Olivier Vanderveken full professor - fund. clinical researcher

Research Olivier Vanderveken

Research team

Antimicrobial potential of Streptococcus salivarius as probiotic for the upper respiratory tract. 01/11/2022 - 31/10/2024

Abstract

The microbiota of the upper respiratory tract (URT) is emerging as a gatekeeper to respiratory health, but it is currently underexplored at the functional level compared to other body sites. URT diseases such as otitis media (OM) form leading causes for antibiotic prescription, while the functional role of bacteria in the disease pathology is still not clear. Consequently, new insights into the functional biology and microbial ecology of OM as a microbial disease are needed to design novel therapeutic strategies. Microbiome sequencing of the URT revealed Streptococcus salivarius as one of the primary colonizers of the oral cavity shortly after birth. It is also significantly more abundant in the nasopharynx of healthy children compared to children with chronic OM. Endogenous beneficial bacteria can indeed play a pivotal role in URT health through inhibition of respiratory pathogens and immunomodulation. As a key beneficial commensal, specific strains of S. salivarius could have high potential as URT probiotics. These strains can produce secreted secondary metabolites with bacteriostatic or bactericidal activity, but their role in probiotic effects is currently underexplored. This project will focus on exploring the metabolic properties and functional potential of S. salivarius isolates, which will be evaluated through dedicated in vitro culturing systems, phenotypic screening assays and comparative genomics, combined with an innovative proof-of-concept study in humans.

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  • Research Project

Insights into the lifestyle and adaptation factors of Dolosigranlum pigrum as probiotic for the upper respiratory tract. 01/10/2021 - 30/09/2025

Abstract

The upper respiratory tract (URT) is a key habitat of the human microbiome, but it is currently underexplored compared to other body sites, especially at the functional level. URT diseases such as chronic rhinosinusitis (CRS) form leading causes for antibiotic prescription, while the functional role of bacteria in the disease pathology is still not clear. As such, CRS is a microbial disease needing new insights in functional biology and microbial ecology to design novel therapeutic strategies. Based on microbiome sequencing of the URT, the underexplored lactic acid bacterium Dolosigranulum pigrum is associated with URT health, highlighting its potential as URT probiotic. Nevertheless, fundamental and molecular research is lacking on its beneficial mechanisms of action, and on its ecological and adaptation mechanisms in the human nasal cavity. This project will therefore focus on exploring the biology and metabolic properties of D. pigrum strains isolated from healthy URT samples, using comparative genomics, phenotypic screening assays and fluorescent microscopy techniques. In addition, the barrier-enhancing and anti-inflammatory properties of D. pigrum isolates will be evaluated in complex in vitro cell culture systems. In parallel, molecular biology tools will be used for further molecular characterization of the isolated strains' mechanisms of action. Finally, the most promising D. pigrum strains will be evaluated in murine models relevant for CRS.

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  • Research Project

Development of a predictive model for endotype-based patient selection for obstructive sleep apnea treatment. 01/10/2021 - 30/09/2024

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent disease, associated with several cardiovascular and cerebrovascular comorbidities. Adequate treatment is thus crucial. Based on the current guidelines, continuous positive airway pressure (CPAP) is considered the standard OSA treatment. While CPAP efficacy is high, patient tolerance and acceptance is only moderate. In general, alternative non-CPAP treatments like mandibular advancement devices, hypoglossal nerve stimulation or pharmacotherapy are well-received, however, their efficacy is potent in some patients but incomplete in others. Efficacy of emerging therapies depends largely on the site of obstruction of the upper airway, key diagnostic information that is notoriously challenging to obtain. In current clinical practice this information is captured during drug-induced sleep endoscopy (DISE), assessing the upper airway during sedation. However, this DISE procedure still requires an additional step in the clinical path involving specialized personnel, time and equipment at the operating theatre. Therefore, I aim to 1) correlate the collapse patterns during DISE with parameters extracted from baseline clinical data in order to develop a prediction model to predict collapse patterns without the need of drug-induced sedation and 2) to apply this model to patients treated with a non-CPAP treatment. In this way, I aim to attain precision OSA medicine using endotype-driven instead of guideline-based OSA treatment.

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  • Research Project

Correlations between upper airway endoscopy and physiological traits of obstructive sleep apnea. 04/01/2021 - 04/07/2021

Abstract

Site, pattern and degree of upper airway collapse is correlated with different obstructive sleep apnea (OSA) treatment outcomes. Currently, assessment requires additional, invasive endoscopy techniques. In the current research proposal I aim to non-invasively associate endoscopic outcomes with baseline overnight sleep study parameters using the technical and analytical skills from the group of Drs. Wellman and Sands at Harvard Medical School and the high quality clinical data of the Antwerp University Hospital. Combining the unique features of both groups into one research project will leverage sleep medicine in both the US and Belgium, paving the way to personalized OSA management.

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  • Research Project

The development of a multifactorial model to predict the outcome of mandibular advancement device therapy for obstructive sleep apnea based on the patients' phenotype. 01/10/2019 - 30/09/2023

Abstract

Obstructive sleep apnea (OSA) is a prevalent public health issue with an attributable risk of cardio- and cerebrovascular morbidity and mortality. Furthermore, OSA is related to a high socioeconomic burden due to its clinical daytime consequences such as excessive daytime sleepiness, impaired cognitive performance and reduced quality of life. Oral appliances that protrude the mandible, the mandibular advancement devices (MAD), significantly reduce OSA severity in the majority of patients. However, in a third of patients, the efficacy is not medically appropriate to reduce the long-term consequences of OSA. Furthermore, the efficacy of MAD therapy is inconsistent among patients. Therefore, a high need exists for upfront prediction of treatment outcome in the individual OSA patient. There is no validated method that can achieve upfront selection of candidates for MAD therapy in an accurate and reliable way. Nowadays, it is increasingly recognized that OSA is a multifactorial disease. In the proposed research project, a prospective prediction model with a combination of different pathophysiological traits will be assessed. Furthermore, up to now, our understanding of MAD therapy relies on relatively small studies lacking power. Therefore, we will evaluate this predictive model, as well as the long-term effectiveness, morbidity and mortality in a large international cohort of patients treated with MAD.

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  • Research Project

In vivo POC of potential respiratory probiotic strains (REINSPIRE). 01/01/2018 - 31/12/2018

Abstract

Probiotics are defined as live microorganisms which, when applied inadequate amounts, confer a health benefit to the host (FAO/WHO, 2001). These microbes are generally applied in the gastrointestinal tract via fermented food products or capsules. In previous research, we isolated bacterial strains with potential probiotic properties for the upper respiratory tract based on in vitro laboratory tests and genome sequencing. Here, we want to deliver the POC that – at least one of - these strains has also interesting properties in vivo, i.e. that this strain is able to –temporarily- colonize the upper respiratory tract of healthy volunteers after oral and nasal application.

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  • Research Project

Integrated approach for the assessment of the anatomical traits for the prospective selection of obstructive sleep apnea patients for upper airway stimulation or its combination therapy with mandibular advancement device. 01/10/2017 - 30/09/2021

Abstract

Obstructive sleep apnea (OSA) is a chronic disease that is caused by partial or complete upper airway collapse during sleep. OSA is a highly prevalent disorder linked to a range of considerable health risks. Application of continuous positive airway pressure (CPAP) is regarded as the gold standard treatment for more severe OSA. The clinical effectiveness of CPAP is often hampered by the inadequate adherence to CPAP mainly due to limited tolerance of the treatment. The techniques that are currently used for the selection of OSA patients for alternative, non-CPAP treatment options such as oral appliance therapy, with mandibular advancement device (MAD), or upper airway stimulation (UAS) synchronized with ventilation, are rather invasive. An integrated, innovative approach that might allow for non-invasive assessment of the anatomical traits of the individual upper airway will be evaluated. The hypothesis of this research project is that these anatomical traits, site of upper airway collapse and degree of pharyngeal collapsibility, can be derived from the respiratory flow signal that is measured during each routine sleep study anyway. The predictive value of this innovative and non-invasive method will be analyzed, also in comparison to the techniques that are currently employed for this purpose of patients' selection. Whether the innovative and non-invasive approach has a better predictive value towards a successful treatment outcome with UAS with or without MAD will be investigated. The main goal is to improve the results with these treatment options for OSA based on the non-invasive assessment of the anatomical traits of the upper airway in the individual OSA patient.

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  • Research Project

Innovative pathophysiological phenotyping of obstructive sleep apnea patients for individualized therapy selection. 01/10/2016 - 30/09/2021

Abstract

Obstructive sleep apnea (OSA) is a common disorder associated with considerable health risks including mortality. The recommended treatment option for more severe OSA is continuous positive airway pressure or CPAP. It has been demonstrated that CPAP is able to mitigate the OSA-associated risks but its effectiveness remains rather low as its use is often hampered by poor tolerance. Consequently there is a high need for non-CPAP therapies. The challenge with these therapies is that the outcome in unselected patients is variable. In this project we will focus on an innovative approach that would allow to determine all pathophysiological traits in the individual OSA patient. First we aim at demonstrating that the anatomical traits, site of upper airway obstruction and tendency of the upper airway to collapse during sleep, can be derived from flow signals that are collected during sleep studies anyway. Secondly we will conduct studies to predict the outcome with non-CPAP therapies integrating the noninvasive anatomical assessment with the validated method for phenotyping. Two distinct types of surgery will thus be analyzed. Lastly we will apply the method for determining the traits of patients that undergo a combination treatment. This project aims at identifying predictors of treatment success in the individual patient based on a better understanding of OSA pathophysiology. This individualized therapy selection will likely yield to better health outcomes with non-CPAP therapies.

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  • Research Project

Study of the microbiota and the potential of probiotics in chronic rhinosinusitis 01/01/2016 - 14/04/2020

Abstract

Upper respiratory tract (URT) infections have a major impact on public and animal health with a high incidence in Flanders. Moreover, these infections predispose to lower respiratory tract and lung infections, which have a higher impact on health worldwide than all other infectious diseases combined. The study of the microbiome and the investigation of new possible bacterio- and probiotic therapies can deliver additional first in line solutions, which will eventually lead to lower antibiotics usage.

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  • Research Project

ProCure : Defining the future of probiotics for upper respiratory tract diseases. 01/01/2016 - 31/12/2019

Abstract

This project aims to explore probiotic microbial approaches that can efficiently reduce the incidence and symptoms of diseases of the upper respiratory tract (URT). Hereto, we will set up an enabling platform to (1) select innovative probiotic strains for this original human body niche of probiotic application, (2) develop innovative processes for the formulation, upscaling and application of these probiotic strains and (3) develop innovative services based on cellular, more complex polymicrobial model systems and microbiome analyses of the URT to monitor the impact of probiotics, food and pharmaceutical compounds on the microbiota of the URT.

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  • Research Project

Pathophysiologic and cardiovascular alterations during continuous positive airway pressure and oral appliance therapies in the optimal therapeutic dose for patients with obstructive sleep apnea. 01/10/2015 - 30/09/2018

Abstract

Obstructive sleep apnea (OSA) is a prevalent public health issue and strong and independent risk factor for cardio- and cerebrovascular diseases. Therefore, adequate treatment is important. Continuous positive airway pressure (CPAP) is considered the gold standard non-invasive treatment modality, although oral appliances that protrude the mandible are increasingly prescribed. Both non-invasive treatment modalities are symptomatic treatments and therefore lifelong device therapies, so the patient's compliance is of primary importance since it is only effective when appropriately used. The therapeutic effectiveness of both therapies is given by the product of efficacy with objective compliance. For both CPAP and oral appliance therapies, it is important to determine the therapeutic effectiveness in the optimal 'dose', being pressure for CPAP and mandibular protrusion for oral appliances. However, in the absence of a gold standard protocol to find the optimal mandibular protrusion for oral appliance therapy, the titration procedure remains 'trial and error'. Therefore, in the proposed research project, the feasibility of a titration procedure during polysomnography will be assessed and compared with a titration procedure under direct visualization of upper airway collapse during drug-induced sedation endoscopy, for both therapies. Furthermore, the pathophysiologic and cardiovascular alterations during both treatment modalities in the established optimal dose will be studied.

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  • Research Project