RU2786010C1 - Method for diagnosis of allergic severe bronchial asthma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to allergology, immunology, therapy, and can be used to diagnose allergic severe bronchial asthma. The allergological history is collected and the venous blood of the patient is examined. Specific E - IgE immunoglobulins to common inhalation allergens are measured in the patient's blood: warty birch, meadow thymothy, common wormwood, high ragweed, cat dandruff, dog dandruff, horse dandruff, D. pteronyssinus, D. farinae, Alternaria alternata, Cladosporium herbarum using the Fadiatop test. Allergic severe bronchial asthma is diagnosed with specific IgE level of ≥1.53 PAU/l. A non-allergic severe bronchial asthma is diagnosed with IgE < 1.53 PAU/l and a negative allergoanamnesis.

EFFECT: simplifying (reduce the number of diagnostic stages), reducing the cost and make the method more accessible while providing sufficient data by conducting a Fadiatop test, during which specific IgE in the blood of patients is measured.

1 cl, 7 tbl, 2 ex

Description

The invention relates to the field of medicine, namely to allergology, immunology, therapy, and can be used for phenotyping of severe bronchial asthma (SBA) when selecting patients for genetically engineered biological therapy.

State of the art

Currently, for the diagnosis and phenotyping of severe bronchial asthma, 3 main diagnostic methods are used: collecting an allergic history, conducting skin allergy tests, and determining specific immunoglobulins E (IgE) for suspected allergens by anamnesis.

Collecting an allergic history includes:

• identification of a clear connection between the development of the disease and its manifestation with the impact of a certain causative factor (allergen), the disappearance of symptoms upon elimination of this factor and the resumption of symptoms upon repeated contact;

• identification of presumably etiologically significant allergens;

• identification of risk factors contributing to the development of an allergic disease;

• detection of hereditary predisposition to allergic diseases (presence of bronchial asthma and/or allergic rhinitis and/or eczema and/or urticaria, Quincke's edema, hypersensitivity to food and/or drugs, insects in close relatives); in patients with allergic diseases, a hereditary predisposition to allergic diseases occurs 2-3 times more often than in healthy individuals;

• determining whether the patient has other allergic diseases;

• identification of the influence of environmental factors (climate, weather, physical factors) on the development and course of the disease;

• determination of the seasonality of symptoms of the disease;

• identification of the influence of household factors on the development and course of the disease - dampness in the room, the presence of upholstered furniture and carpets, pets, fish and birds;

• determination of the relationship of symptoms with food intake and / or drugs, with occupational factors;

• assessment of the clinical effect of the use of antiallergic drugs and / or the elimination of allergens.

When evaluating the data of an allergic history, an assumption is made about an allergic or non-allergic variant of bronchial asthma. The allergic mechanism of development must be confirmed by the results of skin tests and/or specific IgE.

Skin tests are most often performed on the inner surface of the forearm by scarifying the superficial layers of the skin (or by pricking) and applying drops of standardized allergens to the scarification sites. The results are evaluated after 20 minutes of exposure to allergens in accordance with the data in Table No. 1.

Positive skin tests (from + to ++++) identify a causally significant allergen when combined with history data. If, during the history taking, the patient does not note the association of asthma symptoms with exposure to an allergen for which a positive skin test result is obtained, then this sensitization is regarded as latent (clinically insignificant).

However, there are limitations to the use of skin tests: it cannot be carried out during an exacerbation of allergic, somatic, chronic infectious, autoimmune diseases, during acute infectious diseases; require the abolition of certain drugs (antihistamines per os, systemic corticosteroids). In the case of severe bronchial asthma, it is often impossible to conduct skin tests as an in vivo diagnostic method due to the uncontrollability of the disease or the use of systemic corticosteroids. In addition, this type of study requires: a specially equipped room, trained medical personnel, the availability of reagents, the time factor (skin testing requires an average of 30 minutes per patient; after testing, the patient must be near the treatment room for 30-40 minutes to provide assistance in case of possible complications), which can also be attributed to the shortcomings of this study. There is a risk of exacerbation of an allergic disease, the development of anaphylaxis. In addition, false-positive reactions associated with skin irritation during scarification are possible.

If it is impossible to conduct skin allergy tests or if the results of skin testing do not match the data of an allergic anamnesis, specific IgE to allergens in the blood is determined. The patient donates venous blood. The result is considered positive when the level of specific IgE≥0.35 kU _A /l. The clinical significance of the identified sensitization is also assessed in conjunction with the allergy history data.

Disadvantages of determining specific IgE: studies must be carried out separately for each allergen indicated in the anamnesis, therefore, a clear indication of a specific causally significant allergen is necessary; with a large number of suspected allergens, the examination is quite expensive.

The spectrum of allergens used in diagnostics depends on the data of the allergic anamnesis. So in the case of severe bronchial asthma, it is necessary to determine specific IgE to respiratory allergens: household (house dust, library dust, house dust mites), epidermal (allergens of cats, dogs and other animals), pollen (pollen of trees, meadow and weeds), allergens mold fungi.

The task: to simplify (reduce the number of diagnostic steps), reduce the cost and make the method more accessible, while maintaining information content:

• to simplify the identification of patients with an allergic phenotype of SBA for genetically engineered biological therapy at the screening stage of SBA using the Fadiatop test;

• reduce the list of contraindications for allergy diagnostics in patients with TBA by replacing allergy tests and determination of specific IgE in the blood of patients with the Fadiatop test;

• reduce the cost of allergic TBA detection by replacing allergy tests and determination of specific IgE in patients' blood with the Fadiatop test. The essence of the invention

Identification of the allergic phenotype of SBA by collecting an allergic history in combination with the Fadiatop laboratory test in the selection of patients with SBA for genetically engineered biological therapy. If the level of specific IgE≥1.53 PAU/l, then the allergic phenotype of TBA is diagnosed and an anti-IgE drug is prescribed.

Fadiatop - a study during which specific immunoglobulins E are measured in the blood (the patient donates venous blood) to the most common inhalation allergens: warty birch, meadow timothy grass, common wormwood, high ragweed, cat dander, dog dander, horse dander, D. pteronyssinus, D. farinae, Alternaria altemata, Cladosporium herbarum. The result is considered positive (in favor of the allergic mechanism of asthma) when the level of specific IgE≥0.35 PAU/l.

When conducting a study of the information content of Fadiatop in the phenotyping of severe bronchial asthma for the selection of patients for immunobiological therapy in real clinical practice, we showed that the result of the Fadiatop test in patients in the groups of allergic and mixed (allergic and non-allergic) severe bronchial asthma was statistically significantly higher than the results of this test in patients with non-allergic asthma (p<0.001) (Table 2). With a weakly positive result of the Fadiatop test in a patient with TBA, there is no clinically significant reaction.

In the ROC analysis, we identified the threshold value of the Fadiatop test results of 1.530 PAU/l, at which a positive allergic anamnesis is predicted, i.e. if the value of the Fadiatop test results is higher than this value or equal to it, a clinically significant reaction occurs when the patient comes into contact with the allergen, which confirms the presence of allergic severe bronchial asthma. The sensitivity and specificity of the model were 67.4% and 93.8%, respectively.

Comparison of the diagnostic informativity of the methods was carried out individually and in combinations depending on the asthma phenotype. Fadiatop showed a sensitivity of 90.9%, which is inferior to the sensitivity of collecting an allergic anamnesis and standard methods (100% each). But the specificity of the Fadiatop 75% test turned out to be higher than the specificity of history taking and standard methods (66.7% each, respectively). The combination of the Fadiatop test with the collection of an allergic anamnesis increases the specificity of diagnosing the allergic phenotype of SBA to 91.7% (Table 3).

If we rank the results of the characteristics of the methods and their combinations, then Fadiatop is inferior. But in combination with an allergic anamnesis, it shows informativeness at the level of a combination of an allergic anamnesis with standard methods (skin tests and specific IgE) (Table 4).

When comparing the sensitivity and specificity of the methods, it was not possible to prove the superiority of the Fadiatop test in relation to the collection of allergic anamnesis and standard methods (skin tests and specific IgE). However, a non-inferiority study showed that the sensitivity of the Fadiatop test is no worse than the collection of allergy history and standard diagnostic methods. The economic efficiency of Fadiatop was also calculated in comparison with standard methods. The average cost of examination of one patient by the Fadiatop method is 1.9 times cheaper than the examination by skin tests by 1.9 times and specific IgE for each allergen by 4.1 times (Tables 5, 6, 7).

Thus, when using the Fadiatop test in combination with an allergic anamnesis, there is no need for invasive skin testing, which is potentially dangerous for severe asthma patients, and, moreover, the diagnostic period is reduced, and also due to the lower cost of the Fadiatop test compared to skin tests. tests and the determination of specific IgE to allergens, a new method of distinguishing between allergic and non-allergic bronchial asthma can be recommended in clinical practice by methods of collecting allergic anamnesis with the Fadiatop test in the phenotyping of severe bronchial asthma for immunobiological therapy.

Implementation of the invention

Example 1

Patient M., 34 years old, has been suffering from bronchial asthma since the age of 5, when asthma attacks appeared on contact with a cat. From the age of 10, symptoms of rhinoconjunctivitis began to be noted in May annually. Since the age of two, the patient has had atopic dermatitis, remission since the age of 15. The patient's grandmother has bronchial asthma, and her cousin has allergic rhinitis to grass pollen. As a child, asthma was treated with low-dose inhaled glucocorticosteroids (IGCS) with symptom control. At the age of 12, skin tests were performed with household, epidermal, pollen allergens - according to the patient, sensitization to cat hair, tree pollen was detected (the form with the results was lost). From adolescence, she notes a deterioration in the course of asthma - episodes of exacerbations began to appear during SARS and during the flowering period of trees, requiring the appointment of systemic corticosteroids, hospitalizations. For the last 3 years he has been receiving stage 4 therapy: average doses of ICS + long-acting B2-agonist (LABA), year-round need for salbutamol 3-4 r/day, nighttime symptoms 2-3 r/week, exacerbations 2 r/year with /in the introduction of GCS. The patient was referred for consideration of the appointment of genetically engineered biological therapy.

Collecting an allergic anamnesis included:

Taking into account the allergic anamnesis, the patient has allergic severe bronchial asthma. Confirmation of the allergic mechanism is carried out using the Fadiatop test (skin tests in this case cannot be performed due to the uncontrolled course of asthma)

Fadiatop test result - 8.03 PAU/l,

those. the level of specific IgE≥1.53 PAU/l.

The patient is diagnosed with allergic severe bronchial asthma, i. The combination of an allergic anamnesis and the Fadiatop test made it possible to confirm the allergic mechanism of bronchial asthma and to prescribe a genetically engineered biopharmaceutical anti-IgE drug indicated for allergic asthma.

Example 2

Patient A., aged 48, has been suffering from bronchial asthma since the age of 40. The course of asthma from the very beginning is severe, uncontrolled on stage 5 therapy (high-dose ICS + LABA + montelukast), the need for bronchodilators is 5-6 r / day, asthma exacerbations are 3-4 r / year. The patient denies allergic diseases in herself and her relatives. The patient did not notice any reactions to animals, flowering of plants, food and medicines.

Skin testing is contraindicated due to uncontrolled asthma. The determination of specific IgE is difficult, since there is no indication in the anamnesis of certain causally significant allergens.

Studies were carried out using the Fadiatop test.

Fadiatop test result - 0.08 PAU/l,

those. the level of specific IgE<1.53 PAU/l.

The patient is diagnosed with non-allergic severe bronchial asthma.

A negative allergy history and a negative Fadiatop test confirm the non-allergic nature of asthma. The patient is shown an anti-IL5 drug.

Thus, the use of the proposed method makes it possible to simplify and speed up the phenotyping of severe bronchial asthma, which is important for choosing an immunobiological drug for treatment, in addition, the method is quite informative and also more economical in comparison with analogues: skin tests and studies of individual specific IgE.

Used Books.

1. Khaitov R.M. Allergology and clinical immunology // Clinical recommendations / P.M. Khaitov, N.I. Ilyin - Moscow: GEOTAR-Media. - 2019.

2. Khaitov R.M. Federal Clinical Guidelines for the Diagnosis of Allergic Diseases / ed. P.M. Khaitova - Moscow. - 2015.

Claims (1)

A method for diagnosing severe allergic bronchial asthma, including collecting an allergic history and examining the patient's venous blood, characterized in that specific immunoglobulins E - IgE to common inhalation allergens are measured in the patient's blood: warty birch, meadow timothy, common wormwood, high ragweed, cat dander, dog dander, horse dander, D. pteronyssinus, D. farinae, Alternaria alternata, Cladosporium herbarum, using the Fadiatop test, and at a specific IgE level ≥ 1.53 PAU / l, allergic severe bronchial asthma is diagnosed, with IgE < 1.53 PAU / l and negative allergic anamnesis - non-allergic severe bronchial asthma.