Inflammatory Disease Of Upper Airways Research Articles

Method of salivary histatins determination.

Histatins are the most significant antimicrobial peptides (AMP) of saliva and there are 12 types of such AMP. Histatin molecules contain relatively high percent of histidine and tyrosine residues. This property allows to use well known from organic chemistry Pauly reaction for detection of protein bounded histidine and tyrosine residues (BHT), which are in fact characterize the summary content of all histatins in saliva. Aim of the present study was comparison of BHT with antimicrobial activity of salivary AMP fraction in patients with inflammatory diseases of upper airways (IDUA). Group of examined persons include 28 patients with different diagnoses: chronic pharyngitis (n=11), chronic tonsillitis (n=7), nasopharyngitis (n=5), pollinosis (n=5). Degree of intensity of inflammatory symptoms was estimated in balls. The algorithm of BHT analysis include following steps: freezing - thawing of saliva; removal of microparticles by centrifugation; separation of fraction lower than100 kDa; dialysis for free amino acids removal; Pauly reaction carrying out. Antimicrobial activities of saliva and its low molecular fractions were estimated towards Candida albicans cells by the spectrophotometric method with bromocresol purpur. Analysis of saliva sediments for coccoid microbiota was carried out by PCR method. Pauly reaction for histatins estimation in saliva of IDUA patients use here for the first time. The histatins levels (BHT) were significantly correlated with the intensity of inflammatory symptoms (r=0,975) and activity of low molecular salivary fraction (AMP activity) (r=0,824). The AMP activity/ BHT ratio, i.e. antimicrobial activity of histatin unit, decreased together with growth of inflammatory symptoms intensity (r=-0,944). Any considerable differences in coccoid microbiota frequency of finding at different diagnoses were not detected. The S. aureus frequency of occurrence was connected neither with inflammatory symptoms intensity (r=0,118), nor with BHT concentration (r=0,318). However S. pyogenes and S. pneumoniae frequencies of occurrence demonstrated the invert correlation towards these indexes: (r=-0,627/-0,614) and (r=-0,827/-0,864). Probably at the exacerbation forms of IDUA the S. pyogenes and S. pneumoniae growth controlled by high levels of histatins.

Dimethyl fumarate abrogates dust mite-induced allergic asthma by altering dendritic cell function.

IntroductionAllergic asthma is the most common inflammatory disease of upper airways. Airway dendritic cells (DCs) are key antigen presenting cells that regulate T helper 2 (Th2)‐dependent allergic inflammation. Recent studies have shown critical role of airway DCs in the induction of Th2‐mediated allergic inflammation and are attractive therapeutic targets in asthma. However, molecular signaling mechanism that regulate DCs function to Th2 immune responses are poorly understood. Here we aim to evaluate the immunomodulatory effect of dimethyl fumarate (DMF), an FDA approved small molecule drug, in the house dust mite (HDM)‐induced experimental model of allergic asthma.MethodsDMF was administered intranasally in the challenge period of HDM‐induced murine model of experimental asthma. Airway inflammation, airway hyperreactivity, Th2/Th1 cytokine were assessed. The effect of DMF on DC function was further evaluated by adoptive transfer of HDM‐pulsed DMF treated DCs to wild‐type naïve mice.ResultsDMF treatment significantly reduced HDM‐induced airway inflammation, mucous cell metaplasia, and airway hyperactivity to inhaled methacholine. Mechanistically, DMF interferes with the migration of lung DCs to draining mediastinal lymph nodes, thereby attenuates the induction of allergic sensitization and Th2 immune response. Notably, adoptive transfer of DMF treated DCs to naïve mice with HDM challenge similarly reduces the features of allergic asthma.ConclusionThis identifies a novel function of DMF on DC‐mediated adaptive immune responses in the setting of HDM‐induced airway inflammation. Taken together, our results offer a mechanistic rationale for DMF use to target DCs in local lung environment as antiasthmatic therapy.

Remodeling and Repair in Rhinosinusitis.

Remodeling refers to the development of specific but potentially irreversible structural changes in tissue. Caucasian eosinophilic chronic rhinosinusitis (CRS) with polyps associated or not with cystic fibrosis was discriminated by edema from CRS without nasal polyps, characterized by extensive fibrotic fields. However, changes in epithelial and extracellular matrix structures are common findings in all types of chronic inflammatory diseases of upper airways, but rarely specific and highly variable in extend. Recent studies have shown that remodeling in CRS appears to occur in parallel, rather than purely subsequent to inflammation. Furthermore, some preferential remodeling associations can be recognized. Tremendous efforts have been put in research on coagulation factors, cytokines, growth factors, and proteases supporting all phases of upper airway remodeling. The current exploration of other CRS sub-groups and of the particular link with concomitant asthma aims to optimize the classification of CRS and its staging modes and to develop novel therapies.

R459 – Relation Between SPA And Symptoms Of Patients With AR And NP

Problem The aim of this study was to examine if allergic rhinitis and nasal polyposis are associated with the level of surfactant protein-A. Methods Sinus mucosal biopsies were performed in patients with allergic rhinitis(n=15), nasal polyposis(n=21) and controls(n=10). Immunolocalization of surfactant protein was performed with antibodies to SP-A using Streptavidin Peroxidase Conjugated Method and indirect immunofluorescence method. Blood serums were obtained from three subjects in each group for enzyme-linked immunosorbent assay (ELISA) analysis of surfactant protein-A. Results By ELISA, AR (n =15) and NP (n = 21) showed significantly decreased levels of SP-A when compared with controls (n= 10), although these two groups were not statistically significant. Immunohistochemical investigation showed intense SP-A staining in the nasal epithelium of each groups, but weak staining in patients with AR and NP. Conclusion We report for the first time the expression of SP-A in both diseased and normal nasal mucosa using the indirect immunofluorescence method. There was an inverse relation between surfactant protein-A levels and symptoms and signs of rhinitis in patients with AR and NP. Significance SP-A may play a defensive role in the chronic inflammatory diseases of upper airway. Understanding the exact role of SP-A in the upper airway diseases will help develop novel treatment approaches for sinonasal pathoses.

R460 – Relation Between SPA and Symptoms of Patients With AR and NP

Problem The aim of this study was to examine if allergic rhinitis and nasal polyposis are associated with the level of surfactant protein-A. Methods Sinus mucosal biopsies were performed in patients with allergic rhinitis (n= 15), nasal polyposis (n=21) and controls (n= 10). Immunolocalization of surfactant protein was performed with antibodies to SP-A using Streptavidin Peroxidase Conjugated Method and indirect immunofluorescence method. Blood serums were obtained from three subjects in each group for enzyme-linked immunosorbent assay (ELISA) analysis of surfactant protein-A. Results By ELISA, AR (n =15) and NP (n = 21) showed significantly decreased levels of SP-A when compared with controls (n= 10), although these two groups were not statistically significant. Immunohistochemical investigation showed intense SP-A staining in the nasal epithelium of each groups, but weak staining in patients with AR and NP. Conclusion We report for the first time the expression of SP-A in both diseased and normal nasal mucosa using the indirect immunofluorescence method. There was an inverse relation between surfactant protein-A levels and symptoms and signs of rhinitis in patients with AR and NP. Significance SP-A may play a defensive role in the chronic inflammatory diseases of upper airway. Understanding the exact role of SP-A in the upper airway diseases will help develop novel treatment approaches for sinonasal pathoses.

Oxidative stress in nonallergic nasal polyps associated with bronchial hyperresponsiveness1

Nasal polyposis (NP) is a chronic inflammatory disease of upper airway with unknown etiology. NP is frequently associated with asthma; the interaction between these comorbidities remains interesting. Oxidative stress has been implicated in the pathophysiology of NP and asthma. The aim of this study is to investigate the significance of oxidative stress in sinonasal microenvironments by evaluating its association with clinopathological parameters and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP. Polyp biopsy specimens were obtained from 20 nonallergic patients; control mucosas were obtained from 20 volunteers. The levels of free radicals in the tissues and in blood were determined by a sensitive chemiluminescence (CL) method. NP patients were substratified into three subgroups, NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma by the results of provocative testing. Four histological characteristics of NP, inflammatory cells, eosinophil infiltration, edema and fibrosis were estimated and applied to correlate with the tissue-CL. The mean CL level in polyp-tissues, but not in blood, was higher than in the control specimens. In NP patients, tissue-CL was associated with endoscopy score; high tissue-CL levels were positively correlated with the abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score were associated with BHR/asthma phenotype. These results suggest an important role for oxidative stress in the pathophysiology of NP and a causal relation between oxidative stress and inflammatory cells, especially the eosinophils. Free radical levels in polyp-tissues associated with NP severity and with BHR/asthma phenotype in nonallergic NP patients.