Pharynx infectious and inflammatory diseases local etiotropic therapy efficacy comprehensive assessment in preschool and primary school-age children

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Abstract

Background. The oropharyngeal microbiota is important in maintaining resistance, eliminating viruses and regulating local protective reactions in response to inflammation in acute respiratory infections.

Aim. To evaluate of the effect of topical etiotropic therapy on clinical manifestations, elimination of viruses and on oropharyngeal microbiota in the treatment of acute infectious inflammation of the throat that occurred as part of acute respiratory infections in children aged 5–10 years.

Materials and methods. 120 outpatient patients randomized into 3 equal groups were treated for 7 days: in Group 1 – 0.2% hexethidine-containing aerosol, in Group 2 – 0.03 mg combined spray gramicidin S and 0.1 mg cetylpyridinium chloride, in Group 3 – 0.01% topical solution containing benzyldimethyl-myristoylamino-propylammonium. Changes in the severity of clinical manifestations were compared (integral indicator – modified Tonsillopharyngitis Severity Score – TSSm for children, the severity of the "sore throat" symptom on the Wong–Baker scale, the severity of local signs of inflammation according to pharyngoscopy data) in groups at Visit 2 (day 5±1) and Visit 3 (day 12±1) compared with the Visit 1. The elimination of acute respiratory infection pathogens was evaluated: polymerase chain reaction (PCR) of oropharyngeal smears obtained on days 1, 3 and 5 (±1) – PCR-1, PCR-2, PCR-3 respectively, with the detection of 12 respiratory viruses, including SARS-CoV-2. The state of the microbiota was assessed by sequencing the full-size 16S gene in samples obtained before and after treatment 1st and 12th (±1) days, and compared with 19 indicators in healthy.

Results. By Visit 3, the decrease in TSSm indicators was: 4.0±1.07 in Group 1; 5.0±1.48 in Group 2 and 4.0±1.02 in Group 3. The intergroup differences between Group 2 and 1, Group 2 and 3 were statistically significant (p<0.05). The severity of sore throat by Visit 3 decreased in groups 1, 2 and 3 respectively by 2.0±0.90, 2.5±0.61 and 2.1±0.60, intergroup differences between groups 2 and 1, 2 and 3 had statistical significance at p<0.05. The time to achieve complete relief of the disease according to the TSSm indicator was (day, M±SE): 16.6±1.47 in Group 1; 11.9±1.13 in Group 2 and 12.4±1.38 in Group 3, intergroup differences (groups 1 and 2) are significant, p<0.05. The time of complete relief from sore throat for groups 1–3 was 12.6±0.96, 8.0±0.87 and 9.4±1.01 respectively, intergroup differences (groups 1 and 2) were significant, p<0.05. By Visit 2, the proportion of patients with a negative PCR result increased in Group 1 by 25%, in Group 2 by 43% and in Group 3 by 38%, which corresponded to the elimination of 81, 92 and 74% of viruses detected in groups according to PCR-1 and PCR-2. The microbiota of participants in all groups before treatment differed from the microbiota of healthy in terms of alpha and beta diversity, as well as in terms of indicators obtained by the NearesBalance method. After completion of treatment, changes in the microbiota in terms of beta diversity were observed in all groups compared to the initial state. In contrast to groups 1 and 3, in Group 2 there were statistically significant changes in species-level balances between groups of microbes that distinguish between sick and healthy, towards indicators of healthy.

Conclusion. Topical etiotropic medications provide rapid relief of complaints and local signs of inflammation in the treatment of patients aged 5–10 years with sore throat in acute respiratory infections and contribute to the rapid elimination of pathogens of acute respiratory infections. A combined preparation containing an antiseptic and a bacteriocin-like antimicrobial peptide gramicidin S provides a more pronounced therapeutic effect at an earlier time and the elimination of 90% of all respiratory viruses, including SARS-CoV-2, by the fifth day of therapy, and also has the most sparing effect on the oropharyngeal microbiota compared to antiseptic monopreparations, which may explain its more pronounced anti-inflammatory effect.

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About the authors

Irina N. Zakharova

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: zakharova-rmapo@yandex.ru
ORCID iD: 0000-0003-4200-4598

D. Sci. (Med.), Prof., Russian Medical Academy of Continuous Professional Education

Russian Federation, Moscow

Irina S. Kuznetsova

Russian Medical Academy of Continuous Professional Education

Email: doctor_irina_kuznetsova@mail.ru
ORCID iD: 0000-0001-5164-682X

Аssistant, Russian Medical Academy of Continuous Professional Education

Russian Federation, Moscow

Tatiana A. Cherednikova

Children's City Polyclinic №140

Email: zakharova-rmapo@yandex.ru

Pediatrician, Children's City Polyclinic №140

Russian Federation, Moscow

Anastasia V. Makhaeva

Russian Medical Academy of Continuous Professional Education; Children's City Polyclinic №140

Email: avmakhaeva305@yandex.ru
ORCID iD: 0000-0002-0006-5889

Graduate Student, Russian Medical Academy of Continuous Professional Education, Pediatrician, Children's City Polyclinic №140

Russian Federation, Moscow; Moscow

Stanislav I. Koshechkin

Knomics LLC

Email: st.koshechkin@knomx.com
ORCID iD: 0000-0002-7389-0476

Cand. Sci. (Biol.), Knomics LLC

Russian Federation, Moscow

Vladimir A. Romanov

Knomics LLC

Email: romanovv@knomx.com
ORCID iD: 0000-0002-7540-5884

Senior Res. Officer, Knomics LLC

Russian Federation, Moscow

Vera E. Odintsova

Knomics LLC

Email: v.odintsova@knomx.com
ORCID iD: 0000-0003-1897-4033

Department Head, Knomics LLC

Russian Federation, Moscow

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Supplementary files

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2. Fig. 1. The frequency of "sore throat" symptom (a) and the main pharyngoscopic signs of oropharynx inflammation (mucosal hyperemia) by the groups (b) – at Visit 1.

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3. Fig. 2. Decrease in the severity of disease manifestations: a – mean changes in the integral indicator value (TSSm score) by Visit 2; b – by Visit 3 compared to Visit 1.

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4. Fig. 3. Decrease in the "sore throat" symptom severity according to the Wong–Baker scale at Visits 2 and 3 compared to Visit 1.

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5. Fig. 4. Decrease in the severity of local pharyngeal inflammation signs according to pharyngoscopy at Visits 2 and 3 compared to Visit 1.

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6. Fig. 5. The proportion of patients showed relief of the disease symptoms (a), the average time to relief of the disease symptoms (b).

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7. Fig. 6. The results of polymerase chain reaction (PCR) detection during the study: a – the proportion of participants with nuclear acids of acute respiratory infections (ARI) viruses was detected according to PCR-1 and PCR-2 data; b – the change in the proportion of PCR-negative patients according to PCR-3 data; c – the proportion of eliminated viruses according to PCR-3 data, initially detected by PCR-1 and PCR-2.

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8. Fig. 7. Differences in the taxonomic composition of samples from study subjects at Visit 1 and healthy peers: a – heat map of the taxonomic composition of microbiota samples at the species level; b – box-and-whisker graph for balance values.

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9. Fig. 8. Changes in the taxonomic composition of samples from study subjects from Visit 1 to Visit 3. Changes at the species level: a – heat maps for group 1; b – for group 2; c – for group 3; d – box-and-whisker graph for balance values.

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10. Fig. 9. Changes in the balances of microorganisms that distinguish patients from healthy peers between groups.

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