Clinical Research Directory

Viral and Epigenetic Influences in CRSwNP

Background/rationale While multiple disorders feature a Type 2 (T2) inflammation, triggers for T2 remains unknown. In Chronic Rhinosinusitis with Nasal Polyposis CRSwNP), a classic Type 2 disorder, dysfunction of the epithelial barrier is suggested by loss of epithelial cell differentiation, impaired response to wounding, and impairment of innate defense mechanisms. After unsuccessful attempts to describe T2 disorders solely by host genetic or environmental factors, the role of epigenetics in the modification of innate immune response and epithelial integrity appears an important unexplored mechanism for a novel appreciation of T2 disease. In addition, the investigators explore the possibility that these changes may be induced by viral pathogens. This concept has been supported by the recent observation that SARS-CoV-2 viral reduction measures resulted in a reduction of the frequency of respiratory viruses and a concomitant reduction in chronic airway disease, suggesting a role for viruses in T2 disease. Hypothesis The investigators believe T2 chronic rhinosinusitis (CRSwNP) involves epigenetic mechanisms where external factors, possibly viruses, contribute to disease via epigenetic manipulation and/or chronic viral infection. Objectives The investigators aim to identify epigenetic signatures associated with T2 CRS and explore the contribution of viruses. Method A robust methylation profiling with extensive coverage will be used for epigenome-wide association studies in T2 CRS patients assessing healthy subjects, CRS patients in remission, and diseased patients undergoing surgery. Moreover, advanced transcriptomic and metagenomic methods will identify gene expression profiles and viruses. This proposal also includes a cross-sectional study of patients undergoing surgery to assess transcriptomic patterns and epigenetics at the single-cell level. Expected outcome The investigators expect to identify epigenetic biomarkers and implicate several pathogenic viruses to open new targets for novel therapies.

The Sinonasal Microbiome

Chronic rhinosinusitis is an inflammatory disease of the sinonasal mucosa with significant impact and limited treatment options. Chronic rhinosinusitis (CRS) poses an important public health problem and causes a large impact on individual quality of life. Studies of CRS have been limited by access to tissue, the complexity of the sinonasal physiology, a lack of available biomarkers, the absence of useful animal models, a paucity of cohorts with biological samples for analysis, and limited well-designed clinical trials or investigations of immune function. Therefore, novel strategies for identifying biological mechanisms underlying this disease are in great need. Using prospective samples from well characterized subjects, the investigators intend to profile the mucosa associated-bacteria in the nose and sinuses. In parallel, using sinus tissue from patients undergoing surgery, the site will interrogate the epithelium for mucosal immune function to understand host-microbe interaction. This study hypothesizes that the microbial profile of the sinuses initiates an immune responses which leads to chronic inflammation in susceptible people. This study would provide the first comprehensive data on what bacteria are present in the nose and sinus and could lead to important knowledge useful in sinonasal disease.

Functional Endoscopic Sinus Surgery Study

The aim of this study is to evaluate the effect of the addition of epinephrine to bilateral real time ultrasound guided pterygopalatine ganglion blocks on intra-operative bleeding and blood loss during functional endoscopic sinus surgery (FESS).

The Role of IL5 in Epithelial Cell Integrity

The goal of this laboratory study is the examine the effect of mepolizumab drug on the health and function of the cells lining the human nasal airways in vitro cell culture derived from patients with chronic rhinosinusitis with nasal polyposis. The main questions the study aims to study are: 1. To see what mepolizumab does to suppress inflammation of the human cells. 2. To see what mepolizumab does to maintain barrier integrity of epithelial cells

Topical Probiotic Sinus Irrigations for Treating Chronic Sinusitis

The purpose of this randomized study will be to determine whether topical probiotic sinus irrigations are more effective compared to saline sinus irrigation controls in the treatment of active CRS in patients who have had prior sinus surgery based on subjective and objective outcome measures.

Sinus Disease in Young Children With Cystic Fibrosis

This is a prospective, observational study examining the impact of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators on chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) in young children with cystic fibrosis (YCwCF). This study involves two groups: children 2-8 years old, inclusive at initial visit, receiving highly effective modulator therapy (HEMT), and a control group of children 2-8 years old, inclusive at initial visit, not receiving HEMT. Outcomes will include sinus magnetic resonance imaging (MRI) scans, olfactory tests, and quality of life surveys obtained over a two-year period.

Impact of Sinus Surgery on Individuals With Cystic Fibrosis

This study will be a prospective, observational study of patients who undergo endoscopic sinus surgery for cystic fibrosis-related chronic rhinosinusitis (CRS). Individuals who do not undergo surgery but are treated medically for CRS will also be enrolled to serve as a control group. Outcomes analyzed will include pulmonary, quality of life, and others.

Effect of Photobiostimulation Versus Pulsed Electromagnetic Field on Quality of Life in Adults With Chronic Rhinosinusitis

This study was done to find out the effect of photobiostimulation and pulsed electromagnetic field in patients with chronic rhinosinusitis on: * Quality of life. * Pulmonary function. * Mean platelet volume. * headache . * total nasal symptoms.

Moving Towards Precision Medicine in United Airways Disease: Unraveling Inflammatory Patterns in Asthmatic Patients With or Without Nasal Polyps

Asthma and chronic rhinosinusitis (CRS) are inflammatory diseases of the respiratory tract, asthma from the lower part, and CRS, from the upper part. In theory, these parts are correlated as if they are one single organ, namely "united airways", which means that if one is affected by any condition, the other might be impacted as well. However, this relationship has not yet been described down to the cellular and molecular levels. By investigating patients that have (1) asthma and CRS with nasal polyp, (2) asthma and CRS without nasal polyp, and (3) just CRS with nasal polyp, we aim to determine the correlation of the upper and lower part of the respiratory tract. At first, the characterization of disease will be determined by established clinical criteria, such as lung function, blood analysis for the presence of eosinophils (a type of white cells), and nasal polyp score. To continue, in-depth analysis of nose, oropharynx, and lung samples will help gain information about the inflammatory profile and local microbiome of the three different groups of patients through molecular and cellular assays. The results of this study will help to describe the hypothesis of the united airways which will provide better guidance for medical treatment of asthma and CRS with or without polyp, thus improving the life quality of patients.

Ivacaftor for Acquired CFTR Dysfunction in Chronic Rhinosinusitis

The purpose of this pilot study is to explore wither ivacaftor in refractory CRS patients will demonstrate safety and tolerability; restore CFTR-mediated Cl- secretions as measured by EDSPD testing; produce detectable improvements in validated measures of CRS including the SNOT-22 questionnaire, Lund-MacKay CT scan grading, and Lund-Kennedy endoscopic scores; and provide beneficial effects on readily measured markers of sinonasal inflammation and infection (IP-10, IL-8, and Pseudomonas CFUs).

Real-Life Chronic Rhinosinusitis Outcome Registry

An international consortium of leading medical experts in the field of chronic respiratory disease, the research team of Galenus Health and the non-profit organization EUFOREA (European Forum for Research and Education in Allergy and Airway diseases) has been conceived to conduct real-life outcome research. The Galenus Health digital platform consisting of a mobile application for patients and an online dashboard for physicians will be implemented in each of the participating centres. The data will be centralized in a pseudonymized database and will be the basis of the Chronic RhinoSinusitis Outcome Registry.

The Effect of Intra-sinus Application of Betamethasone Dipropionate Nasal Cream on Patients with Chronic Rhinosinusitis Post Functional Endoscopic Sinus Surgery (FESS)

To assess the safety and efficacy of one (single) application of Betamethasone Dipropionate Nasal Cream (BMDP CREAM) onto the sinus mucosa.

Comparative Analysis of Silastic Stenting in Sinus Surgery

Silastic stenting is a measure taken to support tissue healing following sinus surgery. Silastic stents are inserted into the sinus cavities and provide structural support while facilitating healing in the critical period of recovery following surgery. There is controversy over the optimal duration for which silastic stents should be left in place. Having them in place for shorter periods may reduce the likelihood of stent-related reactions, while leaving them for longer periods could promote more tissue healing. The aim of this study is to compare the impact of stent duration on clinical outcomes of patients following sinus surgery.

Xylitol vs Saline Nasal Irrigations in CF-CRS

Cystic fibrosis (CF) is the most common genetic disorder in Belgium, affecting 1 in 2850 children. A defect in the CFTR channel results in increased viscosity of extracellular secretions and decreased mucociliary clearance in the airways. As a result of this mechanism, chronic rhinosinusitis (CRS) occurs in nearly 100% of CF patients. CRS can lead to pronounced sinonasal complaints and can have a negative impact on the quality of life. In addition, several studies have shown that poor upper airway control has a negative impact on the lower airways. Unfortunately, treatment options are limited. Our previous study has shown that only 21% of patients have well-controlled CRS. The aim of this single-center, randomized cross-over study is to compare the effect of nasal rinses with (XNI) and without (SNI) Xylitol in the treatment of CF-CRS. Xylitol is a sugar alcohol that is already used as an antibiofilm agent,eg in the prevention of caries. Previous pilot studies have already shown a beneficial effect of XNI in the treatment of non-CF CRS.

The Nasal Microbiome and Its Importance in Disease

Methods: all studies are case control studies on six different groups: normal individuals, non-COVID-19 patients with olfactory dysfunction, COVID-19 positive patients, previous COVID-19 positive patients with prolonged olfactory dysfunction, patients with chronic rhinosinusitis with and without nasal polyps, and patients with CRS initiating intranasal glucocorticoids.. The patients will be included from the ear-, nose, and throat department and the University Clinic for Flavour, Balance, and Sleep Regional Hospital Gødstrup, as well as Flavour Institute, Department of Clinical Medicine, Aarhus University (AU), and the long COVID-19 clinics in Aarhus and Gødstrup. Microbiome samples will be swabs from the nasal cavity and oral pharynx will be collected and analysed using next-generation sequencing targeting 16S and 18S ribosomal RNA at the Department of Bacteria, Parasite \& Fungi at Staten Serum Institute (SSI), Copenhagen, Denmark. Characterization of the microbiome is performed by 16S/18S amplicon-based metagenomics, and data are analyzed by various bio-informatic tools for determination/visualization of alpha/beta diversity as well as principal coordinates analysis (PCoA). Immunological factors will be collected by means of six swabs: in the nasal cavity and used for either flowcytometry or enzyme-linked immunosorbent assay (ELISA). For comparison, truecut biopsies of the nasal mucosa are collected from a subgroup of patients undergoing surgery in general anaesthesia. Due to the novelty of the current study, little relevant information from previous literature can be used for power calculation. However, with an alpha of 5% and a power of 80%, the population size for each group should be 42 participants, assuming the occurrence of bacteria differs with 30% between populations. Taking 20% drop out into account, the investigators aim to include 60 patients in each group. Perspectives: The perspectives of this study is to begin bridging the gap between gut and upper airway microbiome and immunology research. Looking at the explosion of interest in the gut, and in personalized medicine in general, the investigators likewise foresee a huge potential for both general and individual prevention and treatments starting with a deeper understanding of the nasal microbiome and immunology. Examples beyond the scope of this study could be microbiome transplants for chronic sufferers of diseases such as chronic rhinosinusitis, allergies or asthma, or in selecting which patients could reap the benefits of the expensive biological treatments emerging on the market.

The Causal Relation of Nasal Nitric Oxide Levels to the Severity of Chronic Rhinosinusitis and Its Inflammatory Phenotype

Nitric oxide (NO) reflects changes in inflammatory state of the airways. In pulmonology fractional exhaled nitric oxide concentration (FeNO) has been linked to eosinophilic asthma and is used to guide overall disease control. The measurement of nasal nitric oxide (nNO) may reflect the disease burden and inflammatory phenotype of the paranasal sinuses. The aim of our study is to evaluate the relation of chronic rhino sinusitis (CRS) severity and inflammatory status to nNO, maxillary sinus NO, nitrite, nitrate and cone beam computed tomography (CBCT). Three groups (22 patients in each) of referred patients and and 22 healthy volunteers are recruited. Patients are grouped according to the CBCT score and viewed three times in 4-6 weeks intervals.