Introduction Drug and drug allergies (LA)- this is a secondary increased specific immune response to medicines and medications, accompanied by general or local clinical manifestations. It only develops reintroduction(contact) drugs. Upon initial contact, antibodies and immune T cells appear. Moreover, T-lymphocytes are able to recognize drugs - haptens, as a result of which T-cells are formed with specific alpha-beta and, less often, gamma-delta receptors, hapten-specific clones of which are isolated in vitro. Among them were Th1, Th2 and CD8 T lymphocytes. Pseudoallergic reactions Drug reactions are nonspecific (without antibodies) increased reactions to drugs that are clinically identical to allergic reactions. There are two categories of patients with this allergy. In some, LA occurs as a complication during the treatment of some disease, often allergic in nature, significantly aggravates its course, and often becomes the main cause of disability and mortality. For others it is occupational disease, which is the main, and often the only cause of temporary or permanent disability. As an occupational disease, LA occurs in practically healthy individuals due to their prolonged contact with drugs and medications (doctors, nurses, pharmacists, workers at medical drug factories). Drug allergy (DA) occurs more often in women than in men and children: among the urban population in 30 women and 14.2 men per 1000 people, and in the rural population, respectively, in 20.3 and 11 per 1000. LA is more often observed in individuals at the age of 31-40 years. In 40 - 50% of cases, antibiotics were the cause of allergic reactions. Mechanisms of drug allergy include immediate, delayed, and pseudoallergic reactions. Therefore, their clinical manifestations are varied, which makes diagnosis difficult, especially in patients with allergies to many drugs, multiple drug allergy syndrome (MDAS). If a side effect of a drug or medication occurs, you must: Determine whether the reaction to them is allergic; Identify the causative allergen drug and establish a diagnosis. Basic diagnostic criteria LA: 1. Presence of anamnesis and characteristic clinical manifestations. 2. Paroxysmal, paroxysmal course and rapidly occurring remission when drugs are eliminated; on the contrary, a sharp aggravation in case of repeated use. 7. Identification of allergen-specific T-lymphocytes (especially in PCCT). 8. Positive skin allergy tests with specific allergen. 9. The effectiveness of nonspecific antiallergic (antihistamines, etc.) therapy. Diagnostic criteria serve following signs: 1) establishing a clear connection between clinical manifestations and medication intake; 2) mitigation or disappearance of symptoms after withdrawal; 3) history of allergies; 4) good tolerability of the drug in the past; 5) exclusion of other types of side effects (toxic, pharmacological, etc.); 6) the presence of a period of sensitization - at least 7 days; 7) similarity clinical symptoms with manifestations of allergies, but not with any other effect; 8) positive allergological and immunological tests. Table 1. Relationship between the clinical picture and diagnosis of drug allergies and pseudo-allergies with the types of allergic reactions Reaction type Mechanism Clinical manifestations In vitro and in vivo diagnostic tests Immediate - anaphylactic Antibodies IgE, IgG4 Shock, urticaria, etc. Determination of IgE, IgG4 antibodies in blood serum and fixed by basophils. Skin, sublingual and other tests - cytotoxic Antibodies IgG, IgM Hematological, etc. Determination of IgG, IgM auto- and hapten-specific antibodies in blood serum - immunocomplex IgG antibodies, IgM, immune complexes Serum sickness, vasculitis Determination of IgM and IgG antibodies, identification of immune complexes. Skin and other tests - granulocyte-mediated IgG, IgA antibodies associated with granulocytes Any clinic Reactions of release of potassium ion mediators and enzymes from granulocytes. Skin and other tests - antireceptor reactions IgG and IgM antibodies Autoimmune reactions Antibodies against cell receptors, cell stimulation or inhibition Slow reactions Immune T lymphocytes Contact dermatitis, organ damage Detection of immune T-lymphocytes Skin and other tests after 24-48 hours Mixed Antibodies IgE, IgG and T lymphocytes Various combined, photosensitivity Determination of antibodies and immune T cells. Skin and other tests Pseudoallergy Nonspecific Any Assessment of leukocyte activation and alternative path complement inducing agents 1. Allergy history When collecting a medicinal allergy history, pay attention to special attention on drug tolerance and possible sources of sensitization to them, taking into account the fact that there may be hidden contacts. Therefore, in addition to the usual allergy history, it is necessary to find out the following. 1. Hereditary predisposition: the presence of allergic diseases (BA, urticaria, hay fever, dermatitis, etc.) in blood relatives. 2. Whether the patient was previously treated with any drugs, whether there were reactions to them and how they manifested themselves: whether drugs were used (orally, subcutaneously, intravenously); were there multiple courses; have there been any reactions to ointments and drops; were vaccines and serums administered, were they adverse reactions; what they were expressed in; is there a connection between intolerance to various medications, vaccines and eggs, etc.; available (had) fungal diseases and whether there is a connection with antibiotic intolerance. 3. Is there any professional contact with medications and with which ones; whether there were any allergic reactions to them; whether they become more acute at work and lessened outside of it; whether the symptoms of other diseases are getting worse. 4. Is there any connection with other types of allergies: presence food allergies; portability food additives(tartrazine), drinks, etc.; are there any chemical, household or professional allergies; whether there is hay fever, asthma or other allergic diseases. 5. Previous allergic diseases suffered by the patient (shock, rash and other reactions to food, medications, serums, vaccines, insect bites and others, what and when). Conclusion: 1) the medical history is complicated and there is a connection between the disease and allergens (an allergological examination is necessary); 2) the medical history is not burdened and there is no connection with the action of allergens (does not require examination by an allergist). If there are clear indications in the anamnesis (or records in the medical history) of an allergy to the drug, then it and drugs that have cross-reacting common determinants should not be administered to the patient and provocative tests (skin tests, etc.) with this drug are not recommended. Maybe laboratory examination. It is extremely necessary if the anamnesis is unclear (the patient does not remember what drug the shock was taken on) or it cannot be collected (unconscious state). During the acute period of an allergic disease, specific tests are often negative, and testing of allergens on patients can exacerbate the exacerbation. Therefore, such examination is usually carried out during remission. An alternative to testing on a patient is a laboratory examination. Allergological examination includes two types of methods: 1) laboratory methods, which must precede tests on the patient; 2) provocative tests on the patient. When assessing the examination of a patient, you should always remember that if the laboratory and/or provocative test is positive, the patient may have a reaction to the test drug and its replacement is necessary. In case negative tests(especially if one is placed) the possibility of a reaction cannot be ruled out.

Ecological changes environment, the avalanche-like increase in the amount of synthetic substances, including medicines and food components, has significantly expanded the population suffering from allergic diseases. Allergization of the population is greatly facilitated by the uncontrolled use of medications for the purpose of self-medication. Therefore An allergy history (AA) became an essential part of the medical history.

The main goals of AA are to clarify possible reactions to the use of drugs, changes in the clinical manifestations of infection with concomitant allergic reactions, as well as conduct differential diagnosis allergic diseases with syndrome-like infectious diseases, especially those accompanied by exanthemas.

First of all, facts of intolerance to antibiotics and other medications, the presence of reactions to vaccinations in the past, and intolerance to certain foods (milk, chocolate, citrus fruits, etc.) must be clarified. Particular attention is paid to the previously used drugs that have increased properties of sensitization of the body (heterogeneous serums, antibiotics, in particular ampicillin, etc.). Various clinical forms of allergic diseases are taken into account (hay fever, bronchial asthma, Quincke's edema, urticaria, Lyme disease, etc.), since these patients must be classified as a group at increased risk of severe allergic reactions.

When assessing an allergic history, one should take into account the fact that some diseases (brucellosis, intestinal yersiniosis, pseudotuberculosis, trichinosis and some other helminthic infestations) sometimes occur with a pronounced allergic component, and focal infections (odontogenic, tonsillogenic) contribute to allergization of the body.

In cases of a good allergy history, it is permissible to limit ourselves to recording " There were no history of allergic diseases or reactions, food intolerances or drug intolerances.”

5.5. Life history

This section of the medical history should give a unique socio-biological characteristics of the patient as a subject of examination, the result of which should be a diagnosis of the disease and an assumption about its possible prognosis. In fact, it reflects the well-known position about the role of social factors in morbidity.

The life history includes information about the living conditions, character and characteristics of the patient’s work. Residence or service in the past in unfavorable sanitary and hygienic areas or in natural foci of infections may suggest a certain group of diseases (droplet diseases, viral hepatitis A, malaria, encephalitis, hemorrhagic fever, etc.) Service in unfavorable climatic conditions, in submarines helps reduce the body's resistance.

For the spread of some diseases, the conditions of accommodation and living of people—dormitories—are important. barracks (diseases of meningococcal infection, diphtheria in large overcrowding, outbreaks of acute intestinal infections in cases of failure to provide sanitary and hygienic conditions in accordance with epidemiological requirements).

Clarification of the specifics of the working conditions and the nature of professional work can reveal the influence of unfavorable specific factors (chemical, radiation, microwave exposure, chronic occupational and environmental stress, etc.) on susceptibility to a particular infection, as well as on the severity of its course.

Collecting an allergic history begins with clarifying complaints from the patient or his parents, allergic diseases in the past, and concomitant allergic reactions. Important information can be obtained by identifying the child’s developmental characteristics before the onset of allergic manifestations, it is possible to detect sources of sensitization and factors contributing to its development. Often this is the mother’s excessive consumption of foods with high allergenic activity during pregnancy and breastfeeding, drug therapy mothers during this period and contact with aeroallergens in homes in high concentrations.

Exposure to these allergens after the birth of a child can also cause sensitization of the body.

Information about previous allergic reactions and diseases is essential, which most often indicates the atopic genesis of the developed allergic disease. If there are indications of allergic reactions and diseases in the past, the results of an allergological examination and the effectiveness of pharmacotherapy and specific immunotherapy in the past are clarified. Positive result antiallergic therapy indirectly confirms the allergic nature of the disease.

Particular attention is paid to the features of the development of the disease: the time and causes of the first episode of the disease, the frequency and causes of exacerbations, their seasonality or year-round occurrence are determined. The occurrence of allergic symptoms during the flowering season of plants indicates hay fever, and their year-round existence may be associated with sensitization to aeroallergens in homes. The connection between exacerbations of allergies and the time of day (day or night) is also being clarified.

Patients with hay fever feel worse during the daytime hours, when the concentration of pollen in the air is maximum. In children suffering from tick-borne bronchial asthma and atopic dermatitis, the symptoms of the disease intensify in the evening and at night when in contact with bedding. Symptoms of allergic diseases caused by tick-borne sensitization (bronchial asthma, allergic rhinitis, allergic conjunctivitis), appear more often at home, and when changing place of residence or hospitalization, the condition of patients improves. The well-being of such patients worsens when living in old wooden houses with stove heating and high humidity.

In children with diseases caused by sensitization to mold fungi (fungal bronchial asthma, fungal allergic rhinitis), exacerbation of the disease more often occurs when living in damp rooms, near water bodies, in forest areas with high humidity, upon contact with hay and rotten leaves. Accommodation in premises with a large number upholstered furniture, curtains, carpets can increase sensitization to house dust allergens and can cause frequent exacerbations of respiratory and skin allergies.

The relationship between the occurrence of allergic symptoms and the use of certain products nutrition indicates food sensitization. The manifestation of allergic manifestations upon contact with pets, birds, or when visiting a circus or zoo indirectly indicates sensitization to epidermal allergens. In cases of insect allergies, there is a connection between allergic manifestations and insect bites and contact with insects, for example, cockroaches. An allergy history can provide important information about drug intolerance.

In addition to information characterizing the participation of exogenous allergens in the development of allergic manifestations, anamnesis data allows one to judge the role of infection, pollutants, and nonspecific factors (climatic, weather, neuroendocrine, physical) in the development of allergic diseases.

Anamnesis data allows us to determine the severity of an allergic disease and differentiate anti-relapse therapy and preventive measures, determine the scope and methods of subsequent allergological examination to establish causally significant allergens.

Allergy history is the first stage diagnostics, is collected in parallel with the general clinical history and analyzed along with it. The main objectives of the anamnesis are to establish an allergic disease in the child, its nosological form(taking into account the clinic) and presumably the nature of the causally significant allergen, as well as identifying all the circumstances (risk factors) that contribute to the development of an allergic disease, since their elimination has a positive effect on the prognosis of the disease.

For this purpose, when collecting anamnesis, along with the main complaints, attention is paid to studying the premorbid background. The presence of a hereditary constitutional predisposition to is revealed. The presence of allergic diseases in the family history indicates the atopic nature of the disease in the child, and previous exudative-catarrhal diathesis indicates altered allergic reactivity. It turns out, especially in children of the first years of life, the nature of the course of the antenatal period in order to determine possible intrauterine sensitization, which develops as a result of poor nutrition of a pregnant woman, her taking medications, the presence of toxicosis of pregnancy, occupational and household contacts with chemicals and drugs. Our observations have shown that taking medications by a pregnant woman increases by 5 times the risk of developing an allergic disease in a child in the first year of life, and her poor nutrition causes the development of food allergies in 89% of children. The nature of the child’s nutrition in the first year of life and the diet of the nursing mother are also clarified, since the early development of food allergies is facilitated not only by the premature introduction of supplementary feeding, complementary foods, and juices into the child’s diet, especially in excess amounts, but also by the irrational nutrition of the nursing mother. Comparing the timing of the onset of the disease with the introduction of certain food products into the diet of the child or mother makes it possible to presumably determine the food products that are allergenic for him.

When assessing the premorbid background, we take into account previous diseases, the nature of the treatment, its effectiveness, the presence of reactions to medications and vaccines, etc. The presence of pathology gastrointestinal tract and liver predisposes to the development of food allergies, while frequent ARVI facilitates sensitization to inhalant allergens (household, epidermal, pollen), and the child’s existing foci chronic infection may cause the development of bacterial allergies.

Finding out the child’s everyday life allows us to identify potential household and epidermal allergens.

Much attention is paid to the features of the occurrence and course of allergic diseases. The start date is being determined. In children, this factor is important for determining causally significant allergens, since the development of one or another type of sensitization has age-related patterns, which are characterized by the development in the first years of life of food allergies with the subsequent layering on it after two to three years of household, epidermal, and then 5-7 years - pollen and bacterial (Potemkina A.M. 1980).

The nature of the course of the disease is determined - year-round or seasonal exacerbations. The first option is observed with constant contact with an allergen (house dust, food), the second - with temporary contacts: with pollen allergies - during the spring-summer flowering season of plants, with medicinal allergies - during the period of their use, with bacterial allergies - in cold spring and autumn. year. The connection between the exacerbation of the disease and specific allergens is being clarified: with house dust - exacerbation only at home, with epidermal allergens - after playing with animals, when visiting a circus, zoo; with pollen - the appearance of symptoms of the disease only in summer, worsening of the condition outside in sunny, windy weather; for food and medicinal purposes - after consuming certain foods and medicinal substances. At the same time, it is important to establish whether an elimination effect is observed, that is, the disappearance of symptoms of the disease after separation from a given allergen, and if so, this further confirms the causal relationship of the exacerbation of the disease with it.

1 question

LgE - mediated diseases. Principles of disease diagnosis. Features of anamnesis collection. Hereditary aspects of allergic diseases

Type I (anaphylactic, IgE-dependent). Caused by the formation of a special type of antibodies that have a high affinity for certain cells (for example, mast cells, basophils). These antibodies are called homocytotropic [these include human reagins (IgE and IgG4)], since they have a pronounced affinity for cells (tissues) of the same animal species from which they are obtained. Upon entering the body, the allergen is fragmented in the APC into peptides, which are then presented by these cells to Th2 lymphocytes. Th2 cells, in turn, when activated, produce a number of lymphokines, in particular IL-4 (and/or an alternative molecule - IL-13), IL-5, IL-6, IL-10, and also express a ligand on their surface for CD40 (CD40L or CD154), which provides the necessary signal for B cells to induce IgE synthesis. The resulting allergen-specific IgE interacts with specialized FcεRI receptors that have a very high affinity for them (located on mast cells of the mucous membranes and connective tissue, basophils), as well as low-affinity FcεRII (CD23; expressed on the surface of B lymphocytes, monocytes, eosinophils and, possibly, T lymphocytes). CD23 can be separated from cell membranes and enter the circulation, stimulating the production of IgE by B lymphocytes. Upon re-entry, the allergen is bound by IgE antibodies, which causes a chain of biochemical transformations of membrane lipids (pathochemical phase), which results in the secretion of mediators such as histamine, arachidonic acid metabolites (prostaglandin D2, sulfidopeptide leukotrienes: C4, D4, E4), PAF and plasma kinins are activated. Mediators, interacting with receptors of target organs, induce the pathophysiological phase of the atopic reaction: increased vascular permeability and tissue edema, contraction of smooth muscles, hypersecretion of mucous glands, irritation of peripheral nerve endings. These changes form the basis for rapid (early) phase allergic reaction, developing within the first minutes after contact with the allergen. Preparation for cell migration from vessels to tissue is ensured by changes in blood flow in microvessels and the expression of cell adhesion molecules on endothelium and leukocytes. The sequential involvement of adhesion molecules and chemokines in the process leads to tissue infiltration by basophils, eosinophils, T-lymphocytes, mast cells, Langerhans cells. After activation, they also secrete proallergic (proinflammatory) mediators, which forms late (or delayed) phase of the allergic reaction. Typical examples of this type of reaction are atopic asthma, AR, allergic conjunctivitis (AC), allergic urticaria, AS, etc.

PRINCIPLES OF DIAGNOSIS OF ALLERGIC DISEASES

Diagnostics is aimed at identifying the causes and factors contributing to the formation and manifestation of allergic diseases. For this purpose they use specific And nonspecific examination methods.

Diagnosis always begins with clarifying complaints and collecting an allergic history, the features of which often suggest a preliminary diagnosis, studying the history of life and illness, which is carried out by the doctor during the examination of the patient.

Clinical examination methods include medical examination, clinical laboratory, radiological, instrumental, functional and other research methods (as indicated).

Basic principle specific diagnosis of allergic diseases - identification of a causally significant allergen, for which allergic antibodies (specific IgE) are determined or

sensitized lymphocytes and products of specific interaction of antigens and antibodies.

Specific Allergological examination includes:

Collection of allergy history;

Carrying out skin tests;

Conducting provocative tests;

Laboratory diagnostics.

Collecting an allergy history

When interviewing a patient, special attention is paid to the features of the development of the first symptoms of the disease, their intensity, dynamics of development, duration and sensitivity to prescribed pharmacotherapeutic agents.

Find out the family history of allergies, since it is known that 30-70% of patients with allergic diseases have close relatives suffering from allergies.

When collecting anamnesis, the presence or absence of seasonality of the disease, its connection with a cold, changes in climatic, living or working conditions are noted. For example, an indication of the annual development of respiratory manifestations (rhinorrhea, nasal congestion, attacks of suffocation, etc.) and/or itching of the eyelids, lacrimation in the same periods of time (spring or summer months, during the flowering season of certain plants) is characteristic of hay fever, and testing methods with pollen allergens are included in the examination plan for such patients. Patients with an infectious-allergic form of asthma are characterized by an exacerbation of an allergic disease against the background of acute respiratory viral or bacterial infectious diseases, especially in the cold season.

It is necessary to find out the patient’s living conditions, the presence of upholstered furniture, carpets, books, pets, fish, birds in the apartment, and whether the patient’s contact with house dust, animals and other allergens causes an exacerbation of the disease.

Separately, a nutritional history (relationship of symptoms with the consumption of any food products) and pharmacological history (relationship of the development of a reaction with taking medications, its duration, volume of treatment and its effectiveness) are collected.

Food diary analysis. To diagnose a food allergy, the patient is asked to keep a food diary, which indicates

date, time of food intake, name of the product, taking into account the volume and method of preparation, the nature of the symptoms, indicating the time of their appearance and the dynamics of the condition during the day, the nature of the stool, as well as the medications used and their effectiveness.

A correctly collected anamnesis allows not only to clarify the nature of the disease, but also to suggest its etiology, i.e. the culprit allergen or group of allergens.

These assumptions must be confirmed by specific examination methods - skin, provocative and other tests.

Question 2

In vivo tests for diagnostics LgE - mediated diseases. Skin testing. Types of skin tests. Provocative tests.

Skin tests

There are different methods skin testing with allergens in vivo: prick tests(prick tests), prick tests, patch tests, intradermal tests. Skin testing with inhalant and food allergens is performed to diagnose only IgE-related allergic diseases.

For skin testing, use standard serial ones containing 10 thousand protein nitrogen units (PNU - Protein Nitrogen Unit) in 1 ml, water-salt extracts of allergens. These extracts are prepared from plant pollen, house dust, house dust mites, wool, fluff, epidermis of animals and birds, food and other products.

Contraindications for performing skin tests.

Exacerbation of the underlying disease.

Acute intercurrent infectious diseases.

Tuberculosis and rheumatism during exacerbation.

Nervous and mental illness during the period of exacerbation.

Diseases of the heart, liver, kidneys and blood system in the stage of decompensation.

History of AS.

Pregnancy and lactation period.

It is not recommended to conduct a full allergy examination for children under 3 years of age, patients during treatment with glucocorticoids and histamine H1 receptor blockers (reduce skin sensitivity), as well as after an acute allergic reaction, since during this period samples may turn out to be negative due to for depletion of sensitizing antibodies in the skin.

Most often used prick- tests or scarification tests, which are placed on the inner surface of the forearms at a distance of 3-5 cm from each other. Tests for negative (with test control liquid) and positive control (with histamine) are required. The samples are assessed after 20 minutes, taking into account the presence/absence of hyperemia and the size of the blister.

Intradermal tests are more sensitive, but have less specificity; they are used mainly to detect sensitization to allergens of bacterial and fungal origin.

Application tests (patch tests) carried out using standard sets chemical allergens for testing for allergy diagnosis contact dermatitis(definition of HRT - type IV reactions).

Provocative tests

Provocative tests are used when there is a discrepancy between the medical history and the results of skin testing. Contraindications for provocative tests are the same as for skin testing.

Depending on the type of allergen and the method of its introduction into the body, provocative tests are distinguished: conjunctival, nasal, inhalational, sublingual And oral. Used for diagnosing PA natural leukocyte emigration inhibition test

in vivo(TTEEL), developed by A.D. Ado.

Methods laboratory diagnostics

The main indications for prescribing laboratory methods for specific allergy diagnostics carried out in vitro:

Early childhood;

High degree of patient sensitization;

Presence of contraindications to skin testing;

Continuously relapsing course of the disease without periods of remission;

Inability to discontinue antihistamines and other drugs that affect skin sensitivity;

Polyvalent sensitization when testing is not possible in vivo immediately with all suspected allergens within a limited period of examination;

Sharply changed skin reactivity;

False positive or false negative result during skin testing;

Urticarial dermographism.

The following methods are most widely used in clinical practice: specific diagnostics allergies carried out in vitro:

Enzyme immunoassay methods for identifying specific IgE with colorimetric, fluorimetric and chemiluminescent methods of recording results;

Radioallergosorbent test (PACT) to detect specific IgE;

Indirect basophil test (Shelley test);

Direct basophil test (Shelley test);

The reaction of specific release of histamine from basophils in the patient’s peripheral blood.

These laboratory diagnostic methods can only reveal the state of sensitization (the presence or absence of specific IgE antibodies to allergens without taking into account clinical manifestations). Laboratory diagnostic methods are considered as additional measures to clarify questionable results testing in vivo.

When making a diagnosis, one must rely mainly on the patient’s complaints, allergy history data, examination of the patient, skin testing, as well as on the results of a general clinical examination of the patient.

Question 3

Function Study external respiration. Peak flowmetry. Spirometry. Bronchoprovocation tests. Techniques. Indications. Contraindications

Peak flowmetry is a method of determining at what speed a person can exhale; in other words, it is a way of assessing the degree of narrowing airways(bronchi). This method examination is important for people suffering from difficulty in exhaling, primarily for people diagnosed with bronchial asthma, and allows one to evaluate the effectiveness of the treatment.

How is peak flowmetry performed?

IN sitting position, after several calm inhalations and exhalations, you need to take a deep breath, tightly wrap your lips around the mouthpiece of the peak flow meter, which should be held parallel to the floor surface, and exhale as quickly as possible. After 2-3 minutes, repeat the above steps and record the maximum of the two values

How often should peak flow measurements be performed?

The study is usually carried out in the morning and evening; during the initial selection of therapy, it is advisable to conduct peak flowmetry during the day, i.e. three times a day. All indicators must be recorded in the asthmatic’s diary; it is most convenient to note peak flow meter readings on special graphs, which are often included with peak flow meters.

How should peak flow measurements be assessed?

The norm of exhalation indicators is calculated individually, taking into account gender, age, and height. When the best expiratory flow rates are achieved, close to normal and in the absence of asthma symptoms, it is necessary to calculate three colored zones for the convenience of assessing peak flowmetry data. Your most best indicator Peak flow measurements need to be multiplied by 0.8. For example, if you have best value peak flowmetry = 500 l/min, you need to multiply 500 by 0.8, the result is 400 l/min. Any value above 400 l/min will fall within the so-called green zone, which means - normal level bronchial patency. To determine the boundaries of the yellow zone, you need to multiply your best indicator (for example, 500 l/min) by 0.5, the resulting result (250 l/min) will be the lower limit of the yellow zone, and we already know the upper limit (previously calculated value), t .e. the yellow zone in our example will be between 250 and 400 l/min. The red zone is below the level of the lower border of the yellow zone (i.e., in our case, below 250 l/min), any peak flowmetry indicator should require immediate measures to improve bronchial patency

Spirometry is a clinical method for studying the adequacy of external respiration, which is based on measuring the vital capacity of the lungs and the rates of exhalation and inhalation.

This study is indispensable for finding out:

• 
  The absence or presence of diseases of the respiratory system, when the patient has complaints of cough, shortness of breath, and sputum production.
• 
  What stage of the established disease does the patient currently have and is the treatment effective?
• 
  The degree of influence of environmental factors and bad habits on the bronchi and lungs of the patient.
• 
  Influences physical activity on bronchopulmonary system in athletes before training or competitions.

This test can be prescribed from the age of six. Spirometry is performed in the first half of the day, a few hours after breakfast. Immediately before the procedure, the patient must rest for at least 15 minutes in a sitting position. The personnel who will monitor the procedure must instruct the patient, where they talk in detail about the stages of spirography and the actions of the person being examined.

If the patient is taking theophylline medications, they should be discontinued one day before the study, and if inhaled medications, then 12 hours before.

The procedure will not take much time and will not bring painful or discomfort. A clamp is placed on the person’s nose to prevent air leakage, and the subject is connected to the spirograph using a mouthpiece. For 5 minutes the patient breathes calmly and measuredly. Then he exhales as deeply as possible, followed by an inhalation of the same depth, and again, an exhalation, and again, an inhalation. To obtain reliable results, the above cycles are carried out 3 times.

Basic spirometry indicators and their meanings

To determine the degree of respiratory dysfunction, many indicators are needed, but the most important are:

1. 
   FVC – forced vital capacity of the lungs.
2. 
   FEV1 is the forced expiratory volume in the first second.
3. 
   Gensler index or FEV1/FVC.
4. 
   Vital capacity – vital capacity of the lungs.
5. 
   DO – tidal volume.
6. 
   Tiffno index or FEV1/VC.

Spirography indicators depend on the age, health and constitution of the patient. The following digital values ​​of indicators are considered the norm: BC - 500-800 ml, FEV1 - 75%, Tiffno index - 70% and above. The remaining indicators are calculated using special formulas and do not have specific digital values.

Spirometry is needed to determine the type of respiratory system disorder in a particular patient. Pathophysiologists distinguish 2 types of respiratory dysfunction:

• 
  Obstruction is a violation of patency respiratory tract due to swelling of the mucous membrane, spasm of the smooth muscles of the bronchi, and a large amount of sputum. In this case, FEV1/FVC will be less than 70% and FVC will be greater than 80%.
• 
  Restriction is a decrease in the extensibility of the lung tissue itself or a decrease in its volume. Spirometry indicators will be as follows: FVC below 80%, FEV1/FVC ratio above 70%.

To identify the presence and evaluate the severity of bronchial obstruction in clinical practice, the study of external respiratory function (RF) allows the primary diagnosis of BA, differential diagnosis of BA and COPD to be performed. bronchomotor tests.

The following approach can be proposed as an algorithm for diagnosing broncho-obstructive diseases using bronchomotor tests:

Bronchoprovocation tests. To establish the presence of hyperreactivity (susceptibility) of the respiratory tract in patients with respiratory complaints (episodes of difficulty breathing, a feeling of shortness of breath, cough, wheezing in the lungs, sputum production, etc.) with an initially normal EF, pharmacological tests are used (inhalation of solutions of histamine, methacholine, carbachol) or tests with nonspecific provocateurs (eg, exercise).

Inhalations are carried out through a nebulizer in successively increasing concentrations of the solution (from 0.0001 to 0.1%). Inhalation duration -3 min at calm breathing at an arbitrary frequency using a nose clip. Repeated registration of respiratory function in the flow-volume curve recording mode (pneumotachometry) is carried out 30 and 90 s after each inhalation. For analysis they are used smallest values, reflecting maximum bronchoconstriction at a certain dose of histamine. Significant is a decrease in forced expiratory volume in 1 second (FEV1) by 20% or more from the initial value or the clinical equivalent of a positive test - the development of a typical attack of difficulty breathing and scattered dry rales in the lungs.

In this case, the test is considered positive regardless of what concentration of solution inhalation led to such changes.

sample protocol:

• 
  informs about changes in respiratory function parameters as a percentage of the initial values ​​(before the test), which allows you to assess the impact of inhalation on the patient (P%DV column);
• 
  evaluates the objectivity and reliability of spirometric studies both before and after inhalation, the analysis of which is carried out by the MAS-1 spirometer automatically based on monitoring the reproducibility and quality of respiratory maneuvers (part “Test Quality Criteria”);
• 
  clearly illustrates the effects of inhalation by introducing graphical levels of reliable and unreliable changes (diagram to the left of the table of measured values).

In addition, the expert system of the MAS-1 spirometer provides timing, as a result of which repeated studies can be performed at the required time intervals, which guarantees a correct study.

Bronchodilation tests are used to assess the reversibility of airway obstruction.

A test for reversibility of obstruction is usually performed at the time of diagnosis:

• 
  for differential diagnosis of BA and COPD. If, after inhalation of a bronchodilator, FEV returned to the calculated normal (proper) value or
• 
  increases by 12% or more relative to the proper value, then the speed limit air flow, most likely associated with asthma;
• 
  to assess the best achievable level of lung function at present;
• 
  to assess the prognosis of the disease. Some studies have demonstrated that post-bronchodilator FEV1 is a more reliable prognostic indicator than pre-bronchodilator FEV1. In addition, in a multicenter clinical trial IPPB (Intermittent Positive Pressure Breathing Study) found that the degree of bronchodilator response in patients with COPD is inversely related to the level of decrease in FEV1;
• 
  to assess potential response to treatment.

The following requirements apply to the test:

• 
  Preparation:
  • 
    the test should be performed when the patient is clinically stable and does not have an infectious respiratory disease;
  • 
    The patient should not take short-acting bronchodilators for 6 hours before the test, long-acting ß-agonists for 12 hours before the test, slow-release theophyllines or long-acting anticholinergics for 24 hours before the test.
• 
  Spirometry:
  • 
    before inhalation of a bronchodilator, the initial parameters of respiratory function are recorded;
  • 
    the bronchodilator should be given using a metered dose inhaler via a spacer or nebulizer to ensure that the drug is inhaled;
  • 
    recommended maximum doses of bronchodilators: 400 mcg ß-agonist short acting, 80 mcg of a short-acting anticholinergic or a combination of these drugs;
  • 
    a repeat study should be carried out 10-15 minutes after inhalation of a short-acting ß-agonist and 30-45 minutes after inhalation of a short-acting anticholinergic or combination drug.

The response to a bronchodilator depends on the dose of the drug used; time elapsed after inhalation; bronchial lability and pulmonary function status; reproducibility of indicators used for comparison; the likelihood of repetition of minor research errors.

In clinical practice, the reversibility of obstruction is usually measured by the increase in FEV1, expressed as a percentage of the proper value of this indicator, and is calculated automatically by the MAS-1 spirometer expert system. The variability of FEV1 in the same person on different days is approximately 178 ml, therefore an increase in FEV1 during the test by 12% or more relative to the proper value of this indicator while simultaneously increasing absolute FEV1 by at least 200 ml cannot life is an accident and is diagnostically significant.

Additional criteria for a positive response to a bronchodilation test are an increase in SOS25-75 by 25% or more, as well as an increase in POS by 1 l/s more than the initial values.

The conclusion on the bronchodilator test includes the proper volumes and proper standards, initial data, values ​​of indicators after using the bronchodilator, drug, dose, method of application and time interval from the moment of testing to recording the response.

The bronchodilation test protocol generated by “MAS-1” is presented in Fig. 2.

Thus, the use of bronchomotor tests in clinical practice makes it possible to establish the presence of airway hyperresponsiveness and the degree of reversibility of bronchial obstruction. In addition, the use of different bronchodilators makes it possible to individually select the most prognostically effective drug.

Question 4

In vitro tests for the diagnosis of IgE-mediated diseases

LABORATORY TESTS

PRIST- direct radioimmunosorbent test

Test to determine total IgE in blood serum. A technique is used in which insoluble immunosorbents with “linked” anti-IgE antibodies are incubated for 16 hours with either a standard or the test serum. Then, unbound serum IgE antibodies are removed by washing, after which they are incubated with 125J-labeled anti-IgE antibodies for 2-4 hours. Unbound 125J anti-IgE antibodies are again removed by washing. Based on the associated radioactivity, the amount of total Ig E is determined.
Radioactive labeling with the 131J isotope, and in lately increasingly, 125J is a proven and reliable method. However, because the reagents required in this case are hazardous to health and unstable due to radioactive decay, other types of tags have been proposed.
Enzymes are successfully used, in particular peroxidase and phosphatase, which, when added to the reacting components of a corresponding colorless substrate, called a chromogen, act on the latter to form colored reaction products. In particular, the method for determining antibodies and sometimes antigens, called ELISA (from the English enzyme linked immunosorbent assay) - enzyme-linked immunosorbent assay - ELISA, is based on the use of enzymes.
Direct method for detecting specific Ig E antibodies:
Radioallergosorbent test (PACT)
Used for quantification antigen-specific Ig E antibodies.
Principle of the method: the content of specific Ig E antibodies in serum can be determined using their ability to bind to an antigen (allergen) located on an insoluble sorbent carrier. If the serum used contains the appropriate antibodies, then after incubation they interact with allergens.
Unbound serum antibodies are removed by washing and the remaining complex is incubated with 125J-labeled Ig E antibodies.
If reagins were bound to allergens earlier (at stage 1 of the reaction), then 125J antiIgE molecules interact with these reagins. Unbound 125J antiIg E is removed by washing.
The amount of antigen-specific antibodies is determined from bound radioactivity using appropriate standards.
Advantages of PACT over skin testing:
the patient spends less time on research; the results are not affected by medications taken; performing the test is not associated with a risk of developing anaphylaxis in the patient; there is a possibility of quantitative assessment.
Disadvantages of PACT: does not detect reagin antibodies other than IgE.
Note:
PACT correlates well with other tests, especially provocative ones. Compared to intradermal tests, PACT is less sensitive but more specific, that is, it gives virtually no false-positive results. PACT is preferable in children under 5 years of age in whom skin tests are impractical, in patients with eczema for whom they are contraindicated, and in pathological dermographism when test results false positive.
Enzyme-linked immunosorbent assay (ELISA)
ELISA can be used to quantify total Ig E in serum. The method is based on the "sandwich" principle. The test serum sample is added to the anti-IgE antibodies sorbed on the solid phase, incubated, and washed. Then a conjugate of anti-IgE antibodies with an enzyme is added here in the expectation that this conjugate can contact the second free active center of IgE antibodies located in the immune complexes on the solid phase. Then the stages of incubation and washing, after which the substrate (chromogen) corresponding to the enzyme used is added. The transformation of the substrate is indicated by a change in color in the well or in a test tube with a solid phase, and staining occurs only if there is immunoglobulin E in the sandwich complexes on the solid phase, and accordingly in the blood serum under study. The intensity of the color reaction is assessed spectrophotometrically relative to positive and negative controls samples

Question 5

Age-related features of the formation of allergic diseases. Atopic march.

At all periods of life, even at the moment of pre-existence, the child’s body is influenced by various factors risk of developing allergies:

Unfavorable health status of parents before conception,

Burdened heredity.

Unfavorable course of pregnancy and childbirth,

Exposure to food, infectious antigens and environmental antigens.

The process of sensitization develops evolutionarily, starting from the prenatal stage when potential sensitization occurs. And after birth, there is a progressive expansion of its “springboard” in the form of the manifestation of the “allergic march” already in early childhood

Primary, from the first months of life, develops foodallergy, which is the main and often the only cause of allergic diseases in children of the first three years of life. (due to early transfer to artificial feeding.) With adequate therapy, it clinically fades away, although latent sensitization can persist for many years and often remains undetected. Thus, food allergies in infancy– this is the first clinical manifestation of the “atopic march”.

Continued use allergenic products increases the degree of food polysensitization and often contributes to the development against its background of other types of allergies in a certain sequence:

Household and epidermal from 2 - 3 years of life,

Pollen and bacterial - from 5-7 years; they do not replace each other, but are layered.

At the same time, at first these types of sensitization are subclinical in nature, becoming manifest forms after 6-12 months with continued contact with a specific allergen. This contributes, on the one hand, to the formation of combined sensitization, the frequency and degree of which progressively increases with the duration of the disease.

On the other hand, it determines age characteristics structures of sensitization, namely: the leading types of sensitization in children under three years of age are food, at the age of 4-6 years - food and household, in more than half in combination, and after 7 years, in addition to the previous two, also pollen and bacterial with a predominance polycombined options.

Can develop at all ages drug allergy.

It should be emphasized that the development of the main types of sensitization is completed by 6-7 years, and subsequently there is a transformation of the subclinical stage into the manifest one, which causes the formation of polyallergy and polyetiology of diseases, increasing the severity of their course.

The revealed patterns of allergy formation in children are determined by the age-related anatomical and physiological characteristics of organs and systems, the degree of their maturity during the period of antigenic load, especially excessive load.

Atopic March is the chronological sequence of the formation of sensitization and clinical transformation of allergy symptoms depending on the age of a child with an atopic constitution: atopic dermatitis (AD), bronchial asthma (BA), allergic rhinitis (AR), etc. The atopic march is the natural course of development of manifestations of atopy. It is characterized by the typical sequence of development of clinical symptoms of atopic disease, when some symptoms become more pronounced, while others decline
The “atopic march” is formed during the period of intrauterine development, and clinically manifests itself during early childhood and often accompanies the patient throughout his life.

Clinical symptoms of the “allergic march”
The manifestation of the disease begins with symptoms of food allergy, often manifestedatopic dermatitis . It debuts mainly in the 1st year of life and is the first manifestation of atopic diseases.

In young children, one of the leading provocateurs of allergic diseases are food hypertension: cow's milk, eggs, cereals, fish, soy. With age, the spectrum of food antigens changes both in quality and frequency of detection; the importance of tick-borne and infectious antigens (Staphylococcus aureus and Candida albicans) increases.
Of great importance in the occurrence of food allergies is a violation of the morphofunctional state digestive tract. The formation of the biocenosis of the digestive tract largely depends on breastfeeding. Colonization of the intestines pathogenic microorganisms is inversely dependent on the presence of secretory immunoglobulins and other protective factors supplied with mother's milk. The adult type of microbiocenosis is formed by the 18th month of life. The earlier formation of the adult-type “microbial landscape” of the intestine contributes to the development of gastrointestinal allergies.

First manifestationsatopic dermatitis – erythematous elements, vesicles, weeping – in most children they appear at the 3-4th month of life.

In the 2nd year of life, the processes of infiltration and lichenification predominate with localization on the extensor and flexion surfaces of the extremities, but by the end of the 2nd year of life the process covers mainly the flexor surfaces, and subsides on the face.
In the second age period - from 2 to 12-13 years - blood pressure becomes chronic.
In the third age period (adolescents and adults), excoriations, papules, foci of lichenification and skin infiltration prevail. The typical localization of the process is on the elbow and knee bends, on the back of the neck, the skin of the eyelids, back surface hands and joints.

The peak development of asthma occurs at 5 years of age, allergic rhinitis - in adolescence.
The first manifestations of wheezing syndrome in half of children occur before the age of 2 years. The peak of intermittent (seasonal) AR is observed in adolescents. Regarding persistent (chronic) AR, it should be said: the difficulties of diagnosing infectious and AR at an early age, as well as the stereotype of medical thinking about the predominantly infectious etiology of rhinitis, contribute to the fact that an exacerbation of a nasal allergic reaction is often perceived as another infection, so the diagnosis of AR is made late. Difficulties arise also in diagnosing exacerbations of AR, the trigger of which is often a viral infection.
Since the stages of development of the “allergic march” are considered, first of all, as a sequential transformation of the clinical manifestations of atopy into asthma, one should remember about those children in whom asthma begins with broncho-obstructive syndrome at an early age (47% of cases). Bronchoobstruction or pseudocroup (acute stenosing laryngotracheitis), regardless of the causes of their occurrence (80% - ARVI), subsequently recur in 53% of children. Over time, in 2/3 of children the recurrence of BOS stops, and in 23.3% of patients asthma develops.
Risk factors for biofeedback relapse:
family history of atopy;
increased serum IgE levels;
inhalation sensitization;
passive smoking;
male gender

Conclusions:

1) Atopic diseases occur more often in children with genetic predisposition To allergic diseases, especially on the maternal side. Their formation is facilitated by sensitization food products mothers during pregnancy, early transfer of children to artificial feeding and early (in the first year of life) food sensitization in children.
2) Clinical manifestations of atopic diseases in children are characterized by the sequence of development of symptoms of allergy and sensitization with the onset of AD in the first year of life. With the age of the child, the range of allergens expands and in children over 6 years of age, polyvalent sensitization already predominates, a respiratory syndrome is formed, which, as it progresses, leads to the development of combined forms of atopic diseases (dermatitis, asthma, rhinitis).
3) Children suffering from atopic diseases, regardless of their combination, are characterized by significant disturbances in immunity indicators: cellular, humoral and local, which are generally characterized by an increase in CD3+ - (P Question 6

Inhaled allergens. Classification. Characteristics. The concept of “major” and “minor” allergens.
AND inhalation allergens are allergens that are inhaled into the body along with the air.

Divided into two classes:

1) External (pollen and molds). Represent high risk for the development of seasonal AR

2) Internal (house dust mites, insects, fungi). High risk of developing year-round rhinitis.

3) Professional (sensitizers)
Characteristic.

The small size allows allergen particles to be carried by the wind, penetrate deep into the respiratory tract, and settle on the mucous membranes. Each aeroallergen contains several allergenic proteins that can cause an allergic response in sensitized patients, manifested in the form of respiratory (asthma), skin (urticaria) ), and conjunctival allergy.
Indoor allergens

Latex allergens.

Major (main) allergens (proteins) - these are species-specific proteins (that is, they can be used to determine which group a given protein belongs to). They are usually resistant to heat and larger in size, and are also contained in a given allergen in large quantities.
Minor (minor) allergen proteins- often smaller in size and quantity. They are often found simultaneously in several allergens and it is because of them that cross-reactions (allergies) develop. For example, the dust mite protein, tropomyosin, is part of the proteins not only of mites, but also of crustaceans, cockroaches, roundworm
Question 7

Cross reactivity.

Cross-reaction refers to the fact that a person reacts painfully to more than just one substance, an allergen, from one source. The reason is that in other sources there are very similar allergens of similar composition. They can affect the same organ system with which the allergen came into contact or another.
Cross-reactions between aeroallergens and food allergens occur through three main mechanisms:
- complete identity between the inhaled and food allergen;
- allergenic identity, the culprit protein is present but hidden in the food;
- common epitopes in food and inhaled particles of different origins.

Cross-reaction table for food and/or pollen
Food	Cross reaction
Apple	Potatoes, carrots, birch pollen, hazelnuts
Cod	Tuna, salmon, eel, mackerel, trout
Egg	Yolk, albumen, lysozyme, egg albumin, ovomucoid, inhalation of allergens contained in poultry protein
Peas	Lentils, fennel, guar, soybeans, white beans, peanuts, licorice/sweet cone, tragacanth, chickpeas
Shrimps	Crab, lobster, squid, dwarf lobster
Cereals	Wheat, rye, barley, oats, corn, their pollen, flower pollen
Honey	Pollen admixture (eg Compositae)
Carrot	Celery, anise, apple, potato, rye, wheat, birch pollen, avocado, pineapple
Garlic	Onions, asparagus
Cow's milk	Kumis, sheep milk, mixtures on cow's milk
Pecan	Walnut
Peach	Apricot, plum, guava, banana
Rice	Wheat, rye, oats, barley, corn, rye pollen
Cross-reactions of IgE antibodies of a patient with an allergy to allergens that are not the source of his disease arise due to the fact that different allergens may have very similar areas with which the same antibodies interact. Therefore, patients who are sensitive to one allergen may also react to other allergens. The most known cross-reactivities of allergens are given in the tables:

Cross-reactions of inhaled allergens with food allergens.

Sensitizing allergen	Common cross-reactions
Birch pollen (t3)	hazelnut, potato, tomato, carrot, apple, pear, cherry, plum, peach, apricot, kiwi, celery, parsnip, coriander, chestnut
Ambrosia pollen (w2)	cucumber, bananas, watermelon, cantaloupe, cantaloupe
Artemisia pollen (w6)	carrots, mustard, celery, parsnips, coriander, fennel Classification of food allergens 9. see question 7 =) 10 question Principles of elimination of a causally significant allergen Elimination - removal of factors causing disease. When discussing allergy treatment, elimination refers to the removal of causative allergens. Elimination of allergens refers to etiopathogenetic methods of treatment for food, drug and inhalation allergies. When it comes to inhalant allergens, it is very difficult to control the purity of the inhaled air and eliminate the causative allergens. During the flowering period of wind-pollinated plants, artificially pollen-free air can be provided only in closed rooms by special cleaning using electrostatic filters or air conditioning. In case of increased sensitivity to birch pollen, it is recommended to move to the southern regions, at least while the trees are flowering; to ragweed pollen, it is recommended to move to the north. In order to reduce contact with plant pollen present in the air, it is recommended not to travel to the countryside during the entire flowering period of plants to the pollen of which there is increased sensitivity, close windows at night, and not leave the house in the morning hours, when the maximum concentration of pollen occurs in the air. If carefully carried out elimination measures have no effect, the doctor offers the patient suffering from hay fever allergen-specific treatment and drug therapy.