Periostin as a biomarker of allergic inflammation in atopic bronchial asthma and allergic rhinitis (A pilot study)

© 2020, Privolzhsky Research Medical University. All rights reserved. The involvement of periostin in Th2-dependent allergic inflammation has been documented. However, the significance of periostin as a biomarker of local allergic inflammation in the nasal mucosa (NM) of patients with atopic bronchial asthma (BA) and allergic rhinitis (AR) is yet to be determined. The aim of the study was to determine the presence of periostin and evaluate its role as a non-invasive marker of allergic inflammation in the nasal secretions of children with atopic BA and AR. Materials and Methods. In 43 patients aged 4–17 years with atopic BA and AR, the NM was examined using nasal video-endoscopy and (if indicated) computed tomography; the amount of periostin in the nasal secretion was determined by the enzyme immunoassay. Results. Exacerbation of AR was accompanied by a statistically significant increase in the level of periostin in the nasal secretion: up to 0.84 [0.06; 48.79] ng/mg, whereas in remission, that was 0.13 [0.00; 0.36] ng/mg; p=0.04. This value increased progressively as the severity of AR increased from 0.16 [0.00; 0.36] ng/mg in the mild course to 0.20 [0.00; 9.03] ng/mg in AR of moderate severity, and to 10.70 [0.56; 769.20] ng/mg in most severe cases; p=0.048. Hypertrophy or polyposis of the nasal and/or paranasal mucosa was detected in 34.9% (15/43) of the examined patients. The concentration of periostin in the nasal secretion was lower in children without NM hypertrophy: 0.18 [0.001; 4.30] ng/mg vs 0.78 [0.13; 162.10] ng/mg in patients with NM hypertrophy; the differences were close to statistically significant: p=0.051. The level of nasal periostin depended on the clinical form of hypertrophy in the sinonasal mucosa, reaching 0.17 [0.00; 0.32] ng/mg in children with polyposis hyperplasia of NM and 21.6 [10.70; 1516.80] ng/mg — with hypertrophy of the NM in the medial surface of the concha; p=0.02. Conclusion. Exacerbation and increased severity of AR in patients with atopic BA are accompanied by an increased level of periostin in the nasal secretion. This allows us to consider the level of nasal periostin as a biomarker of local allergic inflammation in the NM of patients with atopic BA combined with AR. Hypertrophic changes in the sinonasal mucosa are generally accompanied by an increased level of nasal periostin; specifically, this level significantly depends on the clinical form of mucous membrane hypertrophy and requires additional studies

Periostin as a biomarker of allergic inflammation in atopic bronchial asthma and allergic rhinitis (A pilot study)

The involvement of periostin in Th2-dependent allergic inflammation has been documented. However, the significance of periostin as a biomarker of local allergic inflammation in the nasal mucosa (NM) of patients with atopic bronchial asthma (BA) and allergic rhinitis (AR) is yet to be determined. The aim of the study was to determine the presence of periostin and evaluate its role as a non-invasive marker of allergic inflammation in the nasal secretions of children with atopic BA and AR. Materials and Methods. In 43 patients aged 4–17 years with atopic BA and AR, the NM was examined using nasal video-endoscopy and (if indicated) computed tomography; the amount of periostin in the nasal secretion was determined by the enzyme immunoassay. Results. Exacerbation of AR was accompanied by a statistically significant increase in the level of periostin in the nasal secretion: up to 0.84 [0.06; 48.79] ng/mg, whereas in remission, that was 0.13 [0.00; 0.36] ng/mg; p=0.04. This value increased progressively as the severity of AR increased from 0.16 [0.00; 0.36] ng/mg in the mild course to 0.20 [0.00; 9.03] ng/mg in AR of moderate severity, and to 10.70 [0.56; 769.20] ng/mg in most severe cases; p=0.048. Hypertrophy or polyposis of the nasal and/or paranasal mucosa was detected in 34.9% (15/43) of the examined patients. The concentration of periostin in the nasal secretion was lower in children without NM hypertrophy: 0.18 [0.001; 4.30] ng/mg vs 0.78 [0.13; 162.10] ng/mg in patients with NM hypertrophy; the differences were close to statistically significant: p=0.051. The level of nasal periostin depended on the clinical form of hypertrophy in the sinonasal mucosa, reaching 0.17 [0.00; 0.32] ng/mg in children with polyposis hyperplasia of NM and 21.6 [10.70; 1516.80] ng/mg — with hypertrophy of the NM in the medial surface of the concha; p=0.02. Conclusion. Exacerbation and increased severity of AR in patients with atopic BA are accompanied by an increased level of periostin in the nasal secretion. This allows us to consider the level of nasal periostin as a biomarker of local allergic inflammation in the NM of patients with atopic BA combined with AR. Hypertrophic changes in the sinonasal mucosa are generally accompanied by an increased level of nasal periostin; specifically, this level significantly depends on the clinical form of mucous membrane hypertrophy and requires additional studies. © 2020, Privolzhsky Research Medical University. All rights reserved

Extracellular matrix markers and methods for their study

The extracellular matrix (ECM) is a complex meshwork consisting mainly of proteins and carbohydrates; it is currently viewed as a key factor of tissue organization and homeostasis. In each organ, the composition of ECM is different: It includes a variety of fibrillar components, such as collagens, fibronectin, and elastin, as well as non-fibrillar molecules: Proteoglycans, hyaluronan, glycoproteins, and matrix proteins. ECM is an active tissue, where the de novo syntheses of structural components are constantly taking place. In parallel, ECM components undergo degradation catalyzed by a number of enzymes including matrix metalloproteinases. The synthesis and degradation of ECM components are controlled by mediators and cytokines, metabolic, epigenetic, and environmental factors. Currently, a large amount of evidence indicates that modifications (remodeling) of ECM play an important role in the pathogenesis of clinical conditions. This may explain the increasing interest in the markers of ECM remodeling both in health and disease. In recent years, many of the ECM markers were considered targets for diagnosing, predicting, and treating diseases. In this review, we discuss some of the currently known ECM markers and methods used for their determination. © 2019, Privolzhsky Research Medical University. All rights reserved

Маркеры состояния экстрацеллюлярного матрикса и методы их исследования (обзор)

The extracellular matrix (ECM) is a complex meshwork consisting mainly of proteins and carbohydrates; it is currently viewed as a key factor of tissue organization and homeostasis. In each organ, the composition of ECM is different: it includes a variety of fibrillar components, such as collagens, fibronectin, and elastin, as well as non-fibrillar molecules: proteoglycans, hyaluronan, glycoproteins, and matrix proteins. ECM is an active tissue, where the de novo syntheses of structural components are constantly taking place. In parallel, ECM components undergo degradation catalyzed by a number of enzymes including matrix metalloproteinases. The synthesis and degradation of ECM components are controlled by mediators and cytokines, metabolic, epigenetic, and environmental factors. Currently, a large amount of evidence indicates that modifications (remodeling) of ECM play an important role in the pathogenesis of clinical conditions. This may explain the increasing interest in the markers of ECM remodeling both in health and disease. In recent years, many of the ECM markers were considered targets for diagnosing, predicting, and treating diseases. In this review, we discuss some of the currently known ECM markers and methods used for their determination.Экстрацеллюлярный (внеклеточный) матрикс (ЭЦМ) представляет собой сложную сетчатую структуру, состоящую преимущественно из белков и углеводов, и рассматривается в настоящее время как ключевой регулятор организации тканей и гомеостаза. В каждом органе состав ЭЦМ различен, включает разнообразные фибриллярные компоненты, такие как коллагены, фибронектин и эластин, и нефибриллярные молекулы - протеогликаны, гиалуронан и гликопротеины, матриксные белки. ЭЦМ является активной структурой, в которой постоянно происходят процессы синтеза de novo структурных компонентов и параллельно - их деградации, осуществляемой преимущественно с участием ферментов, в том числе матриксных металлопротеиназ. Синтез и деградация компонентов матрикса находятся под сложным регуляторным влиянием различных медиаторов и цитокинов, метаболических, эпигенетических и средовых воздействий. В настоящее время накоплено большое количество доказательств, что изменения ЭЦМ играют важную роль при различных патологических состояниях. Этим обусловлен интерес к поиску маркеров, отражающих состояние ЭЦМ в разных органах и тканях как в физиологических условиях, так и при различных вариантах патологии. В последние годы многие из молекул ЭЦМ рассматриваются в качестве мишеней для диагностики, прогнозирования и лечения заболеваний. В данном обзоре мы систематизировали основные описанные в настоящий момент маркеры состояния ЭЦМ и используемые методы их определения

Thymic stromal lymphopoietin as a predictor of hypertrophic changes in the nasal mucosa in children with atopic bronchial asthma and allergic rhinitis

Th2-dependent allergic inflammation in patients with bronchial asthma (BA) and allergic rhinitis (AR) can be associated with nasal mucosa remodeling, accompanied by hypertrophic and hyperplastic processes. Thymic stromal lymphopoietin (TSLP) is a key cytokine produced by epithelial cells and is actively involved in allergic inflammation. Objective of the research: to study TSLP content in nasal secretion of children with atopic BA and AR. Materials and methods: in 43 patients aged 4-17 years with atopic BA and AR, nasal mucosa state was assessed using rhino-endoscopy and TSLP content in nasal secretion by the enzyme immunoassay. Results: hypertrophic or polypouschanges in the nasal mucosa and/or paranasal sinuses were detected in 30% (13/43) of patients. TSLP content in the nasal secretion in these patients was 908, 5 [48, 9; 2098, 7] pg/mg, which is statistically significantly higher than in patients with BA and AR without sinonasal hypertrophy (132, 3 [4, 2; 325, 9] pg/mg, p=0, 036). AR exacerbation was accompanied by a statistically significant increase of TSLP content in the nasal secret compared with the remission period (p=0, 002). Conclusion: hypertrophic changes in the nasal mucosa are accompanied by a statistically significant increase of TSLP content in the nasal secret in children with atopic BA and AR, which allows to consider this biomarker as a potential non-invasive predictor of pathological airway remodeling in patients with chronic allergic airway inflammation. © Springer Nature Switzerland AG 2020

Мультиморбидность патологии верхних дыхательных путей у детей с бронхиальной астмой

Bronchial asthma (BA) is a systemic allergic disease and is associated with upper respiratory tract (URT) pathology. In recent years, attention was focused on allergic diseases multimorbidity, while the spectrum of URT pathology in children with BA is not characterized enough. Objective of the research - to study the structure of URT pathology in children with atopic BA. Study materials and methods: 358 children with atopic BA were examined, the average age of children was 9,91 (9,47, 10,35) years, of which 67,9% were boys (192/358), and 108 children with nasal breathing disorders, comparable in age and sex, but without BA. In addition to the standard all - clinical, allergological, functional examination, all patients underwent video endoscopic examination of the nasal cavity and nasopharynx. Results: аП children with BA were diagnosed with allergic rhinitis (AR) and/ or allergic rhinosinusitis (ARS) with a predominance of persistent forms. The «isolated» course of AR/ARS occurred in 11,7% (42/358) of patients; other children had nasal symptoms due to a combination of AR/ARS with other variants of URT pathology. Pharyngeal tonsilhypertrophy occurred in 61,2% (219/358) of patients, hypertrophic rhinitis - in 9,2% (33/358) of children with BA, nasal architectonics disorders were diagnosed in 50% (179/358) of patients. The combination of two nosological variants of nose pathology occurred in 47,8% (117/358) of patients with BA; 40,5% (145/358) of children with BA had multimorbidity of the nasal pathology - a combination of three or more nosological units. Conclusion: for children with atopic BA and nasal symptoms often have combined and multimorbid forms of URT pathology. Verification of nasal obstruction causes allows to individualize therapy for patients with BA and minimize negative impact of URT pathology on BA course.Бронхиальная астма (БА) является системным аллергическим заболеванием и ассоциирована с патологией верхних дыхательных путей (ВДП). В последние годы акцентируется внимание на мультиморбидности аллергических заболеваний, при этом спектр патологии ВДП у детей с БА охарактеризован недостаточно. Цель исследования - изучить структуру патологии ВДП у детей с атопической БА. Материалы и методы исследования: обследованы 358 детей с атопической БА, средний возраст детей составил 9,91 (9,47; 10,35) лет, из них мальчиков 67,9% (192/358), а также 108 детей с жалобами на нарушения носового дыхания, сопоставимых по возрасту и полу, но не имевших БА. Помимо стандартного общеклинического, аллергологического, функционального обследования у всех пациентов выполнено видеоэндоскопическое исследование полости носа и носоглотки. Результаты: у всех детей с БА был диагностирован аллергический ринит (АР) и/или аллергический риносинусит (АРС) с преобладанием персистирующих форм. «Изолированное» течение АР/АРС имело место у 11,7% (42/358) пациентов, у остальных детей назальные симптомы были обусловлены сочетанием АР/АРС с иными вариантами патологии ВДП. Гипертрофия глоточной миндалины имела место у 61,2% (219/358) пациентов, гипертрофический ринит - у 9,2% (33/358) детей с БА, нарушения архитектоники носа были выявлены у 50% (179/358) пациентов. Сочетание двух нозологических вариантов патологии носа имело место у 47,8% (117/358) пациентов с БА, у 40,5% (145/358) детей с БА была отмечена мультиморбидность назальной патологии - сочетание трех и более нозологических единиц. Заключение: для детей с атопической БА и назальными симптомами характерны сочетанные и мультиморбидные формы патологии ВДП. Верификация причин назальной обструкции позволяет индивидуализировать терапию у пациентов с БА и нивелировать отрицательное влияние патологии ВДП на течение БА

Dependence of Anterior Active Rhinomanometry Indices on Nasal Obstructive Disorders in Children with Atopic Bronchial Asthma Complicated by Nasal Symptoms

Background. Atopic bronchial asthma (BA) in children is associated with upper airways pathology (UAP). Among them, a combination of allergic rhinitis (AR) and nasal obstructive disorders (NOD), including hypertrophy of the pharyngeal tonsil (HPT) and anomalies of the intranasal structures (AINS), is abundant. In such patients, anterior active rhinomanometry (AARM) is an important method of examining nasal patency. However, NOD can influence the AARM parameters in children with BA and nasal symptoms, and this effect must be taken into account in clinical practice. Study goal was to elucidate the effect of NOD on rhinomanometric parameters in this group of patients. Methods. Total of 66 children with BA and AR were examined with AARM, rhinovideoendoscopy, spirometry, and standard clinical tests allowing revealing the structure of comorbid pathologies. In order to avoid the influence of anthropometric parameters of children and their age on AARM parameters, a special index of reduced total nasal airflow was used. Results. It has been established that NOD, especially HPT, have a significant negative impact on the indices of anterior active rhinomanometry during the periods of both AR remission and AR exacerbation. The effect of AINS is much weaker and was remarkable only in combination with HPT. © 2018 Tatyana I. Eliseeva et al

The Relationship Between Indicators of Nasal Respiratory Function and Spirometric Parameters in Children With Bronchial Asthma

Introduction: The relationship between objective indicators of nasal obstruction and airflow limitation in children with bronchial asthma (BA) and allergic rhinitis (AR) has not yet been studied. Objective: To study the relationship between objective parameters of nasal obstruction and airflow limitation, determined using the methods of anterior active rhinomanometry (AARM) and spirometry in children with BA and AR. Materials and Methods: Eighty eight children and adolescents with BA and AR, boys−65.9% (58/88), were examined. The median age was 11.09 [10.42; 11.76] years. To determine airflow limitation, the following spirometric parameters were evaluated: forced vital capacity of the lungs (FVC), forced expiratory volume in 1 s (FEV1), the ratio of FEV1/FVC, and maximum expiratory flow at the point 25% of the flow-volume loop (MEF25). Data were recorded both in absolute values and in relative units (% pred). Nasal respiratory function was determined by AARM based on the total nasal airflow (TNAF) in absolute (Pa/cm3/s) and relative units (RTNAF, % pred). Results: In the general cohort and in boys but not in girls, a statistically significant direct correlation was found between TNAF (Pa/cm3/s) and absolute spirometry parameters of bronchial patency—all had p 0.05. Additional analysis of literature was conducted to ascertain that the identified gender differences were not occasional. Conclusion: The significant positive correlation of absolute values of AARM and spirometric parameters in children with BA and AR was established, which apparently reflects the physical development of children. Of all the relative indicators of spirometry, only MEF25 (% pred), which indirectly reflects the patency of small bronchi, had a distinct direct correlation with RTNAF. These patterns are clearly expressed in boys with BA. In girls with this disease, however, the relationship between nasal respiratory function and spirometric indicators seems to be more complex and requires further study

Effect of Nasal Obstructive Disorders on Sinonasal Symptoms in Children with Different Levels of Bronchial Asthma Control

Allergic rhinitis (AR) and allergic rhinosinusitis (ARS) are typical upper airway pathologies (UAP) in children with bronchial asthma (BA) frequently accompanied with nasal obstructive diseases (NOD). In order to establish the effect of NOD on correlations between nasal and synonasal symptoms with clinical assessments of asthma control, 82 children, 9.8 [8.9; 10.7] years old, with atopic BA were assessed using ACQ-5 for the BA control level, TNSS for nasal symptoms, and SNOT-20 for synonasal quality of life in combination with rhinovideoendoscopy for NOD. All patients had AR/ARS; in 76.3% (63/82) of children, UAP had a multimorbid character with the presence of NOD. Significant correlations were found between ACQ-5 and TNSS (R=0.40, p<0.0001) and ACQ-5 and SNOT-20 (R=0.42, p<0.0001). Correlations between TNSS/ACQ-5 and SNOT-20/ACQ-5 were higher in patients who do not have a combination of AR/ARS with NOD (R=0.67, p=0.0012; R=0.50, p=0.022, resp.) than in patients who have AR/ARS combined with NOD (R=0.30, p=0.015; R=0.26, p=0.04, resp.). Thus, the association of BA control level with the expression of nasal and synonasal symptoms is higher in children who do not have multimorbid UAP. © 2018 T. I. Eliseeva et al