RU2770552C1 - Method for predicting respiratory effects of bronchopulmonary dysplasia in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to the field of medicine, namely, to pulmonology, and can be used to predict respiratory effects of bronchopulmonary dysplasia in children above the age of 3. Anamnestic data, such as the sex of the patient and the nature of respiratory support, are evaluated. Additionally, the provided therapy with inhaled steroids at the intensive care and outpatient stages and the hereditary history of atopic respiratory diseases are considered, and the concentration of glutathione in the blood serum is determined. Based on the combination of the resulting data, the probability of the formation of chronic respiratory pathology in the outcome of bronchopulmonary dysplasia Y is determined by the formula Y = 100% - (1 / (1+e ^-x ))*100%, wherein e is the base of a natural logarithm, x is the sum of the vectors of predictors, equal to 1.06A-1.27B+1.44C+0.67D-0.79E-0.60F, wherein A is the sex of the child: male – 1 point, female – 0 points; B is the nature of respiratory support in the intensive care unit: time in the neonatal period on artificial lung ventilation – 1 point, time in the neonatal period on non-invasive lung ventilation by the method for constant positive pressure through nasal cannulas – 0 points; C is the inhalation therapy in the intensive care unit: prescription of inhaled corticosteroids at the stage of intensive care – 1 point; absence of therapy with inhaled corticosteroids at the stage of intensive care – 0 points; D is the inhalation therapy at the outpatient stage: daily continuous therapy with inhaled corticosteroids for at least 1 month at the outpatient stage – 1 point; non-regular therapy with inhaled corticosteroids at the outpatient stage, or therapy for at least 1 month, or none thereof – 0 points; E is the hereditary history of atopic respiratory diseases: burdened hereditary history of atopic respiratory diseases – 1 point, favourable hereditary history of atopic respiratory diseases – 0 points; F is the concentration of glutathione in the blood serum: concentration of oxidised glutathione above 2.0 mcmol/l and/or concentration of reduced glutathione above 4.0 mcmol/l – 1 point, concentration of oxidised glutathione below 2.0 mcmol/l and/or concentration of reduced glutathione below 4.0 mcmol/l – 0 points. If the value Y is greater than or equal to 50%, a risk of development of chronic respiratory pathology in the outcome of bronchopulmonary dysplasia is predicted in a child.

EFFECT: increase in the accuracy of predicting respiratory effects of bronchopulmonary dysplasia in children above the age of 3 due to the comprehensive evaluation of the catamnesis data and simultaneous evaluation of the current state of respiratory health of children with recent history of bronchopulmonary dysplasia.

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Description

The invention relates to medicine, in particular to pulmonology, and can be used to assess the likelihood of developing chronic lung diseases in children as a result of bronchopulmonary dysplasia (BPD).

A known method for assessing the outcomes of BPD by ultrasound of the lungs [The clinical significance of ultrasound of the lungs in predicting the outcomes of bronchopulmonary dysplasia / I.E. Koltunov, A.V. Gorbunov, M.V. Degtyareva, O.F. Vykhristyuk, A.V. Erokhin // Pediatrics. - 2019. - T. 98, No. 2. – S. 88–93]. EFFECT: method allows evaluating the outcomes of BPD in the neonatal period (severity of the course of the disease, risk of death) based on visualization of changes in the lung tissue during ultrasound examination (atelectasis, including repeated ones, extensive areas of lung tissue compaction, interstitial pulmonary emphysema). The advantage of this method is the ability to assess the volume of lung tissue damage in severe non-transportable patients, as well as the absence of radiation exposure. The disadvantages of this method are the need to train physicians in functional diagnostics, the inability to assess the long-term respiratory effects of BPD.

A method has been proposed (No. 2480753 C1, 27.04.2013, RU), which allows assessing the severity of the course of bronchopulmonary dysplasia against the background of gastroesophageal reflux in newborns who are on artificial lung ventilation. The activity of pepsin isolated from tracheobronchial aspirate is used as a prognostic criterion. The advantage of this method is the early diagnosis of gastroesophageal reflux and timely treatment, which reduces the risk of developing chronic bronchopulmonary pathology and disability. The disadvantages of this method are the need for invasive intervention to collect tracheobronchial aspirate, the catamnesis covers only the first year of a child's life, when the course of BPD is noted and it is not authorized to talk about the respiratory consequences of the disease, predicting the outcomes of BPD without taking into account data on the course of the disease at the outpatient stage.

A known method for diagnosing BPD outcomes as part of a computer program RU 2018611614, 02.02.2018. The neural network underlying the program processes three blocks of input parameters: the state of the mother's health, anamnesis, the course of pregnancy and childbirth (30 indicators); the state of health of a newborn child (15 indicators); social and living conditions of the family (5 indicators). Based on the results of the analysis, the program evaluates the likelihood of developing cerebral leukomalacia, intracranial hemorrhages, hydrocephalus, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity in the neonatal period, and also predicts the outcome (partial or complete recovery, death). The disadvantage of this method is a large amount of data at the input of the neural network, predicting the outcomes of BPD without taking into account data on the course of the disease at the outpatient stage.

Closest to the proposed method is the method described by Yu.V. Sorokolat [Sorokolat Yu.V. Methods for predicting the course of bronchopulmonary dysplasia in children aged one year / Yu.V. Sorokolat // ScienceRise. - 2015. - T. 12, No. 3 (17). – S. 56-59]. Based on a prospective analysis of the characteristics of the course of BPD in children from the neonatal period to three years, predictors of the age-specific course and outcomes of the disease were determined. For each of the predictors, prognostic coefficients and prognostic information content of the gradation of indicators are established. These predictors are the severity of BPD and the nature of the clinical course of the disease in the first 6 months of life, the sex of the patient, anamnestic data (duration of intensive care, treatment with surfactant, gestational maturity and Apgar score), and comorbidities are taken into account.

This method is taken as a prototype. The disadvantage of the prototype: the use of this algorithm for predicting the dynamics of the course of BPD is possible in children not older than 1 year of age (optimally - 6 and 12 months of age).

The objective is to develop a predictive model for assessing the respiratory consequences of BPD in children over 3 years of age.

Bronchopulmonary dysplasia (BPD) is a multifactorial disease in the pathogenesis of which the role of oxidative stress has been proven. The frequency of BPD currently remains high due to improvements in nursing techniques for preterm infants. The formation of BPD and its subsequent transformation at an older age into a chronic pathology of the respiratory organs significantly reduces the quality of life of children, which requires the improvement of approaches to the treatment of the disease and the prevention of its outcomes.

The respiratory consequences of BPD are assessed when patients reach the age of 3 years. As the child grows, clinical recovery may occur, however, a significant proportion of patients are diagnosed with respiratory diseases, such as recurrent bronchitis, chronic bronchitis, bronchiolitis obliterans, bronchial asthma, emphysema, pneumosclerosis, or bronchiectasis [Ovsyannikov D.Yu. Bronchopulmonary dysplasia: natural development, outcomes and control [text] / D.Yu. Ovsyannikov // Pediatrics. - 2011. - T. 90, No. 1. – S. 141-150]. There are currently no objective criteria to predict the risk of developing a particular clinical outcome with a high probability. The development of a method for predicting the respiratory consequences of BPD will make it possible to personalize the program of dispensary observation of children suffering from BPD and timely conduct preventive treatment aimed at reducing the risk of an adverse outcome.

The method is based on the results of a retrospective study of catamnesis data and a one-time assessment of the current state of respiratory health of 60 children aged 3 to 17 years (median 5.0 years, lower quartile 4.0 years, upper quartile 6.0 years) who underwent BPD.

During the dispensary examination of children with BPD, to form a prognosis of the outcome of the disease, the patient's gender is taken into account, such anamnesis data as the nature of respiratory support in the neonatal period, the volume, duration and regularity of drug therapy at the stage of resuscitation and at the outpatient stage, hereditary history of respiratory diseases are evaluated. Additionally, the concentration of glutathione (oxidized or reduced) in the blood serum is estimated.

Positive prognostic characteristics have such parameters as male sex, non-invasive ventilation of the lungs by the method of constant positive pressure through nasal cannulas, therapy with inhaled glucocorticosteroids at the resuscitation stage and / or on an outpatient basis.

The probability of a favorable outcome is reduced by the female gender, artificial ventilation of the lungs, burdened heredity for atopy and lung pathology, as well as the concentration of glutathione above the 10th percentile.

The indicated predictors are binary encoded, the values of the coefficients at the indicated predictors are assigned according to FIG. 1. Characterization of predictors of a favorable BPD outcome.

Next, the sum of vectors of predictors x

x = 1.06A-1.27B+1.44C+0.67D-0.79E-0.60F

If it is not technically possible to estimate the concentration of glutathione in blood serum, the values of the coefficients for predictors are used according to Fig. 2. Characteristics of predictors of a favorable outcome of BPD when it is impossible to study the concentration of glutathione in blood serum.

In this situation, the sum of vectors of predictors x

x = 0.87A-1.55B+1.40C+0.49D-0.83E

Next, the probability of a favorable outcome Y (%) is determined by the formula

Y = (1 / (1+ e ^{- x} ))*100%

where e is the base of the natural logarithm, x is the sum of the predictor vectors.

In order to optimize the practical application of the method, calculations are performed using a computer program that performs calculations and is placed on a computer-readable medium.

Calculations show that in children with the development of chronic lung pathology after BPD, the median probability of recovery is 32%, in the group of patients with clinical recovery - 54%. Based on the foregoing, children with a Y value of less than 50% should be included in the high risk group for developing chronic respiratory pathology as a result of BPD, however, it should be borne in mind that this method is a screening method and can be used as an aid in making decisions about the tactics of dispensary observation of children. with BPD.

The quality of the developed mathematical model is reflected by the ROC curve, the area under which is 0.74, which indicates the "good" quality of the obtained mathematical model. The sensitivity of the proposed method for a comprehensive assessment of the respiratory consequences of BPD in older children is 71.8%, the specificity is 57.1%.

The developed method improves the accuracy of diagnosing the respiratory consequences of BPD in children older than 3 years.

Clinical case #1

Boy K., 7 years old. He was born at a gestational age of 26 weeks with a weight of 660 g. Due to the clinical manifestations of respiratory distress syndrome, he was on artificial lung ventilation for 39 days, for 76 days he needed additional oxygen supply. A diagnosis of bronchopulmonary dysplasia of moderate severity was made. Therapy with inhaled steroids was started at the stage of resuscitation, continued on an outpatient basis regularly; the total duration of therapy is 6 months. Episodes of acute respiratory diseases 2-3 times a year, without symptoms of bronchial obstruction. There are no signs of bronchial hyperreactivity. Heredity for atopic diseases is burdened - the mother has allergic rhinitis. On laboratory examination, the reduced glutathione level was 0.916 µmol/L, which was less than the 10th percentile.

Based on the results of a comprehensive examination, a diagnosis was made - Clinical recovery. history of BPD.

The probability of developing chronic respiratory pathology in the outcome of BPD, taking into account the declared values of predictors, was 24.8%, which indicated a low risk of developing chronic respiratory pathology in the outcome of BPD in this patient.

Clinical case #2

Girl K., 3 years old. She was born at a gestational age of 28 weeks with a weight of 894 g. Due to the clinical manifestations of respiratory distress syndrome, she was on artificial lung ventilation for 11 days, for 41 days she needed additional oxygen supply. A diagnosis of mild bronchopulmonary dysplasia was made. Therapy with inhaled steroids was carried out at the stage of resuscitation, stopped when removed from artificial lung ventilation, was administered on an outpatient basis three times after episodes of exacerbation of BPD, lasting 10-14 days. Episodes of acute respiratory diseases 4-6 times a year, with oral wheezing, sometimes there is involvement of accessory muscles. Sputum is coughed up badly, episodes of coughing. Heredity for atopic diseases is burdened - the older sister has allergic rhinitis, the father has hay fever. In laboratory examination, the level of oxidized glutathione was 6.036 µmol/l, which was more than 10 percentile.

Based on the results of a comprehensive examination, the patient was diagnosed with recurrent bronchitis. history of BPD.

The probability of developing chronic respiratory pathology in the outcome of BPD, taking into account the declared values of predictors, was 77.2%, which indicated a high risk of developing chronic respiratory pathology in the outcome of BPD in this patient.

Conclusion. Thus, the use of the proposed method makes it possible to single out a high-risk group for developing chronic respiratory pathology as a result of BPD, however, it should be taken into account that this method is a screening method. This method can be used as an aid in making decisions about the tactics of dispensary observation of children with BPD.

Claims (8)

A method for predicting the respiratory consequences of bronchopulmonary dysplasia in children over 3 years of age, including an assessment of such anamnestic data as the patient's gender and the nature of respiratory support, characterized in that it additionally takes into account ongoing therapy with inhaled steroids at the stage of the intensive care unit and on an outpatient basis, a hereditary history of atopic respiratory diseases and the concentration of glutathione in the blood serum is determined, then, based on the totality of the data obtained, the probability of developing a chronic pathology of the respiratory organs as a result of bronchopulmonary dysplasia Y is determined using the formula Y = 100% - (1 / (1+ e ^-x )) * 100%, where e - base of the natural logarithm, x is the sum of predictor vectors equal to 1.06A-1.27B+1.44C+0.67D-0.79E-0.60F, where A - gender of the child: male - 1 point, female - 0 points; B - the nature of respiratory support in the intensive care unit: being in the neonatal period on artificial lung ventilation - 1 point, being in the neonatal period on non-invasive ventilation of the lungs by the method of constant positive pressure through nasal cannulas - 0 points; C - inhalation therapy in the intensive care unit: the appointment of inhaled glucocorticosteroids at the stage of resuscitation - 1 point; lack of therapy with inhaled glucocorticosteroids at the stage of resuscitation - 0 points; D - inhalation therapy at the outpatient stage: daily continuous therapy with inhaled glucocorticosteroids for at least 1 month at the outpatient stage - 1 point; irregular therapy with inhaled glucocorticosteroids at the outpatient stage, or therapy for less than 1 month, or its absence - 0 points; E - hereditary history of atopic respiratory diseases: aggravated hereditary history of atopic respiratory diseases - 1 point, favorable hereditary history of atopic respiratory diseases - 0 points; F - concentration of glutathione in the blood serum: the concentration of oxidized glutathione is above 2.0 µmol/l and/or the concentration of reduced glutathione is above 4.0 µmol/l - 1 point, the concentration of oxidized glutathione is below 2.0 µmol/l and/or the concentration of reduced glutathione below 4.0 µmol/l - 0 points; moreover, when the value of Y is greater than or equal to 50%, the risk of developing chronic pathology of the respiratory organs in the outcome of bronchopulmonary dysplasia is predicted in a child.

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