Local mucosal resistance state and microbial colonization of upper airways in children with complicated upper respiratory tract infections

Ju.K. Bolbot, A.V. Karpenko, O.V. Shvarackaja, E.V. Bratus

Abstract


Background. Upper respiratory tract infections (URTIs) are one of the most common diseases of childhood. It is known that some children tend to have recurrent bacterial complications of URTIs; the liability mentioned might be linked to different factors including local mucosal immune resistance malfunction. Infectious respiratory pathology is currently being considered comprehensively in the aspect of viral-bacterial-immune interaction, consequently the study of microbiological and immunological factor relations may be helpful in promoting the development of targeted therapeutic and preventive measures that may improve the efficiency of the management of such patients. Thereby, the study objectives were to investigate the local mucosal resistance state, features of microbial colonization of upper airways along with etiological structure complications in children susceptible to repeated bacterial complications of URTIs. Materials and methods. We enrolled 214 children aged 3 to 18 years with URTIs complicated with acute otitis media (AOM) or acute bacterial rhinosinusitis (ARS). Rate of bacterial complications of URTIs in 128 children was low (group I) and in 86 children it met the criteria of recurrent course (group II). We performed microbiological examination of nasopharyngeal secretions or middle ear exudates as well as local mucosal immunology study: lysozyme, lactoferrin, human cathelicidin hCap-18/LL-37, secretory IgA concentrations in oropharyngeal discharge measured twice during the disease, and after recovery. The controls were 36 children with uncomplicated URTIs, and the reference values were obtained in 30 healthy children. Results. In children with recurrent (versus episodic) bacterial complications of URTIs malfunction of airway local protective innate mucosal immune mechanisms were present: reduction of human cathelicidin level during the whole period of disease, reduction of lactoferrin at the early stages of bacterial process, and reduced concentrations of lysozyme at all phases of the study. It’s noteworthy that concentrations of hCAP/LL-37 and lactoferrin during the disease exceeded control and referent values in both groups; while lysozyme levels obtained from children of the II group were significantly lower compared to referent patients both initially and after recovery. The levels of antimicrobial peptides demonstrated the inverse correlation with URTI symptoms duration. In the II group the level of negative microbiological results for causative pathogen of AOM/ARS was about 35 % vs. about 20 % in group I (p = 0.008). Also lower rate of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (pathogenic bacteria), and higher rate of Haemophilus parainfluenzae and Staphylococcus aureus (associated agents) isolates occurred in group II. Furthermore, associations of two non-causative bacterial agents were obtained only in group II. Non-causative bacteria colonization in general was associated with lower levels of mucosal antimicrobial peptides, but on the background of URTI it might activate tempora­rily lysozyme and lactoferrin response. Conclusions. Recurrent bacterial complications of URTIs are associated with local mucosal resistance insufficiency, and higher rate of St.aureus and H.parainfluenzae colonization. High rate of microbiological failures in determining of causative agent of AOM/ARS may be related to over diagnostics of bacterial complications which might be linked to misinterpretation of prolonged course of the disease due to mucosal immune dysfunction and non-causative bacteria colonization. Thus, di­sease duration shouldn’t be used as an independent criterion of bacterial process in this category of patients because it may lead to misdiagnose and antibiotic overuse.

Keywords


upper respiratory tract infections; antimicrobial peptides; lysozyme; local mucosal resistance; microbial colonization of airways; children

References


Lieberthal AS, Carroll AE, Chonmaitree T, et al. The diagnosis and management of acute otitis media. Pediatrics. 2013;131:e964-e999. doi: 10.1542/peds.2012-3488.

Wald ER, Applegate KE, Bordley C, et al. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years. Pediatrics. 2013 Jul;132(1):e262-e280. doi: 10.1542/peds.2013-1071.

Nesterova IV. The problems of treatment of viral-bacterial respiratory infections in immunocompromised children with the tendency to frequent URTIs. Lechashchiy vrach. 2009; 6:40-3. (In Russian).

Fokkens WJ, Lund VJ, Mullol J. European position paper on rhinosinusitis and nasal polyps. Rhinology. 2007;20(Suppl 20):1-136. PMID: 17844873.

Lopez Campos X, Alvarez Castello M, Massip J. 256 risk factors of recurrent upper respiratory infections in children under 5 years. World Allergy Organ J. 2012 Feb;5(Suppl 2):S101. doi: 10.1097/01.WOX.0000412013.14727.54.

Unger SA, Bogaert D. The respiratory microbiome and respiratory infections. J Infect. 2017 Jun;74 Suppl 1:S84-S88. doi: 10.1016/S0163-4453(17)30196-2.

Gevaert E, Zhang N, Krysko O, et al. Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation. JACI. 2017 Jun;139(6):1849-60.e6. doi: 10.1016/j.jaci.2017.01.019.

Bosch A, Levin E, van Houten M, et al. Development of upper respiratory tract microbiota in infancy is affected by mode of delivery. EBioMedicine. 2016;9:336-45. doi: 10.1016/j.ebiom.2016.05.031.

Man WH, de Steenhuijsen Piters W, Bogaert D. The microbiota of the respiratory tract: Gatekeeper to respiratory health. Nature Reviews Microbiology. 2017 March;15(5):259-70. doi: 10.1038/nrmicro.2017.14.

Russel CD, Unger SA, Walton M, Schwarze J. The human immune response to respiratory syncytial virus infection. Clinical Microbiology Reviews. 2017 April;30(2):481-502. doi: 10.1128/CMR.00090-16.

Wouter AA, de Steenhuijsen Piters W, Heinonen S, Hasrat R, Mejias A. Nasopharyngeal microbiota, host transcriptome and disease severity in children with respiratory syncytial virus infection. American Journal of Respiratory and Critical Care Medicine. 2016 May;194(9). doi: 10.1164/rccm.201602-0220OC.

Dudnyk VM, Zaichko NV, Fedchyshen ОP. Activity of antimicrobial peptides and 25-hydrocholecalciferol in children with asthma. Perinatologiya i pediatriya. 2017;1(69):121-5. doi: 10.15574/PP.2017.69.121. (In Ukrainian).

Schroder JM, Harder J. Antimicrobial skin peptides and proteins. Cellular and Molecular Life Sciences. 2006;63:469-86. doi: 10.1007/s00018-005-5364-0.

Massa HM, Lim DJ, Kurono Y, Cripps AW. Middle ear and eustachian tube mucosal immunology. Mucosal Immunology. 2015;2:1923-42. doi: 10.1016/B978-0-12-415847-4.00101-4.

Actor JK, Hwang SA, Kruzel ML. Lactoferrin as a natural immune modulator. Current Pharmaceutical Design. 2009;15(17):1956-73. PMID: 19519436. PMCID: PMC2915836.

Vandamme D, Landuyt B, Luyten W, Schoofs L. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cellular Immunology. 2012;280(1):22-35. doi: 10.1016/j.cellimm.2012.11.009.

Cerutti A, Chen K, Chorny A. Immunoglobulin responses at the mucosal interface. Annual Review of Immunology. 2011;29:273-93. doi: 10.1146/annurev-immunol-031210-101317.

Lezhenko GA, Abaturov AYe, Pashkova EYe, Gladun KV. The content of antimicrobial proteins in children with inflammatory diseases of the respiratory tract. Zdorov'ye Rebenka. 2017;12(3). (In Ukrainian). doi: 10.22141/2224-0551.12.3.2017.104219.

Marushko JuV, Zelena NA, Mel'nіkov OF, Movchan OS. State of local immunity in children with frequent respiratory infections. Aktual'naya Infektologiya. 2013;1(1). (In Ukrainian). doi: 10.22141/2312-413x.1.01.2013.82609.

Marushko JuV, Movchan OS. Characteristics of local humoral factors of nonspecific resistance in children with recurrent respiratory diseases. Zdorov’ye Rebenka. 2014;12(3):9-13. (In Ukrainian). doi: 10.22141/2224-0551.2.53.2014.75938.

Lezhenko GO, Abaturov OE, Pashkova OE. The role of endogenous antimicrobial peptides in the bacterial colonization of the nasopharynx in children with hyperplasia of the pharyngeal tonsil. Zdorov’ye Rebenka. 2016;74(6):74-82. (In Ukrainian). doi: 10.22141/2224-0551.6.74.2016.82136.

Kuroda K, Okumura K, Isogai H, Isogai E. The human cathelicidin antimicrobial peptide LL-37 and mimics are potential anticancer drugs. Front Oncol. 2015;5:144. doi: 10.3389/fonc.2015.00144.

Krivopustov CP. Acute otitis media in children: pediatrician's opinion about the problem. Dityachiy lіkar. 2010;1:12-8. (In Russian).

Shcheplyagina LA, Kruglova IV. Age characteristics of immunity in children. Russian Medical Journal. 2009;23:1564. (In Russian).

Visochina ІL. Immune status of healthy children of school age from orphanages and its features, depending on the state of bacterial colonization of the upper airway mucous membranes. Zdorov’ye Rebenka. 2012;40(5):45-9. (In Ukrainian).




DOI: https://doi.org/10.22141/2224-0551.12.4.2017.107625

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

 

© Publishing House Zaslavsky, 1997-2017

 

 Яндекс.МетрикаSeo анализ сайта Рейтинг@Mail.ru