RU2789114C1 - Method for assessing the risk of complications of the infectious process in patients with cysistic fissidosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to clinical laboratory diagnostics, microbiology, pulmonology, and can be used to assess the risk of developing complications of an infectious process in patients with cystic fibrosis. The method is implemented in that, in contrast to the known methods for assessing the risk of complications of an infectious process in patients with cystic fibrosis, sputum from patients with cystic fibrosis is collected in a sterile disposable container, centrifuged at 1700 G for 5 minutes, the resulting supernatant is re-centrifuged at 4500 G for 5 minutes. within 5 minutes. After that, the concentration of ferritin is determined on an automatic biochemical analyzer using the immunoturbodimetric method, characterized in that the study is carried out in dynamics with the calculation of the PCV coefficient: if the patient is not exacerbated, then the PCV coefficient is calculated between two consecutive determinations of ferritin in sputum with an interval of 1 time per 3 months, with a PCV value <37.3%, the risk of an exacerbation of the infectious process is low; during an exacerbation, the PCV coefficient is calculated between the last ferritin value determined outside the exacerbation and the ferritin value determined during the exacerbation, a PCV value from 37.3% to 45.7% inclusive corresponds to an exacerbation without seeding microorganisms from the Burkholderia cepacia complex; a value from 45.8% to 78.3% inclusive corresponds to an exacerbation with the inoculation of microorganisms from the Burkholderia cepacia complex; an increase in the PCV value above 78.4% corresponds to the "cepation syndrome".

EFFECT: invention provides an assessment of the risk of complications of the infectious process in patients with cystic fibrosis according to the Personal Change Value (PCV) coefficient for ferritin in sputum.

1 cl, 2 dwg, 4 ex

Description

The field of technology to which the invention belongs

The invention relates to medicine, namely to clinical laboratory diagnostics, microbiology, pulmonology, and can be used to assess the risk of developing complications of an infectious process in patients with cystic fibrosis.

State of the art

Difficulty in assessing the risk of developing complications of the infectious process in the bronchopulmonary system in patients with cystic fibrosis (CF) is a problem for timely clinical decision making in the management of this group of patients. This may be due to various forms of disease mutation, features of the microbiological landscape of the bronchopulmonary system, adherence to treatment, as well as the constant risk of developing severe complications, such as "cepation syndrome" in patients with chronic infection with representatives of the Burkholderia cepacia complex. This complication is characterized by the development of pneumonia, fever, sepsis and can be fatal [AM Jones, ME Dodd, AK Webb. Burkholderia cepacia : current clinical issues, environmental controversies and ethical dilemmas. European Respiratory Journal. 2001; 17 (2): 295-301].

A known method for assessing the inflammatory process, based on the quantitative determination of C-reactive protein in the blood serum, the level of which increases in response to the development of the infectious process [Minaev S.V., Isaeva A.V., Obedin A.N., Bolotov Yu.N. ., Bochnyuk E.A., Chintaeva L.A., Gudiev Ch.G. C-reactive protein is the main marker of the dynamics of the course of acute inflammatory processes in clinical settings. Medical Bulletin of the North Caucasus. - 2011.- №2. - S.95-99].

The disadvantages of this method are the lack of correlation with the inflammatory process caused specifically by microorganisms from the Burkholderia cepacia complex, as well as the impossibility of differentiating inflammation in the respiratory tract from inflammatory processes of other localization.

A known method for assessing the activity of an infectious process caused by non-fermentative gram-negative bacteria in the bronchopulmonary system in patients with cystic fibrosis, which consists in determining the content of ferritin in sputum using the immunoturbodimetric method, while if the amount of ferritin in the study is ≤ 500 μg/l, the infectious process caused by non-fermentative gram-negative bacteria is regarded as inactive; at a ferritin level of 500 to 1000 μg/l, the infectious process is moderately active, if the ferritin level is >1000 μg/l, then the activity of the infectious process is assessed as pronounced [Patent for invention No. RU 2686052].

The disadvantage of this method is the impossibility of its application for dynamic assessment of the course of the infectious process, individual prognosis of the development of infectious complications, including the "cepation-syndrome" in patients with CF. This method is taken as a prototype.

Disclosure of invention

The aim of the invention is to develop a method for assessing the risk of complications of the infectious process in patients with CF according to the Personal Change Value (PCV) coefficient for sputum ferritin.

This is achieved by the fact that, in contrast to the known methods for assessing the risk of complications of the infectious process in patients with CF, the interpretation of the results is carried out as follows: an increase in the PCV value for ferritin in sputum by less than 37.3% inclusive corresponds to the absence of an exacerbation of the infectious process; from 37.3% to 45.7% inclusive corresponds to an exacerbation without seeding microorganisms from the Burkholderia cepacia complex; from 45.8% to 78.3% corresponds to an exacerbation with the inoculation of microorganisms from the Burkholderia cepacia complex; an increase in the PCV value above 78.4% corresponds to the “cepation syndrome”.

The technical result of the invention lies in the fact that the claimed method allows to assess the risk of complications of the infectious process in patients with cystic fibrosis by the PCV value for ferritin in sputum.

Implementation of the invention

The essence of the proposed method is as follows: sputum is collected from patients with CF in a sterile disposable container, then the sputum is centrifuged at 1700 G for 5 minutes, the resulting supernatant is re-centrifuged at 4500 G for 5 minutes. After that, the concentration of ferritin is determined on an automatic biochemical analyzer using the immunoturbodimetric method. This procedure is carried out in dynamics with the calculation of the PCV coefficient: if the patient is not exacerbated, then the PCV coefficient is calculated between two consecutive determinations of ferritin in sputum with an interval of 1 time in 3 months, with a PCV value <37.3%, the risk of an exacerbation of the infectious process is low; during an exacerbation, the PCV coefficient is calculated between the last ferritin value determined outside the exacerbation and the ferritin value determined during the exacerbation, PCV values from 37.3% to 45.7% inclusive correspond to an exacerbation without seeding microorganisms from the Burkholderia cepacia complex; a value from 45.8% to 78.3% inclusive corresponds to an exacerbation with the inoculation of microorganisms from the Burkholderia cepacia complex; an increase in the PCV value above 78.4% corresponds to the “cepation syndrome”.

The proposed method allows to obtain data on the risk of exacerbation of the infectious process in patients with CF according to PCV for ferritin in sputum.

The method can be used in clinical diagnostic laboratories, cystic fibrosis centers, pulmonology departments.

The use of the proposed method does not require the use of expensive equipment, invasive procedures, does not imply the subjectivity of the interpretation of the results, the method is fast and affordable for medical institutions that conduct biochemical studies.

Criteria PCV values for ferritin in sputum in patients with CF were determined by us during the examination of 40 patients; at the first stage, the content of ferritin in sputum was determined and the course of the infectious process of the patient was assessed, including: taking an anamnesis, measuring respiratory rate, assessing respiratory function, pulse oximetry, chest x-ray, thermometry, determining the level of leukocytes and C-reactive protein in the blood. Subsequently, according to the data obtained, the subjects were divided into 4 groups: 1 - patients without exacerbation of the infectious process (n=10), 2 - exacerbation without inoculation of microorganisms from Burkholderia cepacia complex (n=10), 3 - exacerbation with inoculation of microorganisms from Burkholderia cepacia complex (n=10), 4 - with "cepation-syndrome" (n=10). All included in the study underwent a biochemical study of sputum according to the proposed method with the determination of PCV for ferritin. The PCV coefficient was calculated as the difference between later and earlier ferritin content in sputum, expressed as a percentage. It turned out that there are significant differences in the increase in PCV values of ferritin in sputum in patients with CF with different course of the infectious process. In the table - Fig. 1 shows the PCV values for sputum ferritin in patients with CF, depending on the course of the infectious process.

The correlation analysis performed revealed significant strong correlations between PCV values for sputum ferritin in patients with CF over the course of the infectious process (Spearman's correlation coefficient was 0.895; p<0.001).

On FIG. Figure 2 shows the data of the ROC analysis, where A is the ROC curve characterizing the dependence of PCV for ferritin in sputum in patients with CF without exacerbation and during exacerbation without inoculation of microorganisms from the Burkholderia cepacia complex (AUC-0.790; p<0.05; threshold value : ≤37.2%); B - ROC-curve characterizing the dependence of PCV for sputum ferritin in patients with CF during an exacerbation without seeding of microorganisms from the Burkholderia cepacia complex and during an exacerbation with seeding of microorganisms from the Burkholderia cepacia complex (AUC-1.000; p<0.001; threshold value: ≤45 .7%); C- ROC-curve characterizing the dependence of PCV for sputum ferritin in patients with CF during exacerbation with inoculation of microorganisms from the Burkholderia cepacia complex and in the "cepation syndrome"(AUC-0.830;p<0.05; threshold: >78, 3%). The conducted ROC-analysis demonstrated a high predictive ability of PCV determination for sputum ferritin in patients with CF to determine the risk of exacerbation of the infectious process; made it possible to establish the optimal threshold value of this indicator and acceptable levels of sensitivity and specificity for the selected threshold values, indicated in the method for assessing the risk of complications of the infectious process in patients with CF.

The essence of the claimed method is illustrated by the following examples:

Example 1. Patient K., 8 years old, during the year without exacerbation every three months gave sputum for a planned microbiological study. At the same time, a biochemical study of sputum was carried out with the determination of the content of ferritin. On January 17, 2020, the ferritin level was 95.0 µg/L, with a subsequent determination on 04/23/20 - 106.4 µg/L, the calculated PCV coefficient = 10.7%. As of July 2, 2020, the ferritin level was 103.0 µg/L, PCV coefficient = 3.2%. On October 10, 2020, the ferritin level was 112.0 µg/L, PCV coefficient = 8%.

The results of calculating the PCV coefficient turned out to be less than 37.3%, the risk of an exacerbation of the infectious process is low.

Example 2 . Patient S., 14 years old, during the year, without exacerbation, gave sputum for a planned microbiological study. At the same time, a biochemical study of sputum was carried out with the determination of the content of ferritin. On 02/03/20, the ferritin level was 316.0 µg/l, with a subsequent determination on 05/04/20 - 394.3 µg/l, the calculated PCV coefficient = 19.9% - the risk of developing infectious complications is low.

On September 17, 2020, the patient was urgently hospitalized in the regional center of cystic fibrosis with a diagnosis of cystic fibrosis, pulmonary-intestinal form, severe course. Body temperature 38.8°C, SaO ₂ 90%, NPV 32 per minute. The general condition is severe, unstable. According to the results of microbiological examination of sputum at the time of admission, a strain of Pseudomonas aeruginosa 10 ⁵ was isolated, which is sensitive to all tested antibacterial drugs. According to the results of a biochemical study of sputum, the ferritin level was 677.0 µg/L. The calculated PCV ratio based on ferritin values between the result of the last planned study and the value obtained at the time of hospitalization was 41.7%, which corresponds to the range of 37.3% to 45.7% inclusive and exacerbation of the infectious process without seeding microorganisms from the Burkholderia cepacia complex.

Example 3. Patient D., 12 years old, on March 11, 2020, gave sputum for a routine microbiological study. At the same time, a biochemical study of sputum was carried out with the determination of the content of ferritin, the level of which at the time of the study was 445.0 μg/l.

The patient was urgently hospitalized in the regional center of cystic fibrosis on 05/06/2020 with a diagnosis of cystic fibrosis, pulmonary-intestinal form, severe course, exacerbation. At the time of admission, he complained of fever up to 39°C, shortness of breath, cough and difficulty in sputum discharge; body temperature 38.1°C, SaO ₂ 93% with constant inhalation of the oxygen mixture, NPV 34 per minute. The general condition is severe, unstable. According to the results of bacteriological culture of sputum at the time of admission, a Burkholderia cenocepacia 10 ⁴ strain resistant to fluoroquinolones was identified. According to the results of a biochemical study of sputum, at the time of hospitalization, the ferritin level was 961.0 µg/L.

The calculated PCV ratio based on ferritin values between the result of the planned study and the value obtained at the time of hospitalization was 53.7%, which corresponds to the range from 45.8% to 78.3% inclusive and exacerbation of the infectious process with the inoculation of microorganisms from the Burkholderia cepacia complex.

Example 4. Patient T., 11 years old, during the year, without exacerbation, gave sputum for a planned microbiological study. At the same time, a biochemical study of sputum was carried out with the determination of the content of ferritin. On February 15, 2020, the ferritin level was 939.0 µg/L, with a subsequent determination on 05/14/20 - 1008.5 µg/L, the calculated PCV coefficient = 6.9%. On July 24, 2020, the ferritin level was 1004.0 µg/L, PCV coefficient = 0.4%.

On October 12, 2020, the patient was urgently admitted to the regional center of cystic fibrosis with a diagnosis of cystic fibrosis, pulmonary intestinal form, severe course, exacerbation. At the time of admission, she complained of periodic fever up to 40°C, shortness of breath, cough and difficulty in sputum discharge; body temperature 37.9°C, SaO ₂ 91% with constant inhalation of the oxygen mixture, NPV 38 per minute. The general condition is severe, unstable. According to the results of bacteriological culture of sputum at the time of admission, a strain of Burkholderia cenocepacia 10 ⁵ was detected, resistant to fluoroquinolones, IV generation cephalosporins, inhibitor-protected penicillins and cephalosporins. According to the results of a biochemical study of sputum, at the time of emergency hospitalization, the ferritin level was 5117.2 µg/l. The calculated PCV ratio based on ferritin values between the result of the last routine study and the value obtained at the time of hospitalization was 80.4%, which is a value above 78.4% and corresponds to the state of development of the "cepation syndrome".

Claims (1)

A method for assessing the risk of complications of an infectious process in patients with cystic fibrosis, including collecting sputum from patients with cystic fibrosis in a sterile disposable container, centrifuging at 1700 G for 5 minutes, re-centrifuging the resulting supernatant at 4500 G for 5 minutes, determining the concentration of ferritin on an automatic biochemical analyzer using the immunoturbodimetric method, characterized in that the study is carried out in dynamics with the calculation of the PCV coefficient: if the patient is not exacerbated, then the PCV coefficient is calculated between two consecutive determinations of ferritin in sputum with an interval of 1 time in 3 months, with a PCV value <37 .3% risk of exacerbation of the infectious process is low; during an exacerbation, the PCV coefficient is calculated between the last ferritin value determined outside the exacerbation and the ferritin value determined during the exacerbation, a PCV value from 37.3% to 45.7% inclusive corresponds to an exacerbation without seeding microorganisms from the Burkholderia cepacia complex; a value from 45.8% to 78.3% inclusive corresponds to an exacerbation with the inoculation of microorganisms from the Burkholderia cepacia complex; an increase in the PCV value above 78.4% corresponds to the “cepation syndrome”.

Images