RU2440035C2 - Method of determining bronchial asthma control ratio - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely pulmonology, allergology and laboratory diagnostics, and can be used to control bronchial asthma (BA) treatment. For this purpose, BA is controlled by GINA 2006 criteria in the patients taking a background anti-inflammatory therapy in the form of a combination of inhalation corticosteroids and long-acting β2-agonist. Additionally, peripheral blood CD4+ lymphocytes are counted. If BA values are controlled by GINA 2006 criteria and if the CD4+ cell count is 44 or less, the clinical course of bronchial asthma is considered to be controlled. If the CD4+ cell count is higher than 44, it is uncontrolled.

EFFECT: method enables objectification of clinical effectiveness in BA ensured by supplementary assessment of immunological values significant for BA.

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Description

The invention relates to medicine, in particular to pulmonology, immunology and laboratory diagnostics. It can be used to evaluate the effectiveness of anti-asthma therapy.

From the point of view of GINA (Global Initiative for Asthma) experts, the most important goal of treating bronchial asthma (BA) is to achieve and maintain control of the disease, effectively prevent exacerbations and reduce mortality [Chuchalin A.G. (Ed.) Global Strategy for the Treatment and Prevention of Asthma, p.16. M .: Atmosphere; 2006]. Large-scale studies covering most countries of the world demonstrated, in general, a low level of asthma control and, accordingly, insufficiently effective treatment [Arkhipov VV, Tsoi A.N. GINA 2006: new guidelines for the pharmacotherapy of asthma. Rus honey. journal 2007; 15 (4): 255-259].

According to the provisions of GINA 2006, BA is considered controlled under the following criteria: the number of daytime symptoms is less than 2 episodes per week, the absence of nocturnal symptoms and awakenings, activity restrictions, exacerbations, the need for emergency drugs, the presence of no more than two episodes of BA per week, while the indicators of forced expiratory volume in the first second (FEV1) or peak expiratory flow rate (PSV) are within the normal range. Determining the level of control over asthma is necessary for the implementation of the correction of anti-asthma therapy. It is believed that the controlled course of the disease according to GINA 2006 indicates the effectiveness of anti-asthma therapy [Chuchalin A.G. (Ed.) Global Strategy for the Treatment and Prevention of Asthma, p.16. M .: Atmosphere; 2006]. However, ongoing therapy is not always sufficient despite the fact that a controlled course of the disease has been achieved according to GINA 2006 criteria, because most criteria are based on information from patients who are subjective enough. It is known that the absence of clinical symptoms of the disease in most patients does not guarantee the disappearance of other manifestations of inflammation in the bronchial tree. It has been shown that, against the background of continuous therapy with inhaled glucocorticosteroids (IHC), clinical and functional parameters in patients with asthma are improved, but significant changes in immune parameters are preserved [N. Kislova. Quality of life and emotional status of patients with bronchial asthma in a comprehensive assessment of the effectiveness of inhaled steroid therapy: Abstract. dis. ... cand. honey. sciences. Smolensk 2003].

The aim of the invention is the objectification of determining the level of control over bronchial asthma, taking into account immunological parameters.

The essence of the method lies in the fact that in patients with asthma receiving basic anti-inflammatory therapy with a combination of IHC and a long-acting β2-agonist, the course of the disease is evaluated according to GINA criteria 2006 and the CD4 + level of peripheral blood is additionally determined if the number of CD4 + cells is equal to or less than 44, AD is considered controlled, if the number of CD4 + cells is more than 44, then the course of AD is uncontrolled.

It is known that the mechanism of AD development and its course depend on the number and ratio of lymphocyte subpopulations, as well as on the functional activity of CD4 + cells involved in the implementation of the inflammatory process [Shumakova DP, Pribylova NN, Neronov AF Characterization of indicators of immune status and peripheral blood in patients with bronchial asthma. In the book: Collection of summaries of the 10th national congress on respiratory diseases November 1-4, 2000. St. Petersburg, 2000; 65]. However, there is still no relationship between the level of AD control and the quantitative level of CD 4 + lymphocytes.

The proposed method is as follows.

A patient with AD receiving basic anti-inflammatory therapy with a fixed combination of IHC and a long-acting β2-agonist for at least 1 year assesses the level of disease control according to the GINA criteria of 2006. In the morning, on an empty stomach, undergoing aseptic conditions, a cubital vein puncture is performed, 10 ml of blood is taken , the sample is prepared and the absolute and relative content of peripheral blood lymphocytes is calculated and the number of CD4 + lymphocytes is determined by indirect immunofluorescence using a monoclonal panel ntitel produced by TOO "sorbent", Moscow, if the level of CD4 + cells is equal to or less than 44, for asthma is considered controlled, and if higher than 44 - uncontrollable.

Example

Patient S.V.G. (amb. card No. 3624-21), turned to a pulmonologist at the Polyclinic No. 6 MDLP on December 25, 2008, complaining of difficulty breathing during moderate physical exertion, a rare dry cough, Diagnosed with asthma, moderate severity, was issued in 2005 Received a fixed combination of salmeterol 50 mcg and fluticasone 100 mcg twice a day. The need for short-acting β2-agonists 1-2 times a week.

Objectively: the general condition is satisfactory. Nasal breathing is free. In the lungs, vesicular breathing, wheezing is not heard. The number of respiratory movements (NPV) is 18 in 1 minute. Heart sounds are rhythmic, muffled. Heart rate (HR) 82 in 1 minute. The abdomen is soft, painless. No peripheral edema.

FVD dated 12.24.2008. Vital lung capacity (VC) 2.99 liters (90% of due), FEV1 2.15 liters (83%) of due, Tiffno (IT) index 72%. After inhalation of 400 μg of salbutamol with a 20 minute exposure, an increase in FEV1 was observed, amounting to 12%. Conclusion: violations of the ventilation function were not detected.

According to the GINA 2006 criteria, the course of AD was defined as controlled, but the patient's condition was regarded as unsatisfactory, as a result of which there was a need for an immunological study. For this purpose, the level of CD4 + lymphocytes was determined in the patient’s blood. An analysis of cellular immunity indices by the method of indirect immunofluorescence revealed that the number of CD4 + cells is 48. Thus, the course of AD is uncontrolled. A review of basic anti-inflammatory therapy was carried out in the direction of increasing the dose of NTK to 500 mcg per day for fluticasone.

The second examination was carried out on March 25, 2009. The patient did not show complaints. Daily received salmeterol 50 mcg and fluticasone 250 mcg twice a day. Over the past period, β2-agonists of short action were not used.

Objectively: the general condition is satisfactory. Nasal breathing is free. In the lungs, vesicular breathing, wheezing is not heard. NPV 17 in 1 minute. Heart sounds are rhythmic, muffled. Heart rate 72 in 1 minute. The abdomen is soft, painless. No peripheral edema.

FVD of March 25, 2009. ZhEL 3.3 liters (99% of due), FEV1 2.35 liters (91%) of due, IT 71%. After inhalation of 400 μg of salbutamol with a 20 minute exposure, an increase in FEV1 was observed, amounting to 6%. Conclusion: violations of the ventilation function were not detected.

According to the criteria of GINA 2006, she was diagnosed with BA controlled course.

When analyzing indicators of cellular immunity by indirect immunofluorescence using a panel of monoclonal, the number of CD4 + cells is 35, which confirms the controlled course of AD.

The method was tested in 53 outpatients with male BA, the average age of which was 49.9 ± 4.2 years, which were observed during the year. All patients received basic anti-inflammatory therapy with a fixed combination of IHC and a long-acting β2-agonist. In the group of patients (19 people), in whom the number of CD4 + cells was less than 44, clinically and according to GINA criteria 2006, the course of AD was verified as controlled, and in the group of patients (36 people), in whom the number of CD4 + lymphocytes was higher than 44, uncontrolled BA course.

The results of the assessment of quantitative parameters are presented in a table showing the distribution of peripheral blood CD4 + lymphocytes in patients with various levels of control over AD.

Statistical processing of quantitative data was carried out according to standard methods. All numerical data are presented as mediana (M) with a 25-75% interquartile range. The significance of differences between the groups was determined using the Mann-Whitney U test with a given confidence level of 0.95. The quantitative level of CD4 + cells, equal to 44, is due to the fact that this value is the upper limit of 25-75% of the inter-quarter interval used in the statistical processing of quantitative data using the standard methodology for describing the population with a distribution other than normal.

Thus, the level of CD4 + lymphocytes equal to 44 and lower objectively indicates a controlled course of AD, and the number of CD4 + cells equal to or higher than 44 confirms the uncontrolled course of AD.

Using the proposed method for evaluating the effectiveness of anti-asthma therapy has the following advantages:

1. The proposed methodology is technically simple and is carried out in a fairly short time.

2. The method makes it possible to objectively determine the level of control of asthma, given the state of the immune status.

METHOD FOR DETERMINING THE LEVEL OF ACHIEVEMENT OF CONTROL OVER BRONCHIAL ASTHMA Research marker Form of the disease according to GINA 2006 BA controlled (n = 19) BA uncontrolled (n = 36) CD4 + 39 * (36.44) 46 (45.48) * statistical significance of differences between groups of controlled and uncontrolled BA

Claims (1)

A method for determining the level of control of bronchial asthma (AD) in patients receiving basic anti-inflammatory therapy with a combination of IHC and a long-acting β2-agonist, including determining the control of AD according to GINA criteria 2006, characterized in that it also determines the quantitative level of peripheral blood CD4 + and, if CD4 + cells is equal to 44 or lower, the course of AD is considered controlled, if the number of CD4 + cells above 44 is uncontrolled.