Neural Dissimilarity in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Biologics

The sense of smell is essential in social interactions, food intake and hazard detection. Olfactory dysfunction (OD) affects approximately 20% of the adults and likely increased following the COVID-19 pandemic. The pandemic highlighted the substantial burden of OD on daily life and well-being.

A common cause of acquired OD is Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) affecting 2-4% of adult Scandinavian population. The vast majority of CRSwNP in this population is driven by type-2 inflammation. Decreased sense of smell is an almost obligatory complaint in severe CRSwNP with an OD prevalences of ~95% and ranked as one of the most important.

OD is the symptom in CRSwNP with greatest effect on health-related quality of life and at the same time remains difficult to treat.

New treatments for patients with severe CRSwNP have recently become available in form of monoclonal antibodies selectively blocking pro-inflammatory cytokines in the type-2-inflammation cascade. These biologics show substantial improvements in self-reported olfactory tests.

Knowledge of neuroanatomical functional and structural correlates to olfactory function has long existed. However, only few have used functional magnetic resonance imaging (fMRI) to investigate OD in CRS patients. Patients with CRS-related OD offer a unique neurobiological model for studying olfactory plasticity as olfaction potentially improves.

This study aims to determine whether improvement in olfaction represented by TDI scores after medical treatment with biologics (anti IL-5 or anti IL-4/13) for severe CRSwNP is accompanied by functional changes in olfactory brain ROIs as represented by differences in representational dissimilarity matrixes (RDMs).

Patients with olfactory dysfunction (OD) due to CRSwNP are recruited before or shortly after their first injection of monoclonal antibodies/biologic therapy. Nasal endoscopy and a validated olfactory test (TDI) are performed. Participants also undergo fMRI, during which they are presented with three different odors that they are asked to categorize. A group of age- and sex-matched healthy controls with normal olfactory function and no disease of the nasal or paranasal sinus system undergoes the same assessments.

All examinations are repeated in both groups after 24 weeks +/- 2 weeks..

By constructing RDMs based on fMRI-data we will invesitage how central olfactory processing changes following 24 weeks of biologic treatment and whether these neural changes are associated with improvements in olfactory performance.

Inclusion criteria

• Age 18 years or above
• Olfactory dysfunction (i.e., a TDI score < 30.75)
• Eligible for treatment with biologics (i.e., meeting the Danish criteria for treatment with biologics (40) which includes fulfillment of the EPOS criteria for CRS.
• Either treatment naïve to biologics or had their first injection within a maximum of 48 hours prior to the scan.
• No other obvious explanation for the olfactory dysfunction (including, but not limited to: head trauma, sinus surgery, tumors in the nose or brain, upper respiratory infection, neurological or psychiatric disease)
• Control group: normosmic at baseline (i.e., TDI-score >30.75)

Exclusion criteria

• Previously recognized loss of sense of smell and taste due to other sinonasal or neurological conditions.
• Neurodegenerative disorders known to cause olfactory deficits (Parkinson's, Alzheimer's, Lewy-Body Dementia, Amyotrophic lateral Sclerosis etc.)
• Other obvious explanation for the OD (i.e., smell loss occurring in relation to one of the following (including, but not limited to): head trauma, sinus surgery, upper respiratory infection.
• Contraindications for MRI scan including:

• Implants or prostheses of magnetic metal
• Metal foreign bodies
• Pregnancy
• Severe claustrophobia
• Unable to complete the full MRI session.
• Not able to comprehend written and/or spoken Danish language.