission to the Department, beginning with febrile fever (t - 38,9oC) increasing cough. The Rg-Miu chest on the 7th day of the disease identified AT.

Treatment: three courses of antibiotics, aminophylline 5 mg/kg / day), exercise therapy, massage. Conducted three FBS at 9, 12 and 14-day sickness 150, 200 and 300 mg of Surfactant-BL, respectively. After two FBS with the introduction of CT - positive trend, but kept reducing the amount of light. After the third injection ARTICLE full resolution AT. Just the girl received 650 mg of the surfactant with the help of three FBS, AT was resolved on the 16th day and the next day the child was discharged home.

Example 5.

Alexander W. East. B. N 11669, was treated in the eleventh unit of children's hospital No. 19 with 12.10.98 on 20.11.98 with a diagnosis of acute ocharovatelbna, right (S4-S5) bronchopneumonia, a protracted course, DN-1. Complication - AT S4-S5 of the right lung. Admission - SOS shares without wheezing. Radiographically - sided pneumonococcal infiltration with AT S4-S5 on the right. Laboratory - moderate leukocytosis, eosinophilia, sharply accelerated ROHE - 52 mm/hour. Ill 25 days before admission to the hospital, beginning with colds, rhinitis, tracheitis, on the 10th day of the disease the rise of the temperature up to 39oC that lasted for 4 days. The Rg-Miu chest revealed AT on the 25th day of the disease.

Treatment: three courses of antibiotics, aminophylline 8 mg/kg / day, FT, exercise therapy, massage. The traditional treatment with two rehabilitation FBS without the introduction of the ARTICLE. Due to the complete lack of dynamics in the resolution conducted AT three FBS, 35, 38 and 41 day sickness 150 mg of Surfactant-BL at each FBS. Appeared improved, but AT not resolved completely and the child was discharged home. Control of the dynamics AT one month after hospitalization - full resolution AT.

To date, the proposed method, the treatment of 26 children with acute bronchopneumonia complicated by atelectasis.

The proposed method is compared with the known has a number of significant advantages.

1. The method allows to significantly increase the full resolution of atelectasis. In our research in the treatment of 26 children in age is x traditional treatment with the use of rehabilitation FBS without the introduction of the ARTICLE, only 17 children (57%) showed complete resolution AT.

2. The method allows to significantly increase the efficiency of treatment AT (summarie the number of children who have full or partial resolution AT). In our study, 24 children (19 full and 5 partial resolution AT) of 26 was obtained positive effect (92%), whereas in the group of 30 children only in 21 (70%) obtained a positive effect.

3. The method allows to significantly reduce the number of ongoing rehabilitation FBS. In the group of children receiving ART, the number of FBS was 1.67 0,29, and To the group 3,170,36. This significant decrease in the number of FBS for resolution AT extremely important, as it significantly reduces the time of hospitalization and the number of care about traumatic procedures that are used in the treatment. It should be recalled that up to 10 years, children are exposed to FBS under General anesthesia.

4. The method allows to significantly increase the number of resolvable AT long existence. In our study, there were 5 children who have existed AT from 30 to 45 days. 4 of them had received full resolution and 1 - partial. In addition, we have applied the method in the treatment of 3 children (in addition to the 26 children) who have AT peristerona in teeth significantly reduce the time of hospital treatment of patients ABPN, complicated AT. Reducing the number of FBS with an average of 4-5 to 1-2 gives a reduction in the duration of inpatient treatment for 7-15 days. Such a reduction of treatment time and reduces the number of courses of antibiotic therapy is not indifferent and not a cheap component of treatment ABPN.

6. The method significantly reduces the number of children AT that arose as a complication ABPN, becomes chronic, leads to the formation of bronchiectasis and requires further surgical treatment.

7. An important advantage of the proposed method is the use of drugs Surfactant-HL and Surfactant-BL - natural pulmonary surfactants containing 89% - 93.8% of phospholipids, 4,2% - 9% neutral lipids and characterized by a high content of surfactant-associated protein - 2,0%.

Due to such medicines surfactant has the General detoxifying effect and has a positive impact on the severity of the General condition of patients and a positive outcome not only of treatment AT, but the outcome of ABPN. As seen from the above examples and analysis of results of treatment of all 26 children, the time resolution ABPN when using ARTICLE greatly reduced. This is undoubtedly what about surfaceassociated proteins.

The method developed by the staff of the Central research radiological Institute of the RF Ministry of health and staff of the eleventh division (Department of infectious pulmonology) children's hospital (children's hospital) N 19. K. A. St Petersburg (S.-Petersburg). He was clinically tested in the treatment of 26 children with acute bronchopneumonia complicated by atelectasis with positive results.

REFERENCES

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3. Zelinskaya, Doctor of historical Sciences, bayburina A. T., Karpeeva E. E. and other Collection: the Service of health protection of mother and child in 1997, Moscow, 1997, Ed. THE PUBLIC HEALTH MINISTRY.

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5. Holliday H. L. Natural vs synthetic surfactants in neonatal respiratory distress syndrome (Review).// Drugs, 1966.- V. -51, N 2. P - 226 - 237.

6. Rosenberg, A. A. , Chaldean A. A., Aliev A. A. and other Way of getting lung surfactant. 1995 (priority), 1996 (per) N 2066197. Bulletin of inventions No. 25, 1996.

7. Rosenberg, A. A. , Chaldean A. A., Aliev A. A. and other Way of getting ential and nonessential constituents of exogenic surfactants. Surfactant Therapy for Lung Disease. Ed. Robertson B. and Taeusch, H. W. - N. Y., 1995. - P. 217-238.

9. Knoch M; Heoltermann W; Lukasewitz P; Bittersohl, J. Treatment of total atelectasis of the left lung in severe ARDS with side-separated ventilation and surfactant administration.// Anasthesiol Intensivmed Notfallmed Schmerzther. 1996. V. 31, N 4. P-270-273.

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1. The method of treatment of acute bronchopneumonia complicated by atelectasis in children by selective rehabilitation bronchoscopy and the introduction of surfactant-BL, characterized in that in the presence of atelectasis as a complication of acute pneumonia surfactant-BL injected bolus once or 2 to 3 times with an interval in 2 to 3 days at a dose of 100 - 300 mg.

2. The method according to p. 1, characterized in that the re-introduction after 2 to 3 days performed upon detection of pronounced inflammation of the wall of the bronchus.

 

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