The dissertation is devoted to issues of increasing the effectiveness of prevention of recurrent respiratory diseases (RRD) in young children with laryngopharyngeal reflux (LPR) by determining informative prognostic predictors based on the study of clinical, laboratory and functional indicators.
To achieve the set goal, the following tasks were successively performed: study of clinical and anamnestic characteristics of LPR among young children with regurgitation syndrome and establishment of its association with other respiratory and gastrointestinal disorders; studying the effect of lactase deficiency (LD) on the intensity of LPR and determining the informativeness of diagnostic methods of LD in young children; conducting daily monitoring of pepsin level in oral fluid and determining circadian rhythms of its activity to improve diagnosis of LPR in young children; study of the relationships between the activity of pepsin, pro-inflammatory cytokines and oral microbiome in young children with LPR; determination of informative clinical and laboratory predictors of RRD prediction in young children with LPR by building a logistic regression model based on the results of catamnetic observation and assessment of the feasibility of using a respiratory probiotic for the prevention of RRD.
In order to achieve the set goal, at the first stage, a clinical and anamnestic examination of 620 children aged from 1 month to 2 years was conducted using a random sampling method. At the second stage, after determining compliance with the inclusion and exclusion criteria, a detailed clinical, anamnestic, and laboratory-functional study was conducted for 155 children with vomiting syndrome who were included in the main group. As a comparison group, 30 children without regurgitation syndrome were examined. At the third stage, a study was conducted of 36 children from the main group who developed RRD in catamnesis.
In the work, for the first time, the daily circadian rhythms of pepsin activity in the oral cavity fluid were studied and the optimal threshold value of its level was determined for the diagnosis of LPR in young children, and the presence of hidden episodes of reflux was established. Thus, the average daily value of the pepsin level during monitoring was (Me) 446.8 (267.9–534.7) pg/ml, it changed during the day, it was maximal after vomiting, but it probably did not differ with samples on an empty stomach and one hour after feeding (439.4 (257.7–615.3) pg/ml, 514.0 (281.8–581.2) pg/ml, 422.9 (247.1–525.2) pg/ml, respectively, p>0.05), which indicates the presence of hidden episodes of reflux during the day. The level of pepsin on an empty stomach was probably higher in children with a high intensity of LPR (≥ 7 points according to the reflux questionnaire). It was determined that the fasting pepsin level in the oral cavity fluid ≥443.4 pg/ml can be used for the screening diagnosis of LPR in young children with a sensitivity of 66.7%, specificity — 80.0%, predictive value of a positive result — 75.0 % and the predictive value of a negative result — 72.7%.
The paper confirmed that LPR in young children induces a disturbance in the state of the microbiota of the oral cavity, which is characterized by an increase in the number of colony-forming units of gram-negative strains (in particular, K. pneumonia, E. coli, P. vulgaris). The frequency of identification of strains of S. viridans, as a representative of normal microflora, was probably lower in children with RRD, which also had a relationship with the concentration of pepsin in the oral fluid of young children (R=0.61, p<0.05 ).
Based on a multifactorial approach to assessing the risk of developing RRD, the most significant prognostic predictors were: the onset of regurgitation after 6 months (I=1.76), periodic cough and/or hoarseness without signs of ARD (I=1.58), wheezing during the first two years of life without signs of ARD (I=1.36), IL-8 >426.0 pg/ml (I=3.53), lactase deficiency (I=2.24) and fasting pepsin > 500 pg/ml (I=1.04). In the work, convenient prognostic scales for various stages of medical care have been constructed and proposed, which allow to single out a group of young children with LPR who need in-depth examination and preventive measures to reduce the frequency of respiratory infections and prevent the development of their recurrent course.
