Biomarkers In Chronic Rhinosinusitis Research Articles

Active smoking status in chronic rhinosinusitis is associated with higher serum markers of inflammation and lower serum eosinophilia

Smoking negatively affects postoperative evolution in patients with chronic rhinosinusitis (CRS); however, the mechanism remains incompletely described. In the lung, smoking increases expression of proinflammatory genes and is associated with an elevation of inflammatory serum markers. Our objective is to determine the impact of smoking on these biomarkers in CRS. Two existing populations of patients previously phenotyped for genetic association studies (206 patients with refractory CRS and 408 patients with CRS and nasal polyposis) were stratified according to self-reported smoking status and available serum biomarkers (complete blood count [CBC], total immunoglobulin E [IgE]). Asthma and bacterial cultures were evaluated. Active smoking was low in both groups (genetics of chronic rhinosinusitis 1 [GCRS1]: 11.2%; genetics of chronic rhinosinusitis 2 [GCRS2]: 9.4%). Total white blood cell (WBC) count was significantly higher in active smokers than in those who had never smoked and ex-smokers. Serum eosinophilia and prevalence of self-reported asthma was lower in active smokers than never-smokers. In the GCRS2 population, endoscopically-collected cultures trended toward a lower recovery rate of Staphylococcus aureus in smokers (p = 0.07). Never-smokers and ex-smokers had similar levels of WBCs and eosinophils. Our study reveals that active tobacco smoking is associated with increases in markers of systemic inflammation in patients with CRS. The proinflammatory effect of smoking seems not only to act locally on sinus mucosa as previously described, but may also influence levels of inflammatory biomarkers systemically, suggesting that smoking-induced changes have profound implications for health. Nevertheless, these changes may be potentially reversible; thus smoking cessation in CRS patients is strongly advised, and may have an impact on response of CRS to therapy.

Improving patient care via development of a protein-based diagnostic test for microbe-specific detection of chronic rhinosinusitis.

The hypothesis is that signature bacterial proteins can be identified in sinus secretions via high-throughput, proteomic based techniques. Nontypeable Haemophilus influenzae (NTHI) is the most common bacterial pathogen associated with sinusitis and serves as proof of principle pathogen for identifying biomarkers. In vitro and in vivo studies using proteomic-based analysis of cultures of NTHI and a novel, experimental chinchilla polymicrobial sinusitis model. Nano-liquid chromatography /tandem mass spectrometry (nano-LC-MS/MS) was performed to annotate the secretome from an NTHI biofilm. A model of NTHI-induced sinusitis was developed in a chinchilla, and NTHI proteins were detected in chinchilla secretions. A reference standard RT-PCR-based assay was adapted to allow for sensitivity and specificity testing of the identified signature biomarkers in human patients. Outer membrane proteins P2 (OMP-P2) and P5 (OMP-P5) were identified as promising candidates for the detection of NTHI biofilms and positively detected in nasopharyngeal secretions of chinchillas experimentally infected with NTHI. An RT-PCR based test for the presence of NTHI biofilms demonstrated 100% sensitivity and 100% specificity when tested against eight unique strains commonly found in human bacterial rhinosinusitis. Proteomic analysis was successful in identifying signature proteins for possible use as a biomarker for chronic rhinosinusitis (CRS). OMP-P2 and OMP-P5 were validated as promising candidates and were positively detected from nasopharyngeal secretions from chinchillas experimentally infected with NTHI. Collectively, these data support the use of OMP-P2 and OMP-P5 as biomarkers for a human clinical trial to develop a point-of-care medical diagnostic test to assist in the diagnosis and treatment of CRS.

Vascular Endothelial Growth Factor Drives Autocrine Epithelial Cell Proliferation and Survival in Chronic Rhinosinusitis with Nasal Polyposis

The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood. These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps. Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGF-dependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V. VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P < 0.001). We also report elevated expression of VEGF (P < 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P < 0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P < 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P < 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P < 0.05) and resulted in increased apoptosis (P < 0.001) and inhibition of autocrine epithelial VEGF production (P < 0.05). These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis.

SP401 – Symptoms and biomarkers in chronic rhinosinusitis (CRS)

SP401 – Symptoms and biomarkers in chronic rhinosinusitis (CRS)

Overexpression of VEGF from Sinonasal Epithelium is a Biomarker for Chronic Rhinosinusitis with Nasal Polyposis

Overexpression of VEGF from Sinonasal Epithelium is a Biomarker for Chronic Rhinosinusitis with Nasal Polyposis

Chronic Rhinosinusitis Defined at Protein Levels

Problem Chronic rhinosinusitis (CRS) is a leading health care problem worldwide. Although many studies have been performed on different aspects of this disease, there are still no unanimous agreement on the pathophysiology, definition and classification of the disease. Two major groups of CRS are CRS with nasal polyposis (CRSwNP) and CRS without NP (CRSsNP). These 2 groups seem to have different features in pathophysiology, treatment and response to therapy. Recently, a lot of attention has been directed to gene expression and protein biomarkers in CRS. Different proteins were found in CRSwNP and CRSsNP mucosa. Studying CRS at protein level in large scale enables us to get vast information about their structure and function. In this study we investigated the protein profile of CRSwNP and CRSsNP mucosa. Methods Samples were taken from nasal mucosa of CRSwNP and CRSsNP patients. Proteins from these samples were extracted and separated by immobilized pH gradient (IPG)-based two-dimensional difference gel electrophoresis (2-D DIGE). Resulting 2D-gel images were statistically analyzed using Delta2D software and differently expressed protein spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results A reference map of approximately 1250 proteins could be established.74 proteins were significantly different (2-fold, p&lt;0.05) between CRSwNP and CRSsNP mucosa. Up to now several of these significantly changed proteins could be identified by MALDI-TOF/TOF-MS. Conclusion Up to now several of these significantly changed proteins could be identified by MALDI-TOF/TOF-MS and their biological function will be discussed concerning the pathogenesis of human nasal polyps. Significance Knowing the proteome of mucosa in CRSwNP and CRSsNP and biological functions of proteins can lead us to new ways of treatment and open new horizons in CRS research field. Support The first author received a fellowship grant for performing the research from European Academy of Allergology and Clinical Immunology.