RU2118159C1 - Method of acute pneumonia therapy - Google Patents

Abstract

FIELD: medicine, pulmonology. SUBSTANCE: method involves carrying out conventional medicinal therapy and, additionally, inhalation of supernatant obtained from autological culture of mononuclear cells stimulated with ФГА at dose 5 ml (protein concentration is 50-100 mcg/ml) every day for 6-8 days. Method shows effectiveness at processes damaging mainly distal respiratory way sites. EFFECT: enhanced effectiveness of method. 1 ex, 3 tbl

Description

 The invention relates to medicine, in particular to clinical immunology, and can be used in a clinic for the treatment of patients with acute pneumonia, in combination with traditional therapy.

 There is a method of treating acute pneumonia, which includes inhaled administration of stimulated autologous monocytes in traditional drug therapy. The essence of the method is to isolate autologous monocytes, cultivate the latter on nutrient media with the addition of immunomodulators, for example, levamisole, followed by inhalation of monocytes to the patient.

 The disadvantage of this method is that the size of the monocyte is 20-40 microns, and, as you know, particles larger than 8 microns do not reach the small bronchi, and especially the alveoli. Therefore, the method is ineffective in processes affecting mainly the distal sections of the respiratory tract (Immunocorrection in pulmonology / Edited by A.G. Chuchalin. - M .: Medicine, 1989, pp. 141-144.

 The essence of the method of treatment of acute pneumonia is that, along with traditional drug therapy, the patient is inhaled using an ultrasound inhaler using a phytohemagglutinin-stimulated supernatant (PHA) of a culture of autologous mononuclear cells in an amount of 5 ml with a protein concentration of 50-100 μg / ml for 6 -8 days.

 The possibility of inhalation of the supernatant of a PHA-stimulated culture of autologous mononuclear cells is due to the presence of a complex of endogenous cytokines (CEC), such as interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, interferons. The listed cytokines have the property of enhancing bactericidal activity and chemotaxis of phagocytes, inducing the synthesis of cytokines by other cells, and increasing the killer activity of NK lymphocytes. In addition, CEC normalizes repair processes in the focus of inflammation. All these effects of CEC determine the clinical effect in patients with acute pneumonia.

 The need to use ultrasonic inhalers for the introduction of CEC is due to their ability to create a highly dispersed aerosol with a particle size of 0.5-5 microns, which are able to reach the terminal bronchi and alveoli.

 The dosage of CEC for protein (50-100 μg / ml) is determined based on the effectiveness of CEC at this dose in the treatment of other diseases (Kovalchuk L.V., Gankovskaya L.V. Immunocytokines and local immunocorrection // Immunology, 1995, N 1, p. 4-7).

 The volume of CEC per inhalation (5 ml) was chosen because it is precisely such a volume of liquid that is completely consumed in 10 minutes (optimal duration of the procedure).

 The method is as follows. A patient with acute pneumonia receives traditional complex drug therapy, including antibacterial drugs, anti-inflammatory, bronchodilators, expectorants, and vitamin therapy. On admission, 20 ml of venous blood is drawn from the cubital vein into sterile, siliconized dishes containing 0.5 ml of heparin (5000 U / ml). Mononuclear cells are isolated from the obtained blood by centrifugation on a density gradient of ficol-verographin.

The isolated mononuclear cells are washed three times with Versen's solution, then a suspension of cells with a concentration of 5 · 10 ⁶ / ml is prepared in medium 199 containing gentamicin (80 μg / ml). To the resulting suspension of mononuclear cells add PHA at the rate of 20 μg / ml, incubate for 3 hours in an incubator at a temperature of 37 ^o C. Three times wash the cell suspension with Versen solution, add to the original volume of medium 199 and incubate in an incubator for 20 hours at 37 ^o C.

A suspension of mononuclear cells is centrifuged for 10 min at 1500 rpm. The supernatant containing the complex of endogenous cytokines (CEC) is taken into sterile penicillin vials and stored in the freezer compartment of the refrigerator at -20 ^o C. To the remaining cell precipitate is added to the original volume of 199 gentamicin medium and incubated for 20 h in an incubator at 37 ^o C, then the supernatant is harvested as described above.

 All manipulations with a suspension of mononuclear cells and supernatants are performed in a sterile box in compliance with aseptic and antiseptic rules. The resulting supernatants are filtered through sterile synpor or Millipore 0.22 filters.

 In both the first and second portions of the supernatant, the amount of total protein is determined by Lowry spectrophotometrically, and before the patient is prescribed to the patient, the protein concentration in the supernatant is adjusted to 50-100 μg / ml by dilution with sterile saline.

 A 5 ml supernatant is administered to the patient by inhalation with a protein concentration of 50-100 μg / ml using any ultrasonic inhalation device (for example, USI-3, GDR), daily for 6-8 days depending on the clinical picture of the disease.

Example. Patient P., 40 years old, diagnosis at admission: acute left-sided pneumonia, was admitted on the 2nd day of illness. Upon admission, the patient complained of pain in the left half of the chest, chills, cough with sputum, sweating, fever. Respiratory rate - 20 in 1 min. Voice trembling is weakened on the left in the subscapular region, there is also weakened vesicular breathing. To the left in the subscapular and axillary regions are multiple small- and medium-bubbly moist rales. Pulse 96 beats in 1 min, satisfactory qualities. HELL 125/80 mm Hg General blood test from 12.13.95: erythrocytes - 4.19 • 10 ¹² / l, Hb - 135 g / l, CP - 0.96, leukocytes - 6.44 • 10 ⁹ / l, eosinophils - 1%, stab neutrophils - 7%, segmented - 64%, lymphocytes - 20%, monocytes - 8%, ESR - 40 mm / h.

 Sputum examination from 12/13/95: color - gray, character - mucopurulent, consistency - viscous, white blood cells - 5-10 v / v, epithelial cells - moderate, mycobacterium tuberculosis was not detected.

 Chest x-ray in direct projection upon admission: reduced pneumatization of lung tissue in the middle pulmonary field of the left lung due to infiltration. The root is expanded, structureless, sinuses are free.

 Immunogram from 12/14/94. : E-POK - 70%, IgG - 7.7 g / l, IgA - 0.8 g / l, IgM - 1.1, phagocytic index - 50%, phagocytic number - 4, circulating immune complexes - 1.2 g / l, RTML with PHA - 90%.

The patient underwent the following drug therapy:
1) Benzylpenicillin Na salt 0.5 mln., 5 times a day, i / m - 10 days.

 2) Gentamicin sulfate 80 mg, 2 times in knocking, in-in - 6 days.

 3) Eufillin tablets 0.15, 3 times a day.

 4) Cough tablets 3 times a day.

 5) Orthophene tablets 0.025 3 times a day.

 From the fourth day of illness, the patient was injected with a CEC, 5 ml (50 μg protein per 1 ml) daily, using a total of 6 inhalations, using a USI-3 ultrasound inhaler.

 The dynamics of the clinical picture and the severity coefficient of the disease are shown in table 1.

 Chest x-ray in direct projection on the 10th day of illness: positive dynamics, non-homogeneous infiltration in the reed segment of the left lung.

 Chest x-ray in direct projection on day 22 of the disease: the absence of focal and infiltrative shadows.

 On the 23rd day from the onset of the disease, the patient was discharged in satisfactory condition.

At discharge: general blood test - erythrocytes - 4.19 • 10 ¹² / l, Hb - 138 g / l, CP - 0.99, white blood cells - 4.78 • 10 ⁹ / l, eosinophils 2%, stab neutrophils - 6 %, segmented - 59%, lymphocytes - 26%, monocytes - 7%, ESR - 12 mm / h.

 Immunogram - E-POK - 66%, IgG - 8.5 g / l, IgA - 1.6 g / l, IgM - 0.6 g / l, phagocytic index - 58%. phagocytic number - 4, circulating immune complexes - 0.9 g / l, RTML with PHA - 85%.

 We studied 26 patients with acute pneumonia hospitalized in the pulmonary department and the immunology department of the 1st GKB in the period from 1 to 6-7 days from the onset of the disease. All patients were divided into two groups - the main and control. Inclusion of the patient in a particular group was carried out on the day of admission using a table of random numbers. The main group consisted of 9 people, aged 16-60 years, average age 42.5 years; 6 of them are men, 3 are women; the control group consisted of 17 people aged 16-60 years, the average age was 37.5 years, of which 13 men, 4 women.

Patients of the main group received standard therapy, including antibacterial drugs (penicillin, ampicillin, gentamicin, biseptol), expectorants, anti-inflammatory drugs, bronchodilators, a complex of vitamin preparations, physiotherapeutic treatment (UHF, electrophoresis with CaCl ₂ ). In addition, they received CEC inhalations from the 2nd to 4th day of hospital stay, daily, once a day at a dose of 5 ml with a protein concentration of 50-100 μg / ml. In total, from 6 to 8 inhalations per course. Patients in the control group received similar treatment with the only difference being that instead of inhalation with CEC, inhalations with etericide were prescribed.

The effectiveness of treatment was evaluated according to the following criteria:
1) on the dynamics of the clinical coefficient of severity of acute pneumonia using the mathematical method proposed by G.I. Marchuk and E.P. Berebentseva (1986). The method consists in a scoring of 16 clinical symptoms and a radiological picture, with subsequent calculation of the severity coefficient according to the formulas. The advantage of the method is the possibility of an integrated quantitative assessment of the clinical picture of the disease and objectification of the study
2) the timing of the disappearance of some symptoms of acute pneumonia (fever, dry and wet cough, pleural pain, weakening of voice trembling, percussion dullness, the presence of wet rales or crepitus).

 3) the timing of the normalization of the x-ray picture.

 4) by the duration of the bed-day.

 Studies have shown the high efficiency of CEC in the treatment of acute pneumonia. So, in the main group of patients from 2-3 days from the beginning of the use of CEC, a clear tendency to a decrease in the severity of the disease is revealed. On the 4th – 5th day of the use of CEC (day 6–8 of the disease), the decrease in the severity coefficient becomes statistically significant.

 In the main group, there is a clear tendency to reduce the time for the disappearance of clinical signs of acute pneumonia, such as cough, pleural pain, increased vocal trembling, shortness of breath, wheezing. It should be noted that the difference in the timing of the disappearance of dry cough is statistically significant.

 In addition, there is a tendency towards an earlier normalization of percussion data, results of an X-ray examination, as well as a reduction in bed days.

 In patients who were inhaled with CEC, no adverse reactions were observed. The data obtained are presented in tables 2 and 3.

Using the proposed method for the treatment of acute pneumonia provides the following advantages:
- reduces the severity of patients with acute pneumonia;
- reduces the length of the patient’s hospital stay.

Claims (1)

 \\\ 1 A method for the treatment of acute pneumonia, including traditional drug therapy, characterized in that they additionally inhale the supernatant of an autologous culture of mononuclear cells stimulated with PHA in an amount of 5 ml with a protein concentration of 50-100 μg / ml daily for 6-8 days.

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