RU2271828C2 - Method for treatment of bronchial asthma in children suffering from acute respiratory viral infection (arvi) often and/or for a long time - Google Patents

Abstract

FIELD: medicine, pediatrics, pulmonology, allergology.

SUBSTANCE: method involves administration of viferon by rectal way. Viferon-1 is dosed to children of age 3-6 years (150000 IU in one suppository), and viferon-2 is dosed to children of age 7-14 years (500000 IU in one suppository) every day, twice per a day, for 10 days and then for 4 weeks in every other day. Proposed invention promotes to decrease numbers of bronchial asthma exacerbation, diminishing degree of bronchial asthma severe attack, decreasing frequency of bronchial asthma, increasing period of bronchial asthma remission due to activation of the interferon system. Invention can be used in treatment of bronchial asthma in children suffering from ARVI often and/or for a long time.

EFFECT: enhanced effectiveness of treatment.

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Description

The invention relates to medicine and can be used to treat bronchial asthma in children who often and / or have long-term acute respiratory viral infections.

In recent years, a tendency towards an increase in the incidence of bronchial asthma (AD) in children and an increase in its severity has been observed throughout the world (1, 2, 3, 5). Currently, this problem has acquired not only medical, but also socio-economic significance (5).

The most effective treatment for AD is the elimination of a causative allergen, but in practice this is extremely rare. A comprehensive anti-inflammatory (basic) therapy of AD has been developed and put into practice, the choice of which depends on the severity of the disease (5). Basic therapy is primarily aimed at suppressing allergic inflammation, however, concomitant viral infection contributes to the development of frequent exacerbations of AD and worsens the course and prognosis of the disease (1, 2).

It is known that the complex of certain cytokines and the interferon system, in particular, are the regulators of the development of the inflammatory reaction. The results of our studies indicate that in children with AD there is a disruption in the functioning of the interferon system, which is consistent with literature data (1, 2, 3). This serves as the basis for the development of a number of new approaches to the complex treatment of AD using interferon preparations or its inducers.

The essence of the invention lies in the fact that a new method is proposed for the treatment of AD in children who often and / or have long-term acute respiratory viral infections during remission of AD by administering Viferon in addition to basic anti-inflammatory therapy corresponding to the severity of the disease.

Viferon® is a complex of recombinant α2b interferon and antioxidant drugs (α-tocopherol acetate and ascorbic acid) in rectal suppositories. Viferon has antiviral, immunomodulatory and protective effects. The drug does not have side effects of recombinant interferons administered parenterally; inactivating antibodies are not produced to it. Viferon is the only drug in the class of recombinant IFN that is officially approved by the pharmacological committee of the Ministry of Health of the Russian Federation for use in children, including newborns. The drug is available in three versions, differing in the amount of recombinant IFN included in its composition: Viferon-1 contains 150,000 ME in one candle, Viferon-2 contains 500,000 ME in one candle, Viferon-3 - 1,000,000 ME in one candle. The form of administration of the drug in the form of rectal suppositories ensures its effectiveness when taken with an interval of 12 hours and is more convenient in pediatrics compared with parenteral methods of administration.

To assess the effectiveness of the new method of treating AD in children, we conducted a randomized, placebo-controlled study in accordance with international GCP standards. Viferon was used in combination with basic therapy, corresponding to the severity of the disease in 30 children with AD during the period of remission of the disease. 18 children with AD in remission received basic therapy and placebo (suppositories from cocoa butter). The groups were comparable in age, gender and severity of the disease. A moderate form of AD was found in half of all patients; patients with severe and mild forms of AD were distributed approximately equally.

Viferon-1 was prescribed for children aged 3-6 years, Viferon-2 - for children aged 7-14 years. We have developed an original regimen for the administration of the drug: Viferon was used in the form of rectal suppositories 2 times a day for 10 days daily, then 4 weeks - every other day. The study of interferon status was carried out for all children before the appointment of Viferon, 6 weeks after the start of therapy and in some children in the medical history (3 and 6 months after the start of therapy with Viferon).

Assessment of the severity of asthma and the appointment of complex therapy were carried out taking into account the recommendations of the "National program" Bronchial asthma in children. Treatment strategy and prevention ”(5). An objective indicator characterizing the degree of impaired bronchial obstruction in older children was the study of the function of external respiration (VFD) by pneumotachometry (PTM) and peak flow measurement (PFM) in dynamics. Clinical, laboratory and allergological examination corresponded to the standard examination of patients with AD, in addition, included the study of interferon status in dynamics.

Interferon status was studied according to the Grigoryan method (4). The state of the IFN system was assessed by the total amount of serum IFN, the level of production of leukocytes of INFA in response to viral inducers (Newcastle disease virus, Kansas strain (VBN)) and the level of production of lymphocytes of INFA in response to mitogens (phytohemagglutinin (PHA) and staphylococcal entnrotoxin (CEA) ) The study used a diploid culture of human fibroblasts M19.

The essential features of the proposal are the use of the recombinant interferon α-2b preparation in the complex therapy of children with AD in the stage of remission of the disease, the doses and the regimen of the drug administration have been developed. This made it possible to obtain a new result - to reduce the frequency of AD exacerbations in children, often suffering from acute respiratory viral infections (ARVI), to reduce the severity of the attack, to reduce the frequency of ARVI, and to extend the period of AD remission.

To disclose the invention, the results of a clinical trial of the claimed method are presented:

1. Clinical effect - the frequency of exacerbations of asthma in children, often suffering from acute respiratory viral infections, decreased, the severity of the attack decreased, and the period of remission of asthma lasted.

2. Economic effect - the frequency of hospitalizations decreased, the cost of treatment of the onset period decreased.

3. Favorable effect on interferon status - the ability to produce α-INF by leukocytes effectively increased to the level of healthy ones and remained in most children for six months of observation.

4. The protective effect is a reduction in the frequency of subsequent ARVI.

Table 1. The clinical effectiveness of the claimed method compared with the known (observation in the follow-up history of 6 months, M + m). Clinical symptoms Basic Therapy + Viferon Basic Theapia + Placebo The frequency of exacerbations of asthma (for 6 months) 0.5 ± 0.1 1.7 ± 0.3 The severity of the attack (in points) 3.4 ± 0.5 5.2 ± 0.1 The duration of the remission period (months) 5.1 ± 0.6 2.3 ± 0.8 ARVI frequency (for 6 months) 1.2 ± 0.2 4.9 ± 0.1 Table 2. Dynamics of IFN status of patients with AD in remission who received Viferon therapy, depending on the severity of the disease (M + m, IU / ml) IFN serum IFN α IFN γ BA severity Before treatment After treatment Before treatment After treatment Before treatment After treatment Light N = 8 3.96 ± 1.28 3.16 ± 1.26 66.07 ± 1.38 90.79 ± 1.8 ** 6.31 ± 1.18 7.08 ± 1.18 Average N = 15 3.72 ± 1.12 3.09 ± 1.12 74.13 ± 1.31 84.14 ± 1.23 ** 7.94 ± 1.23 12.3 ± 1.5 * Heavy N = 7 3.76 ± 1.19 2.81 ± 1.12 74.99 ± 1.45 100 ± 1.48 ** 6.68 ± 1.23 8.32 ± 1.18 * P <0.05 ** p <0.001

Table 3. Dynamics of IFN status of patients with AD in remission who received placebo therapy, depending on the severity of the disease (M + m, IU / ml) IFN serum IFN α IFN γ BA severity Before treatment After treatment Before treatment After treatment Before treatment After treatment Easy N = 5 3.78 ± 1.02 3.48 ± 1.25 67.27 ± 1.45 66.89 ± 1.05 6.48 ± 1.08 7.01 ± 1.15 Average N = 9 3.74 ± 1.22 3.23 ± 1.08 72.25 ± 1.18 74.18 ± 1.31 7.54 ± 1.12 8.3 ± 0.5 Heavy N = 4 3.78 ± 1.29 3.02 ± 1.08 70.87 ± 1.67 72.15 ± 1.33 6.98 ± 1.03 7.22 ± 1.14

The invention is illustrated by the following examples:

Example 1. Korshunov Pavel, 12 years old, and.b. No. 1125, was in the department from 03/22/00. until 12.04.00. Clinical diagnosis: Bronchial asthma, atopic, severe course, remission. Sensitization to household, pollen allergens. Chronic gastroduodenitis with increased acid-forming function of the stomach, incomplete remission. He entered again, as planned, for an additional examination.

Upon examination, the condition is satisfactory. Physical development by age. The skin is pale, clean. The mucous membranes of the mouth are clean. Nasal breathing is difficult. In the lungs, respiration is carried out in all departments symmetrically vesicular, no wheezing. heart sounds distinct, rhythmic. Chss-88, AD-110/60. The abdomen with deep palpation b / painful. The liver is not enlarged. Pasternatsky’s symptom is negative on both sides. Urination is free. Chair daily. Sexual development by age.

From the anamnesis it is known that the child was born from I pregnancy, which proceeded with toxicosis of the I half, I childbirth, urgent, physiological. At birth, length 56 cm., Weight 4400 g., Apgar score 8/9 points. Heredity is not burdened. He was breastfed for up to 6 months. In the first year of life he suffered ARVI, in subsequent years - ARVI 6-7 times a year. At the age of 1 year, manifestations of atopic dermatitis appeared. Diagnosed with intolerance to cow's milk proteins.

The first occurrence of bronchial obstructive syndrome at the age of 10 years, against the background of SARS. Further, the frequency of attacks is 8-9 times a year, exacerbation is more often associated with emotional stress, weather changes, SARS. Over the past year, a continuously recurring course of the disease has been noted - weekly night attacks of suffocation. Basic therapy with non-steroidal anti-inflammatory drugs (cromolyn sodium) did not produce an effect. Repeatedly hospitalized. For the last 3 months he received basic therapy with medium therapeutic doses of inhaled steroids (flixotide) in combination with theopec with a moderate positive effect: against the background of acute respiratory viral infections, which occur almost every month, peak flow metrics worsen, attacks of shortness of breath are noted, which requires the use of inhalations of sympathomimetics. Sometimes an ambulance intervention is necessary.

Viferon-2 therapy was started during the period of AD remission in addition to basic therapy. Interferon status was investigated before treatment, after 6 weeks, 3 months and 6 months from the start of tepapia.

Table 4 Inspection Dates IFN status indicators (IU / ml) Serum IFN IFN α IFN γ 03/28/00 (before treatment) four 16 four 05.15.00 four 128 four 06/27.00 2 64 8 09/26/00. four 64 four

During the observation period (6-month follow-up), there were no severe asthma attacks, moderate seizures were noted three times (against the background of physical activity twice and once against the background of acute respiratory viral infections), stopped with a single inhalation of salbutamol. ARVI was noted once. Clinical improvement during AD can be associated with a decrease in intercurrent viral infections, which in this child are a trigger for exacerbation of AD.

Example 2

Parfenov Sasha, 4 years old, and.b. No. 11099, was admitted to the hospital 02.15.00 with recurrent bronchial obstructive syndrome in the acute stage. Clinical diagnosis: bronchial asthma, atopic, moderate course, attack period. Atopic dermatitis, stage of exacerbation. From the anamnesis it is known that in a child with a burdened family history of atopy (in mothers - bronchial asthma) from 3 months there are manifestations of atopic dermatitis. From 6 months of age, against the background of acute respiratory viral infections, which are noted 3-4 times a year, wheezing wheezing was heard during auscultation. Three episodes of difficulty in wheezing were noted. As a result of the clinical, laboratory and allergological examination, the child was diagnosed with bronchial asthma, atopic, moderate severity, an attack period and basic therapy was prescribed: taileda inhalation through a spacer 2 times a day, salbutamol inhalation through a nebulizer 3 times a day, then - needs.

In the post-attack period, Viferon-1 was prescribed in complex therapy. Interferon status was investigated before treatment, after 6 weeks, 3 months and 6 months from the start of therapy.

Table 5 Inspection Dates IFN status indicators (IU / ml) Serum IFN IFN α IFN γ 03/02/00. (before treatment) 8 32 8 04/10/00 four 320 four 06.06.00 four 64 8 09/14/00. four 128 four

There were no asthma attacks during the follow-up period (6-month follow-up). ARVI suffered once. Clinical improvement during AD can be associated with the appointment of adequate anti-inflammatory (basic) therapy and with a decrease in intercurrent viral infections, which in this child are a trigger for exacerbation of AD.

Example 3

Fetisova Katya, 8 years old, and.b. No. 11246, was admitted to the hospital on 12.05.00 for planned hospitalization. Clinical diagnosis: bronchial asthma, atopic, mild course, period of remission. From the anamnesis it is known that in a child with a family history of atopy (grandmother-pollinosis) from 6 months of age, recurrent bronchial obstruction syndrome is observed, as a rule, against acute respiratory viral infections, which are noted 3-4 times a year. At the age of 6 years, the child was diagnosed with bronchial asthma, atopic, mild course. He receives basic therapy: inthal inhalation 4 times a day, with a satisfactory effect, however, against the background of acute respiratory viral infections, peak flow metrics are always worsening. In combination with basic anti-inflammatory therapy, the child was assigned Viferon-2. Interferon status was investigated before treatment, after 6 weeks, 3 months and 5.5 months from the start of therapy.

Table 6 Inspection Dates IFN status indicators (IU / ml) Serum IFN IFN α IFN γ 05.15.00. (before treatment) 2 32 8 06/27.00 four 128 16 08/28.00 8 64 8 10/31/00. four 128 four

There were no asthma attacks during the follow-up period (6-month follow-up). ARVI suffered once. Clinical improvement during AD can be associated with a decrease in intercurrent viral infections, which in this child are a trigger for exacerbation of AD.

Thus, from the presented data it follows that the claimed method allows you to objectively improve the treatment of children with AD, often and / or long-term ill ARVI. The claimed method has several advantages:

- Clinical effect - the frequency of exacerbations of asthma in children, often suffering from acute respiratory viral infections, decreased, the severity of the attack decreased, the period of remission of asthma lasted.

- Economic effect - the frequency of hospitalizations has decreased, the cost of treatment of the initial period has decreased

- Favorable effect on interferon status - the ability to produce α-INF by leukocytes effectively increased to the level of healthy ones and remained in most children for six months of observation.

- The protective effect is a reduction in the frequency of subsequent ARVI.

Information sources

1. Allergic diseases in children. Manual for Doctors / Ed. M.Ya. Studenikina, I.I. Balabolkina. M., M., 1998, 344 p.

2. Bronchial asthma in children. Ed. S.Yu. Kaganova. M., M., 1999 (prototype).

3. Bronchial asthma. Ed. A.G. Chuchalina. In 2 volumes. M., 1997.

4. Grigoryan S.S. Interferon inducers: the effect on interferon status is normal and pathological. // Abstract. Dis .... Ph.D. - Moscow. - 1992.

5. National program "Bronchial asthma in children. Treatment strategy and prevention." M., 1997.

Claims (1)

A method of treating bronchial asthma in children who often and / or have long-term acute respiratory viral infections, including basic therapy, characterized in that Viferon is administered rectally additionally during remission, and Viferon-1 (150,000 ME in one candle) is administered to children aged 3-6 years and for children 7-14 years old - Viferon-2 (500,000 ME in one candle), daily 2 times a day for 10 days and then for 4 weeks every other day.