RU2439569C1 - Method of predicting bronchopulmonary displasia in children with inherent pneumonia - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: in newborn babies with intrauterine pneumonia, who are on artificial lung ventilation, content of protein of cells Clara (CC 16) is analyses on the 3-5-th day of life in single portion of bronchoalveolar lavage and if its value is less than 53 ng/ml, development of bronchopulmonary dysplasia is predicted, when there are no clinical manifestations. Claimed method possesses high accuracy, sensitivity, specificity. ^ EFFECT: application of method makes it possible to timely administrate adequate therapy and contributes to reduction of economic expenditure on treatment and prevents disorders in child's health state in future. ^ 2 tbl, 3 ex

Description

The invention relates to medicine, namely to pediatrics, neonatology and pulmonology, and can be used for early prediction of bronchopulmonary dysplasia in children with congenital pneumonia and extremely low birth weight.

The relevance of the proposed method is determined by increased survival and improved nursing of children with congenital pneumonia and extremely low birth weight (ENMT) at birth, which are at risk for the development of bronchopulmonary dysplasia (BPD). The frequency of BPD development depends on body weight at birth, the duration of mechanical ventilation (mechanical ventilation) and is 40-45% in children with EBMT. Mortality in BPD is 14-36% during the first 3 months of life and 11% thereafter in the first year of life. The course of BPD is characterized by chronic respiratory failure, prolonged dependence on oxygen, recurrent bronchial obstructive syndrome, and repeated pneumonia. BPD is often transformed into obliterating bronchiolitis and bronchial asthma [1, 2].

Treatment of bronchopulmonary dysplasia presents serious difficulties and is accompanied by high economic costs. Therefore, the most serious attention should be given to the early prognosis of BPD. This is especially true in newborns with intrauterine pneumonia, which increases the risk of developing bronchopulmonary dysplasia.

There is a method for predicting bronchopulmonary dysplasia on 10-14 days of life in newborns, when a child who is under mechanical ventilation due to respiratory distress syndrome does not have positive dynamics, the oxygen concentration in the inhaled air is 50-80%, the need for high peak inspiratory pressure during mechanical ventilation , the average airway pressure is more than 7-10 cm. of water. Art., X-ray data indicate persistent pulmonary edema or a picture resembling a "honeycomb" [Ovsyannikov D.Yu. Dysplasia: a teaching aid - M .: RUDN University, 2009. - 63 p.].

The disadvantages of the method:

1. Can be used no earlier than the 10-14th day of life, when damage to the lung tissue is quite pronounced.

2. Not used in the early neonatal period.

3. The subjectivity of the method.

4. The accuracy of the method is unknown.

A known method for predicting severe respiratory distress syndrome and bronchopulmonary dysplasia in premature infants by examining the protein of Clara cells (CC16) and IL-6 in umbilical cord blood. With a low concentration of Clara cell protein and an increase in IL-6, severe RDS and BPD are predicted [Cord blood Clara cell protein CC16 predicts the development of bronchopulmonary dysplasia / Schrama AJ, Bernard A, Poorthuis BJ et al. // Eur J Pediatr. - 2008. - Nov .; 167 (11): 1305-12].

The disadvantages of the method:

1. There are no prognostic criteria.

2. The accuracy of the method is not known.

3. It is not always possible to obtain cord blood.

4. It is not possible to predict this pathology in children with congenital pneumonia, but only in children with RDS.

5. There are no criteria for predicting this pathology in children with ENMT who have the highest risk of developing BPD.

These disadvantages can be eliminated in the proposed method.

The claimed technical result is achieved by the fact that in a single portion of bronchoalveolar lavage in children with ENMT and with congenital pneumonia on the 3-5th day of life (when there are no clinical manifestations of bronchopulmonary dysplasia), the protein content of Clara cells is determined (CC 16). With a Clara cell protein level (SS 16) of less than 53 ng / ml, the development of bronchopulmonary dysplasia in newborns under mechanical ventilation is predicted with an accuracy of 80.4%, sensitivity of 80.6% and specificity of 80.0%.

The novelty of the proposed method lies in the fact that for the first time it is proposed to predict (for 3-5 days of life) bronchopulmonary dysplasia in very premature infants with congenital pneumonia who are under mechanical ventilation to determine the protein content of Clara cells (CC 16) in bronchoalveolar lavage.

Clara cells are located in the terminal and respiratory bronchioles and synthesize protein - the protein of Clara cells. This protein is used to evaluate lung parenchyma. Clara cell protein helps detoxify harmful substances, participates in the inactivation of toxins coming in from the inhaled air, prevents the adhesion of bronchioles and the growth of connective tissue in the lungs, and reduces inflammation. A decrease in the content of this protein is possible with the destruction of Clara cells or with inhibition of its synthesis. This situation occurs with bronchial asthma, chronic obstructive pulmonary disease, in people who smoke [3, 4, 5].

For the first time, it was found that in children with ENMT during intrauterine pneumonia (in contrast to children without pneumonia), Clara cells are stimulated, resulting in an increase in the content of Clara cell protein in lavage fluid and peripheral blood. Stimulation of these cells was negligible if newborns later developed BPD. In these children, the protein content of Clara cells in lavage and blood was lower than in newborns who recovered from intrauterine pneumonia.

Clara cell protein is synthesized only in the lungs. After entering the systemic circulation through the airborne barrier, it is rapidly eliminated by glomerular filtration [5]. Therefore, the dynamics of the protein content of Clara cells in the alveolar fluid can be judged by its concentration in peripheral blood. Children without pneumonia were not on mechanical ventilation, therefore, it was not possible to determine the Clara cell protein in lavage fluid, but its content can be indirectly estimated by the concentration in peripheral blood. Therefore, peripheral blood was taken from all children to determine the Clara cell protein.

Table 1 presents data showing the protein content of Clara cells in the peripheral blood in children without pneumonia and with congenital pneumonia. Children with congenital pneumonia are divided into 2 groups according to the outcome: recovery and development of BPD.

Table 1 Clara cell protein content Without pneumonia n = 14 With congenital pneumonia Credibility Outcome - recovery n = 35 Exodus - BPD
n = 15 one 2 3 In plasma 2.042 ± 0.49 4.28 ± 0.73 2.31 ± 0.30 P _1-2 <0.001 blood, ng / ml P _2-3 <0.001 (M ± m) P _1-3 <0.1

This table shows that the protein content of Clara cells in blood plasma in children without pneumonia and BPD was significantly lower than in children with congenital pneumonia with an outcome in recovery. Thus, in children with congenital pneumonia, Clara cells are stimulated, as a result of which their protein content increases, which helps protect the lungs. In children with congenital pneumonia who subsequently developed BPD, the protein content of Clara cells was slightly higher than in children without pneumonia. Stimulation of Clara cells in them was insufficient, the protein content was insufficient to protect the lung, which led to the development of BPD.

The method of implementation.

Newborns undergoing mechanical ventilation require regular reorganization of the tracheobronchial tree (bronchoalveolar lavage - BAL) for the normal functioning of the endotracheal tube and removal of excessive sputum, which must be disposed of. A single portion of sputum collected on 3-5 days of life using bronchoalveolar lavage is sent for examination. The BAL sampling methodology took into account the recommendations of the BAL working group of the European Respiratory Society. The material is taken after the endotracheal tube has been sanitized with a catheter of the appropriate size. A 0.9% NaCl solution was introduced fractionally into the lungs at the rate of 0.5 ml / kg, followed by suction and collection of BAL in sterile tubes. During the procedure, percussion massage of the chest and rotation of the head in accordance with the side of the lavage are performed. In total, the sampling procedure is repeated 2-3 times on each side. The total amount of BAL is about 1.5-2.0 ml. The resulting material is centrifuged for 15 minutes at a speed of 3000 rpm to obtain a supernatant.

Clara cell protein concentration is determined in 0.01 ml of supernatant by ELISA (BioVendor kit). The result is expressed in ng / ml.

Distinctive features of the proposed method are the determination of protein content on 3-5 days of life in a single serving of bronchoalveolar lavage. When its value is less than 53 ng / ml, the development of bronchopulmonary dysplasia in newborns with EBMT at birth and congenital pneumonia on mechanical ventilation is predicted.

The essence of the proposed method is illustrated by the following examples.

Example 1. Child P. from a mother of 26 years old, suffering from chronic pyelonephritis and chronic pharyngitis. Pregnancy proceeded against the background of anemia, the threat of termination of pregnancy, prenatal discharge of amniotic fluid at 27 weeks of pregnancy. Antenatal prophylaxis of respiratory distress syndrome has not been performed. Childbirth at 27 weeks. At birth, the body weight is 990 g, length 33 cm. Apgar score on the 1st minute of life 3 points. Considering the presence of pronounced signs of respiratory failure, gestational age, birth weight, and the absence of antenatal prophylaxis with steroids in accordance with the protocols of the Russian Association of Perinatal Medicine Specialists [6], the child is intubated, the artificial surfactant “Kurosurf” is endotracheally administered, and the child is transferred to prolonged mechanical ventilation of the lungs . After stabilization, the child was transferred to the intensive care unit.

The child was diagnosed with congenital pneumonia.

When examining a newborn on the 3rd day of life, the claimed method determined the level of protein of Clara cells in bronchoalveolar lavage equal to 20.9 ng / ml, which suggested the development of bronchopulmonary dysplasia.

The duration of mechanical ventilation was 13 days 19 hours. Respiratory failure after extubation was characterized by the presence of mixed dyspnea of up to 60 per minute, with retraction of the intercostal spaces, retraction of the sternum, percussion above the lungs - shortening, ascultation - breathing is weakened, carried out uniformly, crepitating wheezing on both sides, with a gradual non-relief of these symptoms. After extubation, the child was transferred to an oxygen subsidy in an oxygen tent for 2 hours, then the child was dependent on oxygen for 2 months 9 days, which was offset by the supply of moistened oxygen through a funnel. X-ray at the age of 1 month 15 days revealed fibrotic changes in the lungs. Diagnosed with BPD.

Conclusion: the prognosis of the development of bronchopulmonary dysplasia in a newborn by the present method was confirmed.

Example 2. Child S. from a mother of 26 years old, suffering from yeast colpitis. Pregnancy was complicated by the protracted course of late gestosis, fetoplacental insufficiency, and central placenta previa. In connection with the development of preeclampsia, pregnancy ended in an operative way in the period of 27 weeks. Antenatal prophylaxis of respiratory distress syndrome with corticosteroids was carried out. At birth, body weight 945 g, length 34 cm. Apgar score in the first minute - 1 point. Given the presence of pronounced signs of respiratory failure, gestational age, birth weight, the baby is intubated, the artificial surfactant Kurosurf is endotracheally administered, and the baby is transferred to prolonged mechanical ventilation. Diagnosed with congenital pneumonia.

When examining a newborn on the 4th day of life by the claimed method, it was found: the protein content of Clara cells is 276.46 ng / ml, which is higher than the claimed level as a criterion for predicting the risk of developing bronchopulmonary dysplasia. The absence of bronchopulmonary dysplasia is predicted.

The duration of mechanical ventilation was 10 days 1 hour 15 minutes. After extubation, the child was transferred to oxygen subsidy in an oxygen tent for 3 hours, then transferred to oxygen therapy through a funnel for 10 days. Subsequently, the child was oxygen-independent. Radiologically at the age of 1 month 10 days there is no data for BPD.

Conclusion The prognosis of the absence of bronchopulmonary dysplasia in a newborn by the present method was confirmed.

Example 3. Child S. from a mother of 27 years old, suffering from yeast colpitis. Pregnancy was complicated by the protracted course of late gestosis, fetoplacental insufficiency, and prenatal outflow of amniotic fluid. Childbirth in 28 weeks. Antenatal prophylaxis of respiratory distress syndrome with corticosteroids was carried out. At birth, body weight 910 g, length 35 cm. Assessment on the Apgar scale in the first minute - 3 points. Given the signs of respiratory failure, gestational age, birth weight, the baby is intubated, the artificial surfactant Kurosurf was endotracheally injected, extubated and transferred to respiratory support using the CPAP method. By the end of the first day of life, an increase in respiratory failure was noted and the child was transferred to prolonged mechanical ventilation. Diagnosed with congenital pneumonia.

When examining a newborn on the 5th day of life by the claimed method, it was found: the protein content of Clara cells is 53.0 ng / ml, which is higher than the claimed level as a criterion for predicting the risk of developing bronchopulmonary dysplasia. The absence of bronchopulmonary dysplasia is predicted.

The duration of mechanical ventilation was 5 days 1 hour 25 minutes. After extubation, the child was transferred to oxygen subsidy in an oxygen tent for 12 hours, then transferred to oxygen therapy through a funnel for 8 days. Subsequently, the child was oxygen-independent. Radiologically at the age of 1 month 10 days there is no data for BPD.

Conclusion The prognosis of the absence of bronchopulmonary dysplasia in a newborn by the present method was confirmed.

In this way, 51 newborns were examined, of which 19 newborns were predicted to develop bronchopulmonary dysplasia, while the diagnosis was confirmed by the claimed method in 12 children. In 32 children, the absence of bronchopulmonary dysplasia was predicted, while the diagnosis was confirmed by the claimed method in 29 newborns. The survey results are presented in table 2.

table 2 Indicators The number of examined by the claimed method Total newborns 51 True positive result 12 False positive 7 True negative result 29th False negative result 3

Total:

- The accuracy of the proposed method: 80.4%.

- The sensitivity of the proposed method: 80.6%.

- The specificity of the proposed method: 80.0%.

The advantages of the proposed method:

1. High accuracy - 80.4%, sensitivity - 80.6% and specificity - 80.0%.

2. It makes it possible to predict the development of bronchopulmonary dysplasia before the development of the clinical picture of the disease on the 3-5th day of the life of a child with congenital pneumonia and extremely low birth weight, who is under mechanical ventilation.

3. Early prediction of bronchopulmonary dysplasia makes it possible to prescribe adequate therapy in a timely manner, reduce the severity of the disease and mortality in this pathology.

4. Timely adequate therapy reduces the cost of treating patients and prevents violations of the child’s health in the future.

5. The method is not invasive.

Literature

1. Neonatology: national leadership / ed. N.N. Volodina. - M .: GEOTAR-Media, 2007 .-- 848 p.

2. Ovsyannikov D.Yu. Bronchopulmonary dysplasia: a teaching aid - M .: RUDN, 2009. - 63 p.

3. Borkina A.N. Structural and functional reorganization of secretory exocrinocytes (Clara cells) and type 2 Alveolocytes under the influence of destabilizing factors and in chronic obstructive pulmonary disease: abstract. dis ... cand. honey. sciences. - Orenburg, 2008 .-- 23 p.

4. Clara cell protein in serum and bronchoalveolar lavage / Bernard A, Merchandise FX, Depelchin S. et al. // Eur Respir J. - 1992 .-- Vol. 5. - P.1231-1238.

5. Hermans C, Petrek M, Kolek V. 16 kDa Clara cell protein (CC16) as a marker of the integrity of the airborne barrier in sarcoidosis // Eur Respir. - 2001. - Vol. 18. - P.507-514.

6. Principles of management of newborns with respiratory distress syndrome: guidelines, ed. Acad. RAMS N.N. Volodina - M., 2009 .-- 34 p.

Claims (1)

A method for predicting the development of bronchopulmonary dysplasia in preterm infants by examining the Clara cell protein (CC 16) in biological fluid, characterized in that the protein content is determined on the 3-5th day of life in a single portion of bronchoalveolar lavage and with its value less than 53 ng / ml predict the development of bronchopulmonary dysplasia in children with extremely low birth weight who are on mechanical ventilation due to congenital pneumonia.