Method of diagnosing bronchial asthma in children of early age using data of induces sputum cytology

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to clinical immunology and allergology, and can be used in pediatrics for diagnostics of bronchial asthma in children of early age. Method includes analysis of anamnesis data, estimation of clinical symptoms, as well as studying of allergologic status, which is carried out taking into account index of eosinophils in general blood test and level of general immunoglobulin E in blood serum. Additionally carried out is analysis of induced sputum with determination of eosinophil percentage in it. If said index is higher or equal 5%, it is considered to be main proof for diagnosis "bronchial asthma".

EFFECT: method allows for the first time to establish diagnosis of disease in children under 5 years old from group of risk on bronchial asthma development.

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The invention relates to medicine, namely to clinical immunology and Allergology, in particular for diagnostics of bronchial asthma in children up to 5 years, and can be used in Pediatrics.

The difficulty lies in the following.

Bronchial asthma in 70-80% of cases will debut in children of early age and has a high clinical variability. A widespread perception of a favorable prognosis of childhood asthma is not fully justified. If asthma manifests up to 3 years, it is more gravity. [Tatochenko VK, 2004]. Bronchial asthma, which debuted in childhood, in 60-80% of cases continues in patients who have reached adulthood [NAC. program 2008; Tatochenko VK, 2006].

Diagnosis of asthma in young children is primarily based on the basis of anamnesis and evaluation of clinical symptoms. Study of the function of external respiration for the purpose of diagnosis of bronchial asthma in children of this age group is not performed. Evaluation of the results of Allergy examination can help to identify cause-significant allergen causing the development of bronchial asthma patient. [NAC. Program 2008; global strategy for treatment and prevention of..., 2006; Clinical guidelines. Pediatrics 2005-2006]. Critical timely diag is astika bronchial asthma, including light of its forms, which often remain undiagnosed, children do not receive adequate therapy and the disease becomes more severe with age. In the diagnosis of bronchial asthma in children of early age it is important to exclude other causes of bronchial obstruction. Thus, in children aged 5 years and younger for the diagnosis of bronchial asthma may need to conduct additional studies [global strategy for treatment and prevention of..., 2008; Furman EVGENIY, 2006].

In addition, there are features of bronchial asthma in children of early age.

Bronchial asthma in children of early age are often masked under such diagnoses as SARS with obstructive syndrome, recurrent bronchitis, obstructive bronchitis, bronchiolitis [NAC. Program 2008; Besh L.V., 2008]. In the national program "Bronchial asthma in children..., 2008 says that you are experiencing episodes of obstruction in a child more than 2 times during the year, you should think about the possible debut of bronchial asthma. Although according to Tatochenko VK in some children, the early episodes of obstruction can be the beginning of bronchial asthma (2004).

Obstructive syndrome (syndrome of bronchial obstruction) is a complex of clinical symptoms developing in the generalized narrowing of the lumen Bron is impressive. Clinical symptoms (shortness of breath expiratory character, cough, initially dry or unproductive difficult to cough up sputum, and then wet) and physical data (boxed shade pulmonary percussion sound, dry rales in the background of the prolonged exhalation auscultatory) [Korovin N.A., 2007; Tatochenko, 2006]. Bronchoobstructive syndrome is the major clinical manifestation of obstructive bronchitis.

The differential diagnosis of obstructive bronchitis and bronchial asthma especially when the first signs is enough complexity that is associated with a similar clinical picture similar x-ray, functional and laboratory (including immunological) changes [NAC. program 2008; Besh L.V., 2008; Geppe, N.A., Kolosova N.G., 2006, Meshcheryakov CENTURIES, 2006; Miernicki UL, 2005]. Diagnosis of asthma in this case made even more difficult by the fact that approximately 30% of children may not be burdened heredity may not be signs of allergies at an early age, such children have bronchial asthma is formed faster as we do not take them into account [Kitarov G.S., 2006; Beland, 2006].

The results of the remote observation (after 4-8 years or more after hospitalization due to severe broncho-obstructive syndrome due to acute respiratory infections in age from one year to 3 years) show the, that more than 50% of these children suffer from typical bronchial asthma is not recognized at an early age, when you could affect natural disease [NAC. Program 2008; Sejal Saglani 2007, Meshcheryakov CENTURIES, 2006; Miernicki, 2005]. Thus, only after years of painting "obstructive bronchitis acquires the features of a typical bronchial asthma.

Given the existence of many of the recommendations of the tables and indexes in the differential diagnosis of bronchial asthma, it can be concluded that the distinction between obstructive bronchitis and bronchial asthma remains uncertain [NAC. Program 2008; Besh L.V., 2008].

In addition to the difficulties of differential diagnosis of broncho-obstructive syndrome in children, there is another problem - atypical bronchial asthma, so called her cough form [NAC. Program 2008; Geppe, N.A., 2006; Goleusova SS, Barysheva NV, I. Ovsyannikov, 2005]. Bronchial asthma in the early stages may show small signs of episodic or predominantly nocturnal cough, occasional wheezing, shortness of breath during physical activity [national programme for 2008; the global strategy for treatment and prevention of bronchial asthma... 2006; Geppe, N.A., 2006; minkailu K.-MO, minkailu E.K., 2006; Meshcheryakov CENTURIES, 2006; Lyapunov A.V., 2003; Gushchin I.S., 2002; Chuch of the Lin A.G., Abrosimov, VN, 2000]. According to some authors to 86% of patients with bronchial asthma do not fall within the field of view pulmonologists because of a lack of typical attacks [Goleusova SS, Barysheva NV, I. Ovsyannikov, 2005].

Thus, the conclusion is that the urgent task of modern medicine is early diagnosis of bronchial asthma, namely the identification of allergic airway inflammation in young children at risk for development of asthma, i.e. suffering from allergic rhinitis, atopic dermatitis, recurrent obstructive bronchitis, sickly children and children with long-lasting cough after suffering respiratory infections [NAC. Program 2008; Zaitseva O.V. 2008; Kozicka D.V., Ogorodova L.M., Deev I.A. and others, 2007; zabolotskikh T.V., Miernicki UL, dorovskikh, VA and others, 2005].

The known method for the diagnosis of atopic form of bronchial asthma, presented in p. the Russian Federation No. 2339951 on CL G01N 33/53.

The known method is that the sample of venous blood lymphocytes secrete add to them simultaneously monoclonal antibodies and CD19 CD23, incubate the mixture at room temperature, and counted on a flow cytometer number of cells labeled (CD19) and cells double labeled (CD19CD23), calculate the index of allergic inflammation by the formula: ((CD19CD23)/(CD10))is 100% and the index more 70%, diagnose atopic form of bronchial asthma.

The disadvantages of this method is its limited operational capabilities, because it is invasive, time-consuming, expensive and cannot routine use as a screening method for diagnosis and it is suitable only for the diagnosis of atopic form of bronchial asthma.

A known method of differential diagnosis of bronchial asthma and obliterating bronchiolitis in children, described in the same patent RF №2159935 on CL G01N 33/52, 33/483, 33/68.

The known method is that the measured intensity of the intrinsic fluorescence of cells in the bronchoalveolar lavage fluid, and measuring the intensity of native fluorescence of intracellular prenucleation (NADH) at a wavelength of 356 nm excitation and wavelength registration 420-480 nm and flavoproteins (AF) at a wavelength of excitation of 440-480 nm, and the wavelength registration of 510-550 nm, determine the ratio of the intensity of intrinsic fluorescence of intracellular prenucleation and flavoproteins, and when the ratio is greater than 1 to be diagnosed with bronchial asthma, and when the ratio is less than 1 - obliterative bronchiolitis.

The disadvantages of this method are not very high reliability, as well as invasiveness, complexity, Dorogova is on.

A known method for the diagnosis of bronchial asthma in children of early age, described in the "Clinical Protocol for the diagnosis and treatment of bronchial asthma" in Annex 7 order No. 807 of the Ministry of health of the Republic of Belarus" from 25.10.02 (ch.3., str-214) (see website:

http://minzdrav.by/med/docs/sprav/DiagnBronhAstma.doc).

The known method is based on the anamnesis, evaluation of clinical symptoms, the study of respiratory function and assessment of bronchial reactivity (in children older than 5 years and adults) and the study of allergic status.

More specifically it includes both mandatory the following operations: collection of anamnesis, complaints; assessment of clinical syndromes through percussion, auscultation, measuring breathing frequency; a study of respiratory function with peak flow reading, x-ray of the lungs and sinuses, spirography and pneumotachography, as well as the study of the function of external respiration when exposed to broncholytics, drug provocation, provocation by exercise; hyperventilation break; study of allergic status provides a General analysis of blood + platelets; cytological examination of mucus from the nose; microscopy of sputum smears; cytological examination of sputum for eosinophils; the study of fecal Giardia and helminths; e is cardiogram; a doctor's consultation of the allergist-immunologist; consultation of the doctor - otolaryngologist; consultation of a physician - pulmonologist.

As an additional diagnostic can also be used if necessary with immunological determination of total and specific IgE. As an additional diagnostic can also be used if necessary with immunological determination of total and specific IgE; triglycerides: the clotting time of blood by the Lee-white, activated partial thromboplastin time, prothrombin time, ethanol test, fibrinogen And retraction blood clot, spontaneous fibrinolysis; the gas composition of the blood (PaO2, PACO2, SatO2); determination of the parameters of acid-base status; computed tomography high-resolution thoracic cavity; bronchoscopy; ultrasound of the heart; consultation of the psychotherapist.

The clinical manifestations of bronchial asthma reveal symptoms such as episodic expiratory dyspnea, wheezing, a feeling of constriction in the chest, coughing, and the dependence of these manifestations depending on sensitization, namely as a manifestation of food Allergy, household sensitization, isolated sensitization to allergens, Pets, manifestations of occupational allergic lesions is letisti nose and eyes. Manifestations of occupational bronchial asthma are below-mentioned, examined bronchoalveolar lavage (if indicated) and perform laboratory immunological tests.

Assessment of respiratory function (respiratory function) is performed using a peak flow reading, the method spirography, pneumotachography (computer flowmetry) registration FVC and FEV1 and relationships FEV1/FVC, and DEDICATED (where FVC - forced vital capacity, FEV1 - forced expiratory volume in the 1st second, DEDICATED to - peak volumetric expiratory flow). There are also tests bronchodilatory to detect hidden bronchospasm sample in the interictal period in bronchial hypersensitivity. Children used non-pharmacological methods for the determination of nonspecific bronchial hyperresponsiveness: the exercise tests, tests with hyperventilation dry chilled air.

Allergy testing for bronchial asthma is carried out using skin tests, in particular "scratch and kolacny" in the period of clinical remission of asthma. In severe bronchial asthma use modern laboratory tests (radioimmune, enzyme immunoassay, chemiluminescent) to determine specific IgE and IgG antibodies in the blood and sencibilizirovannam lymphocytes.

Analyze also the course of studies the environmental aspects.

As clinical criteria for the differential diagnosis of bronchial asthma and obstructive syndrome on the background of acute respiratory infections in children of early age in the Protocol are the following: age; symptoms of obstructive syndrome; repeatability obstructive syndrome; family history of allergic diseases, including the presence of bronchial asthma on maternal line; a history of allergic reactions to foods, medications, immunizations; excessive antigenic load.

Probably, this method of diagnosis with such a full list of mandatory procedures and activities is diagnostically very reliable. However, from the viewpoint of applicants, the disadvantages of this method are its complexity, as well as some unreliability and inconvenience of implementation due to the amount of procedures that cannot be done or are not informative in a child under 5 years, such as radiography of the lungs and sinuses, the study of respiratory function with tests with bronholitikami, exercise and hyperventilation of the lungs.

A known method for the diagnosis of bronchial asthma in children, described in the same as. the USSR №1413532 on CL G01N 33/53, Appl. 18.02.87, publ. 30.07.88 and selected for the prototype.

Known ways what is they spend analysis data of anamnesis, evaluation of clinical symptoms, as well as the study of allergic status, thus determine the level of eosinophils and levels of total immunoglobulin E serum, and additionally determine the titer complimentative antibodies to parainfluenza viruses and respiratory sindicalismo and when it is 1/40 or more diagnosticum autopistol form of bronchial asthma, and when the titre of 1/10-1/20 diagnosticum atopic form.

The disadvantage of this method is that it is designed for the differential diagnosis has already been detected in bronchial asthma, i.e. refinement of an already established diagnosis, namely the separation of atopic and autopistol form, and does not allow to identify in children under 5 years bronchial asthma at an early stage of illness of the child, i.e. first to establish the diagnosis of asthma in children at risk for development of asthma.

The objective of the proposed method is the ability to identify at an early stage of the disease bronchial asthma in children 5 years of age.

The problem is solved in that in the method for the diagnosis of bronchial asthma in children up to 5 years, including the analysis of the data of anamnesis, evaluation of clinical symptoms, as well as the study of allergic status, which is carried out with use what Itanium General analysis of blood, in which determine the level of eosinophils and levels of total immunoglobulin E serum, according to the invention additionally conduct cytological examination of induced sputum, specifying in it the percentage of eosinophils at the level of which is greater than or equal to 5%, consider it a major evidence-based laboratory indicator of the diagnosis of bronchial asthma.

Use as evidence of a biological marker such additional criteria of diagnosis of asthma as the level of eosinophiles in sputum ≥5% in conjunction with confirming his blood eosinophils and serum total immunoglobulin E in serum makes it simple and convenient for the child and reliably determine the diagnosis of bronchial asthma in a child 5 years of age.

The technical result - ensuring detection of bronchial asthma in children under 5 years, at an early stage of the disease at a high confidence level of the diagnosis and the convenience of diagnosis for a child.

The inventive method has the novelty in comparison with the prototype, differing from it in such an essential feature, as the use as the primary evidence-based laboratory criteria for diagnosis of bronchial asthma of the cytological study of induced sputum for eosinophils at their level in the municipalities of the company is greater than or equal to 5%, ensuring the achievement of a specified result.

Although the known analogue (see above) as one of the essential elements of diagnosis of asthma in children and appears cytological examination of sputum for eosinophils, but in the evidence of biological parameters it is not enabled, any valid level of eosinophils in the sputum or in what capacity is not specified, therefore, the applicant believes that the inventive method with these distinctive features, ensuring the achievement of a specified result, meets the criterion of "inventive step".

The inventive method of diagnosis can be widely used in Pediatrics for the diagnosis of bronchial asthma in children up to 5 years, and therefore meets the criterion of "industrial applicability".

The invention is illustrated by drawings, where:

- 1 - table with the data of the average level of eosinophils in induced sputum in the examined children at baseline and after 18 months of follow-up;

- figure 2 - characteristic curve method of diagnosis of asthma in children by level of eosinophils in induced sputum (%);

- figure 3 - characteristic curve method of diagnosis of asthma in children by level of eosinophils in the General analysis of blood (%) (AUC-ROC 0.61);

- 4 - har is charitiesa curve method of diagnosis of asthma in children by level of total IgE in serum (IU/ml) (AUC-ROC 0.67).

The inventive method for the diagnosis of bronchial asthma in children under 5 years is as follows.

A method for the diagnosis of bronchial asthma in children under 5 years includes the analysis of the data of anamnesis, evaluation of clinical symptoms, the study of allergic status. Thus the evaluation of the clinical manifestations of bronchial asthma is to identify such symptoms as occasional expiratory dyspnea, wheezing, a feeling of constriction in the chest and coughing by means of auscultation and percussion. The study of indicators of allergic status, make use of a common blood and cytological studies of a number of secretions, namely sputum. While in the blood to determine the level of eosinophils and levels of total immunoglobulin E, and cytological examination of sputum also determine the level of eosinophils. As the primary evidence-based laboratory indicator of the diagnosis of bronchial asthma use this biological marker as a result of cytological examination of sputum for eosinophils at their level in the specimen is greater than or equal to 5%.

The method is as follows.

First, analyze the data history.

When collecting of the anamnesis it is necessary to clarify the following:

- the presence of a hereditary family history for asthma or other atopic is Kim diseases, related allergic diseases (atopic dermatitis, allergic rhinoconjunctivitis etc) the child now or in history;

the presence of cough, worse mainly at night; recurrent wheezing; repeated episodes of difficult breathing; feeling of tightness in the chest, episodes of bronchospasm caused by exercise;

- a history of repeated episodes of bronchial obstruction, especially occurring against the background of normal temperature;

the deterioration in day, night or pre-dawn hours, when exposed to allergens or triggers. You can change the severity of symptoms during the day and during the year depending on the spectrum of sensitization. The disappearance of the symptoms, eliminating contact with the allergen (effect off), the improvement after applying broncholytics.

Evaluate clinical symptoms. In most children the first appearance of typical attacks expiratory dyspnea, usually preceded by symptoms of atopic dermatitis, severe allergic reactions to various foods, medicines (absentem, urticaria, swelling Kvinke). Attacks obstruction develop at any time of the day and clinically manifest expiratory or mixed with a predominance of expirate the aqueous component shortness of breath with indrawing compliant seats of the chest, it emphysematous swelling, obsessive (sometimes vomiting) dry or productive cough, diffuse dry rales in the lungs, as well as common mixed with moist rales, continued long, for 5-10 days or more, detected by percussion and auscultation. Noisy wheezing is heard even at a distance, expressed pallor of the skin, marked cyanosis of nasolabial triangle, acrocyanosis. Often the child is taking a forced position (orthopnea), pale, feeling violated. Clinical symptoms of bronchial asthma varies throughout the day. You should discuss the whole set of symptoms for the last 3-4 months, paying particular attention to those that bothered during the previous two weeks. Wheezing should be confirmed by a doctor, because parents may misinterpret the sounds of their child during breathing.

In remission pathological symptoms may be absent, that does not exclude the diagnosis of asthma.

Due to the anatomic-physiologic characteristics of children of early age (narrow lumen of the bronchial tree, underdeveloped muscle layer, significant development of blood and lymphatic vessels) bronchospasm is usually not among them leading the mechanism in the pathogenesis of bronchial asthma attacks. On the PE the first place is the inflammation of the bronchial mucous membrane, her edema and hypersecretion of mucus, which leads to a peculiar clinical presentation of humid asthma in this age, is less acute and greater duration of attacks.

Study the allergic status of the patient. To do this, find family history of allergic diseases (especially maternal), set the frequency of allergic reactions to foods, medications, immunizations, determine whether denominated allergic skin manifestations of allergic rhinitis, conjunctivitis. In the process of studying allergic status are taking common blood test for determining the level of eosinophils, are conducting a study of the levels of total immunoglobulin E (IgE) in the serum. Also produce sputum collection for its cytological study to determine the level of eosinophils (%).

Given the fact that the main pathological changes in bronchial asthma occur at the level of the bronchial tree, analyze sputum to study cyto-immunological changes on a topical level. Sputum in children of early age obtained using modified and patented by the authors of the method of induced sputum (see application No. 2008116364, the decision to grant a patent on 18.02.09).

In order to identify cytological is retriev diagnosis of bronchial asthma in induced sputum authors conducted a cohort study.

In the cohort study included 72 children aged from 22 to 48 months. (average age of 36 months.) with atopy and episodes of obstructive bronchitis in history. To account for laboratory and clinical manifestation of asthma at 18 months for children observed with re-examination, history taking and determining the cellular composition of induced sputum every 6 months.

Of the 72 children with episodes of obstructive bronchitis in history for 18 months. observation of bronchial asthma was formed in 43 children (60%). To identify cytological criteria for the formation of bronchial asthma 72 children were divided into 2 groups:

group 1 - children without asthma at study end;

group 2 - children with manifestirovanne bronchial asthma at follow-up. (see figure 1).

The predictive ability of the method of diagnosis may be represented as the area under curve (AUC-ROC): the larger this area, the more effective method of diagnosis (see figure 2). When AUC-ROC of 0.5 is considered that the diagnostic value of the method is practically zero.

In order to be able to compare the sensitivity and specificity of currently in use indicators for the diagnosis of bronchial asthma was spent building a ROC-curve for other diagnostic t the Stam. Characteristic curves were constructed diagnostics on the level of eosinophils in the General analysis of blood (figure 3) and total IgE in the blood (figure 4). These indicators were used, as they are the only laboratory criteria, reflecting the presence of allergies and/or atopy, and are used by doctors, allergists at diagnosis: Bronchial asthma.

From figure 3 and 4 shows that the characteristic curve is closer to the diagonal line connecting the lower left and upper right corners, AUC-ROC is 0.61 and 0.67, respectively, which indicates a low informative value of these tests in the diagnosis it is asthma, but not atopic status in General.

In this study, the AUC-ROC (see figure 2) is 0.95, which indicates a high informative method of diagnostics of bronchial asthma by level of eosinophils in the sputum. In a similar study Rytila P. (2002) involving children older than 5 years have also demonstrated that the percentage of eosinophils in sputum (AUC-ROC 0.88) is the most sensitive and specific marker in comparison with blood eosinophilia and total IgE level in bronchial asthma.

Additional analysis of ROC curves is the establishment of a critical level indicator (so-called point cut off the split point).

Using the ROC-curve (see figure 2), we can determine the optimal value of the points of separation. Split point should be near the "shoulder" of the curve. In this study, the optimal value of the split point was the level of eosinophils in the sputum ≥5%.

Thus, if the criteria of diagnosis of bronchial asthma can take the level of eosinophils in induced sputum ≥5%, 96% of children with this indicator have bronchial asthma.

Diagnosis of bronchial asthma in children of early age with the assessment of the level of eosinophils in induced sputum (≥5%) is highly sensitive and specific test.

Clinical example.

Child Maxim K., 2.5 years, enrolled in the children's Department of pathology early age MUSIC city clinical hospital No. 1 in December 2005, for the first time with the purpose of the survey. Upon receipt of a complaint on rude, unproductive cough, appears in the evening after running, out of breath with wheezing, accumulated mucus in the upper respiratory tract, coughs badly.

The history of life and disease: the Child from 2nd pregnancy going on in the background burdened obstetric and gynecological history. After birth - operation concerning the esophageal atresia and tracheoesophageal fistula. The child was often sick up to 8 times per year. On the 1st year suffered 2 episodes of obstructive bronchitis. Over the years ached obstructive bronchitis to 2 times per year. Was seen by a pulmonologist with a diagnosis of Recurrent obstruct wny bronchitis. Syndrome microaspiration. Cicatricial stenosis with/3 trachea, dyskinesia trachea Art. I, bilateral, diffuse, catarrhal endobronchitis.

Inspected ACC. The Department of gumada - conclusion: Recurrent broncho-obstructive syndrome, bronchial hyperresponsiveness.

Family history my grandmother has chronic bronchitis.

Burdened risk factors from birth manifestations of the EKD, 6 months - atop. the dermatitis.

Taking into account observations associated malformation of the respiratory tract to the child, stenosis of the trachea, bronchopulmonary dysplasia in the history of the changes in the respiratory tract of many specialists, including pulmonologists, was regarded as a consequence of this condition is not assigned adequate therapy, the child has repeated episodes of bronchial obstruction.

For specification of the diagnosis and selection of therapy the child was hospitalized in the Department of pathology of early childhood MUSIC city clinical hospital No. 1.

Given the complex diagnostic case in a young child with the accompanying corrected congenital anomaly of the respiratory tract, tracheal stenosis, the child was a study of induced sputum Cytology modified by the authors of the Protocol induction of sputum for children who are unable to cough effectively independently (see application No. 2008116364, the decision to grant Pat the NTA from 18.02.09).

The received portion of the sputum were subjected to cytological examination using the standard method.

Cytology of induced sputum

dateeosinophils
in the p/SP.
neutrophils
in the p/SP.
macrophages
in the p/SP.
lymphocytes
in the p/SP.
the epithelium
in the p/SP.
mucusBacteria, fungi
19.12.0517%22%53%8%one.+++cocci

Given the repeated episodes (more than 3) bronchial obstruction (against respiratory infections, after exercise), increased levels of eosinophils in the peripheral blood, increased levels of total immunoglobulin E, burdened allergic disease (allergic rhinitis, atopic dermatitis), and given the increased level of eosinophils in induced sputum (the Manual. Clinical recommendations for diagnosis, treatment and prevention of bronchial asthma, shortness of breath. Edited by Chairman of the Russian is aspirating society, academician of RAMS, Professor chukalina, Moscow, 2005 - p.16) detection of sputum eosinophilia when Cytology is an important criterion for confirmation of the diagnosis of asthma), according to the "Scientific-practical program of Bronchial asthma in children: diagnosis, treatment and prevention, Moscow, 2008," the child was diagnosed with Bronchial asthma. Recommendations for basic treatment.

In comparison with the prototype of the proposed method is more simple, has a very high degree of reliability and is more comfortable for the child.

A method for the diagnosis of bronchial asthma in children up to 5 years, including the analysis of the data of anamnesis, evaluation of clinical symptoms, as well as the study of allergic status, which is performed using the General analysis of blood, which determine the level of eosinophils and levels of total IgE in serum, characterized in that it further conduct cytological examination of induced sputum, specifying in it the percentage of eosinophils, with levels greater than or equal to 5%, consider it a major evidence-based laboratory indicator of the diagnosis of bronchial asthma.



 

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1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to diagnostic methods and deals with method of diagnosing entry of nuclei of placenta pili syncyotrophoblast into apoptosis by determining in placenta homogenate content of IgG and IgM antibodies to phosphatidylserine in pregnant women, who had herpes-virus infection in the third trimester of pregnancy. Method lies in determination of IgG and IgM antibodies to phosphatidylserine in placenta homogenate by ELISA method. If titre of antibodies to HSV-1 equalled 1:6400, 4.70±0.08 U/ml of IgG and IgM antibodies to phosphatidylserine were detected; if titre was 1:12800, content of IgG and IgM antibodies to phosphatidylserine increased to 5.60±0.06 U/ml (control - 2.50±0.07 U/ml), number of syncyotrophoblast nuclei in state of apoptosis constituted 4.50±0.20% (control - 1.5±0.20%).

EFFECT: method possesses high sensitivity and allows to predict development of apoptosis in nuclei of placenta pili syncyotrophoblast in case if number of IgG and IgM antibodies to phosphatidylserine in placenta grows.

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to internal diseases, diagnostics. Method is based on determination of general oxidant activity (GOA) and general antioxidant activity (GAA) with further determination of oxidant index (OI), which equals ratio of GOA to GAA. In accordance with the invention oxidant activity is determined by degree of echinochrome A oxidation by components of oxidant system of blood serum or plasma, and general antioxidant activity is determined by degree of echinochrome A oxidation with chloramine B, added to blood serum or plasma. OI index of healthy donor is taken as a unit. OI value higher than a unit testifies to disbalance of general oxidant status of organism. Method ensures up to 20 fold reduction of amount of analysed serum or plasma in comparison with standard methodology, reduction for carrying out analysis from 72 hours to 2 hours. When ranging it is possible to perform analysis of more than 500 samples during one day, using microboards and microplate spectrophotometers.

EFFECT: method is simple in implementation, economical and does not require large volume of thermostatically controlled chambers.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to neuroinfections. In children older than 11 years old, determined are presence of retrobulbar neuritis (XI), foci of white and gray substance of brain and spinal marrow CNC (X2), in blood: progesterone in nmol/k (X3), luteinising hormone (LH) in MU/l (X4), folliculostimulating hormone (FSH) in MU/l 1 (X5), testosterone in nmol/l (X6), estradiol in pkmol/l (X7). By obtained values discriminant function,

is calculated. If Y values are lower than 0.5, favourable outcome is predicted, if Y values are higher than 0.5 - development of disseminated sclerosis is predicted.

EFFECT: method increases accuracy of predicting disseminated sclerosis development, which is achieved due to application of prognostically significant indices and their complex estimation.

3 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to physiology, biochemistry and can be used for express diagnostics of organism adaptation to hypokinesia both in usual conditions, and during space flights. Blood parametres are determined in patients only with hypokinesia and with hypokinesia at the background of desmopressin introduction, obtained results are compared and conclusion is made, as parametres mass-spectral determination of proteomic profiles of blood serum in mass range from 1000 to 17000 with processing of samples with magnetic particles MB WCX and MB IMAC Cu is carried out, and if there is no change in signal intensity after introduction of desmopressin with pre-fractioning by magnetic particles MB IMAC Cu m/z=9133 in comparison with initial data, as well as with reliable reduction of peak intensity m/z=1297, m/z=2769, m/z=7764, m/z=6432, m/z-6630 when pre-fractioning with magnetic particles MB WCX in these users stage of organism adaptation to hypokinesia with introduction of desmopressin is diagnosed.

EFFECT: method acceleration, possibility to determine about 20 parametres during one analysis, minimal amount of biomaterial (5-10 mcl), as well as possibility of said technique automation.

5 cl, 3 tbl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to therapy and gastroenterology. Clinical symptoms and risk factors are determined from life anamnesis: presence of dry cough, presence in anamnesis of chronic obstructive lung disease, presence in anamnesis of bronchial asthma, regular intake of broncholytic medications, presence of tickling in throat, presence in anamnesis of chronic diseases of ENT organs (laryngitis, pharyngitis, sinusitis, recurring otitis media), expression of cardialgia, regular intake of beta-blockers, regular intake of calcium antagonists, remotedness of endured myocardial ischemic attack. Their gradations and numerical values are determined, after which prognostic coefficients are determined. On the basis of comparison of prognostic coefficients values, risk of unfavourable course of gastroesofageal reflux disease is predicted.

EFFECT: method allows to increase accuracy of prediction.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to otorhinolaryngology. Before surgery in patient's nasal cavity type of skull construction is determined by head index. If it corresponds to brachycephaly, hemorrhage from posterior parts of nasal cavity is predicted; in case of dolichocephaly - hemorrhage from anterior parts of nasal cavity or ethmoidal labyrinth, and in case of mesocephaly - possibility of hemorrhage from both anterior and posterior parts of nasal cavity.

EFFECT: method allows to reduce frequency and expression of intra- and post-operative nasal hemorrhages.

2 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to abdominal surgery. It is found out if patient complains of weakness, dizziness, cold sweat and vomiting, determined are anamnesis duration, patient's general state, pallor of skin and mucous membranes, pulse, arterial systolic pressure, type of feces. Endoscopically stomach contents, type of hemorrhage, thrombus colour, vessel visibility are determined. Content of erythrocytes and hemoglobin are determined. In case if expressed weakness, expressed dizziness, cold sweat, repeated coffee-grounds vomiting with blood clots, 1-6 hour anamnesis, extremely severe or severe general state, expressed pallor of skin and mucous membranes, pulse 90 beats/min and more (tachycardia), systolic arterial pressure lower than 90 mm Hg, liquid tarry stool, contents of stomach in form of coffee-ground with fresh blood clots, jet bleeding, thrombus of scarlet colour, visible vessel, number of erythrocytes lower than 2.5×1012/l, hemoglobin concentration less than 83 g/l are present, type of hemorrhage is estimated as arterial and emergency surgery is considered indicated. In case of presence of moderate weakness, slight dizziness, absence of cold sweat, single coffee-ground vomiting, anamnesis of more than 6 hours of relatively satisfactory or middle severity of general state, moderate pallor of skin and mucous membranes, pulse lower than 90 beats/min, systolic arterial pressure 90 mm Hg and higher, formed feces of black colour, stomach contents in form of coffee-ground with remnants of food, blood flowing from edges or bottom of ulcer, thrombus of dark colour, absence of visible vessel, number of erythrocytes 2.5 × 1012/l and higher, hemoglobin concentration 83 g/l and higher, type of hemorrhage is estimated as venous and conservative treatment is considered to be indicated.

EFFECT: invention application increases accuracy and simplifies method.

3 dwg, 1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to infectious diseases, and can be used for prediction of the risk of development of severe hemorrhagic fever with renal syndrome. DNA is recovered from lymphocytes of peripheral venous blood; PCR-analysis of CYP1A1 and GSTP1 polymorphic loci follows. If observing heterozygous genotype AG of GSTP1 gene or combined 1A2C/AG genotypes of CYP1A1 and GSTP1 genes, the high risk of development of severe HFRS is predicted.

EFFECT: invention provides a precise prediction of development of severe disease.

5 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to neuroinfectious pathology, and can be used for life-time diagnostics of acute cerebral vasculitis in children with neuroinfections. It involves acute thrombocyte count - X1 (×109/l), blood D-dimer index - X2 (mcg/l), circulating endotheliocyte count - X3 (cells), state of consciousness - X4 (1 - clear, 2-clouding, 3 - semicoma, 4 - coma), observed pareses - X5 (0 - no pareses, 1 - observed pareses), and discriminant function calculation by formula: LDF1=-15.510+0.021·X1+0.003·X2+3.975·X3+1.033·X4-2.851·X5 LDF2=-46.301+0.055·X1+0.012·X2+4.914·X3-1.307·X4+3.610·X5. If LDF1 > LDF2 is stated, no cerebral vasculitis is diagnosed, while LDF1 < LDF2 shows cerebral vasculitis to be diagnosed.

EFFECT: invention allows more accurate diagnosing, technique is less traumatic, low-cost, most reliable and available, allows the well-timed administration of a required therapy.

5 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to gastroenterology and therapy, can be used to update a prediction of clinical course of the gastric ulcer (GU). It involves the evaluation of an ulcer defect, Helicobacter infection content, and hemolytic resistance parametres. An individual dynamics of ulcer defect cicatrisation of a wall of stomach is calculated by formula: Cicatrisation dynamics = 0.139831+0.853145·S_prior - 0.0000181334· tlat-0.0221184· Kmax - 0.000185502·HP, where S_prior is the defect area prior to the initiation of treatment, Kmax is a maximum erythrocyte hemolysis rate constant, tlat is latent hemolysis time, HP is the Helicobacter infection content. And if the derived coefficient is equal to or less than 0.6, ulcer healing within a therapeutic standard time limit is predicted, if it exceeds 0.6, prolonged gastric ulcer healing is supposed.

EFFECT: method allows to estimate the ulcer defect cicatrisation dynamics even prior to the initiation of treatment that in turn allows to optimise drug therapy.

1 tbl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely phthisiology, and can be used for prediction of development of respiratory tuberculosis.

EFFECT: method provides more effective genetic prediction of respiratory tuberculosis in adults ensured by PCR-based molecular HLA - DQB1* gene typing, and if detecting HLA - DQB1*05 allele in the genotype, the risk of development of respiratory tuberculosis and unfavourable course are predicted.

1 tbl, 1 dwg, 1 ex

FIELD: medicine, clinical toxicology.

SUBSTANCE: at patient's hospitalization one should gather the data of clinical and laboratory values: on the type of chemical substance, patient's age, data of clinical survey and laboratory values: body temperature, the presence or absence of dysphonia, oliguria being below 30 ml/h, hemoglobinuria, erythrocytic hemolysis, exotoxic shock, glucose level in blood, fibrinogen and creatinine concentration in blood serum, general bilirubin, prothrombin index (PTI), Ph-plasma, the state of blood clotting system. The state of every sign should be evaluated in points to be then summed up and at exceeding the sum of points being above "+20" one should predict unfavorable result. At the sum of "-13" prediction should be stated upon as favorable and at "-13" up to "+20" - prediction is considered to be doubtful.

EFFECT: higher accuracy of prediction.

2 ex, 3 tbl

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