Oropharyngeal dysphagia, pathophysiology, neurophysiology and new treatments

PIs: Pere Clavé, Omar Ortega, Noemí Tomsen

Oropharyngeal dysphagia (OD) is a common swallowing disorder that affects > 50% of older hospitalised patients and those who have suffered stroke or other neurological illnesses. OD causes severe nutritional and respiratory complications. Despite this, OD is underestimated and little diagnosed, there is currently no specific pharmacological treatment because the potential therapeutic targets are unknown.

The goal of the group is to better understand its pathophysiology, especially the brain swallowing network, in order to develop neurohabilitation strategies with pharmacological stimulation, electrical intrapharyngeal or transcutaneous stimulation, transcranial magnetic stimulation (rTMS) and electrical transcranial stimulation (tDCS) to move from compensation to the recovery of swallowing function.

These studies have been an important methodological and conceptual step for the group, allowing to evaluate both the sensory or afferent pathway (pharyngeal sensory evoked potentials to intrapharyngeal electrical stimulation) and the motor pathway of swallowing (pharyngeal motor evoked potentials to transcranial magnetic stimulation).

The development of this line of research has made it possible to know in depth the pathophysiology of OD in different patient phenotypes, demonstrating that the alteration in the swallowing response is not only biomechanical but also neurophysiological. With these results, the group has designed a new treatment paradigm that aims to treat the sensory and motor pathways of swallowing and move from the therapeutic concept of "compensation" to the paradigm of "neurostimulation, promotion of neuronal plasticity and recovery of function swallowing".

Oropharyngeal dysphagia, complications and compensatory interventions

PIs: Pere Clavé, Omar Ortega

OD can cause two groups of severe complications with high impact on the health and quality of life of patients: a) If there is impaired efficacy of swallow, the patient will present malnutrition and/or dehydration; up to 50% of institutionalised older people are poorly nourished; b) If there is impaired safety of swallow tracheobronchial aspiration occurs, this can cause pneumonia in 50% of cases with an associated mortality of 50%.

The main aim of the group is to study the risk factors for these complications and to develop protocols to reduce their incidence by using minimal-massive strategies based on compensation (fluid and diet adaptation, nutritional supplementation and oral hygiene). These studies include the study of the therapeutic effect of a new generation of commercial thickeners (industry-sponsored studies: Fresenius Kabi, Nutricia, Nestlé, Morinaga) and the study of optimal massive intervention (OMI) in elderly people hospitalised with oropharyngeal dysphagia.

This last study is the result of a pilot study (PMID: 29806864) based on the treatment of the three main risk factors for the development of respiratory complications in patients with OD: 1) impaired safety of swallow including aspiration through thickeners; 2) altered functional state with malnutrition and immune alteration with the triple adaptation of the Mediterranean diet (textural, caloric-protein and organoleptic) and oral nutritional supplementation; and 3) poor hygiene and oral health with colonisation by respiratory pathogens (professional oral hygiene and basic recommendations). It is a randomized clinical trial with 600 patients and two treatment arms (1) Optimal-massive intervention and (2) standard hospital treatment). The long-term aim of the study is to establish the OMI strategy within the usual clinical practice of CSdM and progress in the adaptation of the OMI in the Special Education School of Arboç where all its users have OD.

TRP receptors and pharmacological treatment of oropharyngeal dysphagia

PIs: Pere Clavé, Noemí Tomsen

The aim is to develop specific active treatments to rehabilitate the swallowing function by chemical oropharyngeal stimulation, being the Transient Receptor Potential (TRP) channel agonists the ones with the most promising results. The group assesses the immediate (acute studies), the mid-term (sub-acute studies) and long-term effects of several TRP agonists and their mechanism of action. In all of their studies, they determine the therapeutic effect on biomechanical and neurophysiological (both, afferent and efferent pathway) swallow response, as well as on brain activation and its neurotopography and on the salivary neuropeptides SP and CGRP.

Neurorehabilitation and neuroplasticity

PIs: Pere Clavé, Omar Ortega

These strategies, of which the group has already demonstrated their potential, include: a) peripheral sensory stimulation with transcutaneous or intrapharyngeal electrical stimulation, and b) non-invasive brain stimulation studies (central stimulation) with repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). With the evidence generated, the goals set for the coming years for the central stimulation strategy are: 1) to evaluate the effect of paired stimulation with tDCS and TRP agonists in patients with acute post-stroke OD; 2) evaluate the therapeutic effect of paired stimulation with rTMS and TRP agonists in patients with chronic post-stroke OD.

Oropharyngeal dysphagia, rheology and texture of alimentary fluids and texture modified diets

PIs: Pere Clavé, Mireia Bolívar

The purpose of food rheology and texture studies is to be able to quantitatively characterise texture-modified diets. Regarding fluids, the viscosity (mPa·s) is evaluated at two shear rates determined by swallowing and the effect of alpha amylase (oral enzyme). To date, the group has demonstrated the safety and efficacy of increasing viscosity with xanthan gum thickeners, as well as determining the two optimal doses to cover 90% of patients in different OD patient phenotypes (PMID: 31402571, 32585942), and has evidenced the risk of marketing thickeners without including a quantitative description of their properties. Regarding solid textures, the quantification of maximal strength (N), adhesiveness (N·s), cohesiveness and the impact of oral and chewing processing, the group is determining the optimal values to establish objective criteria for the modified texture diets prescribed in patients with swallowing and mastication disorders. The goal for the next few years is to develop a range of food fluids and diets of modified texture with rheological and textural properties defined with units of the International System (SI Units).

Big data and artificial intelligence tools for massive screening of prevalent pathologies

PI: Pere Clavé, Alberto Martín

The Mataró General Hospital has been a pioneer in the implementation of a program for Research Data Analysis (ANDARE) in order to exploit the health data generated through daily clinical practice for health research. ANDARE ensures compliance with the General Data Protection Regulation (RGPD 2016) and the Organic Law on Data Protection (LOPD 03/2018), guaranteeing the confidentiality and data protection rights of patients, as well as the legal guarantees to our professionals, treating anonymized and pseudo-anonymized data previously collected.

As a result of this line of research, AIMS RISK (Artificial Intelligence Massive Screening - RISK) has been created, an AI-based software that automatically provides patients' risk of several geriatric syndromes in real time at the clinicians' workstation, analysing the information collected in the electronic medical records, in order to perfom a systematical and universal triage. This is an innovative solution to the challenge of under-diagnosing geriatric syndromes in older patients at different levels of care.

AIMS-RISK has been selected in two Start-up acceleration programs (CaixaImpulse "La Caixa Fundation" and StartHealth (TecnoCampus)) in order to value the asset and form a spin-off for its technology transfer. Other projects that are being worked on in this laboratory and that will take place over the next 3 years are: a) Analysis of clinical signals from electroencephalography, videofluoroscopy, esophageal manometry and mastication in patients with OD and b) Extraction of information from medical reports through Transfer Learning and Natural Language Processing techniques.

Gastro-esophageal motility

PIs: Pere Clavé, Ricard Farré

The aim of this research line is to better know esophageal and gastro-intestinal and vesical motility in order to discover its relation to appetite control in different population groups such as the robust and frail elderly, obese individuals and obese individuals who have undergone bariatric surgery. Specifically, this focuses on understanding if there are alterations in gastrointestinal motility or the neuro-hormonal system which regulates appetite and sating, studying the alterations in gastrointestinal motility and neuro-hormonal appetite control in obese individuals, studying the modifications brought about in gastro-intestinal motility by restrictive bariatric surgery in obese individuals and the associated hormone alterations.

The clinical studies in esophageal motility for this new period continue to be located in: a) study of the physiopathology of gastroesophageal reflux that appears after surgeries for morbid obesity, which can affect 50% of patients, and in post-cholecystectomy patients; and b) characterisation of motor patterns in patients with esophageal achalasia and primary motor disorders before and after treatment. At this point, the group collaborates closely with Prof Farré, trained in the same team and currently a professor at University of Leuven, in studying the role of alterations in epithelial physiology, including barrier function, in the pathophysiology of disorders affecting the upper digestive tract (non-erosive reflux disease, functional dyspepsia) and elucidate the role of TRPs and acid-sensitive ion channels (ASICs), present in the submucosal plexus, in the secretion of water from the upper gastrointestinal tract.

Gastrointestinal basic studies

PIs: Pere Clavé, Noemí Tomsen, Ricard Farré

The aim is to describe the basic process involved in all the gastrointestinal disorders studied in the group’s lab, focused on: 1) In vitro gastrointestinal motility studies using organ bath to establish the motility alterations at the neurotransmission/muscular levels, which occur at different disease stages and as a result of interactions with immune cells, and to evaluate new therapeutic targets; 2) Localisation and quantification of TRP and ASIC receptors in human oropharynx samples, using RT-qPCR, immunohistochemistry and Western Blot; 3) Quantification SP and CGRP in blood and saliva using ELISA in order to describe peripheral biomarkers of pharyngeal sensory impairment and response capacity to neurostimulation treatments. The final objective is to determine which of these neurotransmitters could be used as non-invasive biomarkers of the clinical response to peripheral sensory stimulation in patients with neurogenic or aging-related dysphagia; 4) Description of the humoral immunological alteration of patients with OD that facilitates the development of infectious complications of dysphagia such as respiratory infections and aspiration pneumonia.

Treatment of post-stroke oropharyngeal dysphagia with paired stimulation through peripheral TRVP1 agonists and non-invasive brain stimulation

PI: Pere Clavé, Omar Ortega
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: ICI20/00117
Duration: 2020 - 2024

​ ​

Efectos biomecanicos, neurofisiologicos y clinicos de 6 meses de estimulacion con agonistas TRPV1 y TRPA1 en pacientes ancianos con disfagia orofaríngea

PI: Pere Clavé, Omar Ortega
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI22/01101
End date: 2025

AIMS-OD, a systematic screening for oropharyngeal dysphagia in hospitals using Artificial Intelligence

PI: Alberto Martín
Funding agency: Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) - Generalitat de Catalunya
Agency code: 2021 PROD 00193
Duration: 2022 - 2024

Projectes Transformadors en Salut: Implantació d'un protocol d'innovació assistencial pel maneig de disfàgia orofaríngea: cribatge sistemàtic i protocol·lització del tractament compensatori

PI: Pere Clavé
Funding agency: Servei Català de la Salut
Duration: 2022 - 2025

Grup de Recerca en Disfàgia Orofaríngia i Neurogastroenterologia (DYSPOD). SGR consolidated group

PI: Pere Clavé
Funding agency: Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) - Generalitat de Catalunya
Agency code: 2021 SGR 01344

Efecto subagudo de la estimulación sensorial farmacológica de la orofaringe mediante agonistas de los receptores TRP en la neurofisiología de la deglución en ancianos con disfagia orofaríngea

PI: Pere Clavé, Omar Ortega
Funding agency: Instituto de Salud Carlos III (ISCIII)
Agency code: PI18/00241
Start date: 2018
End date: 2022

Validació de artificial intelligence massive screening-malnutrition (AIMS-MN) per el cribratge massiu de malnutricio i priorització del diagnòstic clínic

PI: Pere Clavé
Funding agency: PERIS. Departament de Salut de la Generalitat de Catalunya
Agency code: SLT033/23/000063
Duration: 2022 - 2023

The Territorial Competitiveness Specialization Project (PECT) of Mataro-Maresme

PI: Alberto Martín
Funding agency: Generalitat de Catalunya within the framework of the European Regional Developments Funds of Catalonia Operational Programme 2019-2024
Agency code: PRE/161/2019
Duration: 2020 - 2023

CaixaImpulse Validate: ARTIFICIAL INTELLIGENCE IN THE SERVICE OF SYSTEMATIC DYSPHAGIA SCREENING - AIMS-OD

PI: Alberto Martín
Funding agency: Fundació la Caixa
Agency code: CI20-00158
Duration: 2020 - 2023

Title: Rheological in vitro and ex vivo characterisation of thickening products used for compensatory treatment of swallow dysfunction in patients with oropharyngeal dysphagia
Author: Mireia Bolívar-Prados
Supervisor: Pere Clavé
University: Universitat Autònoma de Barcelona
Date of defense: 10/02/2023

Title: Desarrollo de un protocolo de innovación asistencial para el manejo de la disfagia orofaríngea en ancianos hospitalizados: cribado sistemático mediante machine learning, diagnóstico clínico y tratamiento compensador con intervenciones mínimas-masivas
Author: Alberto Martín-Martínez
Supervisors: Pere Clavé, Omar Ortega
University: Universitat Autònoma de Barcelona
Date of defense: 14/04/2023