Pediatrician (St. Petersburg)Pediatrician (St. Petersburg)2079-78502587-6252Eco-Vector1914810.17816/PED10513-18Research ArticleAge aspects of the course of chronic otitis media with cholesteatoma in children (clinical and immunological characteristics)VlasovaGalina V.<p>MD, PhD, Associate Professor, Department of Otorhinolaryngology</p>galinav71@mail.ruPavlovPavel V.<p>MD, PhD, Head of Department of Otorhinolaryngology</p>pvpavlov@mail.ruSt. Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation2812201910513182801202028012020Copyright © 2020, Vlasova G.V., Pavlov P.V.2020<p>Cholesteatoma of the middle ear is the disease, the course and prognosis of which can not be considered without taking into account the patients age. In pediatric otorhinolaryngology, such patients require special attention due to the aggressiveness of cholesteatoma in children. The rapid growth and a high number of recurrences after surgical treatment are features of the course of this disease in children. The causes of the aggressiveness of this disease in children have not been studied. Objective: to identify clinical and immunological features in children with middle ear cholesteatoma in different age groups that contribute to the aggressive course of the disease. A retrospective analysis of 143 medical case reports of children from 1 to 17 years old who received surgical treatment of middle ear cholesteatoma was carried out in the Department of othorhinolaryngology (St. Petersburg State Pediatric Medical University) from 2000 to 2018. Comparative analysis of clinical manifestation, anamnesis of ear disease, concomitant diseases, immunological reactivity (the content of lymphocytes, their subpopulations and interleukin-2 in peripheral blood) and results of surgical treatment of middle ear cholesteatoma in different age groups has been performed. Cholesteatoma is more aggressive in young children. Frequent infections of the upper respiratory tract, eustachian tube dysfunctions, immune disorders in children under 7 years of age lead to an unfavorable course and prognosis of middle ear cholesteatoma.</p>middle ear cholesteatoma in childrencongenital cholesteatomachronic otitis mediacytokinesimmunityхолестеатома среднего уха у детейврожденная холестеатомахронический средний отитцитокиныиммунитет<h2>BACKGROUND</h2>
<p>Age is the most important factor to determine the characteristics of the manifestation, course, and choice oftherapeutic approach and prognosis of many diseases. At each agestage, the child has its own morphological, physiological, and immunologicalaspects, which, probably, create the prerequisites for a certain courseof the disease [6]. Interpretation of the disease clinical presentationfrom the age perspective of the child allows a differentiated approach to the patient and prediction of thecourse of the disease, to a certain extent.</p>
<p>A vivid exampleof a disease, in which the course and prognosis cannotbe considered without an age aspect, is cholesteatoma of themiddle ear.</p>
<p>Cholesteatoma is a tumor-like formation that consists of adense mass of epidermis soaked in cholesterol and surrounded bya connective tissue capsule (matrix). There can be congenital andacquired cholesteatoma. Congenital cholesteatoma is considered amalformation of themiddle ear as a result of a disorder of branchialfissure formation, whereas acquired cholesteatoma occurs as a result ofa long inflammatory process in the middle ear. As thecholesteatoma grows, it destroys the bone structures of both themiddle and inner ears, thereby causing life-threatening complications [2].</p>
<p>In pediatricotorhinolaryngology, such patients require especially close attention because of moreaggressive courses of cholesteatoma in children, which is manifested byits very rapid growth and a high number of relapsesafter surgical treatment [11]. However, even in the childrens agecategory, there is a tendency to a more unfavorable courseof the disease in young children [3, 4]. A studyby Stangerup etal.[10] demonstrated that the percentage ofcholesteatoma recurrence in pediatric patients under 8 years old istwice as high as in children over 8 years old(47% and 24%, respectively). The causes of the aggressive courseof middle ear cholesteatoma in pediatric patients are still notfully understood.</p>
<p>This study aimed to reveal the clinical and immunologicalcharacteristics of pediatric patients with middle ear cholesteatoma in differentage groups that contribute to the aggressive course of thedisease.</p>
<h2>MATERIALS AND METHODS</h2>
<p>A retrospective analysis of case histories of143patients aged 1 to 17 years (150 cases, sinceseven patients had cholesteatoma on both sides), who were operatedfor middle ear cholesteatoma in the ear, nose, and throat (ENT) department ofthe St. Petersburg State Pediatric Medical University from 2000 to2018, was performed. Complete clinical, laboratory, bacteriological, radiological, audiometric, anddetailed immunological examinations were conducted to the patients. Within this study,the pediatric patients were divided into groups according to theage periodization proposed by Russian pediatrician Gundobin, namely, toddlers (13 years), preschoolers (37 years), primary school-aged children (711 years old), and secondary school-aged children (1218 years) [1]. Then, the positions were evaluated and comparedin age groups, namely, the clinical manifestation of middle earcholesteatoma, anamnesis of ear disease, concomitant somatic pathology, immunological reactivity state, surgicaltreatment results, and percentage of cholesteatoma relapse.</p>
<p>The state ofcellular immunity (the lymphocytes count and their subpopulations in theperipheral blood) was assessed, and the content of interleukin-2 (IL-2)in the blood serum and its production by peripheral bloodmononuclear cells (PBMC) was determined.</p>
<p>The level of IL-2 in bloodserum and supernatants of blood samples was determined using commercialtest systems developed at the National Research Institute for HighPurity Biologicals (St. Petersburg). These test systems are based onthe sandwich method of enzyme-linked immunosorbent assay using horseradish peroxidaseas an indicator enzyme. The level of IL-2 in thesupernatants of blood samples cultured without inducers was evaluated asspontaneous production of cytokines by peripheral blood cells, and inthe presence of an inducer, it was evaluated as inducedproduction of PBMC cytokines. Phytohemagglutinin at a final concentration of50 g/mL was used to stimulate the production of IL-2.</p>
<p>Lymphocyte subpopulations CD3+ (T-lymphocytes), CD4+ (T-helper cells), CD8+ (T-cytotoxic lymphocytes),CD20+ (B-lymphocytes), CD16+ (natural killer cells), and CD25+ (IL-2 receptors)were identified using monoclonal antibodies made by Medbiospectr (Moscow). Freshheparinized blood was diluted two times with physiological saline and layered on a separationmedium (Ficollverographene gradient with a density of 1.077 g/cm<sup>3</sup>)in a centrifuge tube in a ratio of 2.5:1, afterwhich it was centrifuged for 30min at an accelerationof 400 g. After centrifugation, the resulting mononuclear ring waspipetted, and the resulting cell suspension was washed three timeswith physiological saline and adjusted to a concentration of 2 10<sup>6</sup>cells/mL. For the quantitative determination of peripheral blood lymphocyte subpopulations, the standard method of atwo-stage complement-dependent lymphocytotoxic test was used. Suspension of lymphocytes (1 L) was added to the wells and incubated for40 min at 20C, and then, 5 L of rabbitcomplement was added to each well (Russian Research Institute ofHematology and Transfusiology, St. Petersburg). After this, incubation was performedfor 60 min at 20C. To stain cells,2 L of a 5% aqueous eosin solution was addedto each well, and after 2 min, 5 Lof a 17% formalin solution was fixed. The results wereevaluated using a light microscope at 150-fold magnification. The numberof stained (specifically reacted) lymphocytes was calculated for each subpopulationin three parallels, at least 100 cells in each. Themean value, expressed as a percentage of the number ofcounted cells, was determined. The absolute number of cells in1 mm<sup>3</sup>was calculated using data from a clinical bloodtest performed on the same day (white blood cell countand relative lymphocyte count).</p>
<p>The data of a study by Ketlinsky et al. [5] were takenas normal age indicators of the content of various lymphocytesubpopulations in the peripheral blood. As a control group, immunologicalparameters of pediatric patients aged 4.5 to 16 years (<em>n</em>= 23), who were examined at the Childrens Hospital No.2 withthe diagnoses of cardiac functional murmur and vegetovascular dystonia andwho did not have acute infectious disease manifestations, chronic pathologyexacerbations, and ear disease signs at the time of examination andduring the previous month, were used.</p>
<p>Blood samples were taken forimmunological studies before the start of systemic and topical antibacterialand anti-inflammatory therapy. Immunological studies were conducted in the immunopharmacologylaboratory of the National Research Institute for High Purity Biologicals. Statisticaldata processing was performed using Excel software of Microsoft Office2000. The differences between the two average values were evaluatedaccording to the Students test. The difference between the comparedindices was considered significant at<em>p</em> 0.05.</p>
<h2>RESULTS</h2>
<p><strong>Toddler Group (13 Years Old) Seven Patients (Eight Cases)</strong></p>
<p>Theclinical disease manifestation of this age group is characterized byan acute onset in the form of earache, fever, andintoxication. In a hospital or clinic, acute otitis media wasdiagnosed in the patients; the standard treatment was prescribed; paracentesiswas performed in two patients, but pus was not taken.The lack of normalization of the otoscopic presentation necessitated computedtomography of the temporal bones, which revealed bone-destructive changes. Theperiod from the onset of the disease to surgery was2.3 1.4 months. In all eight cases during thesurgery, a common creeping cholesteatoma was found, which was regardedas congenital in the absence of any history of eardisease. Relapse of the disease was registered in all patients(100%) of this age group 612 months after surgery, becauseof this, the pediatric patients underwent repeat surgery represented byradical general cavity surgery.</p>
<p><strong>Preschool Group (37 Years Old) 29Patients (31 Cases)</strong></p>
<p>In 11 cases (35%), cholesteatoma was regarded ascongenital. The clinical disease manifestation in pediatric patients of thisage group did not differ from the manifestation in pediatricpatients under 3 years of age. Creeping cholesteatoma spreading overthe cavities of the middle ear is typical, which requiresa large amount of surgery.</p>
<p>Nineteen preschoolers (65%) were included inthe group of frequently and chronically ill children (seven ormore episodes per year or 10 acute respiratory diseases overthe past 2 years [7, 9]). The high incidence ofrespiratory viral and bacterial infections and characteristics of pediatric patientsof this age contributed to the infection of the middleear. Of pediatric patients, 79% had a history of atleast one episode of otitis media (23 patients). In 10patients, otitis media had a relapsing course (three or moreepisodes for 6 months or four episodes per year). Theperiod from the disease manifestation to surgery was 8.6 6.3 months.</p>
<p>Because the process of maturation of the childs immunesystem passes through several age stages, and certain specific aspectsof the immune status correspond to each age, it wasinteresting to study the number of lymphocytes and their subpopulationsin peripheral blood in patients with middle ear cholesteatoma [8].</p>
<p>In the group of patients aged 4 to 7 yearswith a cholesteatoma-destructive process, there was a tendency to decrease in all lymphocyte subpopulations compared with the age norm;significant differences were obtained when assessing the absolute count ofCD3 (<em>p</em> 0.01) and CD4 (<em>p</em> 0.001) and the relative count of CD8 and B-lymphocytes (<em>p</em> 0.05). When comparing with the control group, a significantdecrease in the absolute and relative number of CD25 (<em>p</em> 0.01) was revealed, as well as an increase inthe relative count of B-lymphocytes (Table).</p>
<p></p>
<p><em>Table/</em><em>Таблица</em></p>
<p>The content of lymphocytes and their subpopulations in the peripheral blood of patients with middle ear cholesteatoma in different age groups, children of the control group and normal</p>
<p>Содержание лимфоцитов и их субпопуляций в периферической крови у больных с холестеатомой среднего уха в разных возрастных группах, детей контрольной группы и в норме</p>
<table width="623">
<tbody>
<tr>
<td rowspan="2">
<p>Lymphocytes/ Лимфоциты</p>
</td>
<td colspan="4">
<p>Age categories/Возрастные группы</p>
</td>
<td rowspan="2">
<p>Control group 415years(<em>n</em>= 32)/ Контрольная группа 415 лет (<em>n</em>= 23)</p>
</td>
</tr>
<tr>
<td>
<p>46years(<em>n</em>= 11) / 46 лет (<em>n</em>= 11)</p>
</td>
<td>
<p>Norm/ Норма</p>
</td>
<td>
<p>717years(<em>n</em>= 32) / 717 лет (<em>n</em>= 32)</p>
</td>
<td>
<p>Norm/ Норма</p>
</td>
</tr>
<tr>
<td>
<p>Lymph., % / Лимф., отн.,%</p>
</td>
<td>
<p>42.7 12.8</p>
<p>(3267)</p>
</td>
<td>
<p>46</p>
<p>(3853)</p>
</td>
<td>
<p>43.4 12.0</p>
<p>(2166)</p>
</td>
<td>
<p>40</p>
<p>(3643)</p>
</td>
<td>
<p></p>
</td>
</tr>
<tr>
<td>
<p>Lymph., abs/l / Лимф., абс. тыс./мкл</p>
</td>
<td>
<p>2.7 1.3</p>
<p>(1.65.4)</p>
</td>
<td>
<p>3.6</p>
<p>(2.95.1)</p>
</td>
<td>
<p>2.4 0.7</p>
<p>(1.13.8)</p>
</td>
<td>
<p>2.4</p>
<p>(22.7)</p>
</td>
<td>
<p></p>
</td>
</tr>
<tr>
<td>
<p>CD3, % / CD3, отн., %</p>
</td>
<td>
<p>63.3 10.8</p>
<p>(4674)</p>
</td>
<td>
<p>64</p>
<p>(6269)</p>
</td>
<td>
<p>57.3 12.0*</p>
<p>(3580)</p>
</td>
<td>
<p>70</p>
<p>(6676)</p>
</td>
<td>
<p>57.6 1.7</p>
<p>(4866)</p>
</td>
</tr>
<tr>
<td>
<p>CD3, abs/l / CD3, абс. тыс./мкл</p>
</td>
<td>
<p>1.6 0.4*</p>
<p>(1.22.5)</p>
</td>
<td>
<p>2.5</p>
<p>(1.83)</p>
</td>
<td>
<p>1.4 0.5*.**</p>
<p>(0.52.5)</p>
</td>
<td>
<p>1.8</p>
<p>(1.42)</p>
</td>
<td>
<p>1.6</p>
<p>(11.8)</p>
</td>
</tr>
<tr>
<td>
<p>CD4, % / CD4, отн., %</p>
</td>
<td>
<p>32.3 8.7</p>
<p>(1645)</p>
</td>
<td>
<p>37</p>
<p>(3040)</p>
</td>
<td>
<p>32.1 9.6*</p>
<p>(1251)</p>
</td>
<td>
<p>37</p>
<p>(3341)</p>
</td>
<td>
<p>30.7 1.5</p>
<p>(2042)</p>
</td>
</tr>
<tr>
<td>
<p>CD4, abs/l / CD4, абс. тыс./мкл</p>
</td>
<td>
<p>0.8 0.1*</p>
<p>(0.61.0)</p>
</td>
<td>
<p>1.6</p>
<p>(11.8)</p>
</td>
<td>
<p>0.8 0.3</p>
<p>(0.31.7)</p>
</td>
<td>
<p>0.8</p>
<p>(0.71.1)</p>
</td>
<td>
<p>0.8 0.2</p>
<p>(0.31.8)</p>
</td>
</tr>
<tr>
<td>
<p>CD8, % / CD8, отн., %</p>
</td>
<td>
<p>25.7 3.4*</p>
<p>(2130)</p>
</td>
<td>
<p>29</p>
<p>(2532)</p>
</td>
<td>
<p>22.5 5.2*</p>
<p>(1334)</p>
</td>
<td>
<p>30</p>
<p>(2735)</p>
</td>
<td>
<p>24.1 1.5</p>
<p>(1436.5)</p>
</td>
</tr>
<tr>
<td>
<p>CD8, abs/l / CD8, абс. тыс./мкл</p>
</td>
<td>
<p>0.7 0.3</p>
<p>(0.41.4)</p>
</td>
<td>
<p>0.9</p>
<p>(0.81.5)</p>
</td>
<td>
<p>0.6 0.2*</p>
<p>(0.21.2)</p>
</td>
<td>
<p>0.8</p>
<p>(0.60.9)</p>
</td>
<td>
<p>0.6 0.07</p>
<p>(0.21.0)</p>
</td>
</tr>
<tr>
<td>
<p>CD4/CD8 / CD4/CD8</p>
</td>
<td>
<p>1 0.4</p>
<p>(0.61.9)</p>
</td>
<td>
<p>1.3</p>
<p>(1.01.6)</p>
</td>
<td>
<p>1.5 0.7</p>
<p>(0.63.9)</p>
</td>
<td>
<p>1.3</p>
<p>(1.01.4)</p>
</td>
<td>
<p>1.3 0.07</p>
<p>(0.91.9)</p>
</td>
</tr>
<tr>
<td>
<p>B-Cells, %/ B-Лимф., отн., %</p>
</td>
<td>
<p>19.7 6.2*. **</p>
<p>(1229)</p>
</td>
<td>
<p>24</p>
<p>(2128)</p>
</td>
<td>
<p>16.1 6.6**</p>
<p>(530)</p>
</td>
<td>
<p>16</p>
<p>(1222)</p>
</td>
<td>
<p>12.9 0.8</p>
<p>(8.518.3)</p>
</td>
</tr>
<tr>
<td>
<p>B-Cells, abs/l / B-Лимф., абс. тыс./мкл</p>
</td>
<td>
<p>0.6 0.5</p>
<p>(0.31.6)</p>
</td>
<td>
<p>0.9</p>
<p>(0.71.3)</p>
</td>
<td>
<p>0.4 0.2</p>
<p>(0.21.0)</p>
</td>
<td>
<p>0.4</p>
<p>(0.30.5)</p>
</td>
<td>
<p>0.3 0.04</p>
<p>(0.10.5)</p>
</td>
</tr>
<tr>
<td>
<p>CD16, % / CD16, отн., %</p>
</td>
<td>
<p>10.5 5.4</p>
<p>(520)</p>
</td>
<td>
<p>(815)</p>
</td>
<td>
<p>16 8.9</p>
<p>(544)</p>
</td>
<td>
<p>(916)</p>
</td>
<td>
<p>13.1 1.1</p>
<p>(922)</p>
</td>
</tr>
<tr>
<td>
<p>CD16, abs/l / CD16, абс. тыс./мкл</p>
</td>
<td>
<p>0.3 0.3</p>
<p>(0.10.8)</p>
</td>
<td>
<p>0.4</p>
<p>(0.20.6)</p>
</td>
<td>
<p>0.4 0.3</p>
<p>(0.11.5)</p>
</td>
<td>
<p>0.3</p>
<p>(0.20.3)</p>
</td>
<td>
<p>0.4 0.06</p>
<p>(0.10.7)</p>
</td>
</tr>
<tr>
<td>
<p>CD25, % / CD25, отн., %</p>
</td>
<td>
<p>5.4 5.0**</p>
<p>(1.114)</p>
</td>
<td>
<p>(812)</p>
</td>
<td>
<p>7.2 8.6**</p>
<p>(0.636)</p>
</td>
<td>
<p>(1016)</p>
</td>
<td>
<p>16.7 1.1</p>
<p>(1126)</p>
</td>
</tr>
<tr>
<td>
<p>CD25, abs/l / CD25, абс. тыс./мкл</p>
</td>
<td>
<p>0.1 0.1**</p>
<p>(0.030.3)</p>
</td>
<td>
<p>(0.30.48)</p>
</td>
<td>
<p>0.2 0.17**</p>
<p>(0.020.9)</p>
</td>
<td>
<p>(0.20.36)</p>
</td>
<td>
<p>0.4 0.1</p>
<p>(0.20.8)</p>
</td>
</tr>
<tr>
<td colspan="6">
<p><em>Note.</em>*Significance of differences when comparing groups of children with cholesteatoma and content of the age norm. **Significance of differences when comparing groups of children with cholesteatoma and control groups.The range (minimummaximum) is indicated in parentheses.</p>
<p><em>Примечание.</em>*Достоверность различий между группами больных и показателями возрастной нормы. **Между группами больных и контролем. В скобках указан диапазон (минимуммаксимум).</p>
</td>
</tr>
</tbody>
</table>
<p></p>
<p>Given the changes identifiedin the T-system of immunity, a study of IL-2, whichis the main growth factor of T-lymphocytes, was conducted. Spontaneousproduction of PBMC IL-2 was equal to zero, whichcorrespondedto the norm. The average value of the induced productionof IL-2 by PBMC in pediatric patients aged 47 yearswas 1.1 1.0 units/mL, whereas the value in thecontrol group was 11.1 0.44units/mL.</p>
<p>The diseases were identifiedin the structure of concomitant pathology in pediatric patients ofthis age group, namely, cerebral palsy in one patient anddelayed psychoverbal development in one person.</p>
<p>The relapse of cholesteatoma duringhearing-sparing surgeries was 58% with a follow-up period of 6to 12 months.</p>
<p><strong>Primary School-Aged Group (711 Years Old) 52Patients (55 Cases)</strong></p>
<p>The proportion of patients with congenital cholesteatoma inthe primary school-aged children is significantly lower than that inthe younger age groups (11%, six cases). The clinical presentationof the congenital cholesteatoma manifestation has also changed, which includedunilateral conductive hearing loss and epidermal masses behind the tympanicmembrane. The number of frequently and chronically ill children inthis age group decreased to 20% (10 patients). The periodfrom the disease manifestation to the surgery was 28.9 25 months. Typically, 89% of the pediatric patients had ahistory of ear diseases, namely, otitis media episodes (15 patients),recurrent otitis media (15patients), chronic otitis media diagnosis witha defect in the tympanic membrane (16 patients), repeated otoblennorrheahospital treatment (26 patients), ear polypectomy (5 patients), and tympaniccavity shunting (2 patients). A history of adenoidectomy was revealedin 30 patients (58%).</p>
<p>Immunological examination revealed a significant decrease incomparison with the norm of the absolute and relative counts of CD3 and CD8 (<em>p</em> 0.001),as well as relative CD4 (<em>p</em> 0.01).The total count oflymphocytes and CD16, as well asthe content of B-lymphocytes in the peripheral blood, corresponded tothe age norm. When comparing with the control group, asignificant decrease in the absolute and relative number of CD25(<em>p</em> 0.001) and an increase in the relative countof B-lymphocytes were revealed, as well as a decrease in the absolute count ofCD3 (<em>p</em> 0.05; Table).</p>
<p>Induced production of IL-2by PBMC is reduced, but it is twice as highas in the preschool group (2.3and 1.2 units/mL).</p>
<p>The followingdiseases were revealed in the structure of concomitant somatic pathologyin pediatric patients of this age group: heart defects infive patients, obesity in five, juvenile arthritis in one, kyphoscoliosisin one, cerebral palsy in two, bronchial asthma in six,and tuberculosis in two. The relapse of cholesteatoma during hearing-sparingsurgeries was 53% with a follow-up period of 6 to12 months.</p>
<p><strong>Secondary School-Aged Group (1218 Years Old) 55 Patients(56 Cases)</strong></p>
<p>In this age group, congenital cholesteatoma was diagnosed inonly three cases (5.4%). Clinical manifestations of the disease includedunilateral conductive hearing loss and epidermal masses behind the tympanicmembrane.</p>
<p>For secondary school students, as well as for pediatric patientsof primary school age, a rather long period from thedisease manifestation to surgery is typical, 28 20.7 months(2 months to 8 years). Thus, in 30 pediatric patients,the duration of chronic otitis media with a tympanic membranedefect exceeded 2years. During this period, patients repeatedly receivedconservative treatment in an ENT hospital, as well as earpolypectomy, transtympanic bypass surgery, and antibacterial therapy.</p>
<p>An immunological examination revealeda decrease in comparison with the norm of the absoluteand relative amounts of CD3 and CD8, as well asrelative CD4. Twelve patients (21%) had somatic pathology: two hadheart defects, three had kidney malformations or pyelonephritis, one hadulcerative colitis, one had cerebral palsy, two had obesity, onehad Down syndrome, and two had tuberculosis. The relapse ofcholesteatoma during hearing-sparing surgeries in this age group occurred in16 cases and amounted to 29% with a follow-up periodof 6 to 12 months.</p>
<h2>CONCLUSIONS</h2>
<p>Middle ear cholesteatoma tends to havea more unfavorable course in young pediatric patients, which isexpressed in a higher percentage of disease recurrence after surgery.In the toddler group, cholesteatoma recurrence occurred in 100% ofcases, and it was 58%, 53%, and 29% in thepreschool, primary school-aged, and secondary school-aged groups, respectively.</p>
<p>Pediatric patients ofyounger age groups are typically diagnosed with a high rateof congenital cholesteatoma. Congenital cholesteatoma was diagnosed in 100% ofcases in the toddler group, 35% in the preschool group,11% in the primary school-aged group, and 5.4% in thesecondary school-aged group. Moreover, depending on age, the clinical presentationof the manifestation also changes; thus, acute inflammatory onset inpediatric patients under 7 years of age and unilateral conductivehearing loss in school-aged pediatric patients are registered.</p>
<p>Chronic otitis mediawith cholesteatoma in pediatric patients proceeds along with disorders ofthe T-cell system of immunity and systemic production of PBMCIL-2, with more pronounced immunological disorders registered in preschool patients.According to the literature, impaired production of T-cell growth factorIL-2 in combination with a decrease in the number ofcells having mature T-lymphocyte markers indicates the formation of secondaryimmunodeficiency [9].</p>
<p>Frequent upper respiratory tract infections, tubal dysfunctions, and cellularand humoral immunity disorders in preschool pediatric patients constitute thebackground contributing to a more unfavorable course and prognosis ofcholesteatoma of the middle ear.</p>
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